@Article{ SchindlerB2016_2, title = {Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex during Processing of Visual Optic Flow}, journal = {Cerebral Cortex}, year = {2017}, month = {5}, volume = {27}, number = {5}, pages = {2885-2893}, abstract = {Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1–V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding.}, web_url = {https://academic.oup.com/cercor/article-pdf/27/5/2885/14142141/bhw136.pdf}, state = {published}, DOI = {10.1093/cercor/bhw136}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ LeeAW2017, title = {Developmental Microglial Priming in Postmortem Autism Spectrum Disorder Temporal Cortex}, journal = {Brain, Behavior, and Immunity}, year = {2017}, month = {5}, volume = {62}, pages = {193–202}, abstract = {Microglia can shift into different complex morphologies depending on the microenvironment of the central nervous system (CNS). The distinct morphologies correlate with specific functions and can indicate the pathophysiological state of the CNS. Previous postmortem studies of autism spectrum disorder (ASD) showed neuroinflammation in ASD indicated by increased microglial density. These changes in the microglia density can be accompanied by changes in microglia phenotype but the individual contribution of different microglia phenotypes to the pathophysiology of ASD remains unclear. Here, we used an unbiased stereological approach to quantify six structurally and functionally distinct microglia phenotypes in postmortem human temporal cortex, which were immuno-stained with Iba1. The total density of all microglia phenotypes did not differ between ASD donors and typically developing individual donors. However, there was a significant decrease in ramified microglia in both gray matter and white matter of ASD, and a significant increase in primed microglia in gray matter of ASD compared to typically developing individuals. This increase in primed microglia showed a positive correlation with donor age in both gray matter and white of ASD, but not in typically developing individuals. Our results provide evidence of a shift in microglial phenotype that may indicate impaired synaptic plasticity and a chronic vulnerability to exaggerated immune responses.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0889159117300193}, state = {published}, DOI = {10.1016/j.bbi.2017.01.019}, author = {Lee AS{alee}{Department Physiology of Cognitive Processes}; Azmitia EC; Whitaker-Azmitia PM} } @Article{ BesserveSSJ2017, title = {Group invariance principles for causal generative models}, journal = {-}, year = {2017}, month = {5}, abstract = {The postulate of independence of cause and mechanism (ICM) has recently led to several new causal discovery algorithms. The interpretation of independence and the way it is utilized, however, varies across these methods. Our aim in this paper is to propose a group theoretic framework for ICM to unify and generalize these approaches. In our setting, the cause-mechanism relationship is assessed by comparing it against a null hypothesis through the application of random generic group transformations. We show that the group theoretic view provides a very general tool to study the structure of data generating mechanisms with direct applications to machine learning.}, web_url = {https://arxiv.org/abs/1705.02212}, state = {submitted}, author = {Besserve M{besserve}{Department Physiology of Cognitive Processes}; Shajarisales N; Sch\"olkopf B{bs}; Janzing D{janzing}} } @Article{ SafaviDKWHLP2017, title = {Non-monotonic spatial structure of interneuronal correlations in prefrontal microcircuits}, journal = {-}, year = {2017}, month = {5}, abstract = {Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here we show such a spatially non-monotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A non-monotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.}, web_url = {http://biorxiv.org/content/early/2017/04/19/128249}, state = {accepted}, DOI = {10.1101/128249}, author = {Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Dwarakanath A{adwarakanath}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Werner J{joachim}{Department Physiology of Cognitive Processes}; Hatsopoulos NG; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Article{ JusyteZHBS2017, title = {Binocular rivalry transitions predict inattention symptom severity in adult ADHD}, journal = {European Archives of Psychiatry and Clinical Neuroscience}, year = {2017}, month = {4}, volume = {Epub ahead}, abstract = {Attention deficit and hyperactivity disorder (ADHD) is a prevalent childhood disorder that is often maintained throughout the development and persists into adulthood. Established etiology models suggest that deficient inhibition underlies the core ADHD symptoms. While experimental evidence for impaired motor inhibition is overwhelming, little is known about the sensory inhibition processes, their changes throughout the development, and the relationship to ADHD symptoms. Here, we used the well-established binocular rivalry (BR) paradigm to investigate for the very first time the inhibitory processes related to visual perception in adults with ADHD. In BR, perception alternates between two dichoptically presented images throughout the viewing period, with shorter dominant percept durations and longer transition periods indicating poorer suppression/inhibition. Healthy controls (N = 28) and patients with ADHD (N = 32) were presented with two dissimilar images (orthogonal gratings) separately to each eye through a mirror stereoscope and asked to report their perceptual experiences. There were no differences between groups in any of the BR markers. However, an association between transition durations and symptom severity emerged in the ADHD group. Importantly, an exploratory multiple regression analysis revealed that inattention symptoms were the sole predictor for the duration of transition periods. The lack of impairments to sensory inhibition in adult, but not pediatric ADHD may reflect compensatory changes associated with development, while a correlation between inhibition and inattention symptoms may reveal an invariant core of the disorder.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00406-017-0790-1.pdf}, state = {published}, DOI = {10.1007/s00406-017-0790-1}, author = {Jusyte A; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; H\"ohnle NM; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Sch\"onenberg M} } @Article{ PolimeniRZF2017, title = {Analysis strategies for high-resolution UHF-fMRI data}, journal = {NeuroImage}, year = {2017}, month = {4}, volume = {Epub ahead}, abstract = {Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811917303713}, state = {accepted}, DOI = {10.1016/j.neuroimage.2017.04.053}, author = {Polimeni JR; Renvall V; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Fischl B} } @Article{ TakemuraPWKLSYBLFLW2016, title = {Occipital White Matter Tracts in Human and Macaque}, journal = {Cerebral Cortex}, year = {2017}, month = {3}, volume = {Epub ahead}, abstract = {We compare several major white-matter tracts in human and macaque occipital lobe using diffusion magnetic resonance imaging. The comparison suggests similarities but also significant differences in the tracts. There are several apparently homologous tracts in the 2 species, including the vertical occipital fasciculus (VOF), optic radiation, forceps major, and inferior longitudinal fasciculus (ILF). There is one large human tract, the inferior fronto-occipital fasciculus, with no corresponding fasciculus in macaque. We could identify the macaque VOF (mVOF), which has been little studied. Its position is consistent with classical invasive anatomical studies by Wernicke. VOF homology is supported by similarity of the endpoints in V3A and ventral V4 across species. The mVOF fibers intertwine with the dorsal segment of the ILF, but the human VOF appears to be lateral to the ILF. These similarities and differences between the occipital lobe tracts will be useful in establishing which circuitry in the macaque can serve as an accurate model for human visual cortex.}, web_url = {https://academic.oup.com/cercor/article-lookup/doi/10.1093/cercor/bhx070}, state = {published}, DOI = {10.1093/cercor/bhx070}, author = {Takemura H; Pestilli F; Weiner KS; Keliris GA{george}{Department Physiology of Cognitive Processes}; Landi SM; Sliwa J; Ye FQ; Barnett MA; Leopold DA{davidl}{Department Physiology of Cognitive Processes}; Freiwald WA; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Wandell BA} } @Article{ GrassiZB2016_5, title = {Scene segmentation in early visual cortex during suppression of ventral stream regions}, journal = {NeuroImage}, year = {2017}, month = {2}, volume = {146}, pages = {71–80}, abstract = {A growing body of literature suggests that feedback modulation of early visual processing is ubiquitous and central to cortical computation. In particular stimuli with high-level content that invariably activate ventral object responsive regions have been shown to suppress early visual cortex. This suppression was typically interpreted in the framework of predictive coding and feedback from ventral regions. Here we examined early visual modulation during perception of a bistable Gestalt illusion that has previously been shown to be mediated by dorsal parietal cortex rather than by ventral regions that were not activated. The bistable dynamic stimulus consisted of moving dots that could either be perceived as corners of a large moving cube (global Gestalt) or as distributed sets of locally moving elements. We found that perceptual binding of local moving elements into an illusory Gestalt led to spatially segregated differential modulations in both, V1 and V2: representations of illusory lines and foreground were enhanced, while inducers and background were suppressed. Furthermore, correlation analyses suggest that distinct mechanisms govern fore- and background modulation. Our results demonstrate that motion-induced Gestalt perception differentially modulates early visual cortex in the absence of ventral stream activation.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811916306437}, state = {published}, DOI = {10.1016/j.neuroimage.2016.11.024}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ OrtizRiosAKBMKLR2017, title = {Widespread and Opponent fMRI Signals Represent Sound Location in Macaque Auditory Cortex}, journal = {Neuron}, year = {2017}, month = {2}, volume = {93}, number = {4}, pages = {971–983}, abstract = {In primates, posterior auditory cortical areas are thought to be part of a dorsal auditory pathway that processes spatial information. But how posterior (and other) auditory areas represent acoustic space remains a matter of debate. Here we provide new evidence based on functional magnetic resonance imaging (fMRI) of the macaque indicating that space is predominantly represented by a distributed hemifield code rather than by a local spatial topography. Hemifield tuning in cortical and subcortical regions emerges from an opponent hemispheric pattern of activation and deactivation that depends on the availability of interaural delay cues. Importantly, these opponent signals allow responses in posterior regions to segregate space similarly to a hemifield code representation. Taken together, our results reconcile seemingly contradictory views by showing that the representation of space follows closely a hemifield code and suggest that enhanced posterior-dorsal spatial specificity in primates might emerge from this form of coding.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627317300375}, state = {published}, DOI = {10.1016/j.neuron.2017.01.013}, author = {Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}; Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Kuśmierek P; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Munk MH{munk}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker P} } @Article{ TotahNPLE2017, title = {Monitoring large populations of locus coeruleus neurons reveals the non-global nature of the norepinephrine neuromodulatory system}, journal = {-}, year = {2017}, month = {2}, abstract = {The non-specific neuromodulation of the forebrain by the noradrenergic locus coeruleus (LC) is a foundation of wide-ranging theories of cognitive and systems neuroscience. The non-specificity is assumed because of the diffuse projections of the nucleus as well as the synchronous spiking of its neurons. Synchrony, however, has never been assessed in a large population of LC cells, i.e. single units, nor has it been systematically related to specificity of their projection targets. Here, we recorded up to 52 single units simultaneously (3164 unit pairs) in the rat LC, and characterized forebrain projection patterns using antidromic stimulation. Two novel unit types were characterized; they differed by waveform shape, firing rate, and propensity for synchronization. Cross-correlation analysis revealed a surprisingly poor correlation between unit spiking; only 13% of unit pairs had response profiles reflecting synchronization due to common synaptic input or gap junctions. While LC unit spikes were phase locked to cortical slow oscillations (< 2 Hz), they did so intermittently, yielding poor population synchronization. A novel infra-slow (0.01-1 Hz) spiking fluctuation was observed in LC units, yet this too was asynchronous across unit pairs. A highly synchronized minority had a stronger tendency for targeted forebrain neuromodulation. Our findings demonstrate that the LC may convey a more complex and differentiated neuromodulatory signal than is widely assumed.}, web_url = {http://biorxiv.org/content/biorxiv/early/2017/02/18/109710.full.pdf}, state = {submitted}, DOI = {10.1101/109710}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenk O{oeschenko}{Department Physiology of Cognitive Processes}} } @Article{ KwonWFB2016, title = {Attention reorganizes connectivity across networks in a frequency specific manner}, journal = {NeuroImage}, year = {2017}, month = {1}, volume = {144}, number = {Part A}, pages = {217-226}, abstract = {Attention allows our brain to focus its limited resources on a given task. It does so by selective modulation of neural activity and of functional connectivity (FC) across brain-wide networks. While there is extensive literature on activity changes, surprisingly few studies examined brain-wide FC modulations that can be cleanly attributed to attention compared to matched visual processing. In contrast to prior approaches, we used an ultra-long trial design that avoided transients from trial onsets, included slow fluctuations (<0.1 Hz) that carry important information on FC, and allowed for frequency-segregated analyses. We found that FC derived from long blocks had a nearly two-fold higher gain compared to FC derived from traditional (short) block designs. Second, attention enhanced intrinsic (negative or positive) correlations across networks, such as between the default-mode network (DMN), the dorsal attention network (DAN), and the visual system (VIS). In contrast attention de-correlated the intrinsically correlated visual regions. Third, the de-correlation within VIS was driven primarily by high frequencies, whereas the increase in DAN-VIS predominantly by low frequencies. These results pinpoint two fundamentally distinct effects of attention on connectivity. Information flow increases between distinct large-scale networks, and de-correlation within sensory cortex indicates decreased redundancy.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811916305614}, state = {published}, DOI = {10.1016/j.neuroimage.2016.10.014}, author = {Kwon S{soyoung}{Department Physiology of Cognitive Processes}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Fischer E{efischer}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Inbook{ ZaldivarLG2017, title = {Pharmaco-Based fMRI and Neurophysiology in Non-human Primates}, year = {2017}, pages = {37-66}, abstract = {Brain activity is continuously changing, among others reflecting the effects of neuromodulation on multiple spatial and temporal scales. By altering the input–output relationship of neural circuits, neuromodulators can also affect their energy expenditure, with concomitant effects on the hemodynamic responses. Yet, it is still unclear how to study and interpret the effects of different neuromodulators, for instance, how to differentiate their effects from underlying behavior- or stimulus-driven activity. Gaining insights into neuromodulatory processes is largely hampered by the lack of approaches providing information concurrently at different spatio-temporal scales. Here, we provide an overview of the multimodal approach consisting of functional magnetic resonance imaging (fMRI), pharmacology and neurophysiology, which we developed to elucidate causal relationships between neuromodulation and neurovascular coupling in visual cortex of anesthetized macaques.}, web_url = {http://link.springer.com/content/pdf/10.1007%2F978-1-4939-6490-1_3.pdf}, editor = {Philippu, A.}, publisher = {Springer}, address = {New York, NY, USA}, series = {Neuromethods ; 121}, booktitle = {In Vivo Neuropharmacology and Neurophysiology}, state = {published}, ISBN = {978-1-4939-6488-8}, DOI = {10.1007/978-1-4939-6490-1_3}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}} } @Poster{ SchindlerB2017, title = {Examining Egocentric Spatial Representations Referenced to Head and Body in the Healthy Brain}, year = {2017}, month = {6}, day = {28}, number = {3428}, abstract = {Introduction: Spatial representations in distinct reference frames are essential for human behavior. Visual input is received in retinotopic coordinates. Our conscious experience of the environment is however non-retinotopic as eye- and head-movements are typically subtracted from retinal input to provide us with world-centered perceptual stability. Our immediate interactions with the external world occur in self-centered reference frames. Limb-actions are inherently body-centered and need to be invariant to eye- or head-movements. In turn, head- or body-movements shift different parts of the environment in and out of the field of view. Egocentric maps of our full surroundings are thus not only essential for the integration between different senses such as audition, vision, and touch but also assure the stable phenomenal experience of our surrounding based on continual updating of internal spatial maps in the face of changing sensory input. In the present study, we used a novel virtual reality paradigm that involved tilted head-positions during fMRI and multi-variate analyses to identify head- and body-centered representations, as well as attention modulation thereof. Methods: Classically, the participant's fixed head and body orientation inside the scanner prevents disentangling head- from body-centered reference systems. To circumvent this problem, we used a modified version of a virtual reality paradigm we introduced previously (Schindler & Bartels 2013). Participants had to imagine the location of six distinct objects surrounding them arranged in a hexagon, including in front of them and behind them. Importantly, participants' heads were rotated by +60° or -60° in different conditions, such that head and body axes were misaligned. This paradigm allowed us to systematically disentangle head- from body- centered neural representations. In addition, participants performed this task in two distinct attention sets, either involving imagery in head- or body-centered coordinates. This allowed us to probe modulation of head- and body-centered spatial representations by attention to either reference frame. Participants underwent several days of extensive training in which they reached ceiling performance in learning the object locations within the surrounding hexagon. Training was performed outside the scanner using virtual reality goggles. Participants were placed in the center of a virtual hexagonal room that contained a unique object in each corner. Every few trials the participants' viewpoint rotated such that they faced a different corner, i.e., a different allocentric location. This allowed us to isolate six abstract egocentric directions, regardless of the identity of reference objects or of allocentric representations. When performance reached criterion, participants were invited for fMRI scanning and performed a modified task inside the scanner. Using multivariate voxel analysis, we identified egocentric representations beyond the visual field according to body and head coordinates. Results: We found significant decoding of egocentric directions in head- as well as in body-centered reference frames in a network of brain areas associated to spatial processing, attention, and lesion-sites of spatial neglect patients. Among those were pre-cuneus, prefrontal cortex, and parietal cortex. Whereas egocentric codes for body- and head-centered representations overlapped in most regions, we also found biases towards either reference frame in some regions. Attention to body- or head-centered coordinates tended to modulate the decoding accuracy in favor of the respective representation. Conclusions: Our results provide evidence for the presence of both, head- and body-centered neural spatial representations in the human brain. While most of these representations appear to be co-localized, a subset of brain areas was tuned to head or body coordinates. In addition, our results show that the distinct representations can be modulated by attention.}, web_url = {https://ww5.aievolution.com/hbm1701/index.cfm?do=abs.viewAbs&abs=3707}, event_name = {23rd Annual Meeting of the Organization for Human Brain Mapping (OHBM 2017)}, event_place = {Vancouver, BC, Canada}, state = {published}, author = {Schindler A{schindler}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ FichtnerGAMZHK2017_2, title = {Magnetization exchange between water and downfield metabolites in human brain at 9.4T}, year = {2017}, month = {4}, day = {27}, number = {5466}, abstract = {Ultra-high field strengths provide higher signal to noise ratio and improved separation of metabolites in spectroscopy, allowing for more precise characterization of peaks. In particular, this improved peak resolution may be of benefit for characterization of the downfield (5-10ppm) spectrum, which is not yet well characterized; this experiment aims to improve knowledge of downfield peaks by investigating their exchange rates and T1 values at 9.4T, using inversion transfer experiments and metabolite cycling to allow for non-water suppressed acquisition.}, web_url = {http://www.ismrm.org/17/program_files/EP20.htm}, event_name = {25th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2017)}, event_place = {Honolulu, HI, USA}, state = {published}, author = {Fichtner N; Giapitzakis I-A{igiapitzakis}; Avdievich N{navdievi}; Mekle R; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Henning A{ahenning}; Kreis R} } @Poster{ WiesnerBSUZCUP2017, title = {Simultaneous measurement of metabolic rates of oxygen via 17O NMR imaging in brain and muscle tissue of rat at 16.4T}, year = {2017}, month = {4}, day = {27}, number = {5623}, abstract = {In this study, we exploit the feasibility of the 17O MRSI technique for simultaneous measurement of the metabolic rates of oxygen in brain and surrounding muscle based on ROI analysis of dynamics of tissue H217O time courses acquired at 16.4T with 3D 17O MRSI. An established three-phase model originally developed for brain application was extended with certain assumptions applied to the resting temporalis muscle of rats.}, web_url = {http://www.ismrm.org/17/program_files/EP20.htm}, event_name = {25th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2017)}, event_place = {Honolulu, HI, USA}, state = {published}, author = {Wiesner H{wiesner}{Department High-Field Magnetic Resonance}; Balla D{ballad}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Ugurbil K; Zhu X-H; Chen W; Uludag K{kuludag}{Department High-Field Magnetic Resonance}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}} } @Poster{ DelongGARCWN2017, title = {The invisible ventriloquist: can unaware flashes alter sound perception?}, journal = {Brain and Neuroscience Advances}, year = {2017}, month = {4}, day = {10}, volume = {1}, number = {BNA 2017 Festival of Neuroscience: Abstract Book}, pages = {27}, abstract = {Information integration across the senses is fundamental for effective interactions with our environment. A controversial question is whether signals from different senses can interact in the absence of awareness. Models of global workspace would predict that unaware signals are confined to processing in low level sensory areas and thereby prevented from interacting with signals from other senses in higher order association areas. Yet, accumulating evidence suggests that multisensory interactions can emerge – at least to some extent- already at the primary cortical level [1]. These low level interactions may thus potentially mediate interactions between sensory signals in the absence of awareness. Combining the spatial ventriloquist illusion and dynamic continuous flash suppression (dCSF) [2] we investigated whether visual signals that observers did not consciously perceive can influence spatial perception of sounds. Importantly, dCFS obliterated visual awareness only on a fraction of trials allowing us to compare spatial ventriloquism for physically identical flashes that were judged visible or invisible. Our results show a stronger ventriloquist effect for visible than invisible flashes. Yet, a robust ventriloquist effect also emerged for flashes judged invisible. This ventriloquist effect for invisible flashes was even preserved in participants that were not better than chance when locating flashes they judged ‘invisible’. Collectively, our findings demonstrate that physically identical visual signals influence the perceived location of concurrent sounds depending on their subjective visibility. Even visual signals that participants are not aware of can alter sound perception. These results suggest that audiovisual signals are integrated into spatial representations to some extent in the absence of perceptual awareness.}, web_url = {http://journals.sagepub.com/doi/pdf/10.1177/2398212817705279}, event_name = {BNA 2017 Festival of Neuroscience (British Neuroscience Association)}, event_place = {Birmingham, UK}, state = {published}, author = {Delong P; Giani A{giani}{Department Human Perception, Cognition and Action}; Aller M; Rohe T{trohe}{Department Human Perception, Cognition and Action}; Conrad V{conrad}{Department Human Perception, Cognition and Action}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Noppeney U{unoppe}{Department Human Perception, Cognition and Action}} } @Poster{ LiVOSGZB2017, title = {Depicting transcranial magnetic stimulation from a neuronal perspective}, year = {2017}, month = {4}, pages = {86}, abstract = {Background: Despite its rapidly expanding application and fast-rising popularity, transcranial magnetic stimulation (TMS) is poorly understood physiologically. The lack of knowledge on TMS physiology, together with the absence of an experimental platform on which various human TMS applications can be studied, developed and refined in vivo at the neuronal level, block the exciting scientific and therapeutic potential of this non-invasive brain stimulation tool. Methods: We developed a novel experimental method that offers the direct in vivo electrophysiological access to TMS-evoked neuronal activities in the brain. The method, compatible with standard TMS stimulators and coils, attenuates a variety of TMS-induced artifacts in extracellular electrophysiology recordings and allows the recording to resume 0.8 – 1 ms after a variety of Tesla-level strong single or repetitive TMS stimulus. Furthermore, using rodents, a common laboratory animal model, we successfully replicated single-pulse TMS as is routinely used in humans and unveiled TMS-evoked neurons spiking activities in the layer II/III and V of the rodent primary motor cortex. Results: The suprathreshold monophasic TMS stimulus reliably evoked unilateral activation of the forelimb muscles, evidenced by muscle unit action potentials recorded in the m. biceps brachii (onset latency 11 ms post-TMS). On the neuronal level, the cortical evoked multi-unit activity displayed 5 distinct phases: early excitation (< 6 ms), second excitation (8-26 ms), inhibition (33-172 ms) and rebound excitation (199-238 ms), all of which reveal striking relations to various well-known phenomena in human TMS ranging from intracortical facilitation to late cortical disinhibition. Conclusions: The data obtained with our method depicted, for the first time, the neuronal response pattern of the classical single-pulse TMS that is widely used in research and clinical works. By bridging the gap between neurons and behaviors, the advance presented here facilitates a new level of insight into the TMS-brain interaction and is vital for developing and utilizing this non-invasive tool to purposefully explore and effectively treat the human brain.}, web_url = {http://neuromodulation.umn.edu/doc/MNS2017ProgramAndAbstracts.pdf}, event_name = {Minnesota Neuromodulation Symposium (MNS 2017)}, event_place = {Minneapolis, MN, USA}, state = {published}, author = {Li B; Virtanen J; Oeltermann A{axel}; Schwarz C; Giese M{giese}; Ziemann U; Benali A} } @Poster{ BenneggerW2017, title = {Genetic Correlation to Olfactory Bulb Structure in Males of Different Mink Races (Neovison vison var. spec.)}, year = {2017}, month = {4}, abstract = {Genes define the structure and function of the body and brain. Genetic alterations result sometimes in unexpected changes, for example albinism is not only a modification of the coat color but has also an effect on neuronal wiring. Several species are bred specifically for coat colors, such as the American mink. Therefore we were interested, if color mutations in the mink have an effect on the organization of the olfactory bulb, an evolutionary old structure. We investigated adult males of different coat color varieties of the American mink: “standard” (Neovison vison var. atratus), “silverblue” (Neovison vison var. glaucus), “pastel” (Neovison vison var. suffuscus), “wild” (Neovison vison var. carinum) for the absolute volumes of the olfactory bulb layers using a morphometric system. The results reveal significant differences among the color varieties, especially Neovison vison var. glaucus (g) shows differences compared to either Neovison vison var. suffuscus (s) or Neovison vison var. atratus (a) or both, in absolute volume of the glomerular layer (g: 18.1 mm3; s: 23.0 mm3; a: 21.7 mm3), the external plexiform layer (g: 29.4 mm3; s: 35.8 mm3), the mitral cell layer (g: 4.4 mm3; a: 7.2 mm3) and the stratum album (g: 11.8 mm3; s: 16.3 mm3), whereas there was no significant difference in any of the layers compared to Neovison vison var. carinum. Neovison vison var. glaucus is characterized by the modification of the recessive gene (pp), with the genetic modification affecting the myosin- and actin-binding domains – also responsible for intracellular vesicle transport – an important process for neuronal wiring. Thus, our results stronlgy indicate that the genes responsible for pigmentation also define the neuronal structure.}, web_url = {https://achems2017.org/online/mobile/show_presentation.php?abstractno=300}, event_name = {Association for Chemoreception Sciences: AChemS XXXIX}, event_place = {Bonita Springs, FL, USA}, state = {published}, author = {Bennegger W; Weiler E{eweiler}{Department Physiology of Cognitive Processes}} } @Poster{ KorkmazHacialihafizB2017, title = {Real-world Motion Responses in Scene Responsive Regions}, year = {2017}, month = {3}, day = {27}, pages = {84}, abstract = {We perceive scenes as stable even when eye movements induce retinal motion, for example during pursuit of a moving object. Mechanisms mediating perceptual stability have primarily been examined in motion regions of the dorsal visual pathway. Here we examined whether motion responses in human scene regions are encoded in eye- or world centered reference frames. We recorded brain responses in human participants using fMRI while they performed a well-controlled visual pursuit paradigm previously used to examine dorsal motion regions. In addition, we examined effects of content by using either natural scenes or their Fourier scrambles. We found that parahippocampal place area (PPA) responded to motion only in world- but not in eye-centered coordinates, regardless of scene content. The occipital place area (OPA) responded to both, objective and retinal motion equally, and retrosplenial cortex (RSC) had no motion responses but responded to pursuit. Only PPA’s objective motion responses were higher during scenes than scrambled images, although there was a similar trend in OPA. These results indicate a special role of PPA in representing its content in real-world coordinates. Our results question a strict subdivision of dorsal “what” and ventral “where” streams, and suggest a role of PPA in contributing to perceptual stability.}, web_url = {http://www.teap2017.de/scientific-program/}, event_name = {59th Conference of Experimental Psychologists (TeaP 2017)}, event_place = {Dresden, Germany}, state = {published}, author = {Korkmaz-Hacialihafiz D{dkorkmaz}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ WeilerB2017, title = {Absolute reduction of olfactory bulb layer volume during absolute growth of the olfactory bulb: a sign for developmental changes of information processing?}, year = {2017}, month = {3}, day = {22}, pages = {316-317}, abstract = {Information processing requires morphological structures, which develop in mammals not only pre- but also postnatally. Especially in altricial species, the brain growth continues far beyond birth. The American mink (Neovision vison var. atratus) is born with eyes and ears closed and depends primarily on its sense of smell for nutrition and neonatal survival. As reported before (Weiler & Bennegger, 2015) the olfactory bulb, the main station for olfactory information processing, follows its own growth pattern, different to the rest of the brain. Information processing however depends on the composition of the neurons and neuronal layers. Taken the fact, that the olfactory sense is functional already from birth on, the question arises: Is the olfactory bulb growing uniformely or do the layers also show signs of allometric growth? Therefore we analyzed the absolute volume of each olfactory bulb layer in a total of 36 female minks at different postnatal ages (newborns (postnatal day 0 =P0) up to 7 months = P210) using histological sections and a morphometric system. A continuous increase in volume was observed in the external plexiform layer (P0: 0.04±0.01 mm3; P60: 13.62±0.38 mm3; P210: 24.42±1.56 mm3) and granule cell layer (P0: 0.30±0.02 mm3; P60: 12.98±0.47 mm3; P210: 30.85±1.43 mm3) following the continuous increase of the whole olfactory bulb volume. In contrast, volume maxima at P60 with subsequent significant reduction (p<0.01) were reached in the internal plexiform layer (P60: 3.70±0.30 mm3; P90-120: 2.02±0.47 mm3), the internal medullar layer (stratum album: P60: 13.95±0.54 mm3; P90-120: 11.32±0.79 mm3; P210: 9.71±2.27 mm3), and the subependymal layer (P60: 4.69±0.13 mm3; P90-120: 2.64±0.14 mm3; P210: 1.12±0.34 mm3). The mitral cell layer showed a significant maximum at P90-150 (4.50±0.27 mm3; P210: 3.78±0.37 mm3). These results indicate that layer specific growth pattern exist in the olfactory bulb, even with overshoot phenomena. Absolute layer volume reduction in a continuously growing olfactory bulb even maximizes differences in the composition and indicates differential olfactory information processing during specific developmental phases. The specific absolute volume reductions can be caused by different factors. While the overshoot and concomitantly following reduction in the mitral cell layer might be a result of passing cells on their way from the center of the bulb to the outer layers, the absolute reduction of the subependymal layer might be related to the retraction of the ventricle to a more posterior region, out of the bulb, leaving the migratory stream for renewal of neurons. Reduction in the stratum album indicates a retraction of centrifugal fibers from the brain during juvenile brain reduction (reported earlier, Weiler & Bennegger, 2015). All of this concentrates information-processing neurons within the bulb. These results indicate a rearrangement of neurons and underlying networks, by establishing a filtering system, according to the necessity of increasing olfactory challenges during biological phases: as neonates to identify milk and social cues; as juveniles detect family members, enemies, prey, predators; as adults additionally identify sexual partners; suggesting that, although the olfactory system is functional at birth, the information processing changes during postnatal life.}, web_url = {https://www.nwg-goettingen.de/2017/upload/file/Proceedings__NWG2017.pdf}, event_name = {12th Göttingen Meeting of the German Neuroscience Society, 36th Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {Weiler E{eweiler}{Department Physiology of Cognitive Processes}; Bennegger W} } @Poster{ GrassiZB2017, title = {Retinotopic specific modulations in early visual cortex by feedback during bistable Gestalt perception}, year = {2017}, month = {3}, pages = {25}, abstract = {A growing body of literature suggests that feedback modulation of early visual processing is ubiquitous and central to cortical computation. In particular stimuli with high-level content have been shown to suppress early visual regions, typically interpreted in the framework of predictive coding. However, physical stimulus differences can preclude clear interpretations in terms of feedback. Here we examined activity modulation in V1 and V2 during distinct perceptual states associated to the same physical input. This ensures in a unique way that observed signal modulations cannot be accounted for by changes in physical stimulus properties, and can therefore only be accounted for by percept-related feedback interactions from higher level regions. We used a dynamic stimulus consisting of moving dots that could either be perceived as corners of a large moving square (global Gestalt) or as distributed sets of locally moving dots. We found that perceptual binding of local moving elements into an illusory Gestalt led to spatially segregated differential modulations, in both, V1 and V2: representations of illusory lines and foreground were enhanced, while inducers and background suppressed. The results extend prior findings to the illusory-perceptual state of physically un- ‐changed stimuli, and for the first time show background suppression in the human brain. Based on prior work (Zaretskaya et al., 2013), we hypothesize that parietal cortex is responsible for the modulations through recurrent connections in a predictive coding account of visual processing.}, web_url = {http://www.cogsci.uni-jena.de/wa_files/CombinedPages2.pdf}, event_name = {Cortical Feedback Springschool (COFEES 2017)}, event_place = {Jena, Germany}, state = {published}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ DenfieldET2017, title = {The Role of Internal Signals in Structuring V1 Population Activity}, year = {2017}, month = {2}, pages = {31}, abstract = {Neuronal responses to repeated presentations of identical visual stimuli are variable. The source of this variability is unknown, but it is commonly treated as noise. We argue that this variability reflects, and is due to, computations internal to the brain. Relatively little research has examined the effect on neuronal responses of fluctuations in internal signals such as cortical state and attention, leaving a number of uncontrolled parameters that may contribute to neuronal variability. Attention increases neuronal response gain in a spatial and feature selective manner. We hypothesize that fluctuations in the strength and focus of attention are a major source of neuronal response variability and covariability. We first examine a simple model of a gain-modulating signal acting on a population of neurons and show that fluctuations in attention can increase individual and shared variability. To test our model’s predictions experimentally, we devised a cued-spatial attention, change-detection task to induce varying degrees of fluctuation in the subject’s attentional signal. We use multi-electrode recordings in primary visual cortex of macaques performing this task. We demonstrate that attention gain-modulates responses of V1 neurons in a manner consistent with results from higher-order areas. Our results also indicate neuronal covariability is elevated in conditions in which attention fluctuates. Overall, our results suggest that attentional fluctuations are an important contributor to neuronal variability and open the door to the use of statistical methods for inferring the state of these signals on behaviorally relevant timescales.}, web_url = {https://media.bcm.edu/documents/2017/ec/abstract-book-complete.pdf}, event_name = {27th Annual Rush and Helen Record Neuroscience Forum}, event_place = {Galveston, TX, USA}, state = {published}, author = {Denfield GH; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Tolias A{atolias}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2017, title = {NET-fMRI of large-scale brain networks: mapping dynamic connectivity in epochs of synaptic and system consolidation}, year = {2017}, month = {6}, day = {12}, web_url = {http://hippo.euroconferences.org/program.html}, event_name = {Spring Hippocampal Research Conference}, event_place = {Taormina, Italy}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ TuzziHBLNLPV2017, title = {In-vivo and ex-vivo R2* and Quantitative Susceptibility Mapping in Alzheimer’s Disease at Ultra-High Magnetic Field compared to Histology}, year = {2017}, month = {4}, day = {27}, pages = {677-678}, abstract = {Amyloid-β plaques are classical hallmarks of the post-mortem Alzheimer’s Disease (AD) brain. Ultra-High-Field (UHF) MRI provides a compelling means to investigate pathological processes at an unprecedented level of detail. ß-amyloid plaques can be detected in T2* weighted images at UHF, ex-vivo, due to the local iron content and to the plaque geometry per sè. With this study we aim to explore the source of the observed MR signal changes in AD at UHF using quantitative MRI methods in-vivo and ex-vivo.}, web_url = {http://www.ismrm.org/17/program_files/O61.htm}, event_name = {25th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2017)}, event_place = {Honolulu, HI, USA}, state = {published}, author = {Tuzzi E{etuzzi}{Department High-Field Magnetic Resonance}; Hagberg G{ghagberg}{Department High-Field Magnetic Resonance}; Balla D{ballad}{Department Physiology of Cognitive Processes}; Loureiro J{jloureiro}{Department High-Field Magnetic Resonance}; Neumann M; Laske C; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Valverde M{valverde}{Department Physiology of Cognitive Processes}{Department High-Field Magnetic Resonance}} } @Conference{ TakemuraPWKLSYBLFLW2017, title = {Using diffusion MRI and tractography to identify macaque vertical occipital fasciculus}, year = {2017}, month = {4}, day = {24}, pages = {95}, abstract = {We evaluated the ability of diffusion MRI-based tractography to identify macaque vertical occipital fasciculus (VOF), an important but little-studied white-matter tract connecting dorsal and ventral visual cortex. We analyzed four macaque diffusion MRI datasets with different resolution. The high-resolution post-mortem dataset reliably detects the macaque VOF, in a consistent manner with previous invasive anatomical studies. Lower resolution in vivo data showed qualitatively consistent results, but the estimated tract endpoints are restricted to sulcus. Taken together, our results demonstrate that the need for high-resolution diffusion MRI to identify certain critical white matter tracts.}, web_url = {http://www.ismrm.org/17/program_files/O71.htm}, event_name = {25th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2017)}, event_place = {Honolulu, HI, USA}, state = {published}, author = {Takemura H; Pestilli F; Weiner K; Keliris G{george}{Department Physiology of Cognitive Processes}; Landi S; Sliwa J; Ye F; Barnett M; Leopold D{davidl}{Department Physiology of Cognitive Processes}; Freiwald F; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Wandell B} } @Conference{ Panagiotaropoulos2017, title = {Single neuron correlates of conscious perception and episodic memory in the primate brain}, year = {2017}, month = {3}, day = {10}, web_url = {http://www.int.univ-amu.fr/Theofanis-Panagiotaropoulos}, event_name = {Institut de Neurosciences de la Timone}, event_place = {Marseille, France}, state = {published}, author = {Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ FichtnerGAMZHK2017, title = {Measuring Exchange Between Brain Metabolites and Water Using Ultra-High Field Magnetic Resonance Spectroscopy}, year = {2017}, month = {2}, day = {2}, abstract = {Introduction: In the human brain, magnetic resonance spectroscopy is able to measure various metabolites of interest, visualized as peaks along a spectrum, which can be related to metabolism and functional processes. It is also able to measure chemical exchange at equilibrium, without disrupting the system. In this study, proton exchange between water and urea has been measured for the first time in human brain in vivo, at 9.4 tesla, the highest magnetic field strength human scanner available worldwide. Materials and Methods: Magnetic resonance spectroscopy data were acquired on a 9.4T magnet in a white matter region of the brain in eleven healthy volunteers and in a grey matter region of the brain in a further ten volunteers. Exchange with water was measured using an inversion transfer experiment, which involves specifically perturbing (inverting) the water proton magnetization, and waiting for certain delay times before data acquisition in order to measure varying amounts of exchange between the water protons and the other metabolites such as urea. The data were averaged and a model was developed to fit the fourteen visible peaks in the averaged spectra, including urea, at the various delay times. Results and discussion: The inversion transfer average series visualizes peaks that are strongly modulated in intensity by exchanging magnetization with the inverted water signal. In particular, the fast-exchanging peaks include urea at 5.8ppm and amide protons (related to proteins) in the 8.2-8.5ppm range. The preliminary fitting model captures most of the peaks very well, and the improved peak separation at ultra-high field has allowed for more peaks to be included in the model compared to the ones used at lower magnetic field strengths such as 3T (clinical strength) or 7T. Exchange rates for the different peaks will be obtained by Bloch McConnell simulations, which take both magnetization and exchange into account.}, web_url = {https://www.conftool.net/gcb-symp/index.php?page=browseSessions&form_session=27#paperID241}, event_name = {GCB Symposium 2017: Graduate School for Cellular and Biomedical Sciences}, event_place = {Bern, Switzerland}, state = {published}, author = {Fichtner ND; Giapitzakis I-A{igiapitzakis}; Avdievich N{navdievi}; Merkle R; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Henning A{ahenning}; Kreis R} } @Article{ FischerBDELELSPFG2016, title = {A human brain network derived from coma-causing brainstem lesions}, journal = {Neurology}, year = {2016}, month = {12}, volume = {87}, number = {23}, pages = {2427-2434}, abstract = {Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness.}, web_url = {http://www.neurology.org/content/87/23/2427}, state = {published}, DOI = {10.1212/WNL.0000000000003404}, author = {Fischer DB; Boes AD; Demertzi A; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Laureys S; Edlow BL; Liu H; Saper CB; Pascual-Leone A; Fox MD; Geerling JC} } @Article{ GroeschelHSBKHNBPMKS2016, title = {Assessing White Matter Microstructure in Brain Regions with Different Myelin Architecture Using MRI}, journal = {PLoS ONE}, year = {2016}, month = {11}, volume = {11}, number = {11}, pages = {1-23}, abstract = {Objective We investigate how known differences in myelin architecture between regions along the cortico-spinal tract and frontal white matter (WM) in 19 healthy adolescents are reflected in several quantitative MRI parameters that have been proposed to non-invasively probe WM microstructure. In a clinically feasible scan time, both conventional imaging sequences as well as microstructural MRI parameters were assessed in order to quantitatively characterise WM regions that are known to differ in the thickness of their myelin sheaths, and in the presence of crossing or parallel fibre organisation. Results We found that diffusion imaging, MR spectroscopy (MRS), myelin water fraction (MWF), Magnetization Transfer Imaging, and Quantitative Susceptibility Mapping were myelin-sensitive in different ways, giving complementary information for characterising WM microstructure with different underlying fibre architecture. From the diffusion parameters, neurite density (NODDI) was found to be more sensitive than fractional anisotropy (FA), underlining the limitation of FA in WM crossing fibre regions. In terms of sensitivity to different myelin content, we found that MWF, the mean diffusivity and chemical-shift imaging based MRS yielded the best discrimination between areas. Conclusion Multimodal assessment of WM microstructure was possible within clinically feasible scan times using a broad combination of quantitative microstructural MRI sequences. By assessing new microstructural WM parameters we were able to provide normative data and discuss their interpretation in regions with different myelin architecture, as well as their possible application as biomarker for WM disorders.}, web_url = {http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0167274&type=printable}, state = {published}, DOI = {10.1371/journal.pone.0167274}, EPUB = {e0167274}, author = {Groeschel S; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Schultz T{tschultz}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Klose U; Hauser T-K; N\"agele T; Bieri O; Prasloski T; MacKay AL; Kr\"ageloh-Mann I; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Article{ BahmaniW2016, title = {Distorted Low-Level Visual Features Affect Saliency-Based Visual Attention}, journal = {Frontiers in Computational Neuroscience}, year = {2016}, month = {11}, volume = {10}, number = {124}, pages = {1-4}, abstract = {Image distortions can attract attention away from the natural scene saliency (Redi et al., 2011). Performance of viewers in visual search tasks and their fixation patterns are also affected by different types and amounts of distortions (Vu et al., 2008). In this paper, we have discussed the opinion that distortions could largely affect the performance of predictive models of visual attention, and simulated the effects of distorted low-level visual features on the saliency-based bottom-up visual attention. Saliency is a fast and pre-attentive mechanism for orienting visual attention to intrinsically important objects which pop-out more easily in a cluttered scene. Distortion of the low-level features that contribute to saliency may impair the readiness of the visual system in detection of salient objects, which may have major implications for critical situations like driving or locomotion. These distortions in natural life can be introduced by eye diseases such as cataract, or spectacles which may alter color perception (de Fez et al., 2002) or cause undesired optical effects like blurring, non-uniform magnification, and image displacement (Barbero and Portilla, 2016). The extent to which each of these distorted saliency features may affect the attentional performance is addressed in this paper by employing a biologically-inspired predictive model of visual attention. We briefly summarize the current standing of computational work on visual attention models in the following section and suggest a simple and influential model of saliency to examine the above hypothesis. Furthermore, we demonstrate in an example the hindered performance of the predictive saliency model on distorted images.}, web_url = {http://journal.frontiersin.org/article/10.3389/fncom.2016.00124/pdf}, state = {published}, DOI = {10.3389/fncom.2016.00124}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Wahl S} } @Article{ GrassiSD2016, title = {The Role of the Occipital Cortex in Resolving Perceptual Ambiguity}, journal = {Journal of Neuroscience}, year = {2016}, month = {10}, volume = {36}, number = {41}, pages = {10508-10509}, web_url = {http://www.jneurosci.org/content/36/41/10508.full.pdf+html}, state = {published}, DOI = {10.1523/JNEUROSCI.2402-16.2016}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Schauer G{gschauer}{Department Physiology of Cognitive Processes}; Dwarakanath A{adwarakanath}} } @Article{ ShahBKKJVV2015, title = {Cholinergic and serotonergic modulations differentially affect large-scale functional networks in the mouse brain}, journal = {Brain Structure and Function}, year = {2016}, month = {7}, volume = {221}, number = {6}, pages = {3067–3079}, abstract = {Resting-state functional MRI (rsfMRI) is a widely implemented technique used to investigate large-scale topology in the human brain during health and disease. Studies in mice provide additional advantages, including the possibility to flexibly modulate the brain by pharmacological or genetic manipulations in combination with high-throughput functional connectivity (FC) investigations. Pharmacological modulations that target specific neurotransmitter systems, partly mimicking the effect of pathological events, could allow discriminating the effect of specific systems on functional network disruptions. The current study investigated the effect of cholinergic and serotonergic antagonists on large-scale brain networks in mice. The cholinergic system is involved in cognitive functions and is impaired in, e.g., Alzheimer’s disease, while the serotonergic system is involved in emotional and introspective functions and is impaired in, e.g., Alzheimer’s disease, depression and autism. Specific interest goes to the default-mode-network (DMN), which is studied extensively in humans and is affected in many neurological disorders. The results show that both cholinergic and serotonergic antagonists impaired the mouse DMN-like network similarly, except that cholinergic modulation additionally affected the retrosplenial cortex. This suggests that both neurotransmitter systems are involved in maintaining integrity of FC within the DMN-like network in mice. Cholinergic and serotonergic modulations also affected other functional networks, however, serotonergic modulation impaired the frontal and thalamus networks more extensively. In conclusion, this study demonstrates the utility of pharmacological rsfMRI in animal models to provide insights into the role of specific neurotransmitter systems on functional networks in neurological disorders.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00429-015-1087-7.pdf}, state = {published}, DOI = {10.1007/s00429-015-1087-7}, author = {Shah D; Blockx I; Keliris GA{george}{Department Physiology of Cognitive Processes}; Kara F; Jonckers E; Verhoye M; Van der Linden A} } @Article{ HindriksAPBVLD2016, title = {Discrepancies between multi-electrode LFP and CSD phase-patterns: A forward modeling study}, journal = {Frontiers in Neural Circuits}, year = {2016}, month = {7}, volume = {10}, number = {51}, pages = {1-18}, abstract = {Multi-electrode recordings of local field potentials (LFP's) provide the opportunity to investigate the spatiotemporal organization of neural activity on the scale of several millimeters. In particular, the phases of oscillatory LFP's allow studying the coordination of neural oscillations in time and space and to tie it to cognitive processing. Given the computational roles of LFP phases, it is important to know how they relate to the phases of the underlying current source densities (CSD's) that generate them. Although CSD's and LFP's are distinct physical quantities, they are often (implicitly) identified when interpreting experimental observations.That this identification is problematic is clear from the fact that LFP phases change when switching to different electrode montages, while the underlying CSD phases remain unchanged. In this study we use a volume-conductor model to characterize discrepancies between LFP and CSD phase-patterns, to identify the contributing factors, and to assess the effect of different electrode montages. Although we focus on cortical LFP's recorded with two-dimensional (Utah) arrays, our findings are also relevant for other electrode configurations. We found that the main factors that determine the discrepancy between CSD and LFP phase-patterns are the frequency of the neural oscillations and the extent to which the laminar CSD profile is balanced. Furthermore, the presence of laminar phase-differences in cortical oscillations, as commonly observed in experiments, precludes identifying LFP phases with those of the oscillations at a given cortical depth. This observation potentially complicates the interpretation of spike-LFP coherence and spike-triggered CSD averages. With respect to reference strategies, we found that the average-reference montage leads to larger discrepancies between LFP and CSD phases as compared with the referential montage, while the Laplacian montage reduces these discrepancies.}, web_url = {http://journal.frontiersin.org/article/10.3389/fncir.2016.00051/pdf}, state = {published}, DOI = {10.3389/fncir.2016.00051}, author = {Hindriks R; Arsiwalla XD; Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Verschure PF; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco G} } @Article{ RobinsonZRPGBS2016, title = {Real-Time Subject-Independent Pattern Classification of Overt and Covert Movements from fNIRS Signals}, journal = {PLoS ONE}, year = {2016}, month = {7}, volume = {11}, number = {7}, pages = {1-21}, abstract = {Recently, studies have reported the use of Near Infrared Spectroscopy (NIRS) for developing Brain-Computer Interface (BCI) by applying online pattern classification of brain states from subject-specific fNIRS signals. The purpose of the present study was to develop and test a real-time method for subject-specific and subject-independent classification of multi-channel fNIRS signals using support-vector machines (SVM), so as to determine its feasibility as an online neurofeedback system. Towards this goal, we used left versus right hand movement execution and movement imagery as study paradigms in a series of experiments. In the first two experiments, activations in the motor cortex during movement execution and movement imagery were used to develop subject-dependent models that obtained high classification accuracies thereby indicating the robustness of our classification method. In the third experiment, a generalized classifier-model was developed from the first two experimental data, which was then applied for subject-independent neurofeedback training. Application of this method in new participants showed mean classification accuracy of 63% for movement imagery tasks and 80% for movement execution tasks. These results, and their corresponding offline analysis reported in this study demonstrate that SVM based real-time subject-independent classification of fNIRS signals is feasible. This method has important applications in the field of hemodynamic BCIs, and neuro-rehabilitation where patients can be trained to learn spatio-temporal patterns of healthy brain activity.}, web_url = {http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0159959.PDF}, state = {published}, DOI = {10.1371/journal.pone.0159959}, EPUB = {e0159959}, author = {Robinson N; Zaidi AD{azaidi}{Department Physiology of Cognitive Processes}; Rana M; Prasad V; Guan C; Birbaumer N; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}} } @Article{ GoenseBL2016, title = {fMRI at High Spatial Resolution: Implications for BOLD-Models}, journal = {Frontiers in Computational Neuroscience}, year = {2016}, month = {6}, volume = {10}, number = {66}, pages = {1-13}, abstract = {As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI.}, web_url = {http://journal.frontiersin.org/article/10.3389/fncom.2016.00066/pdf}, state = {published}, DOI = {10.3389/fncom.2016.00066}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Bohraus Y{ybohraus}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ GrassiZB2016, title = {Parietal cortex mediates perceptual Gestalt grouping independent of stimulus size}, journal = {NeuroImage}, year = {2016}, month = {6}, volume = {133}, pages = {367–377}, abstract = {The integration of local moving elements into a unified gestalt percept has previously been linked to the posterior parietal cortex. There are two possible interpretations for the lack of involvement of other occipital regions. The first is that parietal cortex is indeed uniquely functionally specialized to perform grouping. Another possibility is that other visual regions can perform grouping as well, but that the large spatial separation of the local elements used previously exceeded their neurons' receptive field (RF) sizes, preventing their involvement. In this study we distinguished between these two alternatives. We measured whole-brain activity using fMRI in response to a bistable motion illusion that induced mutually exclusive percepts of either an illusory global Gestalt or of local elements. The stimulus was presented in two sizes, a large version known to activate IPS only, and a version sufficiently small to fit into the RFs of mid-level dorsal regions such as V5/MT. We found that none of the separately localized motion regions apart from parietal cortex showed a preference for global Gestalt perception, even for the smaller version of the stimulus. This outcome suggests that grouping-by-motion is mediated by a specialized size-invariant mechanism with parietal cortex as its anatomical substrate.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811916002044}, state = {published}, DOI = {10.1016/j.neuroimage.2016.03.008}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ GunduzSPLSA2016, title = {Ratiometric Method for Rapid Monitoring of Biological Processes Using Bioresponsive MRI Contrast Agents}, journal = {ACS Sensors}, year = {2016}, month = {6}, volume = {1}, number = {5}, pages = {483–487}, abstract = {Bioresponsive MRI contrast agents hold great potential for non-invasive tracking of essential biological processes. Consequently, a number of MR sensors for several imaging protocols have been developed, attempting to produce the maximal signal difference for a given event. Here we introduce an approach which could substantially improve the detection of physiological events with fast kinetics. We developed a nanosized, calcium-sensitive dendrimeric probe that changes longitudinal and transverse relaxation times with different magnitudes. The change in their ratio is rapidly recorded by means of a balanced steady-state free precession (bSSFP) imaging protocol. The employed methodology results in an almost four times greater signal gain per unit of time as compared to conventional T1-weighted imaging with small sized contrast agents. Furthermore, it is suitable for high resolution functional MRI at high magnetic fields. This methodology could evolve into a valuable tool for rapid monitoring of various biological events.}, web_url = {http://pubs.acs.org/doi/ipdf/10.1021/acssensors.6b00011}, state = {published}, DOI = {10.1021/acssensors.6b00011}, author = {G\"und\"uz S{sgunduz}; Savić T{tsavic}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ LohmannSZBMBS2015, title = {Task-Related Edge Density (TED): A New Method for Revealing Dynamic Network Formation in fMRI Data of the Human Brain}, journal = {PLoS ONE}, year = {2016}, month = {6}, volume = {11}, number = {6}, pages = {1-22}, abstract = {The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach “Task-related Edge Density” (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.}, web_url = {http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0158185.PDF}, state = {published}, DOI = {10.1371/journal.pone.0158185}, EPUB = {e0158185}, author = {Lohmann G{lohmann}{Department High-Field Magnetic Resonance}; Stelzer J{jstelzer}{Department High-Field Magnetic Resonance}; Zuber V; Buschmann T; Margulies D; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Article{ WiesnerBSSUCUP2015, title = {17O relaxation times in the rat brain at 16.4 tesla}, journal = {Magnetic Resonance in Medicine}, year = {2016}, month = {5}, volume = {75}, number = {5}, pages = {1886–1893}, abstract = {Purpose Measurement of the cerebral metabolic rate of oxygen (CMRO2) by means of direct imaging of the 17O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H217O measurements. Methods Using the improved sensitivity at a field strength of 16.4 Tesla, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. Results In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2* = 1.77 ± 0.04 ms. Postmortem H217O relaxometry at enriched concentrations after inhalation of 17O2 showed similar T2* values for gray matter (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than cerebrospinal fluid (2.30 ± 0.16 ms). Conclusion Relaxation times of brain H217O were measured for the first time in vivo in different types of tissues with high spatial resolution. Because the relaxation times of H217O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/mrm.25814/epdf}, state = {published}, DOI = {10.1002/mrm.25814}, author = {Wiesner HM{wiesner}{Department High-Field Magnetic Resonance}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Ugurbil K; Chen W; Uludag K{kuludag}{Department High-Field Magnetic Resonance}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}} } @Article{ NovitskayaSLE2016, title = {Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation}, journal = {Learning & Memory}, year = {2016}, month = {5}, volume = {23}, number = {5}, pages = {238-248}, abstract = {Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying “off-line” consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following “on-line” detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of “off-line” memory consolidation.}, web_url = {http://learnmem.cshlp.org/content/23/5/238.full.pdf+html}, state = {published}, DOI = {10.1101/lm.040923.115}, author = {Novitskaya Y{ynovitskaya}{Department Physiology of Cognitive Processes}; Sara SJ; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Article{ SchindlerB2016, title = {Visual high-level regions respond to high-level stimulus content in the absence of low-level confounds}, journal = {NeuroImage}, year = {2016}, month = {5}, volume = {132}, pages = {520–525}, abstract = {High-level regions of the ventral stream exhibit strong category selectivity to stimuli such as faces, houses, or objects. However, recent studies suggest that at least part of this selectivity stems from low-level differences inherent to images of the different categories. For example, visual outdoor and indoor scenes as well as houses differ in spatial frequency, rectilinearity and obliqueness when compared to face or object images. Correspondingly, scene responsive para-hippocampal place area (PPA) showed strong preference to low-level properties of visual scenes also in the absence of high-level scene content. This raises the question whether all high-level responses in PPA, the fusiform face area (FFA), or the object-responsive lateral occipital compex (LOC) may actually be explained by systematic differences in low-level features. In the present study we contrasted two classes of simple stimuli consisting of ten rectangles each. While both were matched in visual low-level features only one class of rectangle arrangements gave rise to a percept compatible with a high-level 3D layout such as a scene or an object. We found that areas PPA, transverse occipital sulcus (TOS, also referred to as occipital place area, OPA), as well as FFA and LOC showed robust responses to the visual scene class compared to the low-level matched control. Our results suggest that visual category responsive regions are not purely driven by low-level visual features but also by the high-level perceptual stimulus interpretation.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191600207X}, state = {published}, DOI = {10.1016/j.neuroimage.2016.03.011}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ KleinESHLS2016, title = {Cell-Targeted Optogenetics and Electrical Microstimulation Reveal the Primate Koniocellular Projection to Supra-granular Visual Cortex}, journal = {Neuron}, year = {2016}, month = {4}, volume = {90}, number = {1}, pages = {143–151}, abstract = {Electrical microstimulation and more recently optogenetics are widely used to map large-scale brain circuits. However, the neuronal specificity achieved with both methods is not well understood. Here we compare cell-targeted optogenetics and electrical microstimulation in the macaque monkey brain to functionally map the koniocellular lateral geniculate nucleus (LGN) projection to primary visual cortex (V1). Selective activation of the LGN konio neurons with CamK-specific optogenetics caused selective electrical current inflow in the supra-granular layers of V1. Electrical microstimulation targeted at LGN konio layers revealed the same supra-granular V1 activation pattern as the one elicited by optogenetics. Taken together, these findings establish a selective koniocellular LGN influence on V1 supra-granular layers, and they indicate comparable capacities of both stimulation methods to isolate thalamo-cortical circuits in the primate brain.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627316001732}, state = {published}, DOI = {10.1016/j.neuron.2016.02.036}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Shapcott KA; Haverkamp S; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Schmid MC{mschmid}} } @Article{ MalekshahiSPMBVC2016, title = {Differential neural mechanisms for early and late prediction error detection}, journal = {Scientific Reports}, year = {2016}, month = {4}, volume = {6}, number = {24350}, pages = {1-13}, abstract = {Emerging evidence indicates that prediction, instantiated at different perceptual levels, facilitate visual processing and enable prompt and appropriate reactions. Until now, the mechanisms underlying the effect of predictive coding at different stages of visual processing have still remained unclear. Here, we aimed to investigate early and late processing of spatial prediction violation by performing combined recordings of saccadic eye movements and fast event-related fMRI during a continuous visual detection task. Psychophysical reverse correlation analysis revealed that the degree of mismatch between current perceptual input and prior expectations is mainly processed at late rather than early stage, which is instead responsible for fast but general prediction error detection. Furthermore, our results suggest that conscious late detection of deviant stimuli is elicited by the assessment of prediction error’s extent more than by prediction error per se. Functional MRI and functional connectivity data analyses indicated that higher-level brain systems interactions modulate conscious detection of prediction error through top-down processes for the analysis of its representational content, and possibly regulate subsequent adaptation of predictive models. Overall, our experimental paradigm allowed to dissect explicit from implicit behavioral and neural responses to deviant stimuli in terms of their reliance on predictive models.}, web_url = {http://www.nature.com/articles/srep24350.pdf}, state = {published}, DOI = {10.1038/srep24350}, author = {Malekshahi R{rmalekshahi}{Department Physiology of Cognitive Processes}; Seth A; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Mathews Z; Birbaumer N; Verschure PF; Caria A} } @Article{ GarelloVGLTA2016, title = {Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity}, journal = {Biomacromolecules}, year = {2016}, month = {4}, volume = {17}, number = {4}, pages = {1303–1311}, abstract = {Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in development of functional molecular imaging methods to study the brain physiology or abnormalities in muscle contraction. Great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation which could be detected in a robust way. To this end, the incorporation of small molecular weight bioresponsive agents into nanocarriers can improve the overall properties in a few ways: i) the agent can be delivered into the tissue of interest, increasing the local concentration; ii) its biokinetic properties and retention time will improve; iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesised a novel amphiphilic ligand which was incorporated into the liposome bilayer. A remarkable increase of ~420% in longitudinal relaxivity r1, from 7.3 mM-1s-1 to 38.1 mM-1s-1 at 25 °C and 21.5 MHz in absence and presence of Ca(II), respectively, was achieved by the most active liposomal formulation. To the best of our knowledge, this is the highest change in r1 observed for Ca-sensitive agents at physiological pH and can be explained by simultaneous Ca-triggered increase in hydration and reduction of local motion of Gd(III) complex which can be followed at low magnetic fields.}, web_url = {http://pubs.acs.org/doi/ipdf/10.1021/acs.biomac.5b01668}, state = {published}, DOI = {10.1021/acs.biomac.5b01668}, author = {Garello F; Vibhute S{svibhute}{Department Physiology of Cognitive Processes}; G\"und\"uz S{sgunduz}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Terreno E; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ KaplanAHMMLD2016, title = {Hippocampal Sharp-Wave Ripples Influence Selective Activation of the Default Mode Network}, journal = {Current Biology}, year = {2016}, month = {3}, volume = {26}, number = {5}, pages = {686–691}, abstract = {The default mode network (DMN) is a commonly observed resting-state network (RSN) that includes medial temporal, parietal, and prefrontal regions involved in episodic memory [1, 2 and 3]. The behavioral relevance of endogenous DMN activity remains elusive, despite an emerging literature correlating resting fMRI fluctuations with memory performance [4 and 5]—particularly in DMN regions [6, 7 and 8]. Mechanistic support for the DMN’s role in memory consolidation might come from investigation of large deflections (sharp-waves) in the hippocampal local field potential that co-occur with high-frequency (>80 Hz) oscillations called ripples—both during sleep [9 and 10] and awake deliberative periods [11, 12 and 13]. Ripples are ideally suited for memory consolidation [14 and 15], since the reactivation of hippocampal place cell ensembles occurs during ripples [16, 17, 18 and 19]. Moreover, the number of ripples after learning predicts subsequent memory performance in rodents [20, 21 and 22] and humans [23], whereas electrical stimulation of the hippocampus after learning interferes with memory consolidation [24, 25 and 26]. A recent study in macaques showed diffuse fMRI neocortical activation and subcortical deactivation specifically after ripples [27]. Yet it is unclear whether ripples and other hippocampal neural events influence endogenous fluctuations in specific RSNs—like the DMN—unitarily. Here, we examine fMRI datasets from anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, where we observe a dramatic increase in the DMN fMRI signal following ripples, but not following other hippocampal electrophysiological events. Crucially, we find increases in ongoing DMN activity after ripples, but not in other RSNs. Our results relate endogenous DMN fluctuations to hippocampal ripples, thereby linking network-level resting fMRI fluctuations with behaviorally relevant circuit-level neural dynamics.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0960982216000671}, state = {published}, DOI = {10.1016/j.cub.2016.01.017}, author = {Kaplan R; Adhikari MH; Hindriks R; Mantini D; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco G} } @Article{ HindriksAMGMLD2015, title = {Can sliding-window correlations reveal dynamic functional connectivity in resting-state fMRI?}, journal = {NeuroImage}, year = {2016}, month = {2}, volume = {127}, pages = {242–256}, abstract = {During the last several years, focus of research on resting-state functional magnetic resonance imaging (fMRI) shifted from the analysis of functional connectivity averaged over the duration of scanning sessions, to the analysis of changes of functional connectivity within sessions. Although several studies have reported the presence of dynamic functional connectivity (dFC), statistical assessment of the results is not always carried out in a sound way and in some studies is even omitted. In this study, we explain why appropriate statistical tests are needed to detect dFC, describe how they can be carried out, how to assess the performance of dFC measures, and illustrate the methodology using spontaneous blood-oxygen level-dependent (BOLD) fMRI recordings of macaque monkeys under general anesthesia human subjects under resting-state conditions. We mainly focus on sliding-window correlations since these are most widely used is assessing dFC, but also consider a recently proposed non-linear measure. The simulations and methodology however, are general and can be applied to any measure. The results are twofold. First, through simulations we show that in typical resting-state sessions of 10 minutes, it is almost impossible to detect dFC using sliding-window correlations. This prediction is validated by both the macaque and the human data: in none of the individual recording sessions, evidence for dFC was found. Second, detection power can be considerably increased by session- or subject-averaging of the measures. In doing so, we found that most of the functional connections are in fact dynamic. With this study, we hope to raise awareness of the statistical pitfalls in the assessment of dFC and how they can be avoided by using appropriate statistical methods.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811915010782}, state = {published}, DOI = {10.1016/j.neuroimage.2015.11.055}, author = {Hindriks R; Adhikari MH; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Ganzetti M; Mantini D; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco G} } @Article{ EckerDBT2016, title = {On the Structure of Neuronal Population Activity under Fluctuations in Attentional State}, journal = {Journal of Neuroscience}, year = {2016}, month = {2}, volume = {36}, number = {5}, pages = {1775-1789}, abstract = {Attention is commonly thought to improve behavioral performance by increasing response gain and suppressing shared variability in neuronal populations. However, both the focus and the strength of attention are likely to vary from one experimental trial to the next, thereby inducing response variability unknown to the experimenter. Here we study analytically how fluctuations in attentional state affect the structure of population responses in a simple model of spatial and feature attention. In our model, attention acts on the neural response exclusively by modulating each neuron's gain. Neurons are conditionally independent given the stimulus and the attentional gain, and correlated activity arises only from trial-to-trial fluctuations of the attentional state, which are unknown to the experimenter. We find that this simple model can readily explain many aspects of neural response modulation under attention, such as increased response gain, reduced individual and shared variability, increased correlations with firing rates, limited range correlations, and differential correlations. We therefore suggest that attention may act primarily by increasing response gain of individual neurons without affecting their correlation structure. The experimentally observed reduction in correlations may instead result from reduced variability of the attentional gain when a stimulus is attended. Moreover, we show that attentional gain fluctuations, even if unknown to a downstream readout, do not impair the readout accuracy despite inducing limited-range correlations, whereas fluctuations of the attended feature can in principle limit behavioral performance.}, web_url = {http://www.jneurosci.org/content/36/5/1775.full.pdf+html}, state = {published}, DOI = {10.1523/JNEUROSCI.2044-15.2016}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Denfield GH; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ SchindlerB2015, title = {Motion parallax links visual motion areas and scene regions}, journal = {NeuroImage}, year = {2016}, month = {1}, volume = {125}, pages = {803–812}, abstract = {When we move, the retinal velocities of objects in our surrounding differ according to their relative distances and give rise to a powerful three-dimensional visual cue referred to as motion parallax. Motion parallax allows us to infer our surrounding's 3D structure as well as self-motion based on 2D retinal information. However, the neural substrates mediating the link between visual motion and scene processing are largely unexplored. We used fMRI in human observers to study motion parallax by means of an ecologically relevant yet highly controlled stimulus that mimicked the observer's lateral motion past a depth-layered scene. We found parallax selective responses in parietal regions IPS3 and IPS4, and in a region lateral to scene selective occipital place area (OPA). The traditionally defined scene responsive regions OPA, the para-hippocampal place area (PPA) and the retrosplenial cortex (RSC) did not respond to parallax. During parallax processing, the occipital parallax selective region entertained highly specific functional connectivity with IPS3 and with scene selective PPA. These results establish a network linking dorsal motion and ventral scene processing regions specifically during parallax processing, which may underlie the brain's ability to derive 3D scene information from motion parallax.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811915009830}, state = {published}, DOI = {10.1016/j.neuroimage.2015.10.066}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ TuennerhoffN2015, title = {When sentences live up to your expectations}, journal = {NeuroImage}, year = {2016}, month = {1}, volume = {124}, number = {Part A}, pages = {641–653}, abstract = {Speech recognition is rapid, automatic and amazingly robust. How the brain is able to decode speech from noisy acoustic inputs is unknown. We show that the brain recognizes speech by integrating bottom-up acoustic signals with top-down predictions. Subjects listened to intelligible normal and unintelligible fine structure speech that lacked the predictability of the temporal envelope and did not enable access to higher linguistic representations. Their top-down predictions were manipulated using priming. Activation for unintelligible fine structure speech was confined to primary auditory cortices, but propagated into posterior middle temporal areas when fine structure speech was made intelligible by top-down predictions. By contrast, normal speech engaged posterior middle temporal areas irrespective of subjects’ predictions. Critically, when speech violated subjects’ expectations, activation increases in anterior temporal gyri/sulci signalled a prediction error and the need for new semantic integration. In line with predictive coding, our findings compellingly demonstrate that top-down predictions determine whether and how the brain translates bottom-up acoustic inputs into intelligible speech.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811915008010}, state = {published}, DOI = {10.1016/j.neuroimage.2015.09.004}, author = {Tuennerhoff J{jotue}{Research Group Cognitive Neuroimaging}; Noppeney U{unoppe}{Research Group Cognitive Neuroimaging}} } @Inproceedings{ GatysEB2016_2, title = {Image Style Transfer Using Convolutional Neural Networks}, year = {2016}, month = {6}, pages = {2414-2423}, abstract = {Rendering the semantic content of an image in different styles is a difficult image processing task. Arguably, a major limiting factor for previous approaches has been the lack of image representations that explicitly represent semantic information and, thus, allow to separate image content from style. Here we use image representations derived from Convolutional Neural Networks optimised for object recognition, which make high level image information explicit. We introduce A Neural Algorithm of Artistic Style that can separate and recombine the image content and style of natural images. The algorithm allows us to produce new images of high perceptual quality that combine the content of an arbitrary photograph with the appearance of numerous well-known artworks. Our results provide new insights into the deep image representations learned by Convolutional Neural Networks and demonstrate their potential for high level image synthesis and manipulation.}, web_url = {http://ieeexplore.ieee.org/stamp/stamp.jsp?arnumber=7780634}, publisher = {IEEE}, address = {Piscataway, NJ, USA}, event_name = {IEEE Conference on Computer Vision and Pattern Recognition (CVPR 2016)}, event_place = {Las Vegas, NV, USA}, state = {published}, ISBN = {978-146738851-1}, DOI = {10.1109/CVPR.2016.265}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Inproceedings{ GatysEB2015, title = {Texture Synthesis Using Convolutional Neural Networks}, year = {2016}, pages = {262-270}, abstract = {Here we introduce a new model of natural textures based on the feature spaces of convolutional neural networks optimised for object recognition. Samples from the model are of high perceptual quality demonstrating the generative power of neural networks trained in a purely discriminative fashion. Within the model, textures are represented by the correlations between feature maps in several layers of the network. We show that across layers the texture representations increasingly capture the statistical properties of natural images while making object information more and more explicit. The model provides a new tool to generate stimuli for neuroscience and might offer insights into the deep representations learned by convolutional neural networks.}, web_url = {http://papers.nips.cc/paper/5633-texture-synthesis-using-convolutional-neural-networks}, editor = {Cortes, C. , N.D. Lawrence, D.D. Lee, M. Sugiyama, R. Garnett, R. Garnett}, publisher = {Curran}, address = {Red Hook, NY, USA}, booktitle = {Advances in Neural Information Processing Systems 28}, event_name = {Twenty-Ninth Annual Conference on Neural Information Processing Systems (NIPS 2015)}, event_place = {Montréal, Canada}, state = {published}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Inbook{ PanagiotaropoulosLK2014, title = {Neural approaches to perceptual organization}, year = {2016}, month = {12}, pages = {-}, web_url = {http://www.oxfordhandbooks.com/view/10.1093/oxfordhb/9780199829347.001.0001/oxfordhb-9780199829347}, editor = {Gepshtein, S. , L. Maloney, M. Singh}, publisher = {Oxford University Press}, address = {New York, NY, USA}, booktitle = {Oxford Handbook of Computational Perceptual Organization}, state = {accepted}, ISBN = {978-0-19-998343-8}, DOI = {10.1093/oxfordhb/9780199829347.001.0001}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Inbook{ TotahAHKMMMP2016_2, title = {Complexity and Heterogeneity in Psychiatric Disorders: Opportunities for Computational Psychiatry}, year = {2016}, pages = {33-59}, abstract = {Psychiatry faces a number of challenges, among them are the reconceptualization of symptoms and diagnoses, disease prevention, treatment development and monitoring of its effects, and the provision of individualized, precision medicine. Achieving these goals will require an increase in the biological, quantitative, and theoretical grounding of psychiatry. To address these challenges, psychiatry must confront the complexity and heterogeneity intrinsic to the nature of brain disorders. This chapter seeks to identify the sources of complexity and heterogeneity as a means of confronting the challenges facing the field. These sources include the interplay between genetic and epigenetic factors with the environment and their impact on neural circuits. Moreover, these interactions are expressed dynamically over the course of development and continue to play out during the disease process and treatment. We propose that computational approaches provide a framework for addressing the complexity and heterogeneity that underlie the challenges facing psychiatry. Central to our argument is the idea that these characteristics are not noise to be eliminated from diagnosis and treatment of disorders. Instead, such complexity and heterogeneity arises from intrinsic features of brain function and, therefore, represent opportunities for computational models to provide a more accurate biological foundation for diagnosis and treatment of psychiatric disorders. The challenges to be addressed by a computational framework include the following. First, it must improve the search for risk factors and biomarkers, which can be used toward primary prevention of disease. Second, it must help to represent the biological ground truth of psychiatric disorders, which will improve the accuracy of diagnostic categories, assist in discovering new treatments, and aid in precision medicine. Third, to be useful for secondary prevention, it must represent how risk factors, biomarkers, and the underlying biology change through the course of development, disease progression, and treatment process.}, web_url = {https://www.researchgate.net/publication/311793039_Open_Issues_in_Psychiatry_Complexity_and_Heterogeneity_in_Psychiatric_Disorders_Opportunities_for_Computational_Psychiatry}, web_url2 = {https://mitpress.mit.edu/books/computational-psychiatry}, editor = {Redish, A.D. , J.A. Gordon}, publisher = {MIT Press}, address = {Cambridge, MA, USA}, series = {Strüngmann Forum Reports ; 20}, booktitle = {Computational Psychiatry: New Perspectives on Mental Illness}, state = {published}, ISBN = {978-0-262-03542-2}, author = {Totah N{ntotah}{Department Physiology of Cognitive Processes}; Akil H; Huys QJM; Krystal JH; MacDonald III AW; Maia TV; Malenka RC; Pauli WM} } @Poster{ ZaldivarGLLP2016, title = {Dopamine elicits lamina- and frequency-specific increase of information in the local-field-potentials of the macaque V1}, year = {2016}, month = {11}, day = {16}, number = {712.08}, abstract = {Purpose: Local field potentials (LFPs) reflect the aggregate activity of neural populations generated by different neural mechanisms and expressed in different frequency domains. Each frequency range reflects, at least in part, different aspects of neural activity and capture the activity expressed by different processing pathways1. In particular, previous studies showed the activity reflected in the low (< 20 Hz) and high-frequencies (> 50 Hz) dissociate from the activity of the middle-frequency band (18 – 38 Hz). It has been proposed, based on statistical considerations, that this middle frequency band reflects the influence of neuromodulation pathways1. However, it is not know whether and how this middle-frequency band reflects neuromodulation and whether it relates to stimulus encoding. Methods: We recorded LFPs in four anesthetized non-human primates (macaca mulatta), during spontaneous activity and presentation of movie clips, using 16-contact laminar probes (NeuroNexus) on a single shank of 3 mm long (50 µm thick) and with electrode-sites spaced 150 µm apart spanning the entire cortical depth of V1. We pharmacologically mimicked dopaminergic (DAergic) neuromodulation, by systemically applying L-DOPA+Carbidopa. L-DOPA is metabolic precursor of dopamine (DA) and once it crosses the blood-brain-barrier, is immediately metabolized into DA2. Results and Conclusions: DAergic neuromodulation elicited frequency- and stimulus dependent power changes in the recorded LFPs. During spontaneous activity, we observed a remarkable increase specific to the middle-frequency (18 – 38 Hz) band power accompanied by a decrease of gamma (50 – 150 Hz) power. In contrast, during visual stimulation with movie clips DA increased both the power of gamma and of the middle frequency band. Moreover, DA increased the information in LFP power, particularly superficial and deep layers and in the gamma (50 – 100 Hz) frequency band. Overall, our results show that the middle-frequency band captures endogenous non-stimulus driven oscillations that are modulated by dopamine, and that dopamine regulates gamma-range information coding in visual cortex.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/6809}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}; Lowe S{sloewe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ BesserveL2016, title = {Hippocampal neural events predict ongoing brain-wide BOLD activity}, year = {2016}, month = {11}, day = {16}, number = {756.18}, abstract = {Transient Local Field Potential (LFP) activity exhibits a wide variety of patterns, reflecting local antagonistic or synergistic neural activity changes in the recorded structure. Among them, “events” with a characteristic time-frequency profile can be identified, which may occasionally reflect transient large-scale interactions with other brain structures. Such an event-related multistructure activity can be studied using concurrent fMRI and LFP recordings in an experimental design dubbed as Neural Event Triggered (NET)-fMRI (Logothetis et al, 2012). Recently we used NET-fMRI to describe the brainwide up and down modulation of neural activity associatiated with hippocampal ripples. Here we examine how much the BOLD changes associated with these events can describe the fMRI time series along the entire data acquisition period. To address this question, we develop a generative model of the ongoing neural activity including both hippocampal LFP recordings and BOLD signals in the whole brain. The model was based on 6 types of oscillations detected in the hippocampus: Sharp-waves, ripples, gamma, beta, sigma and low frequency events. We first estimated the time course of the BOLD signature of neural events across brain structures by learning a dictionary of responses using the kSVD algorithm, and performed statistical analysis to extract significantly activated voxels for each neural event. Based on a convolutive model of the LFP-BOLD relationship, we corrected the effects of overlap between successive neural events on the BOLD response by estimating the autocorrelation function of the neural events and used it to obtain deconvolved BOLD signatures, describing the contribution of a single event to the BOLD signal. Preliminary results on 3 sessions show the BOLD signature of each event can be well captured by two dictionaries elements: one with a short response latency (peak response at 2.6s) in a wide range of subcortical and cortical structures, and a long latency (peak response at 5.1s) response restricted to sensory and associative cortical areas. This model enables us to estimate the contribution of hippocampus-related activity to fMRI time series in the whole brain. We thus estimated the overall ongoing single trial fMRI activity averaged across all brain structures at each time point using the model and LFP event time stamps only. The average correlation coefficient between the true fMRI signal and the event based reconstruction was .313, showing that hippocampal neural event carry rich information about global brain dynamics and suggesting that global brain dynamics could in turn be used to infer electrical activity non-invasively.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/24189}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Besserve M{besserve}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ LeeMSAW2016, title = {Increased microglial priming in autism spectrum disorder, an immunocytochemical study in postmortem human temporal cortex}, year = {2016}, month = {11}, day = {16}, number = {776.18}, abstract = {Microglia can shift into different complex morphologies depending on the microenvironment of the central nervous system (CNS). The distinct morphologies correlate with specific functions and indicate the pathophysiological state of the CNS. Previous postmortem studies of autism spectrum disorder (ASD) showed regions of neuroinflammation in ASD resulting in changes in microglia number. These change in the microglia density can be accompanied by changes in microglia phenotype but the individual contribution of different microglia phenotypes to the pathophysiology of ASD remains unclear. Here, we used an unbiased semi-stereological approach to quantify six structurally and functionally distinct microglia phenotypes in postmortem human temporal cortex, which were immuno-stained with an antibody against Iba1. In addition to stereological measures, we used three different methods to quantify Iba1-immunoreactive microglia. We now report in human postmortem cortex measures on six distinct phenotypes including ramified, primed, reactive, amoeboid, rod and dystrophic. The total density of all microglia phenotypes did not differ between ASD donors (n=10, 14.6 yrs, range 2.8-29 yrs) and typically developing individual donors (controls, n=9, 14.9 yrs, 1.8-32 yrs). However, there was a significant decrease in ramified microglia in both gray matter and white matter of ASD, and a significant increase in primed microglia in gray matter of ASD compared to controls. This increase in primed microglia showed a positive correlation with donor age in both gray matter and white of ASD, but not in controls. Our results provide evidence of a shift in microglial phenotype that may indicate impaired synaptic plasticity, and a chronic vulnerability to exaggerated immune responses. We suggest the priming of microglia is most likely due to the disruption of maternal environment during pregnancy and developmental influences rather than genetic predispositions, but the exact mechanism is unclear. Further investigation in the underlying mechanism of the shift in microglia phenotype may be a step forward in understanding the significance of maternal environment and microglial pathology in ASD. Quantitative methods of measuring Iba1-immunoreactive microglia did not show significant difference between ASD and controls, which suggests the importance of using visual categorization or finer and/or more sensitive methods when neuroinflammation is subtle to delineate the complex morphology of microglia.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/19136}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Lee AS{slee}{Department Physiology of Cognitive Processes}; Moore MA; Saccomano ZT; Azmitia EC; Whitaker-Azmitia PM} } @Poster{ deAzevedoOABLLK2016, title = {Simultaneous resting-state and visually-driven functional networks in the macaque brain}, year = {2016}, month = {11}, day = {16}, number = {834.10}, abstract = {The primate brain is a complex dynamical system displaying long-range temporally-correlated functional networks. In the absence of external stimulation, several so called resting state functional networks of spontaneous activity have been identified. Their origin and function are not well understood, but such intrinsic architecture could reflect neural fluctuations within anatomically connected areas or active mechanisms related to perception and awareness. On the other hand, when the brain is being stimulated, a different pattern of stimulus-evoked activity emerges. How the brain orchestrates those interwoven patterns of activity is still unclear. We sought to assess the relationship between resting-state and stimulus-driven functional networks by investigating their topographical correspondence by using functional magnetic resonance imaging (fMRI) under specific stimulus paradigms. To this end, we scanned two monkeys (Macaca mulatta), while anesthetized or awake, stimulated with three main paradigms: a) no visual stimulation, b) visual stimulation using a one-minute block-design displaying natural movie clips alternated with gray background, and c) continuous visual stimulation using uninterrupted natural movies. Using independent component analysis (ICA), we were able to recover topographically similar patterns of resting state networks contained in stimulus-driven datasets. This suggests that, under certain circumstances, the primate brain is able to cope with both types of functional networks independently. Moreover, our results provide implications for bidirectional causal influences between stimulus-driven and spontaneous activity. This work provides insights of how the brain organizes its functional architecture and we expect it can stimulate further analysis and reinterpretation of a wide range of existing neuroimaging and physiological data.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/20730}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {de Azevedo FA{fazevedo}{Department Physiology of Cognitive Processes}; Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}; Azevedo LC{lazevedo}{Department Physiology of Cognitive Processes}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Lohman G{lohmann}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GK{george}{Department Physiology of Cognitive Processes}} } @Poster{ MolaeiVaneghiSB2016, title = {A 9.4T human fMRI study reveals differential laminar responses for visual motion in eye- and world-centered reference frames in area V3A}, year = {2016}, month = {11}, day = {14}, number = {328.06}, abstract = {Neural mechanisms underlying a stable perception of the world during pursuit eye movements are not fully understood. Both, perceptual stability as well as perception of real-world motion are the product of multi-modal integration between retinal motion (visual motion signals) and efference copies of eye movements (non-visual motion signals). The comparison between these two signals allows differentiating between self-induced motion and external, real-world motion. Recently, pursuit-paradigms revealed that human area V3A responds to motion predominantly in a world-centered rather than in a retina-centered reference frame (Fischer et al., 2012). This indicates that V3A integrates retinal motion with non-retinal eye-movement signals. In this study we combined ultra-high-field (9.4T) human fMRI, state of the art pulse sequences, and laminar analysis to find out if there is a differential involvement of cortical layers in the processing of real world motion compared to retinal motion in area V3A. We used a 2D GE EPI sequence with 0.8 mm isotropic resolution to measure BOLD signal at different cortical depths while subjects performed a visual pursuit task. The paradigm involved a 2x2 design containing real motion and visual pursuit, which allowed separating responses to retinal and real motion while fully controlling for pursuit-related effects. A laminar surface-based analysis method was used to study the relationship between spatial localization and activation strength as a function of cortical depth by sampling the BOLD signal from the superficial, middle, or deep cortical lamina in area V3A. The results show that signals related to retinal motion were evenly spread across layers with a bias towards deep layers of V3A while real-motion responses had a gradient with a peak in superficial layers. The differential laminar response profile is compatible with differential local processing for the two motion types. The stronger involvement of superficial layers during real motion processing may be indicative of feedback related processing, possibly through mediation of efference-copy related signals from higher-level regions such as parietal cortex or smooth pursuit fields of the frontal eye fields with which V3A has direct connections. Future studies are needed to clarify the reasons for differential laminar responses and to identify communication pathways leading to V3A.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/26004}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Molaei-Vaneghi F{fmolaei}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ GrassiZB2016_4, title = {A generic mechanism for Gestalt and high-level stimulus interpretation in the human brain}, year = {2016}, month = {11}, day = {14}, number = {360.02}, abstract = {A common denominator in all vision tasks is scene segmentation: what is fore- and background, which visual components belong to the same or different entities? In prior studies we used a bi-stable stimulus that can either be perceived as separate local components or as a global Gestalt. fMRI and TMS showed that posterior parietal cortex (PPC) was selectively and causally involved in global Gestalt perception (Grassi et al., 2016; Zaretskaya et al., 2013). Here we employed three additional such local vs. global bi-stable stimuli. Importantly, we found that apart from the classification of the two possible percepts into local (ungrouped, component) versus global (grouped, Gestalt), the two possible perceptual interpretations can alternatively be classified according to a second dimension: the complexity or sophistication of the interpretation, i.e. default (simple) versus non-default (complex, high-level, sophisticated). As these two dimensions overlapped differentially across the four stimulus classes (for two stimuli, global coincided with complex, in another two with simple), we were able to identify whether parietal cortex involvement reflected grouping, or the complexity of the perceptual interpretation. We found that the involvement of parietal cortex reflected the level of sophistication of the visual interpretation rather than grouping into a single Gestalt. For all four stimuli, we found activity pattern that was highly similar for the contrast of default (simple) vs. non-default (complex, sophisticated) perceptual interpretations. It consistently and prominently involved posterior parietal cortex. Also consistent with previous findings, we found for all stimuli strong early visual cortex deactivations during sophisticated perceptual interpretations. Mid-level regions such as LOC or motion regions were differentially involved with each stimulus class and percept-type. Our results lead us to suggest that PPC is not necessarily involved in mere grouping toward global Gestalt, but instead more generally it is involved in generating the more complex, high-level, or more sophisticated perceptual interpretation of a given stimulus. The activation of high-level dorsal areas (PPC) and the concurrent deactivation of early visual areas during high-level perceptual interpretations is in line with predictions from generative models of visual perception, also known as predictive coding theory, but not with attention. Our findings suggest a generic mechanism for scene segmentation with the PPC as its anatomical substrate.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/30064}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ SchindlerB2016_3, title = {Integration of visual and extra-retinal self-motion during voluntary head movements in the human brain}, year = {2016}, month = {11}, day = {14}, number = {329.01}, abstract = {Our phenomenological experience of the stable world is maintained due to continuous integration of visual self-motion with extra-retinal signals. This mechanism is not only essential for locomotion and navigation but also a crucial prerequisite for virtually any successful interaction with our environment. Constraints in fMRI acquisition methods previously prevented the study of neural processing associated to integration of visual signals with those related to head-movement. Here, we developed a novel and ecologically valid fMRI paradigm that enabled us to study integration of optic flow with extra-retinal heading signals while observers performed voluntary head movements. Our results provide first evidence for the multisensory integration of head-motion in human regions MST, VIP, the cingulate visual area (CSv) and a region in pecuneus (Pc) that are known to process visual self-motion signals. In addition, we found multisensory heading integration in posterior insular cortex (PIC) that we suggest to be homolog to monkey visual posterior sylvian (VPS). In contrast, no integration was found in parieto-insular-vestibular cortex (PIVC). These results identify for the first time head-movement related integration of visual heading signals in the human brain, and identify a clear functional segregation of the human posterior insular cortex.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/30214}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ RamirezVillegasLB2016, title = {Statistical source separation of rhythmic LFP patterns during sharp wave ripples in the macaque hippocampus}, year = {2016}, month = {11}, day = {14}, number = {450.02}, abstract = {Sharp wave-ripples (SWR), episodes in the hippocampal CA1 local field potential (LFP) combining a low-frequency deflection (sharp wave) and a high-frequency oscillation (ripple), are thought to mediate memory consolidation. These events are paradigmatic episodes of the interaction between neuronal ensembles across distinct substructures of the hippocampal formation. However, the detailed neuronal ensemble mechanisms underlying this phenomenon remain largely unknown. This question arises partly due to inherent difficulties in inferring network-level dynamics from neuronal population measurements such as LFP. To address this question, we analysed in-vivo intracortical recordings of the CA1 of macaque monkeys. We devised a statistical source separation technique in order to disentangle the spatio-temporal signature of multichannel LFP in peri-SWR time windows of 1s. The first results of our study revealed that SWR complexes in CA1 can be approximated by a linear combination of four main oscillatory components with distinct spectral signatures. We found that SW (5.4-14.2 Hz) and gamma (31.7-68.1 Hz) components are expressed by stratum radiatum, while ripple (96.9-125.5 Hz) and supra-ripple (188.3-199.4 Hz, 95% confidence intervals) oscillations originate in stratum pyramidale. We then devised a model of the macaque’s CA3-CA1 network. The network consists of two layers, each with 200 pyramidal-neuron and 20 peri-somatic interneuron models of two compartments. The model was able to predict a large number of features of in-vivo SW episodes. In particular, we found that SW (5.6-7.5 Hz), gamma (23.2-34.0 Hz), ripple (155.8-167.4 Hz) and supra-ripple (174.4-194.7 Hz, 95% confidence intervals) are also the main oscillatory components of modelled SWR. Our model suggests that SW and gamma components arise from CA3 bursting in stratum radiatum, while ripple oscillations originate from local interactions between pyramidal cells and interneurons. Notably, CA1 interneurons, also entrained by CA3-gamma oscillations, are responsible for the high-frequency component of the LFP activity, thus establishing the population signature of supra-ripple LFP during SWR. Our experiments suggest that SW, gamma, ripple and supra-ripple rhythms are specific markers of the phenomena occurring in neuronal activity during SWR that can be automatically extracted from LFP data with our approach. Finally, this approach establishes a relationship between neuronal activity over meso- and microscopic scales that can be used to investigate network properties such as excitation-inhibition balance without resorting to single unit analysis.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/7145}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Poster{ KwonB2016, title = {Attention changes connectivity strength in a hierarchical manner across the visual network}, year = {2016}, month = {11}, day = {13}, number = {266.03}, abstract = {Attention improves behavioral performance by selectively enhancing neural responses to attended task-relevant stimuli. Several models have been suggested that explain modulation of neural responses by attention. These models are typically limited to effects of attention on single regions, and do not take into account the hierarchical organization of regions involved in processing. Here, we introduce a model that quantifies the connectivity changes across the visual hierarchy encompassing regions V1, V2, V3, up to hV4 and V5/MT+. We measured fMRI activity in humans performing a demanding visual attention task during ultra-long blocks lasting 2 minutes, alternating with passive viewing blocks involving the same stimuli. This paradigm allowed for high-quality functional connectivity measurements free of confounds related to on- and offset effects of stimulus blocks. Functional connectivity was measured between regions of the dorsal attention network (DAN) and visual regions, as well as between default mode network (DMN) regions and visual regions. We then quantified the slope and baseline of connectivity strength of a given DAN or DMN region with the visual hierarchy, as a function of attention. The results revealed that each of the DAN regions had a gradient in its connectivity strength along the visual processing hierarchy: the DAN regions showed stronger connectivity with high-level areas that decreased towards low-level areas, revealing a descending gradient from V5/MT+ and V4 towards V1. Attention enhanced this baseline connectivity pattern in additive manner for IPS, whereas right FEF additionally increased the slope, thus showing also multiplicative effects along the visual hierarchy. DMN regions had an inversed gradient of connectivity with the visual hierarchy. Attention tended to have multiplicative effects for all regions, but (negative) additive effects only in left lateral parietal cortex. The current study provides a first quantitative model of attention induced changes in connectivity between attention and default mode networks and the hierarchy of early visual areas.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/26072}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kwon S{soyoung}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoNYL2016, title = {Burst-like stimulation of the locus coeruleus leads to thalamo-cortical activation and hippocampal suppression: implication for competing networks}, year = {2016}, month = {11}, day = {13}, number = {181.01}, abstract = {Diffusely projecting noradrenergic (NE) neurons of the brainstem nucleus locus coeruleus (LC) regulate excitatory/inhibitory balance in their multiple forebrain targets. The net effect of LC activation depends on the amount of NE released and mediated by different types of adrenergic receptors. It has been long recognized that a predominant effect of NE in cortex is suppression of spontaneous firing, which increases a signal-to-noise ratio of sensory transmission. However, we have recently reported that a brief phasic activation of LC transiently increases gamma power and spike probability in the prefrontal cortex (PFC). Research on NE effects in hippocampus mainly focused on synaptic plasticity. The vast experimental evidence shows that NE release in hippocampus creates a temporal window of heightened synaptic plasticity, but both potentiation and depression effects have been documented. Here, we recorded simultaneously extracellular activity in multiple cortical and subcortical projection targets of LC including sensory and associative thalamic nuclei, hippocampus, sensory cortex and PFC in the urethane-anesthetized rat using high-density multi-electrode arrays. We quantified the effects of LC phasic activation (direct electric current: 0.5mA, at 50-100Hz for 100-200 ms) on neural activity using band-limited power (BLP) analysis. Briefly, a wide-band (0.1Hz-8kHz) signal was band-pass filtered in different frequency ranges; the BLP for each band was normalized to pre-stimulus values and the magnitude of power modulation was extracted over 1s post-stimulus period. Power increase/decrease in the gamma frequency range was indicative for excitatory/inhibitory net effect, respectively. The LC stimulation produced remarkable dissociation between thalamo-cortical activation and strong suppression of neural activity in hippocampus. The neuromodulatory effects were transient and lasted for 1-3 s post-stimulation. This result suggests that LC phasic activation in response to salient stimuli potentiates broadcasting within thalamo-cortical circuit, while suppresses potentially competing hippocampal-cortical network, which support ‘off-line’ information processing. Present results also consistent with our recent findings that LC stimulation at times of hippocampal ripples after learning reduced the efficiency of ‘off-line’ memory consolidation, possibly by activating a competing thalamo-cortical network and therefore causing interference for hippocampal-cortical communication.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/20802}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Yang M{myang}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ TotahNPLE2016, title = {Monitoring large populations of locus coeruleus single units reveals the heterogeneous and non global nature of the norepinephrine neuromodulatory system}, year = {2016}, month = {11}, day = {13}, number = {181.03}, abstract = {Cognitive theories assume that the locus coeruleus (LC), a brain stem neuromodulatory nucleus, broadcasts a redundant signal to the entire forebrain due to synchronized activity of a homogeneous population of diffusely projecting norepinephrine (NE) neurons. Until recently, technical challenges limited recordings to 1-2 LC single units, which was insufficient for characterizing the diversity of LC cell types and their ensemble activity patterns. We recorded as many as 75 single units simultaneously in the urethane-anesthetized rat using a high-density multi-electrode array and analyzed 11893 unit pairs. To assess input-output specificity of LC units, we electrically stimulated 15 forebrain LC projection sites and analyzed evoked orthodromic and antidromic LC spiking. Using noise and cross correlation analyses, we assessed the heterogeneity of unit activity with respect to input-output circuits. Our results revealed 2 cell populations differing by spike width (Type 1: 461±14μs, Type 2: 1076±9μs) and rate (Type 1: 1.6±0.06Hz, Type 2: 0.84±0.04Hz). NE identity was confirmed for both types by a α2 agonist. Spontaneous noise correlations were weak and did not depend on linear distance, but Type 1 units exhibited higher correlations with one another (pair of Type 1’s: 0.138±0.007, Type 2’s: 0.049±0.001, mixed Type1/2 pair: 0.038±0.002 in 200ms bins). Evoked noise correlations were also weak (Type 1: 0.155±0.009, Type 2: 0.051±0.006, Type 1/2: 0.040±0.008, in 750ms window after five 5mA, 0.5ms, 30Hz foot shocks). Consistent with weak noise correlations, the majority (77%) of pairs did not have any significant spike count change at any cross-correlelogram bin (-2 to +2s). Some pairs were correlated (from 0 to +50ms or +1.0 to 1.5ms) or anticorrelated (+1.0 to 2.0ms). We defined projection targets for 65 of 205 units. 53% of those projected to only 1 forebrain site and the remainder projected to multiple (up to 8) sites. Both cell types projected widely to the forebrain. Unit pairs projecting to thalamus had significantly higher noise correlations (0.198±0.015) than pairs with diverging projections (0.132±0.011). PFC input to the LC was area-specific: PL stimulation decreased and IL increased spiking (PL: 9% of units dec., 3% inc.; IL: 1% dec., 14% inc.). PFC stimulation also decorrelated LC activity (200ms before / after stimulation in PL: 0.063±0.005 / 0.050±0.005 and IL: 0.053±0.006 / 0.038±0.007). Thus, we found 2 LC cell types differing in spike width, rate, and noise correlation; however, overall correlations were weak. These findings challenge the prevailing view that LC cells are physiologically similar and are homogenously driven to provide a global signal.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/20804}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ BallaMHSMPSL2016, title = {Fast fMRI in nonhuman primates at 4.7T with multiband EPI and a 4 Tx/Rx + 1 Rx phased-array concept}, year = {2016}, month = {9}, day = {29}, abstract = {Purpose / Introduction Physiology of neural systems in the brain is a field where fMRI unfolds its unique potentials (i.e. spatial coverage, noninvasiveness), but also clearly shows its limitations. The current technical possibilities combined with the inverse relations between signal-to-noise ratio and acquisition sampling rate, as well as between spatial resolution and full gradient encoding repetition rate, limit the acquisition speed and reduce the range of applications in basic neuroscience. In order to approach the timescale of dynamic processes in the resting brain of nonhuman primates and to detect the faint BOLD contrast induced by the transient activation of neural groups or global baseline changes, we developed RF-hardware, acquisition sequence and offline reconstruction pipeline for whole-brain fMRI subsampled in two dimensions. Subjects and Methods The 26cm inner diameter of the BGA26SL gradient system in our vertical bore Bruker BioSpec 47/40 MR scanner and the 3-point monkey-head stereotaxic system demanded a compact transmit-receive RF-coil-array solution. The water-proof coil components were mounted onto individual 3D-printed head-fixation helmets. Four loops were used for transmission in a circularly polarized manner and were decoupled by overlap. The quality of excitation homogeneity was not sufficient for solutions with more than 4 loops, since the size of the loops had to be reduced for decoupling and positioning. The same four loops were used for reception with a fifth smaller loop added to cover the frontal brain. Power splitters, TR-switches, DC-control, bias-Tees and low noise preamplifiers were custom built and integrated in a stand-alone coil-interface. Bruker’s EPI acquisition method in Paravision 6.0.1 was modified to support calculation and parameter handling of multiband (MB) RF-pulses with programmable spacing, automatic sequence adaptation for blipped simultaneous multi-slice imaging with variable CAIPI-shifts, and manual control of some low-level EPI parameters directly from the method in advanced user mode. Protocol parameters were optimized for SNR per unit time with a gradient duty cycle at limit, based on the primary criterion to achieve whole-brain coverage (18-22 slices of 2mm thickness) within 500ms. For this we took advantage of the original in-plane acceleration handling of the EPI method, which reduced distortions due to long echo-spacing, and combined it with the novel MB acceleration functionality. Fully sampled reference datasets with the same echo-spacing, and the number of segments set to the in-plane acceleration factor, were acquired independently. We tested 2D-GRAPPA, 2D-SENSE, slice-GRAPPA and split-slice-GRAPPA for the reconstruction of missing data. One step techniques suffered from significant leakage artifacts and the expected benefit was not gained by split-slice-GRAPPA, since this algorithm calculates the weights from the reference dataset only, whereas slice-GRAPPA can use source-points from the accelerated dataset. This turned out to be critical and hence, our pipeline uses slice-GRAPPA preceded by 1D trajectory and phase correction. Results Figure 1a presents two slices from the reference dataset (2 segments, no MB, 20 slices), Fig. 1b the best case reconstruction of the two slices unfolded from a reduced version of the reference image (2 bands, 2x in-plane acceleration, FOV/2 CAIPI-shift), Fig. 1c the reconstruction from accelerated acquisition data (TR = 500ms, 0.9x0.9x2.0mm³), Fig. 1d the BOLD-activation map based on a visual stimulation paradigm ([16rest 8stim 36rest]x20 visual stimulation of the left eye with homogeneous light impulses flickering at 32Hz), Fig. 1e the temporal SNR-map and Fig.1f the average hemodynamic response. Discussion Our setup and methods can produce high resolution whole-brain coverage datasets in 500ms and detect BOLD-contrast induced by standard stimulation paradigms. Sampling the hemodynamic response function at a high rate facilitates the detection of transient dynamic effects (i.e stimulus on and stimulus off bumps, as well as breathing “artifact” in Fig.1f).}, file_url = {fileadmin/user_upload/files/publications/2016/ESMRMB-2016-Balla-Poster.pdf}, file_url2 = {fileadmin/user_upload/files/publications/2016/ESMRMB-2016-Balla.pdf}, web_url = {http://www.esmrmb.org/index.php?id=/en/index/esmrmb_2016_congress.htm}, event_name = {33rd Annual Scientific Meeting of the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB 2016)}, event_place = {Wien, Austria}, state = {published}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Hennel F; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Pohmann R{rolf}; Scheffler K{scheffler}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ GrassiZB2016_2, title = {Differential modulation of foreground and background in early visual cortex by feedback during bistable Gestalt perception}, journal = {Perception}, year = {2016}, month = {8}, day = {30}, volume = {45}, number = {ECVP Abstract Supplement}, pages = {155}, abstract = {A growing body of literature suggests that feedback modulation of early processing is ubiquitous and central to cortical computation. In particular stimuli with high-level content have been shown to suppress early visual regions, typically interpreted in the framework of predictive coding. However, physical stimulus differences can preclude clear interpretations in terms of feedback. Here we examined activity modulation in V1-V2 during distinct perceptual states associated to the same physical input. This ensures that observed modulations cannot be accounted for by changes in physical stimulus properties, and can therefore only be due to percept-related feedback from higher-level regions. We used a bistable dynamic stimulus that could either be perceived as a large illusory square or as locally moving dots. We found that perceptual binding of local elements into an illusory Gestalt led to spatially segregated modulations: retinotopic representations of illusory contours and foreground were enhanced, while inducers and background suppressed. The results extend prior findings to the illusory-perceptual state of physically unchanged stimuli, and show also percept-driven background suppression in the human brain. Based on our prior work, we hypothesize that parietal cortex is responsible for the modulations through recurrent connections in a predictive coding account of visual processing.}, web_url = {http://journals.sagepub.com/doi/full/10.1177/0301006616671273}, event_name = {39th European Conference on Visual Perception (ECVP 2016)}, event_place = {Barcelona, Spain}, state = {published}, DOI = {10.1177/0301006616671273}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ MeiLE2016, title = {The midline thalamic nucleus reuniens is essential for spatial memory retrieval}, year = {2016}, month = {7}, day = {5}, pages = {3229}, abstract = {Neural processing in the medial prefrontal cortex (mPFC) and hippocampus (HPC) as well as mPFC-HPC interactions are essential for spatial information acquisition, storage and flexible use. The cross-regional interactions are supported by direct and indirect anatomical pathways. Hippocampal projections to the mPFC critically contribute to spatial encoding. Little is known about the functional role of multi-synaptic communication between HPC and mPFC through the nucleus reuniens of the midline thalamus (nRe), which is reciprocally connected with both HPC and mPFC. To study the role of nRE for memory consolidation we tested the effect of nRe inactivation (muscimol, 0.27µg/µl, 0.27 µl) on acquisition and performance of a HPC- and mPFC-dependent task on a crossword maze. Rats with chronically implanted cannulas received intra-nRe injection immediately after each learning session or prior task performance. To get reward, rats were required to follow specific maze-trajectory, which depending on the start position contained 6 or 7 decision cross-points. There was no effect of post-learning nRe inactivation on the task acquisition, while nRe inactivation before the probe trail (24h after reaching a learning criterion) produced a strong performance deficit in well-trained rats. Our results suggest the direct HPC-mPFC pathway may be sufficient for spatial learning; however indirect HPC-mPFC communication via nRe may be essential for retrieval of newly acquired spatial information. The effects of nRe inactivation on the remote memory will be presented.}, web_url = {http://emdstudio.co.il/ebook/fens2016/files/downloads/FENS%202016%20Programme%20Book.pdf}, event_name = {10th FENS Forum of Neuroscience}, event_place = {Copenhagen, Denmark}, state = {published}, author = {Mei H{hmei}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ ZaidiMFLBS2016, title = {Teasing apart contributions of low-frequency LFPs and spiking activity from hemodynamic responses}, year = {2016}, month = {6}, day = {30}, number = {4307}, abstract = {Introduction: The interpretation of the neuroimaging signal is rendered difficult by the fact that it has been reported to correlate with different neuronal processes, such as multi-unit spiking, and activity in the various frequency bands of the LFP [1]. Spikes and low-frequency LFPs may, however, represent different neural processes, such as features of a visual stimulus or neuro-modulatory inputs [2]. This makes the inability to differentiate between contributions of spiking and low-frequency LFP activity a significant problem in the interpretation of hemodynamic signals. We developed a novel technique to study local neurovascular coupling enabling simultaneous epidural functional near-infrared spectroscopy (fNIRS) and intra-cortical electrophysiology, and aimed to determine if different neuronal processes had different correlates with hemodynamic signals. Methods: We recorded fNIRS together with multiple microelectrode recordings from a small volume of primary visual cortex in two anesthetized monkeys. Both stimulus-induced and spontaneous activity were recorded. Each visual stimulation trial consisted of 5s of a whole-field rotating chequerboard (ON) followed by 15s of a blank screen (OFF). Spontaneous activity was recorded for 15 min per run, in the absence of visual stimulation, and subject's eyes closed. The electrophysiological signal was filtered into eight frequency bands, (namely DeltaTheta (1-8 Hz), Alpha (9-15), Spindle (15-20), low Gamma (20-40), Gamma (40-60), high Gamma (60-120), very high Gamma (120-250) and MUA (1-3k)), and their band envelopes obtained. Multi-unit spike-rates were obtained by counting number of spikes in 50ms bins. Visual modulation for each band was obtained by the forumula: ON-OFF/ON+OFF; where ON and OFF are the band powers during ON and OFF epochs, resp. Results: We observed a negative correlation between the spiking activity and hemodynamic response peak-amplitude, but a positive correlation with its peak-time. Specifically, the total spike count during the ON epoch correlated strongly with the HbO peak-time. The peak-spike rate during the ON epoch also correlated strongly with the HbO initial-dip, demonstrating that it reflects bursts in spiking activity. We observed that the HbO peak-amplitude correlated strongly with modulations in the DeltaTheta and Alpha bands. All these relationships were also observed in spontaneous activity, demonstrating that they do not arise due to strong visual stimulation. We also found a strong difference in the spatial spreads of low versus high-frequency activity. Although we used whole-field visual stimulation, modulations in spike-rates were more spatially localized, but less synchronous than those in the DeltaTheta band. With more synchronous arteriole recruitment, stronger low-frequency LFPs lead to larger HbO response amplitudes. In contrast, vascular responses to spiking integrate temporally. With longer durations of dilation, peak-time is affected more than peak-amplitude. We also observed strong negative correlations between the DeltaTheta modulations and spiking activity. While the DeltaTheta band wasn't visually modulated, it was Conclusions: Briefly, low-frequency LFPs are reflected in hemodynamic peak-amplitude, and high-frequency activity in its peak-time. These results help better understand the mechanisms underlying neurovascular coupling, and enable better interpretations of hemodynamic signals observed during functional neuroimaging studies. anti-correlated with spiking, supporting the notion that high and low-frequency LFPs represent different neuronal processes. Further analysis based on system-identification also showed that the relationship between fNIRS signals and underlying neuronal activity are similar to those reported for fMRI [3].}, web_url = {https://ww5.aievolution.com/hbm1601/index.cfm?do=abs.viewAbs&abs=2258}, event_name = {22nd Annual Meeting of the Organization for Human Brain Mapping (OHBM 2016)}, event_place = {Geneva, Switzerland}, state = {published}, author = {Zaidi A{azaidi}{Department Physiology of Cognitive Processes}; Munk M{munk}{Department Physiology of Cognitive Processes}; Fetz E; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Birbaumer N; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}} } @Poster{ MarreirosEL2016, title = {Whole-brain mapping of state-dependent cortical responses to electrical stimulation}, year = {2016}, month = {6}, day = {27}, number = {1670}, abstract = {Introduction: Brains are strongly characterized by contextual emergence rather than the much-wished reduction, a fact implying that feature description is necessary but not sufficient condition for comprehending high-level behavior-representations. Contextual conditions of neural networks are a strict requirement for explaining any combination of elementary operations, where rules and dynamical laws can (only) be derived by observing behavior at largely different spatial scales. A multi-scale modeling approach, from single cells to neural mass models is worth attempting, although it still remains one of the central research challenges in computational systems neuroscience. Here, we combine electrical recordings, stimulation and functional MRI techniques in an attempt to define "states" and potentially their conditional probabilities with respect to well defined internal or external events. In a companion project we look at Direct Electric Stimulation (DES) of the Locus Coeruleus (LC), the major source of norepinephrine (NE) in the forebrain, which can change spontaneous and task-related neuronal discharge in a large number of LC projection-targets. In fact, the level of NE in the brain modulates a variety of cognitive processes such as attention, perception, learning and memory. Aims: 1. Characterize electrophysiological and fMRI brain evoked responses to induced stimuli and relate them to the endogenous ongoing activity changes (intensified by the anaesthesia); 2. Discover and quantify the norepinephrine whole brain networks as a response of electrical simulations, LC-DES, or combination of both. Methods: We developed a setup for multisite electrophysiological measurement combined with whole-brain imaging and with experimenter induced perturbations, such as sensory, electrical or pharmacological stimulations (Fig,1). Attempting this way to gain deeper insights into the multi-spatiotemporal brain functions. Results: Whole brain BOLD maps were obtained for both noxious electrical stimulation and LC-DES. Both produced similar results with an interesting dichotomy, where neocortex and limbic cortex showed mostly negative BOLD responses, while subcortical structures belonging to metencephalon, mesencephalon and diencephalon cortices, presented strong positive BOLD responses. The broadband activity from mPFC recordings show different oscillations regimes. A rapid foot shock (FS) stimulus induces a pronounced transient disruption on the ongoing oscillations during the 'slow oscillation' (SO) synchronized state. A smaller disruption response is observed during 'Active state' (desynchronized) and no disruption under 'Deep SO' (prolonged DOWN state). Three major cortical states were identified having distinct responses to the same noxious stimulation. The mPFC post-stimulus gamma activity follows a bell-shape curve along the synchronization index (SI), presenting larger responses during the SO state. The analyzed BOLD responses displayed different functional maps according to the cortical SI level. Voxel-wise BOLD maps and fraction of positively (PBR) and negatively (NBR) activated ROIs were computed for the same noxious electrical shock condition and averaged over trials. Conclusions: Our results show that it is possible to produce reliable state-dependent whole brain activity maps following electrical stimulation. Measuring fMRI whole brain activity and classifying it according to endogenous cortical electrophysiological states allows us to get a more realistic picture of brain function at multiple spatial and time scales.}, web_url = {https://ww5.aievolution.com/hbm1601/index.cfm?do=abs.viewAbs&abs=3128}, event_name = {22nd Annual Meeting of the Organization for Human Brain Mapping (OHBM 2016)}, event_place = {Geneva, Switzerland}, state = {published}, author = {Marreiros A{amarreiros}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ CadwellJSBFYFECT2016, title = {Cell Lineage Directs teh Precise Assembly of Excitatory Neocortical Circuits}, year = {2016}, month = {6}, pages = {60}, abstract = {The neocortex carries out complex mental processes such as perception and cognition through the interactions of billions of neurons connected by trillions of synapses. Recent studies suggest that excitatory cortical neurons with a shared developmental lineage are more likely to be synaptically connected to each other than to nearby, unrelated neurons [1, 2]. However, the precise wiring diagram between clonally related neurons is unknown, and the impact of cell lineage on neural computation remains controversial. Here we show that vertical connections linking neurons across cortical layers are specifically enhanced between clonally related neurons (Fig. 1). In contrast, lateral connections within a cortical layer preferentially occur between unrelated neurons (Fig. 1). Importantly, we observed these connection biases for distantly related cousin cells, suggesting that cell lineage influences a larger fraction of connections than previously thought. A simple quantitative model of cortical connectivity based on our empirically measured connection probabilities reveals that both increased vertical connectivity and decreased lateral connectivity between cousins promote the convergence of shared input onto clonally related neurons, providing a novel circuit-level mechanism by which clonal units form functional cell assemblies with similar tuning properties [3, 4]. Taken together, our data suggest that the integration of feedforward, intra-columnar input with lateral, inter-columnar information may represent a fundamental principle of cortical computation that is established, at least initially, by developmental programs.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Cadwell CR; Jiang X; Sinz FH{fabee}; Berens P{berens}; Fahey PG; Yatsenko D; Froudarakis E; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Cotton RJ; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ DenfieldEBT2016, title = {Correlated Variability in Population Activity: Noise or Signature of Internal Computations}, year = {2016}, month = {6}, pages = {63}, abstract = {Neuronal responses to repeated presentations of identical visual stimuli are variable. The source of this variability is unknown, but it is commonly treated as noise and seen as an obstacle to understanding neuronal activity. We argue that this variability is not noise but reflects, and is due to, computations internal to the brain. Internal signals such as cortical state or attention interact with sensory information processing in early sensory areas. However, little research has examined the effect of fluctuations in these signals on neuronal responses, leaving a number of uncontrolled parameters that may contribute to neuronal variability. One such variable is attention, which increases neuronal response gain in a spatial and feature selective manner. Both the strength of this modulation and the focus of attention are likely to vary from trial to trial, and we hypothesize that these fluctuations are a major source of neuronal response variability and covariability. We first examine a simple model of a gain-modulating signal acting on a population of neurons and show that fluctuations in attention can increase individual and shared variability and generate a variety of correlation structures relevant to population coding, including limited range and differential correlations. To test our model’s predictions experimentally, we devised a cued-spatial attention, change-detection task to induce varying degrees of fluctuation in the subject’s attentional signal by changing whether the subject must attend to one stimulus location while ignoring another, or attempt to attend to multiple locations simultaneously. We use multi-electrode recordings with laminar probes in primary visual cortex of macaques performing this task. We demonstrate that attention gain-modulates responses of V1 neurons in a manner consistent with results from higher-order areas. Consistent with our model’s predictions, our preliminary results indicate neuronal covariability is elevated in conditions in which attention fluctuates and that neurons are nearly independent when attention is focused. Overall, our results suggest that attentional fluctuations are an important contributor to neuronal variability and open the door to the use of statistical methods for inferring the state of these signals on behaviorally relevant timescales.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Denfield GH; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ ReimerYEWSBHCST2016, title = {DataJoint: Managing Big Scientific Data Using Matlab or Python}, year = {2016}, month = {6}, pages = {99}, abstract = {The rise of big data in modern research poses serious challenges for data management: Large and intricate datasets from diverse instrumentation must be precisely aligned, annotated, and organized in a flexible way that allows swift exploration and analysis. Data management should guarantee consistency of intermediate results in subsequent multi-step processing pipelines such that changes in one part automatically propagate to all downstream results. Finally, data organization should be self-documenting to ensure that lab members and collaborators can access the data with minimal effort, even years after it was collected. While high levels of data integrity are expected, research teams have diverse backgrounds, are geographically dispersed, and rarely possess a primary interest in data science. While the challenges associated with large, complex data sets may be new to biologists, they have been addressed quite successfully in other contexts by relational databases, which provide a principled approach for effective data management. DataJoint is an open-source framework that provides a clean implementation of core concepts of the relational data model to facilitate multi-user access, effcient queries, distributed computing, and cascading dependencies across multiple data modalities. Critically, while DataJoint relies on an established relational database management system (MySQL) as its backend, data access and manipulation are performed transparently in the commonly-used languages MATLAB or Python, and DataJoint can be integrated into new and existing analyses written in these languages with minimal effort or additional training. DataJoint is not limited to particular file formats, acquisition systems, or data modalities and can be quickly adapted to new experimental designs. DataJoint and related resources are available at http://datajoint.github.com.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Reimer J; Yatsenko D; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Walker EY; Sinz F{fabee}; Berens P{berens}; Hoenselaar A; Cotton RJ; Siapas AG; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ KapoorBLP2016, title = {Sequential Neuronal Activity in the lateral Prefronta Cortex during the Task of Binocular Flash Suppression}, year = {2016}, month = {6}, pages = {78}, abstract = {Neurons in the lateral prefrontal cortex exhibit a huge diversity in their activity patterns mediating various cognitive functions ranging from working memory to monitoring of serial order and even visual awareness. In a previous study, we examined the neuronal activity in this region utilizing an ambiguous visual stimulation paradigm called the binocular flash suppression and found that a majority of the feature selective single unit responses were also perceptually modulated. The proportion of units displaying feature selective responses among all the neurons recorded, were but a minority. The present study aimed at characterizing any other task related patterns if any among the remaining single units. In order to do this, we decomposed the matrix of peristimulus time histograms of the remaining neurons utilizing the non-negative matrix factorization procedure, enabling us to characterize five dominant response patterns. Interestingly, the peak amplitudes of the different patterns were distributed across different phases of a trial. Further, a majority of neurons with firing profiles similar to a given response pattern did not display significant differences in their modulation during the monocular and binocular conditions of the task, thus indicating that sequential firing in the PFC is unaffected by sensory visual competition. Next, we aimed at assessing the functional connectivity as measured with noise correlations between pairs of neurons with modulation patterns similar to the five different response patterns obtained. Pairs of single units with firing profiles similar to identical response patterns displayed higher correlations, thus indicating a stronger functional coupling among units that were temporally coincident. However, when neurons were chosen from temporally separated populations, we observed a reduction in correlations. When positive and negative correlations were evaluated separately, such a correlation structure was observed specifically for positive correlations. Surprisingly, the negative correlations were uniformly distributed across the different populations. This possibly suggests a computational network principle mediating a representation of sequential patterns of activity in the lateral prefrontal cortex.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Poster{ BannertB2016, title = {The invariance of surface color representations across illuminant changes in the human cortex}, journal = {Journal of Vision}, year = {2016}, month = {5}, day = {24}, volume = {16}, number = {12}, pages = {1155}, abstract = {Color is the brain’s estimate of reflectance for a given surface. Reflectance describes how much light a surface reflects at different wavelengths. Since the light reflected from a surface depends on its reflectance and on the spectral power distribution of the incident light, it is impossible to predict surface reflectance directly from the wavelength composition of the reflected light. Despite this computational problem, the human visual system is remarkably accurate at inferring the reflectance – perceived as color – of surfaces across different illuminants. This ability is referred to as color constancy and it is essential for the organism to use color as a cue in object search, recognition, and identification. We devised images of two surfaces presented under three different illuminants using physically realistic rendering methods to study the neural architecture underlying surface color perception. Measuring patterns of fMRI voxel activity elicited by these images, we tested to what extent responses to surface color in various retinotopically mapped areas remained stable across illuminants and which regions encoded illuminant information. We made three important observations: First, patterns of fMRI responses to surface color generalized across illuminants in V1 but not V2, V3, hV4, or VO1. Second, accuracy of illuminant decoding was positively correlated with psychophysically measured color constancy as predicted by the Equivalent Illuminant Model. Third, when fMRI activity was elicited by stimuli that were matched in reflected light but differed in illumination and therefore also differed in perceived surface color, there was a gradient from lower to higher visual areas to distinguish between the two inputs in terms of a difference in surface color rather than illumination. Our results demonstrate that V1 represents chromatic invariances in the stimulus environment (possibly via feedback) whereas downstream visual areas are more biased to link chromatic differences to different surface color percepts.}, web_url = {http://jov.arvojournals.org/article.aspx?articleid=2551130}, event_name = {16th Annual Meeting of the Vision Sciences Society (VSS 2016)}, event_place = {St. Pete Beach, FL, USA}, state = {published}, DOI = {10.1167/16.12.1155}, author = {Bannert M{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ SavicGPLSA2016, title = {A Ratiometric Bioresponsive MRI Contrast Agent for Rapid Monitoring of Biological Processes}, year = {2016}, month = {5}, day = {11}, number = {2307}, abstract = {A number of bioresponsive MRI contrast agents have been developed, with the aim of producing the maximal signal difference for a given biological event. This paper introduces an approach which substantially improves the detection of physiological events with fast kinetics. A nanosized, calcium-sensitive dendrimeric probe was developed and characterized by means of a balanced steady-state free precession imaging protocol. Results show an almost four times greater contrast gain per unit of time as compared to conventional T1-weighted imaging with small sized contrast agents. Consequently, this ratiometric methodology has a profound significance for future studies of biological dynamic processes by means of MRI.}, web_url = {http://www.ismrm.org/16/program_files/TP12.htm}, event_name = {24th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2016)}, event_place = {Singapore}, state = {published}, author = {Savić T{tsavic}; G\"und\"uz S{sgunduz}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Poster{ KaplanAHMMLD2016_2, title = {Hippocampal sharp-wave ripples influence selective activation of the default mode network}, year = {2016}, month = {2}, day = {25}, pages = {56-57}, abstract = {Hippocampal ripples occur during restful periods and are associated with circuit-level memory consolidation. In parallel, the default mode network (DMN), a prominent network observed during the resting-state, includes brain regions involved in memory consolidation, but has unclear behavioral correlates. Large-scale neocortical fMRI activations and subcortical deactivations have been observed in monkeys specifically after hippocampal sharpwave ripple (80 180Hz in monkeys) events, yet it is still unclear whether they and other hippocampal neural events influence cortical resting-state networks (RSNs) differently. Investigating fMRI datasets from two anesthetized monkeys with simultaneous hippocampal electrophysiology recordings, we implemented a recently developed technique that uses spatial independent component analysis (ICA) to define correlated fMRI signal fluctuations measured across multiple scan experiments/sessions and subjects into component brain networks. We then isolated the non-human primate equivalents of the DMN and another prominent RSN, the ventral somato-motor network. We first investigated whether there were positive DMN blood-oxygen-level-dependent (BOLD) responses after 2,831 hippocampal ripple events and whether these positive responses also occurred after the onset of 2,004 hpsigma (8 22Hz) and 1,740 gamma (25 75Hz) hippocampal events. Second, we investigated whether these three different types of hippocampal events, also co-occurred with BOLD signal fluctuations in the ventral somatomotor network, a RSN not implicated in memory consolidation. Consequently, we could determine whether RSN BOLD responses were network and neural-event specific. We observed a dramatic increase in the DMN BOLD signal following ripples, but not other electrophysiological events in the hippocampus. Notably, we found BOLD increases in the DMN after hippocampal ripples, but not in a prominent ventral somatomotor RSN. Our results relate endogenous fluctuations in the DMN BOLD signal to the onset of hippocampal ripple events’ linking resting-state fMRI network fluctuations with behaviorally relevant circuit-level neural dynamics.}, web_url = {http://www.cosyne.org/c/index.php?title=Cosyne_16}, event_name = {Computational and Systems Neuroscience Meeting (COSYNE 2016)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Kaplan R; Adhikari M; Hindriks R; Mantini D; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco G} } @Thesis{ Hernandez2016, title = {Limbic connections with the ventral tegmental area in the nonhuman primate}, year = {2016}, web_url = {https://publikationen.uni-tuebingen.de/xmlui/handle/10900/69305}, state = {published}, type = {PhD}, author = {Hernandez D{dhernandez}{Department Physiology of Cognitive Processes}} } @Conference{ LogothetisMRBE2016, title = {PGO wave-triggered functional MRI: mapping the networks underlying synaptic consolidation}, year = {2016}, month = {11}, day = {16}, number = {670.12}, abstract = {By combining concurrent electrophysiological recordings and fMRI, we recently demonstrated that the events known as hippocampal sharp wave-ripple complexes (SPW-R) are tightly associated with robust cortical activations that occur concurrently with a particularly intriguing strong inhibition of large portions of subcortical brain structures that are closely involved in neural plasticity, such as the basal ganglia (BG), the pontine region (PONS) and the cerebellar cortex (Logothetis, Eschenko et al. 2012, Nature 491:547-53). Particularly intriguing was the strong inhibition of large portions of subcortical brain structures that are closely involved in neural plasticity, such as the basal ganglia (BG), the PONS and the cerebellar cortex. In primates, the negative BOLD in the pontine region was systematically associated with inhibition of the lateral geniculate nucleus (LGN) and foveal V1 activity, despite the overall positive fMRI responses in peripheral V1 and all other primary sensory and associational cortices. The deactivation of PONS may therefore be due to a temporary suppression of cholinergic sites involved in local plasticity and synaptic consolidation, such as those underlying the generation-propagation of theta rhythm, and so-called ponto-geniculo-occipital (PGO) waves. PGO waves have been often associated with the consolidation of procedural memory or synaptic consolidation in general. To examine this hypothesis and better understand the global regulation of brain activity during memory consolidation we set out to employ the methodology of Neural-Event-Triggered fMRI (NET-fMRI), combining simultaneous electrophysiological recordings in the region of the parabrachial nucleus (PBn) and MR imaging in monkeys under opioid anesthesia. First, we established a structural-MRI and angiography-based site-localization approach to access various brainstem regions with long electrodes without potential complications due to vasculature-injury. We subsequently physiologically identified PBn, LGN and the Hippocampal CA1/CA3 fields, and conducted concurrent, uninterrupted multi-site physiological and fMRI recordings in a 4.7T magnet. PGO events were considered to be the large field deflections, with various temporal and repetition profiles that typically co-occur in PBn and LGN. In sharp contrast to isolated LGN or PONS events, the PGO-like events - co-occurring in both pontine and thalamic structures - yielded a robust and striking pattern of up/down modulation, suggesting the PGO events correlated with upregulation of subcortical centers concurrently with inhibition of activity in neocortex.}, web_url = {http://www.abstractsonline.com/pp8/index.html#!/4071/presentation/32988}, event_name = {46th Annual Meeting of the Society for Neuroscience (Neuroscience 2016)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Ramirez-Villegas J{jramirez}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ HofmannJS2016, title = {The role of mouse barrel cortex in tactile trace eye blink conditioning}, year = {2016}, month = {11}, day = {10}, web_url = {http://www.vibrissa.org/Barrels_2016_Program_October25rev.pdf}, event_name = {29th Annual Barrels Meeting (Barrels XXIX)}, event_place = {Los Angeles, CA, USA}, state = {published}, author = {Hofmann J{juho}; Joachimsthaler B{bjoach}{Department Physiology of Cognitive Processes}; Schwarz C} } @Conference{ Logothetis2016_4, title = {NET-fMRI of Large-Scale Brain Networks: Mapping Dynamic Connectivity in Epochs of Synaptic and System Consolidation}, year = {2016}, month = {10}, day = {14}, abstract = {Neural-Event-Triggered fMRI (NET-fMRI) can potentially map whole-brain activity, associated with individual local events – or their interactions – in various brain structures. In my talk, I will describe a number of characteristic states of widespread cortical and subcortical networks that are associated with the occurrence of thalamic, hippocampal and pontine events, which may be related to synaptic and systems consolidation of different memories.}, web_url = {https://talks.stanford.edu/nikos-logothetis-net-fmri-of-large-scale-brain-networks-mapping-dynamic-connectivity-in-epochs-of-synaptic-and-system-consolidation/}, event_name = {Stanford Talks}, event_place = {Stanford, CA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ TuzziHBLNLPVS2016, title = {Ex-vivo and in-vivo ultra-High-Field R2* and QSM microimaging in Alzheimer’s disease}, journal = {Magnetic Resonance Materials in Physics, Biology and Medicine}, year = {2016}, month = {9}, day = {30}, volume = {29}, number = {Supplement 1}, pages = {S144-S145}, abstract = {Purpose/Introduction: Conspicuous advances in MRI imaging in the last decade catalyzed the quest for novel approaches to investigate Alzheimer’s disease. Till now a diagnosis is only unequivocally defined by post-mortem histology. High resolution imaging is potentially feasible at ultra-high magnetic field strength, allowing imaging of pathologic processes at a unique level of detail. Recently it has been demonstrated that cortical phase changes in T2* weighted MRI are characteristic for Alzheimer’s disease [1]. b-amyloid deposits likely contribute significantly to the observed phase effect [2,3]. The orientation dependence of such phase effects can be overcome by the use of quantitative susceptibility mapping (QSM). Our purpose is to explore the source of the observed MR phase signal changes by comparing quantitative susceptibility and R2* maps obtained in vivo at 9.4T as well as in post mortem samples at both 9.4T and 14T. The maps are also investigated by histology and here preliminary data are presented. Subjects and Methods: The same frontal cortex area of two post mortem samples from an Alzheimer’s diseased patient and a healthy subject, respectively, were examined at 14T using a GRE-T2*-weighted image (50 lm isotropic voxels, matrix = 1000 9 749 9 512, FOV = 50 9 37.45 9 25.6 mm3, TR = 34.4 ms, TE = 17.5 ms, 4 averages, total scan time = 14.67 h) for QSM and a multi echo sequence for R2* mapping (100 lm isotropic voxels, matrix = 500 9 300 9 256; FOV = 50 9 30 9 25.6 mm3; TR = 27 ms, TE = 4.5, 11, 17.5 ms, acquisition time = 2.3 h). Phase shift information was used to generate data sets for QSM analysis. At 9.4T coronal post mortem brain slices of the same donors, and in vivo measurements of four patients with AD and frontal lobe dementia were also investigated using multi echo (N = 5) 3D-GRE imaging (0.375 9 0.0.375 9 0.8 mm3 voxelsize, FOV = 192 9 174 9 70.4 mm3, matrixsize = 512 9 464 9 88, TR = 35 ms; TE = 6 to 30 ms in steps of 6 ms, total acquisition time = 8,7 s) and high resolution acquisition-weighted 3D-GRE imaging (0.130 9 0.130 9 0.6 mm3 voxelsize, TR = 30 ms, TE = 18 ms, acquisition time = 14 min). Results: Both in vivo and ex vivo R2* and QSM maps showed distinct cortical layering patterns (Fig 1, 2). Compared to healthy subjects, we observed an apparent broadening of the central cortical layer with increased R2* and QSM values consistent with paramagnetic effects in AD. No single plaques could be observed post mortem at the current isotropic voxel size of 50 micrometers. Discussion/Conclusion: Clinical valid methods for studying and, eventually, diagnosing AD in vivo by MRI are emerging. Quantitative R2* and QSM methods at ultra-high-field hold promise for this endeavor and detect changes that involve the layering pattern of the cortical rim. Future studies that target these structures by multi-modal means are necessary to further characterize the signal sources are necessary.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs10334-016-0569-9.pdf}, event_name = {33rd Annual Scientific Meeting of the European Society for Magnetic Resonance in Medicine and Biology (ESMRMB 2016)}, event_place = {Wien, Austria}, state = {published}, DOI = {10.1007/s10334-016-0569-9}, author = {Tuzzi E{etuzzi}{Department High-Field Magnetic Resonance}; Hagberg G{ghagberg}{Department High-Field Magnetic Resonance}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Loureiro J{jloureiro}{Department High-Field Magnetic Resonance}; Neumann M; Laske C; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Valverde M{valverde}{Department Physiology of Cognitive Processes}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Conference{ Balla2016, title = {Functional Quantitative Susceptibility Mapping}, year = {2016}, month = {9}, day = {27}, web_url = {http://www.neuroimaging.at/qsm2016/pages/program.php}, event_name = {4th International Workshop on MRI Phase Contrast & Quantitative Susceptibility Mapping (QSM 2016)}, event_place = {Graz, Austria}, state = {published}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}} } @Conference{ BannertB2016_2, title = {The constructive nature of color vision: evidence from human fMRI}, year = {2016}, month = {9}, day = {21}, web_url = {http://www.uni-regensburg.de/psychologie-paedagogik-sport/psychologie-greenlee/seeing-colors/index.html}, event_name = {Seeing Colors: International Symposium on Color Vision}, event_place = {Regensburg, Germany}, state = {published}, author = {Bannert MM{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ WallisFEGWB2016, title = {Towards matching the peripheral visual appearance of arbitrary scenes using deep convolutional neural networks}, journal = {Perception}, year = {2016}, month = {8}, day = {30}, volume = {45}, number = {ECVP Abstract Supplement}, pages = {175-176}, abstract = {Distortions of image structure can go unnoticed in the visual periphery, and objects can be harder to identify (crowding). Is it possible to create equivalence classes of images that discard and distort image structure but appear the same as the original images? Here we use deep convolutional neural networks (CNNs) to study peripheral representations that are texture-like, in that summary statistics within some pooling region are preserved but local position is lost. Building on our previous work generating textures by matching CNN responses, we first show that while CNN textures are difficult to discriminate from many natural textures, they fail to match the appearance of scenes at a range of eccentricities and sizes. Because texturising scenes discards long range correlations over too large an area, we next generate images that match CNN features within overlapping pooling regions (see also Freeman and Simoncelli, 2011). These images are more difficult to discriminate from the original scenes, indicating that constraining features by their neighbouring pooling regions provides greater perceptual fidelity. Our ultimate goal is to determine the minimal set of deep CNN features that produce metameric stimuli by varying the feature complexity and pooling regions used to represent the image.}, web_url = {http://journals.sagepub.com/doi/full/10.1177/0301006616671273}, event_name = {39th European Conference on Visual Perception (ECVP 2016)}, event_place = {Barcelona, Spain}, state = {published}, DOI = {10.1177/0301006616671273}, author = {Wallis TS; Funke CM; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Gatys LA; Wichmann FA{felix}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Conference{ Logothetis2016_2, title = {Electrical Stimulation: Mapping mononsynaptic connectivity and cortico-thalamo-cortical loops}, year = {2016}, month = {7}, day = {18}, web_url = {http://www.brainmapping.org/NITP/Summer2016.php}, event_name = {2016 UCLA Advanced Neuroimaging Summer Program}, event_place = {Los Angeles, CA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2016_3, title = {NET-fMRI of Large-Scale Brain Networks}, year = {2016}, month = {7}, day = {18}, web_url = {http://www.brainmapping.org/NITP/Summer2016.php}, event_name = {2016 UCLA Advanced Neuroimaging Summer Program}, event_place = {Los Angeles, CA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ KaplanKKAHMPMBLDF2016, title = {Relating rapid mental simulation to past experience}, year = {2016}, month = {7}, day = {18}, pages = {59}, abstract = {The neural computations that enable us to rapidly simulate the outcome of sequential choices with little or no learning, are unclear. Here, I present data highlighting how distributed neocortical regions potentially support prospective choice and how these regions might be influenced by spontaneous activity in neural circuits. Specifically, I focus on human fMRI results isolating rostro-dorsal mPFC and parietal midline regions that signal uncertainty about choices later in a sequence. I then will present findings showing that hippocampal sharp-wave ripples influence spontaneous fluctuations in similar regions. Taken together, these data provide preliminary evidence that replay of past events might allow the brain to explore past experience in order to prepare for novel decisions.}, web_url = {http://www.icom2016.com/down/ICOM6_program.pdf}, event_name = {6th International Conference on Memory (ICOM-6)}, event_place = {Budapest, Hungary}, state = {published}, author = {Kaplan R; King J; Koster R; Adhikari MH; Hindriks R; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Penny WJ; Mantini D; Burgess N; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco N; Friston KJ} } @Conference{ SafaviDBKLP2016, title = {A Non-Monotonic Correlation Structure in the Macaque Ventrolateral Prefrontal Cortex}, year = {2016}, month = {6}, pages = {53}, abstract = {Anatomical investigations of the primate prefrontal cortex revealed fundamental structural differences compared to early sensory areas, ranging from cell morphology to patterns of intra-areal connectivity. In order to make a bridge between anatomy and function in this area it is necessary to use measures that are functionally interpretable like noise correlation. In the present study, we characterized the spatial structure of pairwise noise correlations in the ventrolateral Prefrontal Cortex (vlPFC) to investigate potential differences in vlPFC functional connectivity compared to early sensory areas. We recorded the spiking activity of spatially distributed neural populations with a Utah array in the vlPFC of two anaesthetized monkeys during visual stimulation with short duration (10 seconds) movie clips. Our findings suggest that many of the correlation properties in the vlPFC are similar to those observed in early sensory areas (e.g., relationship between noise and signal correlations). However, in contrast to early sensory areas, we found that the vlPFC connectivity kernel is neither homogeneous nor monotonic. Specifically, we observed that following an initial monotonic decrease of correlations for intermediate distances (below 2 mm) correlations for remote neurons (inter-electrode distance above 2 mm) increase significantly, and are of equal strength to the magnitude of correlations for nearby neuronal pairs. To further examine the connectivity pattern, we built a functional connectivity graph of the array (based on pairwise noise correlations), and analyzed its topology using eigenvector centrality. This analysis revealed spatially segregated subnetworks with densely connected patches of neurons. The correlation structure within the patches contributes significantly to the overall structure of correlations. Our analysis suggests that the vlPFC circuits are organized in non-homogeneous subnetworks, compatible with anatomical studies of this region [1–3]. Such a connectivity pattern could constrain theoretical models of prefrontal function, as it might be instrumental to large-scale coordination of distributed information processing in prefrontal cortex.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Dwarakanath A{adwarakanath}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ GrassiZB2016_3, title = {Differential modulation of foreground and background in early visual cortex by feedback during bistable Gestalt perception}, year = {2016}, month = {6}, pages = {76-77}, abstract = {A growing body of literature suggests that feedback modulation of early visual processing is ubiquitous and central to cortical computation. In particular stimuli with high-level content have been shown to suppress early visual regions, typically interpreted in the framework of predictive coding. However, physical stimulus differences can preclude clear interpretations in terms of feedback. Here we examined activity modulation in the early visual cortex (V1 and V2) using fMRI during distinct perceptual states associated to the same physical input. This ensures in a unique way that observed signal modulations cannot be accounted for by changes in physical stimulus properties, and can therefore only be accounted for by percept-related feedback interactions from higher level regions. We used a dynamic stimulus consisting of moving dots that could either be perceived as corners of a large moving square (global Gestalt) or as distributed sets of locally moving dots. We found that perceptual binding of local moving elements into an illusory Gestalt led to spatially segregated differential modulations, in both, V1 and V2: retinotopic representations of illusory lines and foreground were enhanced, while inducers and background suppressed. The results extend prior findings to the illusory-perceptual state of physically un-changed stimuli, and show percept-driven background suppression in the human brain. Based on prior work, we hypothesize that parietal cortex is responsible for the modulations through recurrent connections in a predictive coding account of visual processing.}, web_url = {http://www.neurizons.uni-goettingen.de/wp-content/uploads/Neurizons-booklet_2016.pdf}, event_name = {7th Biennial Neuroscience Conference Neurizons 2016: Speak your mind}, event_place = {Göttingen, Germany}, state = {published}, author = {Grassi PR{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ Ecker2016, title = {What's the Signal in the Noise?}, year = {2016}, month = {6}, pages = {28}, abstract = {Responses of cortical neurons are highly variable. Even repeated presentations of the same visual stimulus never elicit the same spike train. Identifying the origins of this variability remains a challenge. There is increasing evidence that it is not just noise arising from stochastic features of neuronal architecture, but at least partly represents meaningful top-down signals. One of the most prominent examples of such top-down modulation in the visual system is covert attention. I will present both theoretical and experimental results showing that trial-totrial fluctuations of attentional state contribute significantly to response variability in primary visual cortex of awake, behaving monkeys. I will argue that much can be learned about information processing in the brain by using latent variable models of neuronal activity to help us identify and account for cognitive variables and make sense of single-trial neural population data.}, web_url = {http://areadne.org/2016/pezaris-hatsopoulos-2016-areadne.pdf}, event_name = {AREADNE 2016: Research in Encoding And Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}} } @Conference{ ZaretskayaGSB2016, title = {Neural bases of bistable perception in the human brain}, year = {2016}, month = {3}, day = {22}, volume = {58}, pages = {383}, abstract = {Ambiguous visual stimuli, and in particular binocular rivalry, provide a great experimental tool to study the neural basis of conscious vision. When viewed continuously, such stimuli cause the perceptual state of the observer to alternate between the two possible interpretations despite unchanged visual input. A great number of neuroimaging studies linked bi-stable perception to activity in lower-level sensory, but also higher-level attention-related areas of the brain such as parietal and frontal regions. In this talk, we will discuss a series of studies from our lab that used fMRI, TMS and tDCS trying to understand how different brain areas contribute to transforming the constant sensory input into a changing perceptual experience.}, web_url = {https://www.teap.de/memory/Abstractband_58_2016_Heidelberg.pdf}, event_name = {58th Conference of Experimental Psychologists (TeaP 2016)}, event_place = {Heidelberg, Germany}, state = {published}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Grassi P{pgrassi}{Department Physiology of Cognitive Processes}; Sipatchin A; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2016, title = {The Insular Cortex: Neuroanatomical and Functional Insights into Interoception, Emotion, and Self-Awareness}, year = {2016}, month = {2}, day = {19}, abstract = {The primate posterior insula is the terminus of a phylogenetically novel ascending pathway encoding the physiological state of the body or interoception. An increasingly complex posterior-to-anterior integration within insula culminates into a representation of subjective corporal, emotional and cognitive feelings in the anterior insula. This region contains the von Economo neuron (VEN), an atypical large spindle-shaped projection neuron that is selectively depleted in psychiatric reductions of self-conscious feelings. Our lab examines the anatomical and functional organization substantiating the role of the insula and the autonomic system in subjective feelings. We demonstrated that the insula in macaque monkeys is divided into 13 sharply-delimited architectonic areas that have each a distinct pattern of neuronal connections. These connections supports the idea of a posterior-to-anterior integration with high-order sensory and limbic activities. We provided optogenetics, microstimulation, functional imaging and tract-tracing evidence in macaques that the anterior insula is a motor output stage for the control of sympathetic and parasympathetic premotor and perhaps preganglionic nuclei. We demonstrated that the VEN occurs in only one architectonic area of the anterior insula in macaques (an “elemental” localization à la Brodmann) and contributes major descending projections. This suggests that the VEN could be the autonomic equivalent of the giant Betz cell controlling voluntary skeletal movements. In comparison with macaques, the VEN occurs in three adjacent architectonic areas in humans, suggesting major evolutionary optimization towards the emergence of human feelings seen here as an abstract perception of bodily homeostasis in an increasingly more controllable environment and interdependent society.}, web_url = {https://www.facebook.com/cmbnrutgers/posts/947485748660444}, event_name = {Center for Molecular and Behavioral Neuroscience: Rutgers University}, event_place = {Newark, NJ, USA}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2016, title = {NET-fMRI of Large-Scale Brain Networks: Mapping Dynamic Connectivity in Epochs of Synaptic and System Consolidation}, year = {2016}, month = {2}, day = {14}, web_url = {https://www.grc.org/programs.aspx?id=17257}, event_name = {Gordon Research Conference: Thalamocortical Interactions - Cell and Circuit Properties of Thalamocortical Interactions}, event_place = {Ventura, CA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ PerrodinKALP2015, title = {Who is That? Brain Networks and Mechanisms for Identifying Individuals}, journal = {Trends in Cognitive Sciences}, year = {2015}, month = {12}, volume = {19}, number = {12}, pages = {783–796}, abstract = {Social animals can identify conspecifics by many forms of sensory input. However, whether the neuronal computations that support this ability to identify individuals rely on modality-independent convergence or involve ongoing synergistic interactions along the multiple sensory streams remains controversial. Direct neuronal measurements at relevant brain sites could address such questions, but this requires better bridging the work in humans and animal models. Here, we overview recent studies in nonhuman primates on voice and face identity-sensitive pathways and evaluate the correspondences to relevant findings in humans. This synthesis provides insights into converging sensory streams in the primate anterior temporal lobe (ATL) for identity processing. Furthermore, we advance a model and suggest how alternative neuronal mechanisms could be tested.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1364661315002260}, state = {published}, DOI = {10.1016/j.tics.2015.09.002}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}; Abel TJ; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Article{ RamirezVillegasLB2015_4, title = {Diversity of sharp-wave–ripple LFP signatures reveals differentiated brain-wide dynamical events}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2015}, month = {11}, volume = {112}, number = {46}, pages = {E6379–E6387}, abstract = {Sharp-wave–ripple (SPW-R) complexes are believed to mediate memory reactivation, transfer, and consolidation. However, their underlying neuronal dynamics at multiple scales remains poorly understood. Using concurrent hippocampal local field potential (LFP) recordings and functional MRI (fMRI), we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. Analysis of the temporal alignment between SPW and ripple components reveals well-differentiated SPW-R subtypes in the CA1 LFP. SPW-R–triggered fMRI maps show that ripples aligned to the positive peak of their SPWs have enhanced neocortical metabolic up-regulation. In contrast, ripples occurring at the trough of their SPWs relate to weaker neocortical up-regulation and absent subcortical down-regulation, indicating differentiated involvement of neuromodulatory pathways in the ripple phenomenon mediated by long-range interactions. To our knowledge, this study provides the first evidence for the existence of SPW-R subtypes with differentiated CA1 activity and metabolic correlates in related brain areas, possibly serving different memory functions.}, web_url = {http://www.pnas.org/content/112/46/E6379.full.pdf}, state = {published}, DOI = {10.1073/pnas.1518257112}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Article{ RegueiroFigueroaGPLETAP2015, title = {Gd3+-Based Magnetic Resonance Imaging Contrast Agent Responsive to Zn2+}, journal = {Inorganic Chemistry}, year = {2015}, month = {11}, volume = {54}, number = {21}, pages = {10342–10350}, abstract = {We report the heteroditopic ligand H5L, which contains a DO3A unit for Gd3+ complexation connected to an NO2A moiety through a N-propylacetamide linker. The synthesis of the ligand followed a convergent route that involved the preparation of 1,4-bis(tert-butoxycarbonylmethyl)-1,4,7-triazacyclononane following the orthoamide strategy. The luminescence lifetimes of the Tb(5D4) excited state measured for the TbL complex point to the absence of coordinated water molecules. Density functional theory calculations and 1H NMR studies indicate that the EuL complex presents a square antiprismatic coordination in aqueous solution, where eight coordination is provided by the seven donor atoms of the DO3A unit and the amide oxygen atom of the N-propylacetamide linker. Addition of Zn2+ to aqueous solutions of the TbL complex provokes a decrease of the emission intensity as the emission lifetime becomes shorter, which is a consequence of the coordination of a water molecule to the Tb3+ ion upon Zn2+ binding to the NO2A moiety. The relaxivity of the GdL complex recorded at 7 T (25 °C) increases by almost 150% in the presence of 1 equiv of Zn2+, while Ca2+ and Mg2+ induced very small relaxivity changes. In vitro magnetic resonance imaging experiments confirmed the ability of GdL to provide response to the presence of Zn2+.}, web_url = {http://pubs.acs.org/doi/10.1021/acs.inorgchem.5b01719}, state = {published}, DOI = {10.1021/acs.inorgchem.5b01719}, author = {Regueiro-Figueroa M; G\"und\"uz S{sgunduz}; Patinec V; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Esteban-G{\'o}mez D; Tripier R; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Platas-Iglesias C} } @Article{ JiangSCBSEPT2015, title = {Principles of connectivity among morphologically defined cell types in adult neocortex}, journal = {Science}, year = {2015}, month = {11}, volume = {350}, number = {6264}, pages = {1055: 1-10}, abstract = {Since the work of Ramón y Cajal in the late 19th and early 20th centuries, neuroscientists have speculated that a complete understanding of neuronal cell types and their connections is key to explaining complex brain functions. However, a complete census of the constituent cell types and their wiring diagram in mature neocortex remains elusive. By combining octuple whole-cell recordings with an optimized avidin-biotin-peroxidase staining technique, we carried out a morphological and electrophysiological census of neuronal types in layers 1, 2/3, and 5 of mature neocortex and mapped the connectivity between more than 11,000 pairs of identified neurons. We categorized 15 types of interneurons, and each exhibited a characteristic pattern of connectivity with other interneuron types and pyramidal cells. The essential connectivity structure of the neocortical microcircuit could be captured by only a few connectivity motifs.}, web_url = {http://www.sciencemag.org/content/350/6264/aac9462.full.pdf}, state = {published}, DOI = {10.1126/science.aac9462}, EPUB = {aac9462}, author = {Jiang X; Shen S; Cadwell CR; Berens P{berens}; Sinz F{fabee}; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Patel S; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ AzadbakhtPHALdDP2015, title = {Validation of High-Resolution Tractography Against In Vivo Tracing in the Macaque Visual Cortex}, journal = {Cerebral Cortex}, year = {2015}, month = {11}, volume = {25}, number = {11}, pages = {4299-4309}, abstract = {Diffusion magnetic resonance imaging (MRI) allows for the noninvasive in vivo examination of anatomical connections in the human brain, which has an important role in understanding brain function. Validation of this technique is vital, but has proved difficult due to the lack of an adequate gold standard. In this work, the macaque visual system was used as a model as an extensive body of literature of in vivo and postmortem tracer studies has established a detailed understanding of the underlying connections. We performed probabilistic tractography on high angular resolution diffusion imaging data of 2 ex vivo, in vitro macaque brains. Comparisons were made between identified connections at different thresholds of probabilistic connection “strength,” and with various tracking optimization strategies previously proposed in the literature, and known connections from the detailed visual system wiring map described by Felleman and Van Essen (1991; FVE91). On average, 74% of connections that were identified by FVE91 were reproduced by performing the most successfully optimized probabilistic diffusion MRI tractography. Further comparison with the results of a more recent tracer study (Markov et al. 2012) suggests that the fidelity of tractography in estimating the presence or absence of interareal connections may be greater than this.}, web_url = {http://cercor.oxfordjournals.org/content/25/11/4299.full.pdf+html}, state = {published}, DOI = {10.1093/cercor/bhu326}, author = {Azadbakht H; Parkes LM; Haroon HA; Augath M{mark}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; de Crespigny E; D'Arceuil HE; Parker GJM} } @Article{ TotahLE2015, title = {Atomoxetine accelerates attentional set shifting without affecting learning rate in the rat}, journal = {Psychopharmacology}, year = {2015}, month = {10}, volume = {232}, number = {20}, pages = {3697-3707}, abstract = {Rationale Shifting to a new rule is a form of behavioral flexibility that is impaired in numerous psychiatric and neurological illnesses. Animal studies have revealed that this form of flexibility depends upon norepinephrine (NE) neurotransmission. Atomoxetine, a NE reuptake inhibitor, improves performance of humans in set shifting tasks. Objective Our objective was to validate its effects in a rodent set shifting task. Methods We tested the drug effect using an operant task that required a shift from a visual cue-guided behavior to a novel location-guided rule. Results A 1.0-mg/kg dose significantly accelerated rule shifting without affecting learning strategies, such as win-stay or lose-shift. Fitting behavioral performance with a learning function provided a measure of learning rate. Conclusion This novel analysis revealed that atomoxetine accelerated shifting to the new rule without affecting learning rate.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00213-015-4028-5.pdf}, state = {published}, DOI = {10.1007/s00213-015-4028-5}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Article{ SafaaiNELP2015, title = {Modeling the effect of locus coeruleus firing on cortical state dynamics and single-trial sensory processing}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2015}, month = {10}, volume = {112}, number = {41}, pages = {12834–12839}, abstract = {Neuronal responses to sensory stimuli are not only driven by feedforward sensory pathways but also depend upon intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation. To understand how these factors together regulate cortical dynamics, we recorded simultaneously spontaneous and somatosensory-evoked multiunit activity from primary somatosensory cortex and from the locus coeruleus (LC) (the neuromodulatory nucleus releasing norepinephrine) in urethane-anesthetized rats. We found that bursts of ipsilateral-LC firing preceded by few tens of milliseconds increases of cortical excitability, and that the 1- to 10-Hz rhythmicity of LC discharge appeared to increase the power of delta-band (1–4 Hz) cortical synchronization. To investigate quantitatively how LC firing might causally influence spontaneous and stimulus-driven cortical dynamics, we then constructed and fitted to these data a model describing the dynamical interaction of stimulus drive, ongoing synchronized cortical activity, and noradrenergic neuromodulation. The model proposes a coupling between LC and cortex that can amplify delta-range cortical fluctuations, and shows how suitably timed phasic LC bursts can lead to enhanced cortical responses to weaker stimuli and increased temporal precision of cortical stimulus-evoked responses. Thus, the temporal structure of noradrenergic modulation may selectively and dynamically enhance or attenuate cortical responses to stimuli. Finally, using the model prediction of single-trial cortical stimulus-evoked responses to discount single-trial state-dependent variability increased by ∼70% the sensory information extracted from cortical responses. This suggests that downstream circuits may extract information more effectively after estimating the state of the circuit transmitting the sensory message.}, web_url = {http://www.pnas.org/content/112/41/12834.full.pdf}, state = {published}, DOI = {10.1073/pnas.1516539112}, author = {Safaai H; Neves R{ricardo}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Article{ PapanikolaouKLLS2015, title = {Nonlinear population receptive field changes in human area V5/MT + of healthy subjects with simulated visual field scotomas}, journal = {NeuroImage}, year = {2015}, month = {10}, volume = {120}, pages = {176–190}, abstract = {There is extensive controversy over whether the adult visual cortex is able to reorganize following visual field loss (scotoma) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the aggregate receptive field properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT +, are affected by partial stimulus deprivation. We measured population receptive field (pRF) responses in human area V5/MT + of 5 healthy participants under full stimulation and compared them with responses obtained from the same area while masking the left superior quadrant of the visual field (“artificial scotoma” or AS). We found that pRF estimations in area hV5/MT + are nonlinearly affected by the AS. Specifically, pRF centers shift towards the AS, while the pRF amplitude increases and the pRF size decreases near the AS border. The observed pRF changes do not reflect reorganization but reveal important properties of normal visual processing under different test-stimulus conditions.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191500590X}, state = {published}, DOI = {10.1016/j.neuroimage.2015.06.085}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Lee S{slee}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Article{ ZaidiMSRBFLBS2015, title = {Simultaneous epidural functional near-infrared spectroscopy and cortical electrophysiology as a tool for studying local neurovascular coupling in primates}, journal = {NeuroImage}, year = {2015}, month = {10}, volume = {120}, pages = {394–399}, abstract = {Simultaneous measurements of intra-cortical electrophysiology and hemodynamic signals in primates are essential for relating human neuroimaging studies with intra-cortical electrophysiology in monkeys. Previously, technically challenging and resourcefully demanding techniques such as fMRI and intrinsic-signal optical imaging have been used for such studies. Functional near-infrared spectroscopy is a relatively less cumbersome neuroimaging method that uses near-infrared light to detect small changes in concentrations of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total hemoglobin (HbT) in a volume of tissue with high specificity and temporal resolution. fNIRS is thus a good candidate for hemodynamic measurements in primates to acquire local hemodynamic signals during electrophysiological recordings. To test the feasibility of using epidural fNIRS with concomitant extracellular electrophysiology, we recorded neuronal and hemodynamic activity from the primary visual cortex of two anesthetized monkeys during visual stimulation. We recorded fNIRS epidurally, using one emitter and two detectors. We performed simultaneous cortical electrophysiology using tetrodes placed between the fNIRS sensors. We observed robust and reliable responses to the visual stimulation in both [HbO] and [HbR] signals, and quantified the signal-to-noise ratio of the epidurally measured signals. We also observed a positive correlation between stimulus-induced modulation of [HbO] and [HbR] signals and strength of neural modulation. Briefly, our results show that epidural fNIRS detects single-trial responses to visual stimuli on a trial-by-trial basis, and when coupled with cortical electrophysiology, is a promising tool for studying local hemodynamic signals and neurovascular coupling.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191500628X}, state = {published}, DOI = {10.1016/j.neuroimage.2015.07.019}, author = {Zaidi AD{azaidi}{Department Physiology of Cognitive Processes}; Munk MHJ{munk}{Department Physiology of Cognitive Processes}; Schmidt A{aschmidt}{Department Physiology of Cognitive Processes}; Risueno-Segovia C{crisueno}{Department Physiology of Cognitive Processes}; Bernard R{rbernard}{Department Physiology of Cognitive Processes}; Fetz E; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Bierbaumer N; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}} } @Article{ FrankePAMGOM2015, title = {Spike Sorting of Synchronous Spikes from Local Neuron Ensembles}, journal = {Journal of Neurophysiology}, year = {2015}, month = {10}, volume = {114}, number = {4}, pages = {2535-2549}, abstract = {Synchronous spike discharge of cortical neurons is thought to be a fingerprint of neuronal cooperativity. Because neighboring neurons are more densely connected to one another than neurons that are located further apart, near-synchronous spike discharge can be expected to be prevalent and it might provide an important basis for cortical computations. Using microelectrodes to record local groups of neurons does not allow for the reliable separation of synchronous spikes from different cells, because available spike sorting algorithms cannot correctly resolve the temporally overlapping waveforms. We show that high spike sorting performance of in vivo recordings, including overlapping spikes, can be achieved using a recently developed filter-based template matching procedure. Using tetrodes with a 3-dimensional structure, we demonstrate with simulated data and ground truth in vitro data, obtained by dual intracellular recording of two neurons located next to a tetrode, that the spike sorting of synchronous spikes can be as successful as the spike sorting of non-overlapping spikes, and that the spatial information provided by multielectrodes greatly reduces the error rates. We apply the method to tetrode recordings from the prefrontal cortex of behaving primates and we show that overlapping spikes can be identified and assigned to individual neurons to study synchronous activity in local groups of neurons.}, web_url = {http://jn.physiology.org/content/114/4/2535.full-text.pdf+html}, state = {published}, DOI = {10.1152/jn.00993.2014}, author = {Franke F{ffranke}{Department Physiology of Cognitive Processes}; Pr\"opper R; Alle H; Meier P; Geiger JRP; Obermayer K; Munk MHJ{munk}{Department Physiology of Cognitive Processes}} } @Article{ MoussaronVBGKSMRCLLTA2015, title = {Ultrasmall Nanoplatforms as Calcium-Responsive Contrast Agents for Magnetic Resonance Imaging}, journal = {Small}, year = {2015}, month = {10}, volume = {11}, number = {37}, pages = {4900–4909}, abstract = {The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca2+. Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/smll.201500312/epdf}, state = {published}, DOI = {10.1002/smll.201500312}, author = {Moussaron A; Vibhute S{svibhute}{Department Physiology of Cognitive Processes}; Bianchi A; G\"und\"uz S{sgunduz}; Kolb S; Sancey L; Motto-Ros V; Rizzitelli S; Cr{\'e}millieux Y; Lux F; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Tillement O; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ GatysEB2015_3, title = {A Neural Algorithm of Artistic Style}, journal = {Nature Communications}, year = {2015}, month = {10}, abstract = {In fine art, especially painting, humans have mastered the skill to create unique visual experiences through composing a complex interplay between the content and style of an image. Thus far the algorithmic basis of this process is unknown and there exists no artificial system with similar capabilities. However, in other key areas of visual perception such as object and face recognition near-human performance was recently demonstrated by a class of biologically inspired vision models called Deep Neural Networks. Here we introduce an artificial system based on a Deep Neural Network that creates artistic images of high perceptual quality. The system uses neural representations to separate and recombine content and style of arbitrary images, providing a neural algorithm for the creation of artistic images. Moreover, in light of the striking similarities between performance-optimised artificial neural networks and biological vision, our work offers a path forward to an algorithmic understanding of how humans create and perceive artistic imagery.}, web_url = {http://arxiv.org/abs/1508.06576}, state = {submitted}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Article{ KorkmazHacialihafizB2015, title = {Motion responses in scene-selective regions}, journal = {NeuroImage}, year = {2015}, month = {9}, volume = {118}, pages = {438–444}, abstract = {The vast majority of studies on scene processing were conducted using stationary scenes. However, during natural vision, scene views change dynamically due to self-induced eye-, head-, and body-motion, and these dynamic changes are crucial for other higher-level functions such as navigation, self-motion perception, and spatial updating. Yet, we do not know whether or how scene selective regions are modulated by visual motion and to which degree their motion response depends on scene content. In this study, we used fMRI to examine both questions using a 2 × 2 factorial design with the factors 2D planar motion (motion versus static) and scene content (natural scenes versus their Fourier scrambles). We found that among independently localized scene-responsive regions, parahippocampal place area (PPA) and transverse occipital sulcus (TOS), also referred to as occipital place area (OPA), were significantly motion responsive, whereas retrosplenial cortex (RSC) was not. Additionally, PPA showed an interaction between motion and scene in that it responded more to motion in context of scenes than scramble, with similar trends in TOS and RSC. These results provide a novel functional dissociation between motion-responsive PPA and TOS/OPA versus motion-unresponsive RSC and suggest a strong role for PPA in integrating motion and scene content.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811915005340}, state = {published}, DOI = {10.1016/j.neuroimage.2015.06.031}, author = {Korkmaz Hacialihafiz D; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ BesserveLLSP2015, title = {Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer}, journal = {PLoS Biology}, year = {2015}, month = {9}, volume = {13}, number = {9}, pages = {1-29}, abstract = {Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections.}, web_url = {http://www.plosbiology.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pbio.1002257&representation=PDF}, state = {published}, DOI = {10.1371/journal.pbio.1002257}, EPUB = {e1002257}, author = {Besserve M{besserve}{Department Physiology of Cognitive Processes}; Lowe SC; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Sch\"olkopf B{bs}; Panzeri S{stefano}} } @Article{ MatzRensingHWFHRMK2015, title = {Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient}, journal = {Journal of Comparative Pathology}, year = {2015}, month = {8}, volume = {153}, number = {2-3}, pages = {81–91}, abstract = {Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0021997515000985}, state = {published}, DOI = {10.1016/j.jcpa.2015.05.006}, author = {M\"atz-Rensing K; Hartmann T; Wendel GM{gwendel}{Department Physiology of Cognitive Processes}; Frick JS; Homolka S; Richter E; Munk MH{munk}{Department Physiology of Cognitive Processes}; Kaup F-J} } @Article{ AzevedoOLLK2015, title = {A Potential Role of Auditory Induced Modulations in Primary Visual Cortex}, journal = {Multisensory Research}, year = {2015}, month = {7}, volume = {28}, number = {3-4}, pages = {331-349}, abstract = {A biologically relevant event is normally the source of multiple, typically correlated, sensory inputs. To optimize perception of the outer world, our brain combines the independent sensory measurements into a coherent estimate. However, if sensory information is not readily available for every pertinent sense, the brain tries to acquire additional information via covert/overt orienting behaviors or uses internal knowledge to modulate sensory sensitivity based on prior expectations. Cross-modal functional modulation of low-level auditory areas due to visual input has been often described; however, less is known about auditory modulations of primary visual cortex. Here, based on some recent evidence, we propose that an unexpected auditory signal could trigger a reflexive overt orienting response towards its source and concomitantly increase the primary visual cortex sensitivity at the locations where the object is expected to enter the visual field. To this end, we propose that three major functionally specific pathways are employed in parallel. A stream orchestrated by the superior colliculus is responsible for the overt orienting behavior, while direct and indirect (via higher-level areas) projections from A1 to V1 respectively enhance spatiotemporal sensitivity and facilitate object detectability.}, web_url = {http://booksandjournals.brillonline.com/content/journals/10.1163/22134808-00002494}, state = {published}, DOI = {10.1163/22134808-00002494}, author = {Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}; Li Q{qinglinli}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Article{ OukhatarMLLPAT2015, title = {Macrocyclic Gd3+ Complexes with Pendant Crown Ethers Designed for Binding Zwitterionic Neurotransmitters}, journal = {Chemistry - A European Journal}, year = {2015}, month = {7}, volume = {21}, number = {31}, pages = {11226–11237}, abstract = {A series of Gd3+ complexes exhibiting a relaxometric response to zwitterionic amino acid neurotransmitters was synthesized. The design concept involves ditopic interactions 1) between a positively charged and coordinatively unsaturated Gd3+ chelate and the carboxylate group of the neurotransmitters and 2) between an azacrown ether appended to the chelate and the amino group of the neurotransmitters. The chelates differ in the nature and length of the linker connecting the cyclen-type macrocycle that binds the Ln3+ ion and the crown ether. The complexes are monohydrated, but they exhibit high proton relaxivities (up to 7.7 mM−1 s−1 at 60 MHz, 310 K) due to slow molecular tumbling. The formation of ternary complexes with neurotransmitters was monitored by 1H relaxometric titrations of the Gd3+ complexes and by luminescence measurements on the Eu3+ and Tb3+ analogues at pH 7.4. The remarkable relaxivity decrease (≈80 %) observed on neurotransmitter binding is related to the decrease in the hydration number, as evidenced by luminescence lifetime measurements on the Eu3+ complexes. These complexes show affinity for amino acid neurotransmitters in the millimolar range, which can be suited to imaging concentrations of synaptically released neurotransmitters. They display good selectivity over non-amino acid neurotransmitters (acetylcholine, serotonin, and noradrenaline) and hydrogenphosphate, but selectivity over hydrogencarbonate was not achieved.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/chem.201500542/epdf}, state = {published}, DOI = {10.1002/chem.201500542}, author = {Oukhatar F{oukhatar}{Department Physiology of Cognitive Processes}; Meudal H; Landon C; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Platas-Iglesias C; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Toth E} } @Article{ GatysETB2015_2, title = {Synaptic unreliability facilitates information transmission in balanced cortical populations}, journal = {Physical Review E}, year = {2015}, month = {6}, volume = {91}, number = {062707}, pages = {1-7}, abstract = {Synaptic unreliability is one of the major sources of biophysical noise in the brain. In the context of neural information processing, it is a central question how neural systems can afford this unreliability. Here we examine how synaptic noise affects signal transmission in cortical circuits, where excitation and inhibition are thought to be tightly balanced. Surprisingly, we find that in this balanced state synaptic response variability actually facilitates information transmission, rather than impairing it. In particular, the transmission of fast-varying signals benefits from synaptic noise, as it instantaneously increases the amount of information shared between presynaptic signal and postsynaptic current. Furthermore we show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not reach an optimum at a finite noise level. PDFHTML}, web_url = {http://journals.aps.org/pre/pdf/10.1103/PhysRevE.91.062707}, state = {published}, DOI = {10.1103/PhysRevE.91.062707}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Tchumatchenko T; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Article{ FlorinWL2015, title = {The role of sub-second neural events in spontaneous brain activity}, journal = {Current Opinion in Neurobiology}, year = {2015}, month = {6}, volume = {32}, pages = {24–30}, abstract = {Human fMRI studies have identified well-reproducible resting-state networks (RSN) from spontaneous recordings. These networks are extracted from correlation metrics across the brain using several minutes of data. However, a majority of electrophysiological events occur at a sub-second time scale and their contribution to RSN generation is likely. According to recent fMRI studies RSNs separate into smaller networks when studied with higher temporal resolution. Moreover, using simultaneous electrophysiology and fMRI recordings it was shown that transient functional networks form around neural events. Therefore, considering neural events as sources of functional networks might improve the understanding of spontaneous brain activity. This endeavor will benefit from technical advances in simultaneous BOLD and electrophysiology recordings, as well as a more principled modeling of neurovascular coupling.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0959438814002062}, state = {published}, DOI = {10.1016/j.conb.2014.10.006}, author = {Florin E{eflorin}{Department Physiology of Cognitive Processes}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ OrtizRiosKDAASJKR2015, title = {Functional MRI of the vocalization-processing network in the macaque brain}, journal = {Frontiers in Neuroscience}, year = {2015}, month = {4}, volume = {9}, number = {113}, pages = {1-10}, abstract = {Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC), medial geniculate nucleus (MGN), auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG) and sulcus (STS). Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls (“scrambled calls”) also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.}, web_url = {http://journal.frontiersin.org/article/10.3389/fnins.2015.00113/pdf}, state = {published}, DOI = {10.3389/fnins.2015.00113}, author = {Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}; Kuśmierek P; DeWitt I; Archakov IA; Azevedo FA{fazevedo}{Department Physiology of Cognitive Processes}; Sams M; J\"a\"askel\"ainen I; Keliris GA{george}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Article{ Logothetis2015, title = {Neural-Event-Triggered fMRI of large-scale neural networks}, journal = {Current Opinion in Neurobiology}, year = {2015}, month = {4}, volume = {31}, pages = {214–222}, abstract = {Brains are dynamic systems, consisting of huge number of massively interconnected elementary components. The activity of these components results in an initial condition-sensitive evolution of network states through highly non-linear, probabilistic interactions. The dynamics of such systems cannot be described merely by studying the behavior of their components; instead their study benefits from employing multimodal methods. Neural-Event-Triggered (NET) fMRI is a novel method allowing identification of events that can be used to examine multi-structure activity in the brain. First results offered insights into the networks that might be involved in memory consolidation. On-going work examines the physiological underpinnings of the up and down modulation of metabolic activity, mapped with this methodology.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0959438814002359}, state = {published}, DOI = {10.1016/j.conb.2014.11.009}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MahmoodiBOZSBSHAFRRB2015, title = {Equality bias impairs collective decision-making across cultures}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2015}, month = {3}, volume = {112}, number = {12}, pages = {3835–3840}, abstract = {We tend to think that everyone deserves an equal say in a debate. This seemingly innocuous assumption can be damaging when we make decisions together as part of a group. To make optimal decisions, group members should weight their differing opinions according to how competent they are relative to one another; whenever they differ in competence, an equal weighting is suboptimal. Here, we asked how people deal with individual differences in competence in the context of a collective perceptual decision-making task. We developed a metric for estimating how participants weight their partner’s opinion relative to their own and compared this weighting to an optimal benchmark. Replicated across three countries (Denmark, Iran, and China), we show that participants assigned nearly equal weights to each other’s opinions regardless of true differences in their competence—even when informed by explicit feedback about their competence gap or under monetary incentives to maximize collective accuracy. This equality bias, whereby people behave as if they are as good or as bad as their partner, is particularly costly for a group when a competence gap separates its members.}, web_url = {http://www.pnas.org/content/112/12/3835.full.pdf}, state = {published}, DOI = {10.1073/pnas.1421692112}, author = {Mahmoodi A; Bang D; Olsen K; Zhao YA; Shi Z; Broberg K; Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Han S; Ahmadabadi MN; Frith CD; Roepstorff A; Rees G; Bahrami B} } @Article{ YatsenkoJEFCT2015, title = {Improved Estimation and Interpretation of Correlations in Neural Circuits}, journal = {PLoS Computational Biology}, year = {2015}, month = {3}, volume = {11}, number = {3}, pages = {1-28}, abstract = {Ambitious projects aim to record the activity of ever larger and denser neuronal populations in vivo. Correlations in neural activity measured in such recordings can reveal important aspects of neural circuit organization. However, estimating and interpreting large correlation matrices is statistically challenging. Estimation can be improved by regularization, i.e. by imposing a structure on the estimate. The amount of improvement depends on how closely the assumed structure represents dependencies in the data. Therefore, the selection of the most efficient correlation matrix estimator for a given neural circuit must be determined empirically. Importantly, the identity and structure of the most efficient estimator informs about the types of dominant dependencies governing the system. We sought statistically efficient estimators of neural correlation matrices in recordings from large, dense groups of cortical neurons. Using fast 3D random-access laser scanning microscopy of calcium signals, we recorded the activity of nearly every neuron in volumes 200 μm wide and 100 μm deep (150–350 cells) in mouse visual cortex. We hypothesized that in these densely sampled recordings, the correlation matrix should be best modeled as the combination of a sparse graph of pairwise partial correlations representing local interactions and a low-rank component representing common fluctuations and external inputs. Indeed, in cross-validation tests, the covariance matrix estimator with this structure consistently outperformed other regularized estimators. The sparse component of the estimate defined a graph of interactions. These interactions reflected the physical distances and orientation tuning properties of cells: The density of positive ‘excitatory’ interactions decreased rapidly with geometric distances and with differences in orientation preference whereas negative ‘inhibitory’ interactions were less selective. Because of its superior performance, this ‘sparse+latent’ estimator likely provides a more physiologically relevant representation of the functional connectivity in densely sampled recordings than the sample correlation matrix.}, web_url = {http://www.ploscompbiol.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pcbi.1004083&representation=PDF}, state = {published}, DOI = {10.1371/journal.pcbi.1004083}, EPUB = {e1004083}, author = {Yatsenko D; Josić K; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Froudarakis E; Cotton RJ; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ PanzeriMGk2015, title = {Neural population coding: combining insights from microscopic and mass signals}, journal = {Trends in Cognitive Sciences}, year = {2015}, month = {3}, volume = {19}, number = {3}, pages = {162–172}, abstract = {Behavior relies on the distributed and coordinated activity of neural populations. Population activity can be measured using multi-neuron recordings and neuroimaging. Neural recordings reveal how the heterogeneity, sparseness, timing, and correlation of population activity shape information processing in local networks, whereas neuroimaging shows how long-range coupling and brain states impact on local activity and perception. To obtain an integrated perspective on neural information processing we need to combine knowledge from both levels of investigation. We review recent progress of how neural recordings, neuroimaging, and computational approaches begin to elucidate how interactions between local neural population activity and large-scale dynamics shape the structure and coding capacity of local information representations, make them state-dependent, and control distributed populations that collectively shape behavior.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1364661315000030}, state = {published}, DOI = {10.1016/j.tics.2015.01.002}, author = {Panzeri S{stefano}; Macke JH{jakob}; Gross J; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ GunduzPMLA2014, title = {Synthesis and Characterization of a Biotinylated Multivalent Targeted Contrast Agent}, journal = {ChemPlusChem}, year = {2015}, month = {3}, volume = {80}, number = {3}, pages = {612–622}, abstract = {A new bimodal and multivalent dendritic contrast agent (CA) that targets the protein avidin was prepared and characterized. The tripartite lysine core was used to link the ligand biotin, the fluorescent dye, and the dendron carrying GdDOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelates for amplification of the magnetic resonance imaging (MRI) signal. The longitudinal relaxivity of this dendrimeric CA was greater than those of its GdDOTA chelate and most of the common commercial agents at the investigated high magnetic field (7 T). The capacity of the dendrimeric CA to bind to the target protein was confirmed by fluorescence measurements upon its treatment with NeutrAvidin–agarose gel or NeutrAvidin-coated microspheres and the results were compared with those of its monomeric analogue. The fluorescence intensity of monomer-treated targets was found to be greater than that from those treated with dendrimeric CA; however, a several-fold increase in the MRI signal was observed on the same samples treated with the dendrimeric CA. The inductively coupled plasma mass spectrometry analysis of the digested samples indicated somewhat higher Gd3+ content and hence slightly better binding of monomeric versus dendrimeric CA. This bimodal and multivalent targeted probe opens an avenue for the preparation of new nanosized CAs that allow high-resolution MRI of various targets, such as cellular receptors or specific cellular populations.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cplu.201402329/pdf}, state = {published}, DOI = {10.1002/cplu.201402329}, author = {G\"und\"uz S{sgunduz}; Power A{apower}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ AllerGCWN2015, title = {A spatially collocated sound thrusts a flash into awareness}, journal = {Frontiers in Integrative Neuroscience}, year = {2015}, month = {2}, volume = {9}, number = {16}, pages = {1-8}, abstract = {To interact effectively with the environment the brain integrates signals from multiple senses. It is currently unclear to what extent spatial information can be integrated across different senses in the absence of awareness. Combining dynamic continuous flash suppression and spatial audiovisual stimulation, the current study investigated whether a sound facilitates a concurrent visual flash to elude flash suppression and enter perceptual awareness depending on audiovisual spatial congruency. Our results demonstrate that a concurrent sound boosts unaware visual signals into perceptual awareness. Critically, this process depended on the spatial congruency of the auditory and visual signals pointing towards low level mechanisms of audiovisual integration. Moreover, the concurrent sound biased the reported location of the flash as a function of flash visibility. The spatial bias of sounds on reported flash location was strongest for flashes that were judged invisible. Our results suggest that multisensory integration is a critical mechanism that enables signals to enter conscious perception.}, web_url = {http://journal.frontiersin.org/Article/10.3389/fnint.2015.00016/pdf}, state = {published}, DOI = {10.3389/fnint.2015.00016}, author = {Aller M; Giani A{giani}{Department Human Perception, Cognition and Action}{Research Group Cognitive Neuroimaging}; Conrad V{conrad}{Department Human Perception, Cognition and Action}{Research Group Multisensory Perception and Action}{Research Group Cognitive Neuroimaging}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Noppeney U{unoppe}{Department Human Perception, Cognition and Action}{Research Group Cognitive Neuroimaging}} } @Article{ HuberGKTGRINGTM2014, title = {Cortical lamina-dependent blood volume changes in human brain at 7 T}, journal = {NeuroImage}, year = {2015}, month = {2}, volume = {107}, pages = {23–33}, abstract = {Cortical layer-dependent high (sub-millimeter) resolution functional magnetic resonance imaging (fMRI) in human or animal brain can be used to address questions regarding the functioning of cortical circuits, such as the effect of different afferent and efferent connectivities on activity in specific cortical layers. The sensitivity of gradient echo (GE) blood oxygenation level-dependent (BOLD) responses to large draining veins reduces its local specificity and can render the interpretation of the underlying laminar neural activity impossible. The application of the more spatially specific cerebral blood volume (CBV)-based fMRI in humans has been hindered by the low sensitivity of the noninvasive modalities available. Here, a vascular space occupancy (VASO) variant, adapted for use at high field, is further optimized to capture layer-dependent activity changes in human motor cortex at sub-millimeter resolution. Acquired activation maps and cortical profiles show that the VASO signal peaks in gray matter at 0.8–1.6 mm depth, and deeper compared to the superficial and vein-dominated GE-BOLD responses. Validation of the VASO signal change versus well-established iron-oxide contrast agent based fMRI methods in animals showed the same cortical profiles of CBV change, after normalization for lamina-dependent baseline CBV. In order to evaluate its potential of revealing small lamina-dependent signal differences due to modulations of the input-output characteristics, layer-dependent VASO responses were investigated in the ipsilateral hemisphere during unilateral finger tapping. Positive activation in ipsilateral primary motor cortex and negative activation in ipsilateral primary sensory cortex were observed. This feature is only visible in high-resolution fMRI where opposing sides of a sulcus can be investigated independently because of a lack of partial volume effects. Based on the results presented here, we conclude that VASO offers good reproducibility, high sensitivity and lower sensitivity than GE-BOLD to changes in larger vessels, making it a valuable tool for layer-dependent fMRI studies in humans.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811914009768}, state = {published}, DOI = {10.1016/j.neuroimage.2014.11.046}, author = {Huber L; Goense J{jozien}{Department Physiology of Cognitive Processes}; Kennerley AJ; Trampel R; Guidi M; Reimer E; Ivanov D; Neef N; Gauthier CJ; Turner R; M\"oller HE} } @Article{ LopesdosSantosPKDQ2015, title = {Extracting information in spike time patterns with wavelets and information theory}, journal = {Journal of Neurophysiology}, year = {2015}, month = {2}, volume = {113}, number = {3}, pages = {1015-1033}, abstract = {We present a new method to assess the information carried by temporal patterns in spike trains. The method first performs a wavelet decomposition of the spike trains, then uses Shannon information to select a subset of coefficients carrying information, and finally assesses timing information in terms of decoding performance: the ability to identify the presented stimuli from spike train patterns. We show that the method allows: 1) a robust assessment of the information carried by spike time patterns even when this is distributed across multiple time scales and time points; 2) an effective denoising of the raster plots that improves the estimate of stimulus tuning of spike trains; and 3) an assessment of the information carried by temporally coordinated spikes across neurons. Using simulated data, we demonstrate that the Wavelet-Information (WI) method performs better and is more robust to spike time-jitter, background noise, and sample size than well-established approaches, such as principal component analysis, direct estimates of information from digitized spike trains, or a metric-based method. Furthermore, when applied to real spike trains from monkey auditory cortex and from rat barrel cortex, the WI method allows extracting larger amounts of spike timing information. Importantly, the fact that the WI method incorporates multiple time scales makes it robust to the choice of partly arbitrary parameters such as temporal resolution, response window length, number of response features considered, and the number of available trials. These results highlight the potential of the proposed method for accurate and objective assessments of how spike timing encodes information.}, web_url = {http://jn.physiology.org/content/113/3/1015.full-text.pdf+html}, state = {published}, DOI = {10.1152/jn.00380.2014}, author = {Lopes-dos-Santos V; Panzeri S{stefano}; Kayser C{kayser}{Department Physiology of Cognitive Processes}; Diamond ME; Quian Quiroga R} } @Article{ OukhatarMMSLAT2014, title = {MRI sensing of neurotransmitters with a crown-ether appended Gd3+ complex}, journal = {ACS Chemical Neuroscience}, year = {2015}, month = {2}, volume = {6}, number = {2}, pages = {219–225}, abstract = {Molecular MRI approaches that detect biomarkers associated to neural activity would allow more direct observation of brain function than current functional MRI based on blood-oxygen-level-dependent contrast. Our objective was to create a synthetic molecular platform with appropriate recognition moieties for zwitterionic neurotransmitters that generate an MR signal change upon neurotransmitter binding. The gadolinium complex (GdL) we report offers ditopic binding for zwitterionic amino acid neurotransmitters, via: i) interactions between the positively charged and coordinatively unsaturated metal centre and the carboxylate function and ii) between a triazacrown ether and the amine group of the neurotransmitters. GdL discriminates zwitterionic neurotransmitters from monoamines. Neurotransmitter binding leads to a remarkable relaxivity change, related to a decrease in hydration number. GdL was successfully used to monitor neural activity in ex vivo mouse brain slices by MRI.}, web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn500289y}, state = {published}, DOI = {10.1021/cn500289y}, author = {Oukhatar F{oukhatar}{Department Physiology of Cognitive Processes}; M{\^e}me S; M{\^e}me W; Szeremeta F; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Toth E} } @Article{ LeePKS2014, title = {Topographical estimation of visual population receptive fields by fMRI}, journal = {Journal of Visualized Experiments}, year = {2015}, month = {2}, number = {96}, pages = {1-8}, abstract = {Visual cortex is retinotopically organized so that neighboring populations of cells map to neighboring parts of the visual field. Functional magnetic resonance imaging allows us to estimate voxel-based population receptive fields (pRF), i.e., the part of the visual field that activates the cells within each voxel. Prior, direct, pRF estimation methods1 suffer from certain limitations: 1) the pRF model is chosen a-priori and may not fully capture the actual pRF shape, and 2) pRF centers are prone to mislocalization near the border of the stimulus space. Here a new topographical pRF estimation method2 is proposed that largely circumvents these limitations. A linear model is used to predict the Blood Oxygen Level-Dependent (BOLD) signal by convolving the linear response of the pRF to the visual stimulus with the canonical hemodynamic response function. PRF topography is represented as a weight vector whose components represent the strength of the aggregate response of voxel neurons to stimuli presented at different visual field locations. The resulting linear equations can be solved for the pRF weight vector using ridge regression3, yielding the pRF topography. A pRF model that is matched to the estimated topography can then be chosen post-hoc, thereby improving the estimates of pRF parameters such as pRF-center location, pRF orientation, size, etc. Having the pRF topography available also allows the visual verification of pRF parameter estimates allowing the extraction of various pRF properties without having to make a-priori assumptions about the pRF structure. This approach promises to be particularly useful for investigating the pRF organization of patients with disorders of the visual system.}, web_url = {https://www.jove.com/video/51811/topographical-estimation-of-visual-population-receptive-fields-by-fmri}, state = {published}, DOI = {10.3791/51811}, EPUB = {e51811}, author = {Lee S{slee}{Department Physiology of Cognitive Processes}; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Article{ GunduzNVSMLAA2014, title = {Dendrimeric Calcium-responsive MRI Contrast Agents with Slow in vivo Diffusion}, journal = {Chemical Communications}, year = {2015}, month = {1}, volume = {51}, number = {14}, pages = {2782-2785}, abstract = {We report a methodology which enables preparation of dendrimeric contrast agents sensitive to Ca2+ when starting from the monomeric analogue. The Ca-triggered longitudinal relaxivity response of these agents is not compromised by undertaken synthetic transformations, despite structural changes. The in vivo MRI studies in rat cerebral cortex indicate that diffusion property of dendrimeric contrast agent has great advantages as compared to its monomeric equivalent.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2014/cc/c4cc07540d}, state = {published}, DOI = {10.1039/C4CC07540D}, author = {G\"und\"uz S{sgunduz}; Nitta N; Vibhute SM{svibhute}{Department Physiology of Cognitive Processes}; Shibata S; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Aoki I; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ PetkovKMMRL2015, title = {Different forms of effective connectivity in primate frontotemporal pathways}, journal = {Nature Communications}, year = {2015}, month = {1}, volume = {6}, number = {6000}, pages = {1-12}, abstract = {It is generally held that non-primary sensory regions of the brain have a strong impact on frontal cortex. However, the effective connectivity of pathways to frontal cortex is poorly understood. Here we microstimulate sites in the superior temporal and ventral frontal cortex of monkeys and use functional magnetic resonance imaging to evaluate the functional activity resulting from the stimulation of interconnected regions. Surprisingly, we find that, although certain earlier stages of auditory cortical processing can strongly activate frontal cortex, downstream auditory regions, such as voice-sensitive cortex, appear to functionally engage primarily an ipsilateral temporal lobe network. Stimulating other sites within this activated temporal lobe network shows strong activation of frontal cortex. The results indicate that the relative stage of sensory processing does not predict the level of functional access to the frontal lobes. Rather, certain brain regions engage local networks, only parts of which have a strong functional impact on frontal cortex.}, web_url = {http://www.nature.com/ncomms/2015/150123/ncomms7000/pdf/ncomms7000.pdf}, state = {published}, DOI = {10.1038/ncomms7000}, author = {Petkov CI{chrisp}{Department Physiology of Cognitive Processes}; Kikuchi Y; Milne AE; Mishkin M; Rauschecker JP; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ PerrodinKLP2014_2, title = {Natural asynchronies in audiovisual communication signals regulate neuronal multisensory interactions in voice-sensitive cortex}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2015}, month = {1}, volume = {112}, number = {1}, pages = {273–278}, abstract = {When social animals communicate, the onset of informative content in one modality varies considerably relative to the other, such as when visual orofacial movements precede a vocalization. These naturally occurring asynchronies do not disrupt intelligibility or perceptual coherence. However, they occur on time scales where they likely affect integrative neuronal activity in ways that have remained unclear, especially for hierarchically downstream regions in which neurons exhibit temporally imprecise but highly selective responses to communication signals. To address this, we exploited naturally occurring face- and voice-onset asynchronies in primate vocalizations. Using these as stimuli we recorded cortical oscillations and neuronal spiking responses from functional MRI (fMRI)-localized voice-sensitive cortex in the anterior temporal lobe of macaques. We show that the onset of the visual face stimulus resets the phase of low-frequency oscillations, and that the face–voice asynchrony affects the prominence of two key types of neuronal multisensory responses: enhancement or suppression. Our findings show a three-way association between temporal delays in audiovisual communication signals, phase-resetting of ongoing oscillations, and the sign of multisensory responses. The results reveal how natural onset asynchronies in cross-sensory inputs regulate network oscillations and neuronal excitability in the voice-sensitive cortex of macaques, a suggested animal model for human voice areas. These findings also advance predictions on the impact of multisensory input on neuronal processes in face areas and other brain regions.}, web_url = {http://www.pnas.org/content/112/1/273.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.1412817112}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Inproceedings{ ShajarisalesJSB2015, title = {Telling Cause from Effect in Deterministic Linear Dynamical Systems}, year = {2015}, month = {7}, pages = {285–294}, abstract = {Telling a cause from its effect using observed time series data is a major challenge in natural and social sciences. Assuming the effect is generated by the cause through a linear system, we propose a new approach based on the hypothesis that nature chooses the “cause” and the “mechanism generating the effect from the cause” independently of each other. Specifically we postulate that the power spectrum of the “cause” time series is uncorrelated with the square of the frequency response of the linear filter (system) generating the effect. While most causal discovery methods for time series mainly rely on the noise, our method relies on asymmetries of the power spectral density properties that exist even in deterministic systems. We describe mathematical assumptions in a deterministic model under which the causal direction is identifiable. In particular, we show a scenario where the method works but Granger causality fails. Experiments show encouraging results on synthetic as well as real-world data. Overall, this suggests that the postulate of Independence of Cause and Mechanism is a promising principle for causal inference on observed time series.}, web_url = {http://jmlr.org/proceedings/papers/v37/shajarisales15.html}, editor = {Bach, F. , D. Blei}, publisher = {International Machine Learning Society}, address = {Madison, WI, USA}, series = {JMLR Workshop and Conference Proceedings ; 37}, event_name = {32nd International Conference on Machine Learning (ICML 2015)}, event_place = {Lille, France}, state = {published}, author = {Shajarisales N; Janzing D{janzing}; Sch\"olkopf B{bs}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Inproceedings{ PutzkyFBM2014, title = {A Bayesian model for identifying hierarchically organised states in neural population activity}, year = {2015}, pages = {3095-3103}, abstract = {Neural population activity in cortical circuits is not solely driven by external inputs, but is also modulated by endogenous states. These cortical states vary on multiple time-scales and also across areas and layers of the neocortex. To understand information processing in cortical circuits, we need to understand the statistical structure of internal states and their interaction with sensory inputs. Here, we present a statistical model for extracting hierarchically organized neural population states from multi-channel recordings of neural spiking activity. We model population states using a hidden Markov decision tree with state-dependent tuning parameters and a generalized linear observation model. Using variational Bayesian inference, we estimate the posterior distribution over parameters from population recordings of neural spike trains. On simulated data, we show that we can identify the underlying sequence of population states over time and reconstruct the ground truth parameters. Using extracellular population recordings from visual cortex, we find that a model with two levels of population states outperforms a generalized linear model which does not include state-dependence, as well as models which only including a binary state. Finally, modelling of state-dependence via our model also improves the accuracy with which sensory stimuli can be decoded from the population response.}, file_url = {fileadmin/user_upload/files/publications/2014/NIPS-2014-Putzky-Paper.pdf}, file_url2 = {fileadmin/user_upload/files/publications/2014/NIPS-2014-Putzky-Suppl.pdf}, web_url = {http://papers.nips.cc/paper/5338-a-bayesian-model-for-identifying-hierarchically-organised-states-in-neural-population-activity}, editor = {Ghahramani, Z. , M. Welling, C. Cortes, N. D. Lawrence, K. Q. Weinberger}, publisher = {Curran}, address = {Red Hook, NY, USA}, booktitle = {Advances in Neural Information Processing Systems 27}, event_name = {Twenty-Eighth Annual Conference on Neural Information Processing Systems (NIPS 2014)}, event_place = {Montréal, Quebec, Canada}, state = {published}, ISBN = {978-1-5108-0041-0}, author = {Putzky P{pputzky}; Franzen F{ffranzen}; Bassetto G{gbassetto}; Macke JH{jakob}} } @Inbook{ MarreirosPBF2015, title = {DCM, Conductance Based Models and Clinical Applications}, year = {2015}, month = {10}, pages = {43-70}, abstract = {This chapter reviews some recent advances in dynamic causal modelling (DCM) of electrophysiology, in particular with respect to conductance based models and clinical applications. DCM addresses observed responses of complex neuronal systems by looking at the neuronal interactions that generate them and how these responses reflect the underlying neurobiology. DCM is a technique for inferring the biophysical properties of cortical sources and their directed connectivity based on distinct neuronal and observation models. The DCM framework uses mathematical formalisms of neural masses, neural fields and mean-fields as forward or generative models for observed neuronal activity. We here consider conductance based neural mass, mean-field and field models—and review their latest technical developments. We use dynamically rich conductance based models to generate responses in laminar-specific populations of excitatory and inhibitory cells. These models allow for the evaluation of neuronal connections and high-order statistics of neuronal states, using Bayesian estimation and inference. We also discuss recent clinical applications of DCM for convolution based neural mass models, in particular for the study of Parkinson’s disease. We present a study of data from Parkinsonian patients, and model the large-scale network changes underlying the pathological excess of beta oscillations that characterise the Parkinsonian state.}, web_url = {http://link.springer.com/content/pdf/10.1007%2F978-3-319-20037-8_3.pdf}, editor = {Bhattacharya, B.S. , F.N. Chowdhury}, publisher = {Springer International Publishing}, address = {Cham, Switzerland}, series = {Springer Series in Computational Neuroscience ; 14}, booktitle = {Validating Neuro-Computational Models of Neurological and Psychiatric Disorders}, state = {published}, ISBN = {978-3-319-20036-1}, DOI = {10.1007/978-3-319-20037-8_3}, author = {Marreiros AC{amarreiros}{Department Physiology of Cognitive Processes}; Pinotsis DA; Brown P; Friston KJ} } @Inbook{ EvrardB2015, title = {Insular Cortex}, year = {2015}, volume = {2: Anatomy and Physiology, Systems}, pages = {387–393}, abstract = {The insula lies hidden within the sylvian fissure, the first sulcus that forms during development. Its three general sectors each comprise several sharply delimited architectonic areas with different connections and functional roles. It is anchored by the interoceptive cortex, a high-resolution representation of the physiological condition of the body that is unique to primates. A posterior-to-mid-to-anterior progression of multimodal integration culminates in highly interconnected hubs in the anterior insula that underpin all subjective feelings. The anterior insula and the spindle-shaped von Economo neurons it contains contribute to embodied cognition and human self-awareness. Most pathologies of the insular cortex disrupt interoceptive and self-conscious feelings.}, web_url = {http://www.sciencedirect.com/science/article/pii/B9780123970251002372}, editor = {Toga, A.W.}, publisher = {Academic Press / Elsevier}, address = {Amsterdam, The Netherlands}, booktitle = {Brain Mapping: An Encyclopedic Reference}, state = {published}, ISBN = {978-0-12-803293-0}, DOI = {10.1016/B978-0-12-397025-1.00237-2}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; (Bud) Craig AD} } @Inbook{ LogothetisP2014, title = {Local Field Potential, Relationship to BOLD Signal}, year = {2015}, pages = {1560-1568}, abstract = {Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has rapidly become the leading research tool in cognitive neuroscience. Understanding how BOLD signal relates to activity of neural populations is crucial for constraining the interpretation of any fMRI in humans or animals. Here we review how the mean extracellular field potential (mEFP) recorded with extracellular electrodes samples different components of neural activity and how these components relate to the BOLD fMRI signal.}, web_url = {http://link.springer.com/content/pdf/10.1007%2F978-1-4614-7320-6_726-1.pdf}, editor = {Jaeger, D. , R. Jung}, publisher = {Springer}, address = {New York, NY, USA}, booktitle = {Encyclopedia of Computational Neuroscience}, state = {published}, ISBN = {978-1-4614-6674-1}, DOI = {10.1007/978-1-4614-7320-6_726-1}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ PeysakhovichB2015, title = {Role of the insular cortex in interpersonal attachment}, year = {2015}, month = {11}, day = {24}, pages = {50}, abstract = {Maternal and romantic attachment have been shown to recruit a distinct network of limbic regions including the insular cortex, which has extensive anatomical and functional connections to other brain regions. In order to further characterize the involvement of the insula in interpersonal attachment, we investigated attachment-induced changes in functional connectivity between the insula and the rest of the brain. Participants (n = 36) underwent an fMRI scan while passively viewing photographs of loved individuals (their own child or romantic partner; love condition) or another acquainted person. K-means clustering based on time-series correlations between insular voxels and all other brain voxels was used to identify subdivisions of the insula. The clustering produced three subregions in each hemisphere that were left-right symmetric. These subregions were then used as seeds in a psychophysiological interaction (PPI) analysis, which characterizes condition-specific changes in functional connectivity between seed regions and other brain regions. The analyses revealed increased connectivity during the love condition between the insula and regions within the ventral attention network (VAN), including the temporoparietal junction and inferior frontal gyrus, and areas in the dorsal attention network (DAN), including the intraparietal sulcus and middle frontal gyrus. Increased connectivity was also shown in the striatum and inferior temporal cortex. Decreased insular connectivity during the love condition was observed in sensorimotor areas and within default mode network (DMN) regions including the posterior cingulate cortex and precuneus. These connectivity patterns were highly similar for corresponding subdivisions of the left and right insula. These preliminary results suggest that attachment may be mediated by increased communication between the insula and the VAN, which is important for detecting behaviorally-relevant stimuli, and the DAN, which is involved in internal goal-directed attention.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Peysakhovich B; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ GrassiZb2015, title = {Parietal cortex mediates perceptual Gestalt grouping independent of stimulus size}, year = {2015}, month = {11}, day = {23}, volume = {43}, abstract = {The integration of local moving elements into a unified Gestalt percept has previously been linked to the posterior parietal cortex. There are two possible interpretations for the lack of involvement of other occipital regions. The first is that parietal cortex is indeed uniquely functionally specialized to perform grouping. Another possibility is that other visual regions can perform grouping as well, but that the large spatial separation of the local elements used previously exceeded their neurons' receptive field (RF) sizes, preventing their involvement. In this study we distinguished between these two alternatives. We measured whole-brain activity using fMRI in response to a bistable motion illusion that induced mutually exclusive percepts of either an illusory global Gestalt or of local elements. The stimulus was presented in two sizes, a large version known to activate IPS only, and a version sufficiently small to fit into the RFs of mid-level dorsal regions such as V5/MT. We found that none of the separately localized motion regions apart from parietal cortex showed a preference for global Gestalt perception, even for the smaller version of the stimulus. This outcome suggests that grouping is mediated by a specialized size-invariant mechanism with parietal cortex as its anatomical substrate.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Grassi P{pgrassi}{Department Physiology of Cognitive Processes}; Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ FosterB2015, title = {Perception of Global Flow and Local Motion under Natural Conditions}, year = {2015}, month = {11}, day = {23}, pages = {42}, abstract = {Our natural visual world contains a variety of different types of motion. Two of the most prominent are global ow, the movement of the entire visual scene that occurs whenever we make an eye or head movement, and local motion, the real movement of people and objects in our environment. We constantly have a mixture of these two kinds of motion, but generally have no problems distinguishing between the two, even though they can produce similar movements on the retina. This ability of the visual system was explored in the present study. Subjects watched a feature movie, used as an approximation to the natural visual world whilst functional magnetic resonance images (fMRI) were made of their brains. Relative amounts of global ow and local motion in the movie were determined using a motion algorithm, and compared to bloodoxygenation level dependent (BOLD) activations in specific visual regions of interest, which were determined from standard retinotopic mapping and localizer techniques. A significant preference to local motion was identified in areas MST, V5/MT, V3A, V2 and V3. Furthermore whole brain analyses showed additional areas with a preference to local motion, and responses to global flow in activity in areas commonly involved in perception of our surrounding spatial environment. These findings further support the idea that there are different brain areas involved in the processing of global flow and local motion.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Foster C{cfoster}{Department Human Perception, Cognition and Action}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ NauSB2015, title = {Human early visual cortex, V3A, V6 and VIP signal the direction of retinal motion relative to the direction of eye movements}, year = {2015}, month = {11}, day = {5}, pages = {68}, abstract = {It is still not clear how the visual system compensates for self-induced visual motion. Doing so is crucial to convey visual stability and to recognize motion in the external world. Substantial evidence suggests that efference copies of eye movement commands are integrated with visual input, allowing to separate self-induced retinal motion from external objective motion. Here we used fMRI to investigate functional responses of sixteen visual areas to planar objective motion during pursuit. At two pursuit speeds, observers were exposed to objective motion that was faster, matched or slower relative to pursuit. We found that areas V3A, V6, VIP and the early visual cortex preferred objective motion faster than pursuit to objective motion slower than pursuit and thus signaled the direction of retinal motion relative to the direction of eye movements. Additionally, we examined functional connectivity between area V3A and the thalamus, which is known to contribute to cortico-cortical communication and the transmission of efference copies, and found a retinal motion dependent functional link between V3A and the dorsal thalamus. The present results emphasize the key role of area V3A in compensating self-induced visual motion and further point to an involvement of both early visual cortex and the thalamus.}, web_url = {http://www.ru.nl/dondersdiscussions/previous-events/dd2015/programme2015/}, event_name = {Donders Discussions 2015}, event_place = {Nijmegen, The Netherlands}, state = {published}, author = {Nau M{mnau}{Department Physiology of Cognitive Processes}; Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ KorkmazHacialihafizDB2015, title = {Speed encoding in motion processing areas during objective and retinal motion}, year = {2015}, month = {11}, day = {5}, pages = {72}, abstract = {Previously, human visual areas V3A and V6 have been shown to compensate for self-induced retinal motion and to encode objective motion during smooth pursuit eye movements. However, it is unclear how responses to objective and retinal motion vary as a function of speed in these and other human motion responsive regions. Prior studies examining fMRI responses as a function of speed always measured joint responses to objective and retinal motion, as speed of the background motion was varied during fixation. In this study we used a pursuit paradigm that allowed us to measure responses to objective and retinal motion separately. We did this for 6 different levels of speed (1, 2, 4, 8, 16, and 24 degrees per second) in order to obtain speed tuning profiles for separately localized visual motion regions. Stimuli consisted of moving fourier scrambles derived from natural images. We found that all regions had a response increase with higher speeds for both, retinal and objective motion. V3A stood out in that it was the only region in which speed increases in objective motion lead to a higher signal modulation than speed increases in retinal motion. V6, CSv, V5/MT and MST did not differ in objective and retinal speed slopes, even though all all them tended to respond more to objective motion at all speeds. These results support the view that human V3A plays a predominant role in integrating visual signals with efference copies, and that it encodes primarily objective rather than retinal motion signals.}, web_url = {http://www.ru.nl/dondersdiscussions/previous-events/dd2015/programme2015/}, event_name = {Donders Discussions 2015}, event_place = {Nijmegen, The Netherlands}, state = {published}, author = {Korkmaz Hacialihafiz D{dkorkmaz}{Department Physiology of Cognitive Processes}; Darmani G; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ BannertB2015, title = {The invariance of surface color representations across illuminant changes in the human cortex}, year = {2015}, month = {11}, day = {5}, pages = {67}, abstract = {The light reflected from a surface depends on the reflectance of that surface and the spectral power distribution of the incident light, thus making it impossible to predict surface color directly from its wavelength composition. Despite this computational problem, the human visual system is remarkably accurate at inferring the color of surfaces across different illuminants. This ability is referred to as color constancy and it is essential for the organism to use color as a cue in object search, recognition, and identification. We devised images of two surfaces presented under three different illuminants using physically realistic rendering methods to disentangle the influences of wavelength composition, surface reflectance, and illumination. Measuring patterns of fMRI voxel activity elicited by these images we tested to what extent responses to surface color in various retinotopically mapped visual areas remained stable across illuminants. While surface color could be decoded in all ROIs when the illuminants did not differ between training and test sets, we found generalization across illuminants in V1 only. When viewing the scene in a cue conflict condition that abolished color constancy as measured psychophysically, generalization also broke down in V1. When fMRI activity was elicited by stimuli that were matched in reflected light but differed in illumination and therefore also perceived surface color, higher visual areas showed an increasing bias towards surface color representation and a decrease in illuminant color representation. Our results demonstrate the differential roles that V1 and V4 areas play in transforming chromatic input into color constant percepts.}, web_url = {http://www.ru.nl/dondersdiscussions/previous-events/dd2015/programme2015/}, event_name = {Donders Discussions 2015}, event_place = {Nijmegen, The Netherlands}, state = {published}, author = {Bannert MM{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ FischerBDELESPFG2015, title = {A human brain network linking arousal to awareness}, year = {2015}, month = {10}, day = {21}, volume = {45}, number = {819.02}, abstract = {OBJECTIVE: Arousal, or wakefulness, is a fundamental brain process on which all cognitive functions rely, and which has important clinical applications. However, the neurobiology of arousal in humans remains incompletely characterized. The underlying neuroanatomy can be studied through focal lesions that induce coma, with evidence suggesting that such lesions commonly involve the pontine tegmentum. However, the precise location of the brainstem region critical for arousal remains unclear. Furthermore, the brainstem is thought to promote arousal through ascending projections to a distributed network, but the nodes of this network in humans are poorly defined. METHODS: To identify the brainstem region critical for arousal and its associated network in humans, we integrated a lesion overlap analysis with resting state functional connectivity MRI (rs-fcMRI). We collected 36 focal brainstem lesions: 12 lesions caused coma, and 24 control lesions caused motor deficits with preservation of consciousness/arousal. By overlapping the coma lesions and subtracting the control lesions, we identified a coma-specific region of the brainstem. We then used rs-fcMRI collected from 98 healthy individuals to identify the functionally connected network of this coma-specific region. RESULTS: The coma-specific region of the brainstem localized to the lateral pontine tegmentum, overlying the medial parabrachial nucleus (PB). The rs-fcMRI analysis revealed two functionally connected nodes: the agranular insula (AI) and anterior cingulate cortex (ACC). These regions exhibited significantly more connectivity to coma lesions than control lesions. Based on connectivity to the AI and ACC, the PB most closely resembled the coma-specific region, compared to other nearby nuclei. CONCLUSIONS: Coma-causing lesions appear to involve the PB, which exhibits connectivity to the AI and ACC in a three-node network. Damage to the PB region may therefore be integral to the pathophysiology of coma; as the PB is critical to arousal in non-human animals, our findings suggest a homologous neural system of arousal between animals and humans. The AI and ACC are the primary sites of Von Economo neurons, and have been implicated in conscious awareness in humans. Our findings therefore link a brainstem nucleus of arousal to cortical regions associated with human awareness, offering a neural basis for integration of these two processes.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Fischer DB; Boes A; Demertzi A; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Laureys S; Edlow B; Saper CB; Pascual-Leone A; Fox MD; Geerling JC} } @Poster{ TakemuraPWKLSYBLFLW2015, title = {Occipital vertical fiber system in human and macaque}, year = {2015}, month = {10}, day = {21}, volume = {45}, number = {700.01}, abstract = {The large size of the human brain imposes computational constraints that are reflected in its structural organization. For example, specialized visual processing of spatial and categorical information is partially segregated in dorsal and ventral regions in the occipital and temporal lobes; these regions are widely separated in cortex. For effective vision and action, the processing performed in these regions must be coordinated. Classical as well as recent studies identify the human Vertical Occipital Fasciculus (VOF), as a likely white matter bundle that includes axons that communicate between the dorsal and ventral regions. In this study, we compare the human vertical occipital pathways with similar tracts in the much smaller macaque brain in order to better understand similarities and differences across species. Methods. We obtained diffusion MRI (dMRI) at several spatial resolutions, and we used fiber tractography to estimate the trajectories of several different occipital pathways. DMRI data were acquired from 4 macaque monkeys and many humans (Takemura et al., 2015). We analyzed the data using constrained spherical deconvolution (CSD) and an ensemble of probabilistic tractography methods. We optimized the tractography results and tested statistical hypotheses using Linear Fascicle Evaluation methods (Pestilli et al., 2014). Results. A substantial bundle of vertical occipital fibers could be found in all the macaque and human datasets. The location of the macaque VOF (mVOF) is consistent with a schematic description in a post-morterm monkey brain described by Wernicke (1881). The mVOF terminates near cortical areas V3d, V3A, V4d and MT dorsally and V4v/TEO ventrally. The pattern of mVOF terminations is similar to those of human VOF, which are principally V3A/B dorsally and hV4 ventrally. In both species, the VOF is lateral to the optic radiation (sagittal stratum). In human, the VOF is also lateral to the Inferior Longitudinal Fasciculus (ILF) and clearly distinguishable from the ILF; but the mVOF intermingles with the vertical component of macaque ILF and does not form a very distinct bundle. The estimates of the position, size and cortical terminations of the mVOF depend on instrumental parameters, such as dMRI resolution; but in all cases the core of the tract can be identified and the estimates are consistent. These findings suggest that the human and macaque vertical occipital fiber systems diverged from a common ancestor. The human system significantly enlarged and became separated from the ILF. The change in white matter may be part of the general evolution of the size and position of extrastriate maps with the increase in brain size.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Takemura H; Pestilli F; Weiner KS; Keliris GA{george}{Department Physiology of Cognitive Processes}; Landi S; Sliwa J; Ye FQ; Barnett M; Leopold DA; Freiwald WA; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Wandell BA} } @Poster{ PapanikolaouKLLS2015_2, title = {Population receptive field changes in hV5/MT+ of healthy subjects with simulated visual field scotomas}, year = {2015}, month = {10}, day = {21}, volume = {45}, number = {700.02}, abstract = {An important question is whether the adult visual cortex is able to reorganize in subjects with visual field defects (scotomas) as a result of retinal or cortical lesions. Functional magnetic resonance imaging (fMRI) methods provide a useful tool to study the population receptive field (pRF) properties and assess the capacity of the human visual cortex to reorganize following injury. However, these methods are prone to biases near the boundaries of the scotoma. Retinotopic changes resembling reorganization have been observed in the early visual cortex of normal subjects when the visual stimulus is masked to simulate retinal or cortical scotomas. It is not known how the receptive fields of higher visual areas, like hV5/MT+, are affected by partial stimulus deprivation. Here, we measured responses in human area V5/MT+ in five healthy subjects under two stimulation conditions. FMRI measurements were obtained under the presentation of a moving bar stimulus spanning the entire visual field while the subjects were fixating. In a second session the stimulus was masked in the left upper quadrant of the visual field to simulate a quadrantanopic scotoma (“artificial scotoma” or AS) occurring often as a result of partial V1 or optic radiation lesions. PRF estimates were obtained using a recent method of pRF topography estimation (Lee et al., A new method for estimating population receptive field topography in visual cortex, NeuroImage, 2013) which is consistent with other pRF methods. Responses obtained under the AS condition were compared with simulations obtained from a linear AS model (or LAS model). The LAS model provides an estimation of the pRF changes expected to occur as a result of the truncated stimulus assuming that the pRF linearly integrates the AS. We found that pRFs in hV5/MT+ are nonlinearly affected by the truncated stimulus presented: pRF centers shifted towards the border of the AS, pRF size decreased and pRF amplitude increased near the AS border. In addition, using the full bar stimulus to estimate the pRF topography (when in fact the stimulus presented included the AS) produced erroneous pRF estimates inside the region of the artificial scotoma. These biases are not the result of a trivial methodological artifact but appear to originate partly from asymmetric BOLD responses occurring when the stimulus moves from seeing to non-seeing locations of the visual field. Distinguishing between pRF changes that occur as the result of true reorganization versus different test-stimulus presentation conditions is an important task that needs to be undertaken when studying visual cortex organization in patients with visual field deficits.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Lee S{slee}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Poster{ LohmannSBZMBS2015, title = {Task-induced edge density as a marker for dynamic network formation in fMRI}, year = {2015}, month = {10}, day = {21}, volume = {45}, number = {830.12}, abstract = {The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, in the past twenty years, task-based fMRI studies have primarily focused on signal amplitude changes or connectivity related to a few selected nodes. Shifting focus away from signal amplitudes or constraining connectivity patterns of a few selected nodes, we propose an alternative view on fMRI data analysis by considering large-scale, task-induced synchronization networks. Networks consist of nodes and edges connecting them, where nodes in our method correspond to voxels in fMRI data, and the weight of an edge between any two voxels is determined via task-induced changes in dynamic synchronization between their respective times series. Based on these definitions, we developed a new data analysis algorithm that is designed to identify time series of voxels in an fMRI image that collectively synchronize in response to a task. At the heart of our approach is the concept of spatially localized and task-induced edge density motivating us to call this algorithm "TED" (Task induced Edge Density). In short, TED identifies edges in a brain network that differentially respond in unison to a task onset and that occur in dense packs of edges with similar responses to tasks. We found TED to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical approaches such as the local false discovery rate (local fdr). A major advantage of TED compared to other network-based methods is that it does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. Because its conceptual basis is task-induced synchronization it does not depend on a hemodynamic response model. We applied TED to task-based fMRI data provided by the Human Connectome Project focusing on the motor, social recognition and working memory tasks. In all cases, TED identified several task-specific, large-scale patterns of synchronization. We conclude that the new TED method provides us with an entirely new window into the immense complexity of human brain function.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Lohmann G{lohmann}{Department High-Field Magnetic Resonance}; Stelzer J{jstelzer}{Department High-Field Magnetic Resonance}; Buschmann T; Zuber V; Margulies D; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ KwonWB2015, title = {Top-down attention de-correlates early visual cortex}, year = {2015}, month = {10}, day = {21}, volume = {45}, number = {793.18}, abstract = {Attention allows our brain to focus its limited resources on a selected task. It does so by the selective modulation of neuronal activity of task-relevant cortical areas, and by the simultaneous change of communication between sets of regions. Previous fMRI evidence in the human brain showed selective increases in functional connectivity within visual cortex and between visual with fronto-parietal networks. However, these studies examined relatively brief attention periods that are affected by task-induced signal transients. We designed an experiment involving very long (2 min) trials of attention and rest that would allow us to discard initial transient periods (30 s), and to analyze slow (0.004-0.05Hz) and fast frequency (0.05-0.2Hz) bands of fMRI signals driving connectivity changes. We analyzed functional connectivity between visual regions, the dorsal attention network, and the resting state network. We found that attention increased long-distance connectivity between the dorsal attention network and visual regions and within the resting-state network. It decreased connectivity between resting-state and attention networks, but also between distinct visual regions and within distinct parts of the same visual region (left/right, dorsal/ventral parts). The change in connectivity strength was correlated with hierarchical distance, such that the increase between the dorsal attention network and visual cortex was more pronounced for higher than lower visual regions. Correspondingly, the decrease within visual cortex was the more pronounced the closer the hierarchical proximity was between neighboring regions, and was highest within regions. A frequency-segregated analysis showed that long-distance effects between dorsal attention network and visual regions were mediated by slow and fast fluctuations, whereas only fast fluctuations mediated de-correlation among visual regions. These results may pinpoint two fundamentally distinct effects of attention on connectivity. A long-range facilitation of information flow between distinct networks, and a short-range de-correlation within sensory cortex that may indicate and increase of information and decrease of redundancy.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Kwon S{soyoung}{Department Physiology of Cognitive Processes}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ LiLK2015, title = {Neural signals of motion integration are modulated by perception}, year = {2015}, month = {10}, day = {20}, volume = {45}, number = {600.11}, abstract = {A very important feature of primate vision is the ability to integrate motion signals into a coherent percept. To this end, a two-stage motion integration model has been proposed that selectively integrates local signals over time and space to reconstruct the global motion pattern. It has been suggested that the first stage responsible for local motion detection takes place in lower level visual area(s), while a second stage in higher area(s) integrates the local motion signals in order to extract the global motion direction. Support for this hypothesis stems mainly from recordings in anesthetized non-human primates while evidence in awake-behaving ones is very limited. Furthermore, very little is known about how motion integration is influenced by perception. In this study, we designed a novel pseudo-plaid stimulus that can parametrically modulate coherent or transparent motion perception by changing local feature information. The stimulus consists of two types of apertures over a line plaid display. The first group of apertures allows only single contours to pass through while the second only intersections. Human psychophysics demonstrated that the motion perception changes parametrically with the proportion of the two types of apertures from 100% transparent when only single-contour apertures are present to 100% coherent when only intersection apertures are displayed. Then, we used this stimulus and performed multi-electrode recordings in areas V1 and MT of alert macaques. Analysis of the firing rates during the whole trial (1000 ms) demonstrated that MT neurons were strongly modulated by the proportion of different aperture types reflecting the perception. Specifically, MT neural responses increased when motion perception was more coherent. In contrast V1 neurons did not show any significant changes by using this measure. These data corroborate the hierarchical organization of motion integration and demonstrate the relationship of neural signals with subjective perception.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Li Q{qinglinli}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ MarreirosLE2015, title = {State-dependent processing in the brain}, year = {2015}, month = {10}, day = {20}, volume = {45}, number = {512.01}, abstract = {The level of norepinephrine (NE) in the brain modulates a variety of cognitive processes such as attention, perception, learning and memory. Stimulation of the Locus Coeruleus (LC), the major source of NE in the forebrain, can change spontaneous and task-related neuronal discharge in a large number of LC projection-targets. Few advances have been done on the study of the effects of phasic NE release on the responsiveness of mPFC cortical areas. In order to have a more complete understanding of the widespread projections of LC we need a multimodal approach. Here, we investigate the effects of LC discharge on ongoing and sensory-evoked cortical activity, by combining LC direct electrical stimulation (LC-DES) with multisite extracellular recordings and whole-brain fMRI in rats under anesthesia. The combination of these methods allows the acquirement of a richer dataset which carries unique insight into the mechanism of large scale NE modulation. The aim of this project is to combine multi-site extracellular recordings, DES and functional MRI techniques in an attempt to define brain “states” and their conditional probabilities with respect to the LC activity level and salient external events. The activity of the noradrenergic system is expected to strongly contribute to the modulation of the cortical state [Neuron 69:1061-1068, 2011]. The cortical recordings, from mPFC, are used to determine the network state prior to sensory stimulation and the neurophysiological responses to sensory stimuli with or without LC stimulation. In order to characterize the different cortical states induced by the anesthesia level and classify its maps accordingly, we computed a cortical synchronization index (SI) proxy [J Neurosci 29: 10600-10612, 2009] using the baseline preceding stimulation. We obtained representations for the distributions of a lower (a) and a higher (b) synchronization index during the same foot-shock (FS) condition. Subsequently, we looked at the cortical state-dependent effect of the FS stimulation, which shows the Z-score of the BOLD time course difference between the SI distributions. Furthermore, fMRI maps for LC-DES have shown to produce an interesting dichotomy between BOLD responses of cortical and subcortical structures (belonging to metencephalon, mesencephalon and diencephalon cortices). Namely, they show the fraction of positively and negatively activated ROIs for the same LC-DES condition averaged over 10 sessions. This study suggests that it is possible to map the whole brain noradrenergic system by characterizing the FS or LC-DES stimuli responses and contextualize it according to the endogenous cortical synchronization state.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Marreiros A{amarreiros}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ HernandezMombielaUILAE2015, title = {Anterograde examination of the projections of the hippocampal formation and basal amygdala to the ventral tegmental area in the macaque monkey}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {445.17}, abstract = {The subiculum (Sub) of the hippocampal formation (HF) and the basal amygdala (Amy) control memory and other critical cognitive processes in part through the regulation of dopamine release from mesodiencephalic projecting neurons of the ventral tegmental area (VTA) (Phillips et al. 2003 Nsci Biobehav Rev 27:543-54; Belujon & Grace 2011 ANYAS 1216:114-21). Models of the dopaminergic system proposed that HF regulates the activity of VTA through strong indirect pathways involving the striatum and lateral septum, without direct connections between HF and VTA (e.g., Lisman et al. 2005 Neuron 46:703-13). A prior tracing study in macaque monkeys showed that the central nucleus of Amy (CeA) projects to VTA (Amaral et al. 1981 J Nsci 1:1242-59); but evidence for a direct projection from other Amy nuclei, in particular the basal nucleus, is still missing. Here, we examined whether HF and amygdala nuclei other than CeA contribute direct monosynaptic projections to VTA. We analyzed the distribution of anterograde labeling produced in VTA with injections of biotin dextran amine and Phaseolus vulgaris leucoagglutinin in distinct architectonic regions in HF and Amy. Within HF, injections in the subiculum (Sub) produced dense anterograde labeling dispersed throughout VTA. Injections in the Ammon horns (CA1-3), dentate gyrus (DG) produced no labeling in VTA; and injections in entorhinal cortex (EC) produced labeling only in cases in which the injection contaminated the basal amygdala. Accordingly, baring CeA, injections in the amygdala produced labeling in VTA only for these injections that involved the magnocellular (Bmc), intermediate (Bi) or parvocellular (Bpc) parts of the basal nucleus, or the primate-specific paralaminar nucleus (PL). A comparison of the spatial distribution of anterogradely labeled fibers in VTA revealed a considerable overlap with only a subtle trend for two distinct labelling patterns; that is, either restricted to the rostral level of VTA, or dispersed throughout the rostrocaudal extent of VTA. While tenuous, the direct projections of Sub and basal Amy to VTA in the macaque monkey could produce direct regulation of dopaminergic release in parallel and/or independently of the classical indirect pathways involving ventral striatum and lateral septum.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Hernandez-Mombiela D{dhernandez}{Department Physiology of Cognitive Processes}; Ubero M{mubero}{Department Physiology of Cognitive Processes}; Insausti R; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Amaral D; Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Poster{ WatanabeLVLKB2015, title = {Behavioral and neural effects of visual masking and optogenetic V1 suppression in mice}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {DP04.05}, abstract = {The necessary condition for sensory information to enter consciousness remains an open question. Studies on humans and non-human primates indicate the need for reverberant neural activity lasting for 10s-100s of milliseconds. Properties of this reverberant activity, especially the involvement of early sensory areas, are heavily debated. Here, we addressed these issues using behavior and causal circuit manipulation in mice. Using visual backward masking, we first tested whether visual perception in mice requires reverberant neural activity. Mice were trained to discriminate between locations (± 45 deg eccentricity) of a briefly presented target (grating, 16 ms duration, 10% contrast). After reaching threshold discriminability (d’ > 2), bilateral masks (plaids, 16 ms, 100% contrast) were introduced at various delays to target onset. Mice performed at chance up to stimulus onset asynchronies (SOAs) of 66.7 ms. Together with the results of rats (Watanabe et al. SfN 2014), the capacity of the mask to render the target invisible beyond the time of target offset indicates the necessity of reverberant activity for rodent visual perception. Next, to investigate whether V1 takes part in the crucial circuitry for perception, we replaced the visual mask with optogenetic suppression of V1. Unlike the visual mask eliciting activity throughout the visual system, optogenetic suppression acts locally and is ideal for testing the necessity of activity in distinct processing stages. We trained mice with ChR2 expression targeted at V1 PV+ inhibitory interneurons in the position discrimination task, in which we replaced the visual mask by bilateral optogenetic suppression of V1 activity. We induced suppression by activation of inhibitory interneurons (1.5 s duration) at various delays. Behavioral performance was at chance when V1 was suppressed before the onset of target evoked activity, but was significantly above chance when suppressed later (> 32 ms). Since only the initial transient V1 response, and not the later sustained V1 activity, is required for perception, V1 seems to function as an initial supplier of visual information to the reverberant loop, but does not play a crucial role in its maintenance. Finally we investigated visual forward masking where a visual mask (16 ms, 100% contrast) precedes the target (16 ms, 10% contrast). Behavioral results showed extended SOA ranges of invisibility (16-150 ms). Interestingly, neural responses to high contrast masks (16 ms duration) resulted in a prolonged neural suppression effect (150 ms) that matched the SOAs of invisibility. The results indicate that forward masking blocks relaying of visual information as early as area V1.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Loewe S{sloewe}{Department Physiology of Cognitive Processes}; Vaiceliunaite A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Katzner S; Busse L} } @Poster{ RamirezVillegasLB2015_2, title = {Diversity of sharp wave-ripples in the CA1 of the macaque hippocampus and their brain wide signatures}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {293.02}, abstract = {Sharp wave-ripple complexes are thought to play a major role in memory reactivation, transfer and consolidation. However, the large-scale cooperative mechanisms associated to these episodes and their relationship to the observed SPW-R electrical signature remains largely unknown. A better understanding of the underlying mechanisms of these interactions requires a finer characterization of the SPW-R phenomenon and its associated brain-wide signatures. To address this question, we hypothesize that SPW-R dynamics vary, reflecting distinct interactions with neocortical and subcortical systems depending on the state of the animal. Specifically, the wide-range network reconfiguration required by this process may bring different electrical signatures of SPW-Rs, thus reflecting different memory-related functional roles. Using concurrent hippocampal local field potentials (LFP) recordings and functional Magnetic Resonance Imaging (fMRI) in anesthetized macaques, we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. After detecting SPW-R episodes based on power increases in the ripple frequency band (80-180 Hz), analysis of peri-event SPW-R complexes reveals four well-differentiated SPW-R subtypes in the CA1 LFP. Event-triggered fMRI maps show that SPW-R subtypes relate to differentiated multi-structure activity (MSA). We found that ripples aligned to the positive peak of their SPWs were associated with significantly higher BOLD up-regulations within the hippocampal formation, and in cortical associative areas (namely, anterior cingulate cortex, retrosplenial area, prefrontal, temporal and parietal cortices), as compared to ripples occurring at the trough of their SPW (p<0.01 Wilcoxon rank-sum test, FDR-corrected with q<0.05). Conversely, detailed analysis of all subcortical domains revealed differentiated BOLD activations in locus coeruleus (LC) and dorsal raphe nucleus (p<0.002, pairwise Wilcoxon rank-sum test, FDR-corrected with q<0.05), suggesting that emergence of different SPW-R signatures may be influenced by state-dependent neuromodulatory inputs of differentiated nature into the hippocampal formation. Altogether, our results suggest that the variability of CA1 SPW-R episodes reflect different levels of activation over cortical and subcortical domains. We hypothesize that these distinct patterns of SPW-R complexes reflect brain-wide cooperative events, possibly involved in different memory-related functions.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Poster{ KleinESHLS2015, title = {Functional identification of primate lateral geniculate nucleus projections to visual cortex using optogenetics and electrical stimulation}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {449.09}, abstract = {Optogenetics and electrical stimulation are routinely used to assess neuronal connectivity. However cell-specific approaches, especially in primates, are still very limited. Here we compare the capacities of optogenetics and electrical stimulation to isolate the specific pathways from the lateral geniculate nucleus (LGN) to primary visual cortex (V1) in the macaque visual system. The organization of LGN into three anatomically separate and neurochemically distinct cell projection systems with virtually no cross-talk provides unique conditions to test for cell-specific targeting by electrical and optogenetic stimulation techniques. For the optogenetics experiments, we injected AAV5-CamKIIα-ChR2-eYFP into the LGN of four macaque monkeys. Histological analysis revealed primarily the predicted laminar expression pattern of the optogenetic construct in CamKIIα-rich LGN konio layers, but also showed some expression in parvalbumin positive magno- and parvo cells. We also observed a retrograde tracing mechanism of the AAV5 virus particles that labeled V1 layer 6 cortico-thalamic feedback neurons and retinal ganglion cells. That expression of the construct also allowed modulation of spiking activity in LGN was confirmed in prior electrophysiology experiments. Neurons expressing ChR2 could be identified reliably based on their short latency (<5ms) spiking responses to direct blue light (473nm) stimulation. Parallel laminar-resolved recordings of the V1 local field potential showed that selective activation of LGN konio layers with optogenetics caused selective electrical current inflow in the supra-granular layers of V1 in agreement with anatomical predictions about the koniocellular projection. Electrical stimulation of LGN konio layers revealed the same supra-granular V1 activation pattern. In contrast, electrical stimulation of LGN parvo layers activated also V1 granular layers in a way that closely resembled visual stimulus driven responses. These findings indicate comparable capacities of both stimulation methods to isolate and identify spatially segregated thalamo-cortical circuit mechanisms of the primate brain.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Shapcott K; Haverkamp S; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Schmid MC} } @Poster{ UberoMartinezHAILE2015, title = {Hippocampal formation and amygdalar projections to the locus coeruleus in the macaque monkey}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {445.18}, abstract = {The locus coeruleus (LC) neuromodulates the limbic system through direct projections to the hippocampal formation (HF) and amygdala (Amy) (Morgane et al. 2005 Prog Neurobiol 75:143-60). HF and Amy could in turn regulate noradrenergic activity necessary for memory processes (McIntyre et al. 2012 Neurosci Biobehav Rev 36:1750-62). Here, we examined whether such regulation could be substantiated by direct monosynaptic projections from HF and Amy to LC. We analyzed the distribution of anterograde labeling produced in LC in macaque monkeys with injections of biotin-dextran amine or Phaseolus vulgaris leucoagglutinin in the entorhinal cortex (EC), Ammon horn (CA1-3), dentate gyrus (DG), and subiculum (Sub), as well as in different nuclei of the amygdala, baring the central nucleus which was previously shown to project to LC (Price & Amaral 1981 J Nsci 1:1242-59). Within HF, injections in Sub resulted in the highest number of labeled terminals in LC, particularly throughout the entire rostrocaudal extent of the lateral portion of the nucleus. Injections placed in EC produced labeling only in cases where Amy was also involved. However, different labeling patterns were obtained in LC after injections in the same amygdala nuclei with contamination of different EC fields. Injections in CA1-3 or DG did not label LC. Within the amygdala, only injections made in the basal magnocellular nucleus (Bmc) and in the paralaminar nucleus (PL) produced labeling in the lateral portion of LC, similar to the labeling produced with injections in Sub. Prior studies showed that both Sub and basal Amy receive projections from LC; the present study suggests that these projections are bidirectional in primates. Notably, whereas prior rodent studies proposed that basolateral amygdala regulates LC indirectly through CeA (Bouret et al. 2003 J Neurosci 23:3491-7), the present tracing data indicates that the primate Bmc can directly regulate LC. Although it is unclear whether the converging hippocampo- and amygdalo-coerulean projections identified here are functionally related, prior evidence from animal and human studies suggests that both could have a role in memory. The subicular projection to LC offers an ideal substrate for the hippocampal regulation of forebrain noradrenergic activity necessary for memory retrieval (Eldridge et al. 2005 J Nsci 25:3280-6; Sara 2010 Front Behav Nsci 4: 1-5). Accordingly, the direct projections from Bmc to LC could contribute in restoring central arousal states that promote emotional memory consolidation (Sterpenich et al. 2006 J Neursci 26:7416-23). Supported by the Max Planck Society and the Center for Integrative Neuroscience.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Ubero Martinez M{mubero}{Department Physiology of Cognitive Processes}; Hernandez Mombiela D{dhernandez}{Department Physiology of Cognitive Processes}; Amaral DG; Insausti R; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}} } @Poster{ CottonEFBBST2015, title = {Scaling of information in large sensory neuronal populations}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {331.01}, abstract = {Individual neurons are noisy. Therefore, it seems necessary to pool the activity of many neurons to obtain an accurate representation of the environment. However, it is widely believed that shared noise in the activity of nearby neurons renders such pooling ineffective, limiting the accuracy of the population code and, ultimately, behavior. However, these predictions are based on extrapolating models fit to small numbers of neurons and have not been tested experimentally. Using a novel high-speed 3D-microscope we densely recorded from hundreds of neurons in the mouse visual cortex and measured the amount of information encoded. We find that the information in this sensory population increases approximately linearly with population size and does not saturate, even for several hundred neurons. This information growth is facilitated by a correlation structure that is not aligned with the tuning, making it less harmful than would be predicted from pairwise measurements. Accordingly, a decoder that accounts for the correlation structure outperforms one that does not. Our findings suggest that sensory representations may be more accurate than previously thought and therefore that psychophysical limitations may arise from downstream neural processes rather than limitations in the sensory encoding.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Cotton JR; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Froudarakis E; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Saggau P; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ LoeweWLK2015, title = {Temporal predictability of visual target onset by audition leads to decrease in evoked neural activity in mouse V1}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {415.16}, abstract = {The influential theoretical framework of predictive coding states that low-level sensory areas subtract top-down predictions from bottom-up signals to calculate prediction errors, which are used for perceptual inference. So far, only few single-unit studies have directly tested predictions of this model. Here, we measured responses of single neurons in mouse primary visual cortex (V1) and asked how temporal predictability affects the processing of a visual stimulus. Head-fixed mice were free to run or sit on a spherical treadmill in front of a gray screen, on which we flashed a visual stimulus (black square, 100 ms duration) in the absence of any task. To manipulate stimulus predictability, we presented an auditory cue (5 KHz pure tone) shortly before the stimulus appeared. In a standard condition (80% of the trials), the interval between cue and stimulus (ISI) was fixed at 500 ms. In 20% of the trials, ISIs deviated from this value (± 100, ±200 ms) to test the precision of prediction. In an unpredictable condition, the auditory cue was omitted. We recorded from V1 neurons simultaneously across cortical layers and found that stimulus predictability robustly decreased V1 responses. This decrease was seen in both the initial transient and later components of neural activity. The standard ISI condition led to the strongest decrease, resulting in a “U-shaped” curve of evoked activity versus ISIs. In control experiments conducted under anesthesia the difference in evoked activity between predictable and unpredictable conditions disappeared. Furthermore, we replaced the auditory cue by a distant visual cue, which, when presented by itself, did not affect the firing rates of the recorded neurons. Here, predictable stimuli still decreased evoked responses, ruling out low-level, multi-sensory interactions. To investigate the local neural circuitry, we expressed Archaerhodopsin (Arch) in V1 parvalbumin-positive inhibitory interneurons. We suppressed interneuron activity by shining yellow light (590nm, 500ms duration) at the time of stimulus onset. Our preliminary data show a reversed effect, with evoked activity being larger for predictable stimuli and suggest that local inhibitory neurons might convert the effect of the external modulatory signal from facilitation to suppression. One interesting observation is that we found no modulation of responses in ‘cue only’ conditions. This observation is inconsistent with the predictive coding model, which predicts response suppression at the time when the omitted stimulus would have appeared. Overall, these results point to an external modulatory signal that is broadly aligned with the timing of the visual stimulus.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Loewe S{sloewe}{Department Physiology of Cognitive Processes}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Busse L; Katzner S} } @Poster{ CadwellJBFYFET2015, title = {Sibling rivalry and cooperation among excitatory neurons in the neocortex}, year = {2015}, month = {10}, day = {17}, volume = {45}, number = {59.13}, abstract = {The mammalian neocortex carries out complex mental processes such as cognition, perception and decision-making through the interactions of billions of neurons connected by trillions of synapses. We are just beginning to understand how networks of neurons become wired together during development to give rise to cortical computations. Recent studies have shown that excitatory cortical neurons with a shared ontogenetic lineage form vertical columns spanning multiple cortical layers and that these “sister cells” are more likely to be synaptically connected to each other than to nearby, unrelated neurons. However, the precise wiring diagram between sister cells is unknown. Here we show that connectivity between sister cells depends on the laminar position of the pre- and post-synaptic neurons. In contrast to previous studies, we find that although sister cells residing in different cortical layers are more likely to be connected, sister cells located within the same layer are less likely to be connected to each other compared to distance-matched controls. Avoidance of cells that receive common input may be a fundamental principle of information processing within a cortical column. Our findings challenge the prevailing hypothesis that shared developmental lineage is always associated with an increase in connectivity, and suggest that both attraction and repulsion play an important role in shaping cortical circuits.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Cadwell CR; Jiang X; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Fahey PG; Yatsenko D; Froudarakis E; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ YangLE2015_2, title = {A gating role of mediodorsal thalamus for ripple-associated hippocampal-cortical information transfer}, year = {2015}, month = {10}, day = {10}, number = {NC7}, web_url = {http://ffrm2015.com/}, event_name = {Federation of European Neuroscience Society Featured Regional Meeting (FFRM 2015)}, event_place = {Thessaloniki, Greece}, state = {published}, author = {Yang M{myang}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ Antoniou2015, title = {Perceptual modulation of pupillary reflex in macaque monkeys}, year = {2015}, month = {10}, day = {9}, number = {CO64}, web_url = {http://ffrm2015.com/}, event_name = {Federation of European Neuroscience Society Featured Regional Meeting (FFRM 2015)}, event_place = {Thessaloniki, Greece}, state = {published}, author = {Antoniou R{rantoniou}{Department Physiology of Cognitive Processes}; Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}} } @Poster{ KapoorBLP2015_2, title = {Single unit responses in the lateral prefrontal cortex reflect trial phase dependent modulation}, year = {2015}, month = {9}, day = {19}, pages = {107}, abstract = {Neuronal responses in the lateral prefrontal cortex (LPFC) of the macaques engaged in various behavioral paradigms exhibit a large diversity of patterns underlying multiple cognitive functions ranging from working memory to serial order and even visual awareness. We have previously examined single unit activity in the LPFC with an ambiguous visual stimulation paradigm called binocular flash suppression in order to understand its role in conscious visual perception. We observed feature selective visual responses among 11 percent of the recorded neurons. The present study aimed at elucidating any other dominant pattern among the remaining majority of single units. We therefore clustered the peristimulus time histograms of remaining neurons with a non-negative matrix factorization procedure. This led to the identification of five major response patterns whose peak amplitude was distributed chronologically across different phases of a trial. Moreover, majority of single units displaying activity similar to a given response pattern did not exhibit significant difference in their responses during the monocular and binocular conditions of the task, thus suggesting that their firing was unaffected by ambiguous visual input. We therefore report the existence of temporally contingent trial phase dependent spiking activity among single neurons during a passive fixation paradigm which does not require any explicit mnemonic demands or a behavioral report associated motor action. In addition, this trial phase preference activity remains unchanged across monocular or binocular conditions thus supporting the existence of a neural process, unaffected by incongruent visual stimulation and most likely related to tracking the progress of a trial.}, web_url = {https://cnpsymposium2015.files.wordpress.com/2015/02/abstractbookcnsymp152015-09-16-compressed.pdf}, event_name = {4th Champalimaud Neuroscience Symposium: Perspectives on Social Behavior}, event_place = {Lisboa, Portugal}, state = {published}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Poster{ BassettoSEM2015, title = {A statistical characterization of neural population responses in V1}, year = {2015}, month = {9}, day = {16}, pages = {146-147}, abstract = {Population activity in primary visual cortex exhibits substantial variability that is correlated on multiple time scales and across neurons [1]. A quantitative account of how visual information is encoded in population of neurons in primary visual cortex therefore requires an accurate characterization of this variability. Our goal is provide a statistical model for capturing the statistical structure of this variability and its dependence on external stimuli, with particular focus on temporal correlations both on short (withintrial) and long (across-trial) time-scales [2]. We address this question using neural population recordings from primary visual cortex in response to drifting gratings [3], using the framework of generalized linear models (GLMs). To model stimulus-driven responses, we take a non-parametric approach and employ Gaussian-process priors to model the smoothness of response-profiles across time and different stimulus orientations, and low-rank constraints to facilitate inference from limited data. We find that the parameters which control the prior smoothness are consistent across neurons within each recording session, but differ markedly across recordings. For most neurons, the time-varying response across all stimulus orientations can be well captured using a lowrank decomposition with k = 4 dimensions. To capture slow modulations in firing rates, we include covariates in the GLM which are constrained to vary smoothly across trials, and find that including these terms leads to significant improvements in goodness-of-fit. Finally, we use latent dynamical systems [3] with point-process observation models [4] to capture variations and co-variations in firing rates on fast time-scales. While we focus our analysis on modelling neural population responses in V1, our approach provides a general formalism for obtaining an accurate quantitative model of response variability in neural populations.}, web_url = {http://www.nncn.de/de/bernstein-conference/2015/program}, event_name = {Bernstein Conference 2015}, event_place = {Heidelberg, Germany}, state = {published}, DOI = {10.12751/nncn.bc2015.0139}, author = {Bassetto G{gbassetto}; Sandhaeger F{fsandhaeger}; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Macke JH{jakob}} } @Poster{ EckerDTB2015, title = {On the structure of population activity under fluctuations in attentional state}, year = {2015}, month = {9}, day = {16}, pages = {185}, abstract = {Attention is commonly thought to improve behavioral performance by increasing response gain and suppressing shared variability in neuronal populations. However, both the focus and the strength of attention are likely to vary from one experimental trial to the next, thereby inducing response variability unknown to the experimenter. Here we study analytically how fluctuations in attentional state affect the structure of population responses in a simple model of spatial and feature attention. In our model, attention acts on the neural response exclusively by modulating each neuron’s gain. Neurons are conditionally independent given the stimulus and the attentional gain, and correlated activity arises only from trial-to-trial fluctuations of the attentional state, which are unknown to the experimenter. We find that this simple model can readily explain many aspects of neural response modulation under attention, such as increased response gain, reduced individual and shared variability, increased correlations with firing rates, limited range correlations, and differential correlations. We therefore suggest that attention may act primarily by increasing response gain of individual neurons without affecting their correlation structure. The experimentally observed reduction in correlations may instead result from reduced variability of the attentional gain when a stimulus is attended. Moreover, we show that attentional gain fluctuations – even if unknown to a downstream readout – do not impair the readout accuracy despite inducing limited-range correlations.}, web_url = {http://www.nncn.de/de/bernstein-conference/2015/program}, event_name = {Bernstein Conference 2015}, event_place = {Heidelberg, Germany}, state = {published}, DOI = {10.12751/nncn.bc2015.0179}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Denfield GH; Tolias AS{atolias}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Poster{ GatysEB2015_2, title = {Texture synthesis and the controlled generation of natural stimuli using convolutional neural networks}, year = {2015}, month = {9}, day = {16}, pages = {219}, abstract = {It is a long standing question how biological systems transform visual inputs to robustly infer high level visual information. Research in the last decades has established that much of the underlying computations take place in a hierarchical fashion along the ventral visual pathway. However, the exact processing stages along this hierarchy are difficult to characterise. Here we present a method to generate stimuli that will allow a principled description of the processing stages along the ventral stream. We introduce a new parametric texture model based on the powerful feature spaces of convolutional neural networks optimised for object recognition. We show that constraining spatial summary statistic on feature maps suffices to synthesise high quality natural textures. Moreover we establish that our texture representations continuously disentangle high level visual information and demonstrate that the hierarchical parameterisation of the texture model naturally enables us to generate novel types of stimuli for systematically probing mid-level vision.}, web_url = {http://www.nncn.de/de/bernstein-conference/2015/program}, event_name = {Bernstein Conference 2015}, event_place = {Heidelberg, Germany}, state = {published}, DOI = {10.12751/nncn.bc2015.0220}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Poster{ YangLE2015, title = {A Gating Role of Mediodorsal Thalamus for Ripple-Associated Hippocampal-Cortical Information Transfer}, year = {2015}, month = {9}, day = {14}, pages = {56}, abstract = {Hippocampal sharp wave-ripple complexes (SPW-Rs) have been postulated to be involved in hippocampal-cortical information transfer underlying declarative memory consolidation. Our recent neural event-triggered fMRI study showed that occurrence of SPW-Rs was associated with activity suppression in a number of subcortical regions, including thalamus. Description of such specific activation/deactivation pattern of the whole-brain activity associated with SPW-Rs extended the predominant view on the SPW-Rs as indicators of hippocampal-cortical functional connectivity, and SPW-R has been suggested to indicate a global network state supporting declarative memory. The midline thalamic nuclei have been implicated to play a role for learning and memory. However, it remains unexplored how thalamic neural activity contributes to hippocampal-cortical dialogue. The medial dorsal nucleus of thalamus (MD) receives input from the entorhinal cortex and is reciprocally connected with the prefrontal cortex (PFC). The MD anatomical connectivity combined with the results of MD lesion studies suggested a critical role of MD for associative and mnemonic functions. In the present study, we characterized MD neural activity associated with hippocampal SPW-Rs. We performed simultaneous extracellular electrophysiological recordings in MD and hippocampus in urethane-anesthetized and behaving rats. We then examined the firing rate modulation of the MD single units (n = 151) around SPW-Rs. Nearly half of MD single units (46.4%) showed the firing rate inhibition at times of SPW-R occurrence. Moreover, about 37% (26 of 70) of this MD population decreased their firing at least ~1s prior the SPW-R onset. Similar dynamics was observed for MD multiunit activity and gamma-power during rat spontaneous behavior. Our results suggest that MD inhibition plays a permissive role for initiating SPW-R-associated information transfer underlying ‘off-line’ memory consolidation.}, web_url = {http://ebbsebpsverona2015jointmeeting.info/wp-content/uploads/2015/09/abstracts-poster-verona2015.pdf}, event_name = {European Brain Behaviour Society (EBBS) & European Behavioural Pharmacology Society (EBPS) Joint Meeting 2015}, event_place = {Verona, Italy}, state = {published}, author = {Yang M{myang}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ RamirezVillegasLB2015, title = {Sharp wave-ripple complexes in a reduced model of the hippocampal CA3-CA1 network of the macaque monkey}, journal = {BMC Neuroscience}, year = {2015}, month = {7}, day = {19}, volume = {16}, number = {Supplement 1}, pages = {24}, abstract = {Sharp wave-ripple complexes observed in the hippocampal CA1 local field potential (LFP) are thought to play a major role in memory reactivation, transfer and consolidation. SPW-Rs are known to result from a complex interplay between local and upstream hippocampal ensembles. However, the key mechanisms that underlie these events remain partly unknown. In this work, we introduce a reduced, but realistic multi-compartmental model of the macaque monkey´s hippocampal CA3-CA1 network. The model consists of two semi-linear layers, each consisting of two-compartmental pyramidal neurons and one-compartmental perisomatic-targeting basket cells. Connections in the network were modeled as AMPA synapses, based on physiological and anatomical data. Notably, while auto-association fibers were prevalent in CA3, CA1 connectivity -inspired by recent findings- implemented a "feedback and reciprocal inhibition", dominated by recurrent inhibition and pyramidal cells-interneurons synapses. SPW-R episodes emerge spontaneously in the CA1 subfield LFP (which is assumed proportional to transmembrane currents across all compartments and medium resistivity): Episodes of short-lived high-frequency oscillations (ripples, 80-180 Hz) on top of a massive dendritic depolarization (< 20 Hz) with visual and quantitative characteristics observed experimentally [1]. Concomitantly, the CA3 subfield LFP presents episodes of quasi-synchronous neuronal bursting in the form of gamma episodes (25-75 Hz). The model reveals a lower bound for the minimal network that may generate SPW-R activity, and predicts a large number of features of in vivo hippocampal recordings in macaque monkeys [1]. Spike-LFP coherence analysis in CA1 displays reliable synchrony of spiking activity in the ripple LFP frequency band, suggesting that modeled SPW-R episodes reflect a genuine network oscillatory regime. Interestingly, interneuronal firing shows coherence increases concomitant with the beginning and the end of the SPW-R event, together with increases over gamma frequencies. The model suggests that activity of both pyramidal neurons and interneurons is critical for the local genesis and dynamics of physiological SPW-R activity. Unlike other models, we found that it is interneuronal silence, not interneuronal firing that triggers these fast oscillatory events, in line with the fact that unbalanced excitability of selected pyramidal cells marks the beginning of single network episodes. Interneuronal silence quickly increases population firing of pyramidal cells. The interneuronal population activity increases with some latency due to the unbalanced excitatory drive, becoming pivotal to pyramidal cell activity, and further pacing pyramidal cells due to interneuronal fast kinetic properties. Our modeled data suggests that this effect is possibly mediated by a silencing-and-rebound-excitation mechanism, maintaining the frequency of the field oscillation bounded to the ripple range. The reduced model suggests a simple mechanism for the occurrence of SPW-Rs, in light of recent experimental evidence. We provide new insights into the dynamics of the hippocampal CA3-CA1 network during ripples, and the relation between neuronal circuits' activity at meso- and microscopic scales. Finally, our model exhibits characteristic cell type-specific activity that might be critical for the emergence of physiological SPW-R activity and therefore, for the formation of hippocampus-dependent memory representations.}, web_url = {http://www.biomedcentral.com/1471-2202/16/S1/P15}, event_name = {Twenty-Fourth Annual Computational Neuroscience Meeting (CNS*2015)}, event_place = {Praha, Czech Republic}, state = {published}, DOI = {10.1186/1471-2202-16-S1-P15}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Poster{ KapoorBLP2015, title = {Activity Patterns in the Lateral Prefrontal Cortex Reflect Trial Phase Dependent Response Modulations}, year = {2015}, month = {7}, day = {10}, volume = {9}, number = {PO1028}, web_url = {http://ibro2015.org/?page_id=434}, event_name = {9th IBRO World Congress on Neuroscience (IBRO 2015)}, event_place = {Rio de Janeiro, Brazil}, state = {published}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Poster{ OrtizAABLLK2015, title = {Dynamic Functional Connectivity Reflects Complex Audiovisual Scenes Changes during Cognitive Processing}, year = {2015}, month = {7}, day = {10}, volume = {9}, number = {PO1002}, web_url = {http://ibro2015.org/?page_id=434}, event_name = {9th IBRO World Congress on Neuroscience (IBRO 2015)}, event_place = {Rio de Janeiro, Brazil}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}; Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Azevedo LC{lazevedo}{Department Physiology of Cognitive Processes}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Lohmann G{lohmann}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ AzevedoOABLLK2015, title = {Eingenvector Centrality Mapping during Natural Viewing in the Macaque Brain}, year = {2015}, month = {7}, day = {10}, volume = {9}, number = {PO1078}, web_url = {http://ibro2015.org/?page_id=434}, event_name = {9th IBRO World Congress on Neuroscience (IBRO 2015)}, event_place = {Rio de Janeiro, Brazil}, state = {published}, author = {Azevedo F{fazevedo}{Department Physiology of Cognitive Processes}; Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}; Azevedo LC{lazevedo}{Department Physiology of Cognitive Processes}; Balla D{ballad}{Department Physiology of Cognitive Processes}; Lohmann G{lohmann}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ BahmaniLLK2015, title = {Spike-Field Coherence Reflects Perceptual State in Monkey Primary Visual Cortex}, year = {2015}, month = {7}, day = {8}, volume = {9}, number = {PO221}, web_url = {http://ibro2015.org/?page_id=434}, event_name = {9th IBRO World Congress on Neuroscience (IBRO 2015)}, event_place = {Rio de Janeiro, Brazil}, state = {published}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Lakshminarasimhan KJ; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ Klein2015, title = {Functional identification of primate lateral geniculate nucleus projections to visual cortex using optogenetics and electrical stimulation}, year = {2015}, month = {6}, day = {22}, pages = {14}, abstract = {The lateral geniculate nucleus (LGN) of macaque monkeys relays signals from the retina to the primary visual cortex (V1) via three anatomically segregated projection streams. Axons of the magno- and parvo-cellular system terminated mainly in the granular layer 4 of V1 while konio cells project to the superficial layers 1,2 and 3 of V1. Further among all LGN cells konio cells are the only ones that express the calcium binding protein CamKIIα. Because of these clear anatomical and biochemical distinctions the LGN-V1 circuit is an ideal candidate to test circuit mapping approaches. Here we used electrical microstimulation and konio-cell specific optogenetics to functionally test the feedforward connectivity between the LGN and V1. Selective activation of the LGN konio layers with either optogenetics or electrical mircrostimulation caused an electrical current inflow in the V1 supra-granular layers following the anatomical predictions of the konio pathway. Microstimulation of LGN parvo layers caused an initial sink in the granular layer 4 of V1 and an additional sink in the supra-granular layers, closely resembling the visually evoked pattern of cortical activity. Histological analysis confirmed the predominant expression of the optogenetic construct in cells of the konio cellular system but also an unexpected retrograde traveling mechanism that resulted in labelling of V1 layer 6 cortico-thalamic cells and retinal ganglion cells. Taken together, these findings indicate comparable capacities of both stimulation methods to isolate and identify thalamo-cortical circuit mechanisms of the primate brain.}, web_url = {http://www.esi-frankfurt.de/fileadmin/user_upload/ESI-SyNC-2015_fullprogram.pdf}, event_name = {ESI-Systems Neuroscience Conference: Brain Codes (ESI-SyNC 2015)}, event_place = {Frankfurt a.M. Germany}, state = {published}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}} } @Poster{ MarreirosEL2015, title = {State-dependent Processing in the Brain}, year = {2015}, month = {6}, day = {18}, volume = {21}, number = {3017}, abstract = {Introduction: The level of norepinephrine (NE) in the brain modulates a variety of cognitive processes such as attention, perception, learning and memory. Accordingly, stimulation of the Locus Coeruleus (LC), the major source of NE in the forebrain, can change spontaneous and task-related neuronal discharge in a large number of LC projection-targets. The LC phasic response to a salient stimulus is thought to beneficially contribute to attention, working memory, or behavioral flexibility by affecting the prefrontal NE neurotransmission [1-4]. Recently, some advances have been done on the study of the effects of phasic NE release on the responsiveness of mPFC cortical areas; although to have a more complete understanding of the widespread projections of LC we will need a multimodal approach. Here we set out to investigate the effects of LC phasic discharge on ongoing and sensory-evoked cortical activity, by combining LC direct electrical stimulation (LC-DES) [5] with multisite extracellular recordings and whole-brain fMRI in rats under anesthesia. The combination of these methods allows the acquirement of a richer dataset which carries unique insight into the mechanism of large scale norepinephrine modulation. Methods: We have begun to study the effects of ongoing cortical state in prefrontal (mPFC) and somatosensory (S1) cortex during NE manipulation. Specifically, in a series of experiments, we stimulate the LC (directly through DES or indirectly through foot shock, FS) while recording its responses in the mPFC and S1 cortices. The activity of the NE system is expected to strongly contribute to the modulation of the cortical state [6]. Cortical recordings are used to determine both the network state prior to stimulation and the neurophysiological responses to FS or LC-DES. The fMRI combined with electrophysiological recordings and microstimulation capitalizes on previous approaches conducted in the lab [7] and is continuously optimized for the specific requirements of this project. Results: In order to characterize the different cortical states induced by the anesthesia level and classify its maps accordingly, we computed a cortical synchronization index (SI) proxy [8] in the 5-sec interval preceding stimulation. In Fig.1 it is plotted the distributions of a lower (a) and a higher (b) synchronization index for the same FS condition. Subsequently, we looked at the associated FS response dependency on cortical synchronization. Fig.2 shows the Z-score of the BOLD time course difference between the SI distributions of Fig.1 (a) and (b). Furthermore, fMRI maps for LC-DES have shown to produce an interesting dichotomy between BOLD responses of cortical and subcortical structures (belonging to metencephalon, mesencephalon and diencephalon cortices). Fig.3 shows the fraction of positively and negatively activated regions of interest (ROIs) for the same LC-DES condition averaged over sessions.}, web_url = {http://www.humanbrainmapping.org/i4a/pages/index.cfm?pageID=3625}, event_name = {21st Annual Meeting of the Organization for Human Brain Mapping (OHBM 2015)}, event_place = {Honolulu, HI, USA}, state = {published}, author = {Marreiros A{amarreiros}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ SchefflerEHMY2015, title = {Functional imaging at 14.1T using high-resolution pass band bSSFP}, year = {2015}, month = {6}, day = {3}, volume = {23}, number = {2038}, abstract = {Sub-millimeter fMRI at very high fields with EPI is challenging due to the rapid signal decay and B0-related distortions. Balanced SSFP offers the possibility of high-resolution (100 um) acquisitions without spatial distortions and significantly higher temporal resolution compared to FLASH. Observed signal changes largely depend on T2 rather than T2* indicating a higher spatial selectivity compared to gradient echo-based methods.}, web_url = {http://www.ismrm.org/15/program_files/WedTP03.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Ehses P{ehses}{Department High-Field Magnetic Resonance}; He Y{yhe}{Department High-Field Magnetic Resonance}; Merkle H{hellmut}; Yu X{xyu}{Department High-Field Magnetic Resonance}} } @Poster{ WangHTMY2015, title = {Identify the “single unit” of neurovascular coupling by single-vessel fMRI and optogenetics}, year = {2015}, month = {6}, day = {3}, volume = {23}, number = {2041}, abstract = {It has been demonstrated that the hemodynamic signal from individual venules can be detected directly with fMRI. Here, the hemodynamic signal from BOLD and CBV fMRI was measured at high temporal(100ms) and spatial resolution(150x150µm) in layer 4/5 of the rat forepaw S1with fast gradient-echo MRI. Distinctly different voxels were activated in BOLD vs CBV fMRI. In contrast to the BOLD activated voxels primarily located at the penetrating venules, CBV activated voxels were primarily located at penetrating arterioles. This result makes it possible to directly image the CBV and BOLD response at the single-vessel level to understand neurovascular coupling.}, web_url = {http://www.ismrm.org/15/program_files/WedTP03.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Wang M{mwang}; He Y{yhe}; Tang Y{ytang}; Merkle H{hellmut}; Yu X{xyu}} } @Poster{ GarelloVGLAT2015, title = {Improved liposomes-based Ca(II) responsive MRI contrast agents}, year = {2015}, month = {6}, day = {3}, volume = {23}, number = {1899}, abstract = {This contribution reports a methodology that enables the preparation of paramagnetic liposomes loaded with an amphiphilic ligand capable to coordinate selectively and sequentially Gd(III) and Ca(II) ions, respectively. The presence of Gd(III) imparts the ability to generate MRI contrast, which is remarkably boosted (ca. 400%) by the coordination of Ca(II), thus improving the calcium responsiveness of the nanoprobes with respect similar agents previously investigated.}, web_url = {http://www.ismrm.org/15/program_files/WedTP01.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Garello F; Vibhute S{svibhute}{Department Physiology of Cognitive Processes}; G\"und\"uz S{sgunduz}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Terreno E} } @Poster{ WangHTBQY2015, title = {Map the light-driven fMRI signal in combination with in vivo recording}, year = {2015}, month = {6}, day = {3}, volume = {23}, number = {2117}, abstract = {It remains ambiguous how the direct fiber optic insertion affects the local fMRI signal by optical stimulation. The fiber optic was inserted to target the deep layer cortex expressing Channelrhodopsin 2(ChR2). Robust fMRI signal was detected in the cortical regions close to the fiber tip with varied light pulse parameters on frequency, pulse duration and power level. The light evoked local field potential was also recorded by electrodes inserted into the cortex expressing ChR2. This work provides us a robust light-driven fMRI platform in combination with in vivo recording, which will facilitate the study to decipher cellular contribution to fMRI signal from the local neurovascular network.}, web_url = {http://www.ismrm.org/15/program_files/WedTP03.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Wang M{mwang}; He Y{yhe}; Tang Y{ytang}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Qian C; Yu X{xyu}} } @Poster{ BallaPSENSMOMMBELS2015, title = {500 ms temporal and 750 μm spatial inplane resolution for whole-brain fMRI applications in the macaque at 7T}, year = {2015}, month = {6}, day = {2}, volume = {23}, number = {3910}, abstract = {We developed fast MRI methods facilitating concurrent electrophysiological recordings and fMRI with high spatio-temporal resolution (500ms / 750µm) and full brain coverage in macaques. The significant improvements in MR signal sampling efficiency without and with the use of parallel imaging are demonstrated by presenting activation maps and time-courses of fMRI experiments using a simple visual stimulation paradigm.}, file_url = {fileadmin/user_upload/files/publications/2015/ISMRM-2015-Balla.pdf}, web_url = {http://www.ismrm.org/15/program_files/TueEPS04.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {accepted}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Ehses P{ehses}{Department High-Field Magnetic Resonance}; Nauerth A{arno}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Munk MH{munk}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ ShajanBSEMLPS2015, title = {A 7T transmit and receive array combination for simultaneous investigation of electrophysiology and fMRI in non-human primates}, year = {2015}, month = {6}, day = {1}, volume = {23}, number = {3182}, abstract = {Simultaneous investigation of electrophysiology and fMRI in non-human primates presents several challenges on RF coil design. Transmit coil structure should allow access for electrodes from different orientations to allow recordings from different brain regions. Receive arrays must be designed around head posts fixed on the animal head, leading to non-optimum coil orientations in the helmet. In cases with more than one head posts, the receive array must be on two separable halves of the helmet. We developed an RF coil arrangement that optimizes the SNR and provides access for recordings from different regions of the brain.}, web_url = {http://www.ismrm.org/15/program_files/MonEPS03.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Shajan G{shajang}{Department High-Field Magnetic Resonance}; Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Ehses P{ehses}{Department High-Field Magnetic Resonance}; Merkle H{hellmut}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ GarelloVGMLA2015, title = {Improved liposomes-based Ca(II) responsive MRI contrast agents}, year = {2015}, month = {3}, day = {20}, volume = {10}, number = {122}, abstract = {Introduction Calcium responsive contrast agents could be considered of great interest in MRI as they could assess pathophysiological and biological processes in vivo at the cellular and molecular levels, with a remarkable spatial and temporal resolution.In this work liposomes carrying a Ca(II) sensitive Gd(III) complex have been prepared to improve both the overall sensitivity in the MRI detection of the probe and the Ca(II) responsiveness.The structure of the complex consisted of two coordination cages: one (macrocyclic, DO3A-like) selective for Gd(III), and the other (linear, EGTA-like) selective for Ca(II) linked to two C18 aliphatic chains (Fig.1). Similar ligands have been already demonstrated to act as Ca(II) sensors under the form of monomer, dimer, and dendrimer.1 Methods Liposomes formulated with DPPC, DSPE-PEG2000, and the amphiphilic ligand I (85:5:10) were prepared by the film hydration method followed by sequential extrusion.Size and polydispersion index (PDI) of the nanovesicles were measured by Dynamic Light Scattering.Titration with Gd(III) was performed and NMRD profiles,reporting the longitudinal relaxivity as a function of the magnetic field strength in the range 0.01-70 MHz, were acquired. Results The hydrodynamic diameter of the liposomes was 140±8 nm with a PDI value around 0.1. Upon titrating liposomes with Gd(III), the relaxivity showed a non linear behavior.Three regions can be detected corresponding to the binding of the metal to: A) the DO3A-like cage, B) the EGTA-like cage, and C) the phosphatidyl heads exposed on the liposomes surface.This finding has been confirmed by performing the titration on liposomes lacking ligand I. To remove Gd(III) bound to sites B and C, a controlled excess of EDTA was added.The relaxivity of the Gd-I-liposomes, measured after exhaustive dialysis,was around 7.0 s-1mMGd-1, thus indicating that no water molecules are bound to the paramagnetic center. However, the NMRD profile of such a species shows a relaxivity hump consistent with relaxation contributions from outer- and second-sphere water protons (Fig.2). Upon addition of equimolar amount of Ca(II), a five-fold increase in relaxivity was observed.This unprecedented large enhancement reflected the change in the hydration state of Gd(III) (from 0 to 1) that occurs when one donor atom of the EGTA-like cage detaches from Gd(III) and moves to coordinate Ca(II). Moreover,the binding of Ca(II) rigidifies the overall structure,causing a further increase in relaxivity. Conclusions The herein presented results demonstrate that the incorporation of Ca(II) responsive Gd(III) complexes into liposomes can represent a valuable option to improve the overall performance of this class of smart MRI probes.}, web_url = {http://www.e-smi.eu/index.php?id=emim-2015-tubingen}, event_name = {10th Annual Meeting of the European Society for Molecular Imaging (EMIM 2015)}, event_place = {Tübingen, Germany}, state = {published}, author = {Garello F; Vibhute S{svibhute}{Department Physiology of Cognitive Processes}; G\"und\"uz S{sgunduz}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Poster{ WangHTBY2015, title = {Light-driven fMRI and Electrophysiological Responses in Rat Brain}, year = {2015}, month = {3}, day = {19}, volume = {10}, number = {151}, abstract = {Introduction Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is widely used as a measure of neuronal activity. However, the neural basis of BOLD signal is still elusive[1]. In this work, we established a robust light-driven fMRI platform mediated by channelrhodopsin-2 (ChR2). Meanwhile, we performed the in vivo recording to characterize the light-evoked local field potential from the activated cortex. This platform will allow us to target specific cell types by optical stimulation, and directly study the coupled fMRI signal from the local cerebrovasculature[2] . Methods All images were acquired with a 14.1 T/26cm horizontal bore magnet (Magnex), interfaced to an AVANCE III console (Bruker) and equipped with a 12 cm gradient set, capable of providing 100 G/cm with a rise time of 150 us (Resonance Research). A transreceiver surface coil with 10 mm diameter was used to acquire fMRI images. ChR2 was expressed by AAV5 virus in the barrel cortex with CaMKII promoter for optical stimulation. Fiber optic (400um) was inserted into the deep layer cortex for optical stimulation. The optical pulse was modulated with frequency from 1 to 10Hz. The pulse duration was tested from 1ms to 50ms. And the light power was set from 0.05mw, 0.25mw, 1mw and 1.8mw, which will not lead to the heating-induced pseudo fMRI signal. The block design was set with light on for 5s, 15s and 30s. Light-driven data were acquired from 2 rats. Local field potential was recorded by the ERS module from Biopac. Animal surgical procedures were described previously [3]. The light pulse was delivered through the 470nm laser (2Hz, 6s duration, pulse duration=45ms, 15 epoch). AFNI software was used to perform the linear regression analysis to acquire functional maps. Results Fig 1 shows the fiber optic insertion into the deep layer cortex, where the ChR2 was expressed by AAV viral vectors. The fiber optic trace was also visible in the brain slice by immunostaining. The light-driven fMRI signal was detected in the barrel cortex close to the fiber tips, where the time course from the activated cortical ROI was shown with different duration of optical stimulation (Fig 1B). Fig 2. The time course of the light-driven fMRI response with different frequency, pulse duration and power level was represented. Fig 3 demonstrated the local field potential recorded in the FP-S1 by optical stimulation. Conclusions After optical stimulation through optical fiber, it shows robust fMRI and neural response in the cortex close to the optical fiber where expressing ChR2. This work provides us a reliable platform to study the neurovascular coupling mechanism of BOLD-fMRI signal.}, web_url = {http://www.e-smi.eu/index.php?id=emim-2015-tubingen}, event_name = {10th Annual Meeting of the European Society for Molecular Imaging (EMIM 2015)}, event_place = {Tübingen, Germany}, state = {published}, author = {Wang M{mwang}; He Y{yhe}; Tang Y{ytang}; Balla D{ballad}{Department Physiology of Cognitive Processes}; Yu X{xyu}} } @Poster{ RoldanSMSY2015, title = {Magnetic field-induced otolith fusion of the zebrafish larvae}, year = {2015}, month = {3}, day = {19}, volume = {10}, number = {121}, abstract = {Introduction The effect of the high magnetic field (MF) on biological processes can provide us a unique strategy to search for biological sources of MR contrast. Here we characterized the potential interaction of a high MF with inner ear formation in the zebrafish larvae. Otolith fusion in the larvae ear constitutes a good example of MF interference with biological processes. The mechanistic analysis of otolith fusion may lead us to certain biological targets sensing MF. Methods Zebrafish larvae were transferred to the bore of a 14T magnet for exposure times ranging from 3 to 62h in Petri dishes containing either Embryonic medium 3 (E3), agarose or E3 + Tricaine-S (fish anesthetic). After exposure, optical and confocal microscopes were used for observation of the inner ear. Ethovision (video tracking software) helped for balance assessment. To check for MF dependent effects, dishes containing the larvae were placed at different distances from the 14T magnet, being influenced by consequent different MF intensities. Results Wild-type larvae exhibit two otoliths (CaCO3 crystals that transmit acceleration forces and sound vibrations) in each ear (Fig.1A). Larvae exposed to a 14T MF in E3 were characterized by fused otoliths (Fig.1B). This anatomical observation was accompanied by aberrant swimming behavior. MF strength dependency was confirmed with a higher prevalence of altered phenotype in larvae kept at higher MF. The most vulnerable period for inner ear alteration upon high MF exposure occurs after 24hpf (once otoliths are formed) (Fig.2). 3h of exposure were sufficient to induce fusion of otoliths in larvae kept in E3, while in larvae embedded in agarose or under the effect of an anesthetic, this effect was barely noticeable. Conclusions High MF exposure led to otolith fusion in the zebrafish larvae. This scenario was largely hindered when larvae were treated by anesthetic or put into agarose medium, but resumed after the anesthetic was removed or with normal E3 medium in the same larvae. Both, agarose and the anesthetic, are expected to cause lower oxygen consumption rates and diminished metabolism, which may impede the interaction of the biological system with the strong MF. This result suggests that MF-induced otolith fusion may bear specific biological interactions. The mechanism behind our main finding might be related to the one underlying nystagmus and vertigo reported by human patients undergoing MRI.}, web_url = {http://www.e-smi.eu/index.php?id=emim-2015-tubingen}, event_name = {10th Annual Meeting of the European Society for Molecular Imaging (EMIM 2015)}, event_place = {Tübingen, Germany}, state = {published}, author = {Pais Rold{\'a}n P{ppais}{Department High-Field Magnetic Resonance}; Singh A; Merkle H{hellmut}; Schulz H{hischu}{Department High-Field Magnetic Resonance}; Yu X{xyu}{Department High-Field Magnetic Resonance}} } @Thesis{ OrtizRios2015, title = {Functional Neuroimaging of Ventral and Dorsal Stream Pathways in the Macaque Auditory System}, year = {2015}, month = {11}, web_url = {https://publikationen.uni-tuebingen.de/xmlui/handle/10900/70712}, state = {published}, type = {PhD}, author = {Ortiz-Rios M{mortiz}{Department Physiology of Cognitive Processes}} } @Thesis{ Papanikolaou2015, title = {Functional Neuroimaging of Cortical Plasticity in the Human Visual System}, year = {2015}, month = {5}, web_url = {https://publikationen.uni-tuebingen.de/xmlui/handle/10900/63567}, state = {published}, type = {PhD}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2015_4, title = {Cortico-cortical long-range connectivity. Part 2: the human cortical white matter}, year = {2015}, month = {11}, day = {27}, abstract = {This last lecture will deal with cortico-cortical fibers in the white matter of the human brain, such as the number of fibers connecting the various cortical lobes, as well as axon diameters and their role for cortical function.}, web_url = {http://neuromat.numec.prp.usp.br/rgbrain}, web_url2 = {http://neuromat.numec.prp.usp.br/sites/default/files/random_graphs_in_the_brain/cortico-cortical_long-range_connectivity_part_2.pdf}, event_name = {NeuroMat Workshop: Random Graphs in the Brain}, event_place = {São Paulo, Brazil}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2015_3, title = {Cortico-cortical long- and middle-range connectivity: anatomical data from mouse and monkey}, year = {2015}, month = {11}, day = {26}, abstract = {Here I will briefly introduce into the field of tracer methods and then report about global connectivity in the mouse cortex, such as the arrangement and extension of terminal fields, as well as density of projections to distant places. I will then move on to the monkey brain and the phenomenon of patchy connections.}, web_url = {http://neuromat.numec.prp.usp.br/rgbrain}, web_url2 = {http://neuromat.numec.prp.usp.br/sites/default/files/random_graphs_in_the_brain/cortico-cortical_long-range_connectivity.pdf}, event_name = {NeuroMat Workshop: Random Graphs in the Brain}, event_place = {São Paulo, Brazil}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2015_2, title = {Quantitative neuroanatomy as a tool to understand cortical function. Part 2: network structure and functional conclusions}, year = {2015}, month = {11}, day = {25}, abstract = {In the second lecture I will present results of such measurements and what they tell us about the network properties of the cerebral cortex, as well as its basic function.}, web_url = {http://neuromat.numec.prp.usp.br/rgbrain}, web_url2 = {http://neuromat.numec.prp.usp.br/sites/default/files/random_graphs_in_the_brain/quantitative_neuroanatomy_as_a_tool_to_understand_cortical_function_part_2.pdf}, event_name = {NeuroMat Workshop: Random Graphs in the Brain}, event_place = {São Paulo, Brazil}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ Bahmani2015, title = {Effects of attention on accommodative response}, year = {2015}, month = {11}, day = {24}, pages = {15}, abstract = {Accommodation is known as the process by which the vertebrate eye changes optical power to maintain focus on an object as its distance varies. In the present study, we test the hypothesis that higher cognitive functions in the brain, such as attention, can modulate eye's accommodative response. It has been shown extensively that attentional state is reected in the pupil size and dynamics. There is also enough evidence that pupil size and accommodation are tightened to each other. There is no direct evidence, however, for attentional modulation of accommodative response. I will present an experimental design for the suggested study.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}} } @Conference{ Hartig2015, title = {Pro-Test Deutschland, a voice for science}, year = {2015}, month = {11}, day = {24}, pages = {21}, abstract = {Scientists often fail to communicate their moral decisions and ethical reasoning for their work to the broader public. It is of no surprise then that some scientists are accused of a supposed lack of ethics, and those scientists conducting research with animals are attacked for alleged inhumane and immoral treatment of animals. Pro-Test Deutschland (PTD) does not think animal research lacks ethical standards or moral fiber. Rather, PTD believes what is missing is an open line of communication. Pro-Test Deutschland understands that it is often hard for people outside of the scientific community to obtain reliable information about the appropriate applications for animal research and why it is needed. Thus, to facilitate an informed and fair debate for the entire society, PTD supplies information through its website and social media platforms. By offering clarification on many scientific, ethical, legal, social, and psychological aspects of animal research, PTD provides a common ground to all those who wish to stand up for science.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Hartig R{rhartig}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2015, title = {Quantitative neuroanatomy as a tool to understand cortical function Part 1: methodological aspects}, year = {2015}, month = {11}, day = {24}, abstract = {In the first lecture I will talk about neuroanatomical methods and, based on those, about approaches for quantification of anatomical aspects, such as cell density, synaptic densities, lengths and densities of cell processes, or density of dendritic spines and synapses along dendrites.}, web_url = {http://neuromat.numec.prp.usp.br/rgbrain}, web_url2 = {http://neuromat.numec.prp.usp.br/sites/default/files/random_graphs_in_the_brain/quantitative_neuroanatomy_as_a_tool_to_understand_cortical_function_part_1.pdf}, event_name = {NeuroMat Workshop: Random Graphs in the Brain}, event_place = {São Paulo, Brazil}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ DwarakanathSKLP2015, title = {Temporal Regimes of State-Dependent Correlated Variability in the Macaque Ventrolateral Prefrontal Cortex}, year = {2015}, month = {11}, day = {23}, pages = {18}, abstract = {Repeated presentation of the same stimulus results in variability in the spiking of neurons, often being correlated across neuronal pairs. However, apart from common input, a number of factors like local circuitry or dominant global states are known to induce this correlated variability. For example, slow (0.5-2.5 Hz) state transitions arising during anesthesia drive correlations in the primary visual cortex (V1). To investigate if a mechanism operating on a similar temporal regime drives correlations in the final stages of the ventral visual stream we recorded from the ventro-lateral prefrontal cortex (vlPFC) of anesthetized macaques using 10*10 Utah Arrays during periods of repeated visual stimulation (10s movie clip) and silence (10s). A Gaussian Process based factorization algorithm, previously used to unravel the underlying temporal regime of correlations in V1. returned a timescale of 14-16ms as the width of the temporal kernel, which translated to a frequency between 13-17 Hz after using an appropriate attenuation value in the spectrum of the estimated latent variable. This result indicates that apart from slow, anesthesia-induced fluctuations, intrinsic activity on a faster scale could be the source of pairwise correlations. Indeed, previous analyses of the local field potentials (LFPs) in vlPFC revealed a dominant oscillation in the beta band (13-25Hz) in both anesthetized and alert animals. Moreover, spike{spike Coherence, spike{field Coherence and other measures of spike{spike/LFP coupling suggest a significant interaction between spikes and LFP in the beta band. Despite these findings the Gaussian Process algorithm did not capture a significant amount of variance in our data, and even after accounting for the latent variable, the residual covariances remain significantly different from zero. We are currently exploring other state-space models.}, file_url = {fileadmin/user_upload/files/publications/2015/NeNa-2015-Abstract-Book.pdf}, web_url = {https://sites.google.com/site/nenaconference/home}, event_name = {16th Conference of Junior Neuroscientists of Tübingen (NeNa 2015)}, event_place = {Schramberg, Germany}, state = {published}, author = {Dwarakanath A{adwarakanath}; Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ DenfieldET2015, title = {Correlated variability in population activity: noise or signature of internal computations?}, year = {2015}, month = {10}, day = {19}, volume = {45}, number = {372.05}, abstract = {Neuronal responses to repeated presentations of identical visual stimuli are variable. The source of this variability is unknown, but it is commonly treated as noise and seen as an obstacle to understanding neuronal activity. We argue that this variability is not noise but reflects, and is due to, computations internal to the brain. Internal signals such as cortical state or attention interact with sensory information processing in early sensory areas. However, little research has examined the effect of fluctuations in these signals on neuronal responses, leaving a number of uncontrolled parameters that may contribute to neuronal variability. One such variable is attention, which increases neuronal response gain in a spatial and feature selective manner. Both the strength of this modulation and the focus of attention are likely to vary from trial to trial, and we hypothesize that these fluctuations are a major source of neuronal response variability and covariability. We first examine a simple model of a gain-modulating signal acting on a population of neurons and show that fluctuations in attention can increase individual and shared variability and generate a variety of correlation structures that are relevant to population coding, including limited range and differential correlations. To test our model’s predictions experimentally, we devised a cued-spatial attention, change-detection task to induce varying degrees of fluctuation in the subject’s attentional signal by changing whether the subject must attend to one stimulus location while ignoring another, or attempt to attend to multiple locations simultaneously. We use multi-electrode recordings with laminar probes in primary visual cortex of macaques performing this task. We demonstrate that attention gain-modulates responses of V1 neurons in a manner that is consistent with results from higher-order areas. Consistent with our model’s predictions, our preliminary results indicate neuronal covariability is elevated in conditions in which attention fluctuates and that neurons are nearly independent when attention is focused. Overall, our results suggest that attentional fluctuations are an important contributor to neuronal variability and open the door to the use of statistical methods for inferring the state of these signals on a trial-by-trial basis.}, web_url = {http://www.sfn.org/am2015/}, event_name = {45th Annual Meeting of the Society for Neuroscience (Neuroscience 2015)}, event_place = {Chicago, IL, USA}, state = {published}, author = {Denfield G; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Tolias A{atolias}{Department Physiology of Cognitive Processes}} } @Conference{ Papanikolaou2015_2, title = {Functional organization of human visual areas following lesions of the primary visual cortex}, year = {2015}, month = {10}, day = {15}, web_url = {http://www.hih-tuebingen.de/fileadmin/user_upload/NK_WS2015_16.pdf}, event_name = {Neurocolloquium}, event_place = {Tübingen, Germany}, state = {published}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2015, title = {Insular cortex: a neuroanatomical insight into interoception, emotion and "self-awareness"}, year = {2015}, month = {10}, day = {14}, abstract = {The insular cortex (or insula) is a major component of the autonomous and affective brain circuits. Our team uses multiple experimental approaches (tract-tracing, fMRI, recording, cross-species comparison) to examine the anatomical organization and functional organization of the insula in primates, including macaque monkeys and humans. We demonstrated that the macaque insula is divided into 15 small and sharply delimited architectonic areas that have each distinct sets of neuronal connections. One of these areas specifically contains the large spindle-shaped von Economo neuron and its companion the Fork neuron. These neurons are selectively depleted in the behavioral variant of the frontotemporal lobe dementia in humans; alteration of the activity and connectivity of the insular area containing von Economo neurons has been recently associated with loss of consciousness and parabrachial coma. Our work shows that both neurons project to subcortical nuclei that are crucial for the regulation of bodily physiology and emotional behaviors.}, web_url = {http://www.sbri.fr/news/news_0.html}, event_name = {Stem-Cell and Brain Research Institute}, event_place = {Lyon, France}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2015_2, title = {NET-fMRI of Large-Scale Brain Networks: Mapping Dynamic Connectivity during Epochs of Synaptic and System Consolidation}, year = {2015}, month = {10}, day = {8}, web_url = {http://ffrm2015.com/}, event_name = {Federation of European Neuroscience Society Featured Regional Meeting (FFRM 2015)}, event_place = {Thessaloniki, Greece}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2015_3, title = {NET-fMRI of Large-Scale Brain Networks: Mapping Dynamic Connectivity in Epochs of Synaptic and System Consolidation}, year = {2015}, month = {9}, day = {23}, abstract = {Neural-Event-Triggered fMRI (NET-fMRI) can potentially map whole-brain activity, associated with individual local events - or their interactions - in various brain structures. In my talk, I’ll describe a number of characteristic states of widespread cortical and subcortical networks that are associated with the occurrence of thalamic, hippocampal and pontine events, which may be related to synaptic and systems consolidation of different memories.}, web_url = {http://www.neural-engineering.eu/ICSLANEschedule/index.html}, event_name = {International Conference on System Level Approaches to Neural Engineering (ICSLANE 2015)}, event_place = {Barcelona, Spain}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2015_4, title = {NET-fMRI of large-scale brain networks: mapping dynamic connectivity in epochs of synaptic and system consolidation}, year = {2015}, month = {9}, day = {18}, web_url = {http://www.escop2015.org/programme/}, event_name = {19th Conference of the European Society for Cognitive Psychology (ESCOP 2015)}, event_place = {Paphros, Cyprus}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Keliris2015, title = {fMRI responses to dynamic checkerboards reveal average single neuron receptive fields in early visual cortex}, year = {2015}, month = {7}, day = {7}, web_url = {http://ibro2015.org/?page_id=434}, event_name = {9th IBRO World Congress on Neuroscience (IBRO 2015)}, event_place = {Rio de Janeiro, Brazil}, state = {published}, author = {Keliris G{george}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2015_6, title = {NET-fMRI of large-scale brain networks: mapping dynamic connectivity in epochs of synaptic and system consolidation}, year = {2015}, month = {6}, day = {23}, abstract = {Neural-Event-Triggered fMRI(NET-fMRI)can potentially map whole-brain activity, associated with individual local events - or their interactions - in various brain structures. In my talk, I’ll describe a number of characteristic states of widespread cortical and subcortical networks that are associated with the occurrence of thalamic, hippocampal and pontine events, which may be related to synaptic and systems consolidation of different memories.}, web_url = {http://elsc.huji.ac.il/elsc-conference-4}, event_name = {Brainy Days in Jerusalem: an Interdisciplinary Celebration}, event_place = {Jerusalem, Israel}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Zaldivar2015_2, title = {Laminar Differences in Neural Activity During Positive and Negative BOLD Conditions, and the Effect of Neuromodulation}, year = {2015}, month = {6}, day = {3}, event_name = {McGovern Institute for Brain Research: Massachusetts Institute of Technology}, event_place = {Cambridge, MA, USA}, state = {published}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}} } @Conference{ PaisRoldanSMSY2015, title = {Sensing the high magnetic field: Fusion of otoliths in zebrafish larvae entails a hint}, year = {2015}, month = {6}, day = {3}, volume = {23}, number = {0695}, abstract = {Here we described the impact of the high magnetic field (MF) on zebrafish larvae aiming to identify potential biological MR sensors. 14T-MF exposures longer than 2 hours in zebrafish larvae led to fusion of 2 otoliths (CaCO3 crystals in the inner ear responsible for balance and hearing) and a subsequent aberrant balance behavior, a phenotype already described in genetic mutants. Identification of the cellular and molecular mechanisms underlying this MF-induced otolith-fusion may be tackled with a zebrafish mutagenesis approach and might contribute in an efficient way to search for MR sensors in biological models.}, web_url = {http://www.ismrm.org/15/program_files/WedSci13.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Pais Rold{\'a}n P{ppais}{Department High-Field Magnetic Resonance}; Singh A; Merkle H{hellmut}; Schulz H{hischu}{Department High-Field Magnetic Resonance}; Yu X{xyu}{Department High-Field Magnetic Resonance}} } @Conference{ ZaldivarLG2015, title = {Laminar Differences in Neural Activity During Positive and Negative Bold Conditions}, year = {2015}, month = {6}, day = {2}, volume = {23}, number = {0357}, abstract = {There is still debate whether negative BOLD responses have a neural or vascular origin. Laminar differences in neurovascular coupling have also been observed during the negative-BOLD response. We investigated whether these differences have a neural origin by performing laminar recordings in V1. We positioned two laminar electrodes in V1; one of these was located in the negative-BOLD area whereas the other in the positive-BOLD area. We observed that the middle cortical layers did not decrease their neural activity while all other layers did, suggesting that the negative BOLD response is driven by the neural activity reductions in the supragranular and infragranular layers.}, web_url = {http://www.ismrm.org/15/program_files/TueSci07.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, DOI = {10.13140/RG.2.1.2547.6328}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}} } @Conference{ HeMY2015, title = {Single Venule Multi-Echo Line-Scanning fMRI (MELS-fMRI)}, year = {2015}, month = {6}, day = {2}, volume = {23}, number = {0361}, abstract = {In contrast to the traditional T2*-weighted EPI-fMRI signal, the T2* fMRI signal is more specific with less temporal noise interference. We developed a multi-Echo Line-Scanning fMRI (MELS-fMRI) method to map T2* signal in a block design stimulation paradigm with 100ms sampling rate. Individual penetrating venules can be directly identified from the raw image with 100x100¦Ìm spatial resolution. The spatial pattern of single-venule fMRI signal was detected from 3 ms to 20.5 ms with 3.5ms interval. It is the first step to decipher the millisecond scale fMRI signal propagation across cerebrovasculature in the deep layer cortex.}, web_url = {http://www.ismrm.org/15/program_files/TueSci07.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {He Y{yhe}; Merkle H{hellmut}; Yu X{xyu}} } @Conference{ MolaeiVaneghiBESB2015, title = {Encoding Self-Motion and External Motion during Pursuit Eye Movement, A Study at 9.4T}, year = {2015}, month = {6}, day = {1}, volume = {23}, number = {0139}, abstract = {Here we propose to use ultra-high-field (9.4T) human fMRI in order to answer two questions: firstly, is there a differential involvement of cortical layers in the processing of retinal motion and of objective motion in high-level visual areas? Second: is there a columnar organisation segregating retinal and objective motion processing? A differential laminar response profile to the two motion types would provide important cues with regards to the hierarchy of processing involved in different areas, with modulation of upper, middle, or lower layers speaking for feedback, bottom-up or output sources of the different signals, respectively. A columnar segregation would indicate specialized and segregated circuits within a given area.}, web_url = {http://www.ismrm.org/15/program_files/Monsci10.htm}, event_name = {23rd Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2015)}, event_place = {Toronto, Canada}, state = {published}, author = {Molaei-Vaneghi F{fmolaei}{Department High-Field Magnetic Resonance}; Bause J{jbause}{Department High-Field Magnetic Resonance}; Ehses P{ehses}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2015_2, title = {The insular cortex in primates, neuroanatomical insights into interoception and emotion}, year = {2015}, month = {5}, day = {5}, web_url = {https://medweb4.unige.ch/labnic/news/B&C_Program_AprJun2015.pdf}, event_name = {Université de Gèneve: Brain and Cognition Seminar}, event_place = {Gèneve, Switzerland}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Eschenko2015, title = {The role of Locus Coeruleus for sensory processing within mesocortical dopaminergic pathway}, year = {2015}, month = {4}, day = {29}, abstract = {Salient events evoke burst-like responses of noradrenergic (NE) neurons of the Locus Coeruleus (LC) and dopaminergic (DA) neurons of the ventral tegmenta l area (VTA). The associated NE and DA release modulates information processing in the projection targets of LC and VTA. In the rat, terminal fields of both LC-NE and VTA-DA neurons converge in the medial prefrontal cortex (mPFC), a cortical area controlling many cognitive capacities. We investigated the role of LC phasic activation for sensory responses in VTA and mPFC. Under urhetaine anestesia, noxious stimulatio n (foot shock, FS) produces a robust short-latency (~20 ms) excitation of LC-NE neurons. In VTA and mPFC, the firing rate modulation induced by FS was present in ~30% of neurons. We classified FS-induced responses of VTA neurons according to latency (early: ~40 ms or late: ~150 ms) and duration (phasic: < 300 ms or sustained: > 300 ms). Similarly, the mPFC single-unit responses differed by latency and/or duration. Supression of LC ongoing and FS-evoked activity by iontophoretic injection of clonidine, an alpha2-adrenergic receptor agonist, reduced responsiveness in both VTA and mPFC. Population of initially ‘non-responsive’ mPFC neurons showed ‘gating-effect’. Spontaneous discharge of substantial proportion of VTA and mPFC neurons was bidirectionally modulated. These results suggest that depending on the motivational valence of a salient event, LC phasic activation and associated NE release may selectively enhance or supress signalling within different and, possibly competing mesolimbic and mesocortical pathways. The behavioral data supporting this hypothesis will be presented.}, web_url = {http://www.ruhr-uni-bochum.de/igsn/events/conference/2015-04-28/}, event_name = {SFB 874 / IGSN Conference: Cortical and Subcortical Representation of Sensory and Cognitive Memory}, event_place = {Bochum, Germany}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2015_5, title = {The neural orchestration of memory consolidation}, year = {2015}, month = {4}, day = {13}, web_url = {http://www.fondation-ipsen.org/wp-content/uploads/2014/06/Flyer_MMM-dynamics-of-the-brain1.pdf}, event_name = {23rd Colloque Médecine et Recherche of the Fondation IPSEN: Micro-, meso-, and macro-dynamics of the brain}, event_place = {Paris, France}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ NauKSDB2015, title = {Area V3A encodes objective motion velocity regardless of eye movement velocity}, year = {2015}, month = {3}, day = {18}, pages = {45}, abstract = {It is still not very clear how the visual system compensates for self-induced visual motion. This mechanism is crucial to convey visual stability, and also to recognize motion in the external world. There are two possibilities how an object can change its position in your visual field. Either it moves in the outside world or we move our eyes. In both cases its image will move across the retina. The mechanisms enabling us to discriminate between these two options are still not well understood. It is thought that efference copies of eye movement commands are integrated with visual input, allowing to separate self-induced retinal motion from external objective motion. A recent fMRI study showed that area V3A encodes visual motion almost exclusively in world-centered (objective) coordinates, while being almost unresponsive to retinal motion per se. Conversely, the human motion complex (V5/MT and MST) encoded both, objective and retinal motion with equal strength (Fischer, Bülthoff, Logothetis and Bartels, 2012). In the present study we asked two related questions. First, we asked whether human motion regions differentiate between outside objective motion being faster or slower than eye movements with different speeds (i.e. resulting in either positively or negatively signed retinal motion). Second, do these regions encode retinal and objective motion in absolute units or in units relative to the velocity of eye movements? To answer these questions, we created 2D random dot stimuli that moved either slower or faster than a fixation dot. All velocities were chosen so that we could examine neural responses to slower, matched and faster background motion relative to 0°/s, 2°/s and 3°/s eye movement speed. Moreover, we ran a functional localizer scan for each subject, allowing us to identify areas V5/MT, MST, V3A, V6, and CSv for region of interest (ROI) analyses. In our analysis, we tested each ROI’s response using a separate set of general linear models (GLM). The GLMs incorporated each of the above hypothesized response properties, and F-tests were used to identify which of the competing models accounted for significantly more variance. We found that all regions encoded both, retinal and objective motion in absolute, not in relative units, and that V3A, but not CSv or V5/MT does differentiate between negatively and positively signed retinal motion. These results suggest that motion is encoded in absolute units throughout the visual motion system, and that V3A has indeed a special role among human motion processing regions in that it represents motion signed with respect to eye movement direction.}, web_url = {https://www.nwg-goettingen.de/2015/upload/file/Proceedings_NWG2015.pdf}, event_name = {11th Göttingen Meeting of the German Neuroscience Society, 35th Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {Nau M{mnau}{Department Physiology of Cognitive Processes}; Korkmaz-Hacialihafiz D{dkorkmaz}{Department Physiology of Cognitive Processes}; Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Darmani G; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ GatysETB2015, title = {Synaptic unreliability facilitates information transmission in balanced cortical populations}, year = {2015}, month = {3}, day = {16}, abstract = {Synaptic unreliability is one of the major sources of biophysical noise in the brain. In the context of neural information processing, it is a central question how neural systems can afford this unreliability. Here we examined how synaptic noise affects signal transmission in cortical circuits, where excitation and inhibition are thought to be tightly balanced. Surprisingly, we found that in this balanced state synaptic response variability actually facilitates information transmission, rather than impairing it. In particular, the transmission of fast-varying signals benefits from synaptic noise, as it instantaneously increases the amount of information shared between presynaptic signal and postsynaptic current. This finding provides a parsimonious explanation why cortex can afford to operate with noisy synapses.}, web_url = {http://www.dpg-verhandlungen.de/year/2015/conference/berlin/part/bp/session/8/contribution/5}, event_name = {79. Jahrestagung der Deutschen Physikalischen Gesellschaft und DPG-Frühjahrstagung}, event_place = {Berlin, Germany}, state = {published}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Tchumatchenko T; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Conference{ DenfieldET2015_2, title = {The Role of Internal Signals in Structuring V1 Population Activity}, year = {2015}, month = {2}, pages = {19}, abstract = {Neuronal responses to repeated presentations of identical visual stimuli are variable. The cause of this variability is unknown, but it is commonly treated as noise and seen as an obstacle to understanding neuronal activity. We offer an alternative explanation: this variability is not noise but reflects, and is due to, computations internal to the brain. Internal signals such as cortical state or attention interact with sensory information processing in early sensory areas. However, little research has examined the effect of fluctuations in these signals on neuronal responses, leaving a number of uncontrolled parameters that may contribute to neuronal variability. One such variable is attention. We hypothesize that fluctuations in attentional signals contribute to neuronal response variability and that controlling for such fluctuations will reduce this variability. To study this interaction, we use multi-electrode recordings with laminar probes in primary visual cortex of macaques while subjects perform a cued-spatial attention, change-detection task. We induce varying degrees of fluctuation in the subject’s attentional signal by changing whether the subject must attend to one stimulus location while ignoring another, or attempt to attend to both locations simultaneously. We demonstrate that attention increases stimulusevoked firing rates and gain-modulates the tuning curves of V1 neurons in a manner that is consistent with results from higher order areas. Future experiments will examine the effect of attentional fluctuations on neuronal response variability and interneuronal correlations as well as the laminar profile of these effects. Under this hypothesis, this variability can aid, rather than hinder, our understanding of brain function.}, web_url = {https://media.bcm.edu/documents/2015/93/neuroscienceabstractbook2015.pdf}, event_name = {25th Annual Rush and Helen Record Neuroscience Forum}, event_place = {Houston, TX, USA}, state = {published}, author = {Denfield GH; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Tolias A{atolias}{Department Physiology of Cognitive Processes}} } @Conference{ Zaldivar2015, title = {Neurophysiological correlates of fMRI signals and the effects of neuromodulation at shaping neurovascular coupling relationship}, year = {2015}, month = {1}, day = {13}, event_name = {Institute of Neurobiology: Universidad Nacional Autónoma de México}, event_place = {Querétaro, México}, state = {published}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}} } @Article{ ZaldivarRWLG2014, title = {Dopamine-Induced Dissociation of BOLD and Neural Activity in Macaque Visual Cortex}, journal = {Current Biology}, year = {2014}, month = {12}, volume = {24}, number = {23}, pages = {2805–2811}, abstract = {Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory [1]. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear [2, 3 and 4], limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA’s involvement in diseases such as Parkinson’s and schizophrenia, it also plays a role in visual perception [5, 6, 7 and 8]. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0960982214012822}, state = {published}, DOI = {10.1016/j.cub.2014.10.006}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Whittingstall K{kevin}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}} } @Article{ SimPPEMG2014, title = {Magnetic resonance and optical imaging probes for NMDA receptors on the cell surface of neurons: synthesis and evaluation in cellulo}, journal = {Organic & Biomolecular Chemistry}, year = {2014}, month = {12}, volume = {12}, number = {46}, pages = {9389-9404}, abstract = {A second generation of N-methyl-D-aspartate (NMDA) receptor-targeted MRI contrast agents has been synthesised and evaluated in cellulo, based on established bicyclic NMDA receptor antagonists. Their use as responsive MR imaging probes has been evaluated in suspensions of NSC-34 cells, and one agent exhibited significant enhancements in measured longitudinal and transverse water proton relaxation rates (19 and 38% respectively; 3 T, 298 K). A biotin derivative of the lead compound was prepared and the specificity and reversibility of binding to the NMDA cell surface receptors demonstrated using confocal laser scanning microscopy. Competitive and reversible binding of glutamate to the receptors was also visualised, suggesting that the receptor-targeted approach may allow MRI to be used to monitor neuronal events associated with modulation of local glutamate concentrations.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2014/ob/c4ob01848f}, state = {published}, DOI = {10.1039/C4OB01848F}, author = {Sim N; Pal R; Parker D; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}} } @Article{ ReinlB2014, title = {Face processing regions are sensitive to distinct aspects of temporal sequence in facial dynamics}, journal = {NeuroImage}, year = {2014}, month = {11}, volume = {102}, number = {2}, pages = {407–415}, abstract = {Facial movement conveys important information for social interactions, yet its neural processing is poorly understood. Computational models propose that shape- and temporal sequence sensitive mechanisms interact in processing dynamic faces. While face processing regions are known to respond to facial movement, their sensitivity to particular temporal sequences has barely been studied. Here we used fMRI to examine the sensitivity of human face-processing regions to two aspects of directionality in facial movement trajectories. We presented genuine movie recordings of increasing and decreasing fear expressions, each of which were played in natural or reversed frame order. This two-by-two factorial design matched low-level visual properties, static content and motion energy within each factor, emotion-direction (increasing or decreasing emotion) and timeline (natural versus artificial). The results showed sensitivity for emotion-direction in FFA, which was timeline-dependent as it only occurred within the natural frame order, and sensitivity to timeline in the STS, which was emotion-direction-dependent as it only occurred for decreased fear. The occipital face area (OFA) was sensitive to the factor timeline. These findings reveal interacting temporal sequence sensitive mechanisms that are responsive to both ecological meaning and to prototypical unfolding of facial dynamics. These mechanisms are temporally directional, provide socially relevant information regarding emotional state or naturalness of behavior, and agree with predictions from modeling and predictive coding theory.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811914006612}, state = {published}, DOI = {10.1016/j.neuroimage.2014.08.011}, author = {Reinl M{mreinl}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ PalmKHS2014, title = {Cell Assemblies in the Cerebral Cortex}, journal = {Biological Cybernetics}, year = {2014}, month = {10}, volume = {108}, number = {5}, pages = {559-572}, abstract = {Donald Hebb’s concept of cell assemblies is a physiology-based idea for a distributed neural representation of behaviorally relevant objects, concepts, or constellations. In the late 70s Valentino Braitenberg started the endeavor to spell out the hypothesis that the cerebral cortex is the structure where cell assemblies are formed, maintained and used, in terms of neuroanatomy (which was his main concern) and also neurophysiology. This endeavor has been carried on over the last 30 years corroborating most of his findings and interpretations. This paper summarizes the present state of cell assembly theory, realized in a network of associative memories, and of the anatomical evidence for its location in the cerebral cortex.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00422-014-0596-4.pdf}, state = {published}, DOI = {10.1007/s00422-014-0596-4}, author = {Palm G; Knoblauch A; Hauser F; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Article{ LiewaldMLWS2014, title = {Distribution of axon diameters in cortical white matter: an electron-microscopic study on three human brains and a macaque}, journal = {Biological Cybernetics}, year = {2014}, month = {10}, volume = {108}, number = {5}, pages = {541-557}, abstract = {The aim of this study was to obtain information on the axonal diameters of cortico-cortical fibres in the human brain, connecting distant regions of the same hemisphere via the white matter. Samples for electron microscopy were taken from the region of the superior longitudinal fascicle and from the transitional white matter between temporal and frontal lobe where the uncinate and inferior occipitofrontal fascicle merge. We measured the inner diameter of cross sections of myelinated axons. For comparison with data from the literature on the human corpus callosum, we also took samples from that region. For comparison with well-fixed material, we also included samples from corresponding regions of a monkey brain (Macaca mulatta). Fibre diameters in human brains ranged from 0.16 to 9 μm . Distributions of diameters were similar in the three systems of cortico-cortical fibres investigated, both in humans and the monkey, with most of the average values below 1 μ m diameter and a small population of much thicker fibres. Within individual human brains, the averages were larger in the superior longitudinal fascicle than in the transitional zone between temporal and frontal lobe. An asymmetry between left and right could be found in one of the human brains, as well as in the monkey brain. A correlation was also found between the thickness of the myelin sheath and the inner axon diameter for axons whose calibre was greater than about 0.6 μm . The results are compared to white matter data in other mammals and are discussed with respect to conduction velocity, brain size, cognition, as well as diffusion weighted imaging studies.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00422-014-0626-2.pdf}, state = {published}, DOI = {10.1007/s00422-014-0626-2}, author = {Liewald D{liewald}{Department Physiology of Cognitive Processes}; Miller R; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Wagner H-J; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Article{ BallaSWHSFB2014, title = {Functional quantitative susceptibility mapping (fQSM)}, journal = {NeuroImage}, year = {2014}, month = {10}, volume = {100}, pages = {112–124}, abstract = {Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a powerful technique, typically based on the statistical analysis of the magnitude component of the complex time-series. Here, we additionally interrogated the phase data of the fMRI time-series and used quantitative susceptibility mapping (QSM) in order to investigate the potential of functional QSM (fQSM) relative to standard magnitude BOLD fMRI. High spatial resolution data (1 mm isotropic) were acquired every 3 seconds using zoomed multi-slice gradient-echo EPI collected at 7 T in single orientation (SO) and multiple orientation (MO) experiments, the latter involving 4 repetitions with the subject’s head rotated relative to B0. Statistical parametric maps (SPM) were reconstructed for magnitude, phase and QSM time-series and each was subjected to detailed analysis. Several fQSM pipelines were evaluated and compared based on the relative number of voxels that were coincidentally found to be significant in QSM and magnitude SPMs (common voxels). We found that sensitivity and spatial reliability of fQSM relative to the magnitude data depended strongly on the arbitrary significance threshold defining “activated” voxels in SPMs, and on the efficiency of spatio-temporal filtering of the phase time-series. Sensitivity and spatial reliability depended slightly on whether MO or SO fQSM was performed and on the QSM calculation approach used for SO data. Our results present the potential of fQSM as a quantitative method of mapping BOLD changes. We also critically discuss the technical challenges and issues linked to this intriguing new technique.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811914004881}, state = {published}, DOI = {10.1016/j.neuroimage.2014.06.011}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Sanchez-Panchuelo RM; Wharton SJ; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Francis ST; Bowtell R} } @Article{ BarbieriMLPB2014, title = {Stimulus Dependence of Local Field Potential Spectra: Experiment versus Theory}, journal = {Journal of Neuroscience}, year = {2014}, month = {10}, volume = {34}, number = {44}, pages = {14589-14605}, abstract = {The local field potential (LFP) captures different neural processes, including integrative synaptic dynamics that cannot be observed by measuring only the spiking activity of small populations. Therefore, investigating how LFP power is modulated by external stimuli can offer important insights into sensory neural representations. However, gaining such insight requires developing data-driven computational models that can identify and disambiguate the neural contributions to the LFP. Here, we investigated how networks of excitatory and inhibitory integrate-and-fire neurons responding to time-dependent inputs can be used to interpret sensory modulations of LFP spectra. We computed analytically from such models the LFP spectra and the information that they convey about input and used these analytical expressions to fit the model to LFPs recorded in V1 of anesthetized macaques (Macaca mulatta) during the presentation of color movies. Our expressions explain 60%–98% of the variance of the LFP spectrum shape and its dependency upon movie scenes and we achieved this with realistic values for the best-fit parameters. In particular, synaptic best-fit parameters were compatible with experimental measurements and the predictions of firing rates, based only on the fit of LFP data, correlated with the multiunit spike rate recorded from the same location. Moreover, the parameters characterizing the input to the network across different movie scenes correlated with cross-scene changes of several image features. Our findings suggest that analytical descriptions of spiking neuron networks may become a crucial tool for the interpretation of field recordings.}, web_url = {http://www.jneurosci.org/content/34/44/14589.full.pdf+html}, state = {published}, DOI = {10.1523/JNEUROSCI.5365-13.2014}, author = {Barbieri F; Mazzoni A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Brunel N} } @Article{ vanHemmenSA2014, title = {Structural aspects of biological cybernetics: Valentino Braitenberg, neuroanatomy, and brain function}, journal = {Biological Cybernetics}, year = {2014}, month = {10}, volume = {108}, number = {5}, pages = {517-525}, abstract = {The best way of introducing Valentino Braitenberg is by quoting one of his distinctive arguments [99, p. 31]: The referencing in this Foreword is twofold. For the Foreword itself, the Harvard style referring to authors by year is used whereas for the publications of Braitenberg himself recourse has been taken to the Vancouver style, which uses angular brackets such as [1]. Both lists appear at the end in the order as just described. “When a new science emerges every couple of centuries, those who are privileged enough to witness it from its very beginnings to its full development during the span of their own lifetime can indeed count themselves lucky. My colleagues and I, who became fully fledged after World War II, had precisely this privilege. The science to which I refer still has no proper name, but its existence can be testified to by the matter-of-course way in which physicists, biologists, and logicians discuss issues that do not fall into any of the categories of phys ...}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00422-014-0630-6.pdf}, state = {published}, DOI = {10.1007/s00422-014-0630-6}, author = {van Hemmen JL; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Aertsen A} } @Article{ OnkenKKP2014, title = {Understanding neural population coding: information-theoretic insights from the auditory system}, journal = {Advances in Neuroscience}, year = {2014}, month = {10}, volume = {2014}, number = {907851}, pages = {1-14}, abstract = {In recent years, our research in computational neuroscience has focused on understanding how populations of neurons encode naturalistic stimuli. In particular, we focused on how populations of neurons use the time domain to encode sensory information. In this focused review, we summarize this recent work from our laboratory. We focus in particular on the mathematical methods that we developed for the quantification of how information is encoded by populations of neurons and on how we used these methods to investigate the encoding of complex naturalistic sounds in auditory cortex. We review how these methods revealed a complementary role of low frequency oscillations and millisecond precise spike patterns in encoding complex sounds and in making these representations robust to imprecise knowledge about the timing of the external stimulus. Further, we discuss challenges in extending this work to understand how large populations of neurons encode sensory information. Overall, this previous work provides analytical tools and conceptual understanding necessary to study the principles of how neural populations reflect sensory inputs and achieve a stable representation despite many uncertainties in the environment.}, web_url = {http://www.hindawi.com/journals/aneu/2014/907851/}, state = {published}, DOI = {10.1155/2014/907851}, author = {Onken A; Karunasekara PPCR; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Panzeri S{stefano}} } @Article{ BahmaniMLK2014, title = {Binocular Flash Suppression in the Primary Visual Cortex of Anesthetized and Awake Macaques}, journal = {PLoS ONE}, year = {2014}, month = {9}, volume = {9}, number = {9}, pages = {1-8}, abstract = {Primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies. However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1. In particular, only a moderate percentage of neurons in V1 were found to modulate in parallel with perception with magnitude substantially smaller than the physical preference of these neurons. It is yet unclear whether these small modulations are rooted from local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. We found that a small but significant modulation was present in both the anesthetized and awake states during the flash suppression presentation. Furthermore, the relative amplitudes of the perceptual modulations were not significantly different in the two states. We suggest that these early effects of perceptual suppression might occur locally in V1, in prior processing stages or within early visual cortical areas in the absence of top-down feedback from higher cognitive stages that are suppressed under anesthesia.}, web_url = {http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0107628&representation=PDF}, state = {published}, DOI = {10.1371/journal.pone.0107628}, EPUB = {e107628}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Article{ SafaviKLP2014, title = {Is the frontal lobe involved in conscious perception?}, journal = {Frontiers in Psychology}, year = {2014}, month = {9}, volume = {5}, number = {1063}, pages = {1-2}, abstract = {When studying the neural mechanisms underlying conscious perception we should be careful not to misinterpret evidence, and delineate these mechanisms from activity which could reflect the prerequisites or consequences of conscious experiences (Aru et al., 2012; de Graaf et al., 2012). However, at the same time, we need to be careful not to exclude any relevant evidence about the phenomenon. Recently, novel paradigms have attempted to dissociate activity related to conscious perception from activity reflecting its prerequisites and consequences. In particular, one of these studies focused on resolving the role of frontal lobe in conscious perception (Frassle et al., 2014). Through a clever experimental design that contrasted blood-oxygen-level-dependent (BOLD) activity elicited during binocular rivalry with and without behavioral reports, Frassle et al. (2014) suggested that frontal lobe, or a large part of it, may not be necessary for conscious perception per se. Rather frontal areas are involved in processing the consequences of conscious perception like monitoring the perceptual content in order to elicit the appropriate report of the subjective experience. In particular, Frässle et al. showed that behavioral reports of conscious experiences resulted in increased and more widespread activity of the frontal lobe compared to a condition without behavioral reports, where spontaneous transitions in the content of consciousness were estimated through the objective measures like optokinetic nystagmus (OKN) and pupil dilation. The authors of this study concluded that “frontal areas are associated with active report and introspection rather than with rivalry per se”. Therefore activity in prefrontal regions could be considered as a consequence rather than a direct neural correlate of conscious experience. However, a previous study (Panagiotaropoulos et al., 2012) that measured directly neural activity in the macaque lateral prefrontal cortex (LPFC) using extracellular electrophysiological recordings could help to narrow down the role of frontal activity in conscious perception and exclude the contribution of cognitive or motor consequences in prefrontal neural activity during visual awareness. Specifically, the activity of feature selective neurons in the macaque LFPC was shown to be modulated in accordance with the content of subjective perception, without any confound from motor action (i.e. behavioral reports). Using binocular flash suppression (BFS), a paradigm of robust, externally induced perceptual suppression and without any requirement of behavioral reports, neurons in the LPFC were found to increase or decrease their discharge activity when their preferred stimulus was perceptually dominant or suppressed, respectively. Therefore, since neuronal discharges in the LPFC follow the content of conscious perception even without any motor action, the conclusion of Frassle et al. (2014) about the role of frontal lobe activity in rivalrous perception needs to be refined. Prefrontal activity can indeed reflect the content of conscious perception under conditions of rivalrous stimulation and this activity should not be necessarily considered as the result of a motor action or self-monitoring required for active report. Moreover, the results obtained by Frassle et al. (2014) do not anatomically preclude the entire prefrontal cortex from having a role in conscious perception. Specifically, the BOLD activity related to rivalry in their experiment is still present in the right inferior frontal lobe and right superior frontal lobe (Zaretskaya and Narinyan, 2014). Further, activation of dorso-lateral prefrontal cortex in conscious perception of Mooney images was also reported in a study that explicitly controlled for activity elicited by motor action (Imamoglu et al., 2012). It is true that the BFS-related prefrontal activity cannot conclude on a mechanistic, causal involvement of prefrontal activity in driving spontaneous transitions in conscious perception. This is because BFS is a paradigm of externally induced perceptual suppression and is therefore not directly informative about the role of recorded activity in spontaneous transitions. Therefore, the possibility remains open that the kind of prefrontal activity observed in the macaque LPFC during BFS is not a causal factor for conscious perception but rather reflects some other aspects of monitoring that are not directly related to motor action. For example, prefrontal activity could just reflect a read-out from other areas like the inferior temporal cortex (Sheinberg and Logothetis, 1997) that also reliably reflects the content of conscious perception. However, if this is the case, it triggers the question why this activity that closely follows the content of subjective perception is observed in the LPFC even in the absence of any behavioral report. Overall, it motivates further investigation to understand whether prefrontal activity has a mechanistic role in conscious perception or it might underlie some monitoring functions that are not necessarily bound to motor action. Similar to this debate on the role of LPFC in visual awareness, the last decade witnessed disagreement on whether activity in primary visual cortex reflects subjective perception as monitored with electrophysiology and fMRI (Leopold and Logothetis, 1996;Tong, 2003;Maier et al., 2008;Keliris et al., 2010;Leopold, 2012). Measuring both electrophysiological activity and the BOLD signal in the same macaques engaged in an identical task of perceptual suppression finally provided the solution (Maier et al., 2008;Leopold, 2012). Therefore, in order to investigate and resolve the role of PFC in visual perception, one must take a similar approach that utilizes multiple measurement techniques simultaneously or in the same animal along with a careful experimental design. The experimental tasks should not only segregate the effect of various cognitive processes such as attention or introspection in comparison to awareness (Watanabe et al., 2011; Frassle et al., 2014), but also use an objective criterion to decode the content of conscious experience (Frassle et al., 2014), therefore separating perception-related activities from the subsequent behavioral report. Such an approach could therefore robustly delineate the prerequisites and consequences of conscious experience and reveal the true correlates of conscious perception. Lastly, although such a multimodal approach could provide us substantial insights into the activity underlying the representation of conscious content, whether or not this activity has a causal role in mediating perception remains to be understood. Although a number of studies indeed point to a causal involvement of prefrontal cortex in conscious perception (reviewed in Dehaene and Changeux (2011)), a systematic study which directly interferes with prefrontal activity during a task of subjective perception is currently, to the best of our knowledge, missing. While utilizing objective criteria as indicators of perceptual transitions, systematic perturbation of the PFC (such as cooling, transcranial magnetic stimulation, microstimulation or optogenetics) and observing concomitant changes in the temporal dynamics of perceptual transitions could reveal its causal contribution. Indeed, patients with frontal lesions are impaired in their ability to switch from one subjective view of an ambiguous figure to the other (for example see Ricci and Blundo (1990) but also see a different case study from Valle-Inclán and Gallego (2006)). We would like to conclude that in formulating our conclusions related to prerequisites, consequences and true correlates of conscious experiences, we need to have an integrative view on the available evidence. Our investigations and conclusions about the neural correlates of consciousness must not only entail better-designed experiments but also diverse experimental techniques (e.g. BOLD fMRI, electrophysiology) that could measure brain activity on different spatial and temporal scales (Panagiotaropoulos et al., 2014). Such a multi-modal approach holds great promise in refining our current understanding of conscious processing.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fpsyg.2014.01063/pdf}, state = {published}, DOI = {10.3389/fpsyg.2014.01063}, author = {Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Article{ HuberGKIKLTTM2014, title = {Investigation of the neurovascular coupling in positive and negative BOLD responses in human brain at 7 T}, journal = {NeuroImage}, year = {2014}, month = {8}, volume = {97}, pages = {349–362}, abstract = {Decreases in stimulus-dependent blood oxygenation level dependent (BOLD) signal and their underlying neurovascular origins have recently gained considerable interest. In this study a multi-echo, BOLD-corrected vascular space occupancy (VASO) functional magnetic resonance imaging (fMRI) technique was used to investigate neurovascular responses during stimuli that elicit positive and negative BOLD responses in human brain at 7 T. Stimulus-induced BOLD, cerebral blood volume (CBV), and cerebral blood flow (CBF) changes were measured and analyzed in ‘arterial’ and ‘venous’ blood compartments in macro- and microvasculature. We found that the overall interplay of mean CBV, CBF and BOLD responses is similar for tasks inducing positive and negative BOLD responses. Some aspects of the neurovascular coupling however, such as the temporal response, cortical depth dependence, and the weighting between ‘arterial’ and ‘venous’ contributions, are significantly different for the different task conditions. Namely, while for excitatory tasks the BOLD response peaks at the cortical surface, and the CBV change is similar in cortex and pial vasculature, inhibitory tasks are associated with a maximum negative BOLD response in deeper layers, with CBV showing strong constriction of surface arteries and a faster return to baseline. The different interplays of CBV, CBF and BOLD during excitatory and inhibitory responses suggests different underlying hemodynamic mechanisms.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811914002778}, state = {published}, DOI = {10.1016/j.neuroimage.2014.04.022}, author = {Huber L; Goense J{jozien}{Department Physiology of Cognitive Processes}; Kennerley AJ; Ivanov D; Krieger SN; Lepsien J; Trampel R; Turner R; M\"oller HE} } @Article{ SchmidK2014, title = {Filling-in versus filling-out: patterns of cortical short-term plasticity}, journal = {Trends in Cognitive Sciences}, year = {2014}, month = {7}, volume = {18}, number = {7}, pages = {342–344}, abstract = {Investigations of topographic cortical plasticity following peripheral nervous injury predominantly report receptive field (RF) shifts toward the intact periphery. A recent study on visual cortex plasticity following retinal lesions by Botelho et al. finds RF coverage of the lesion affected space when global retinotopic mapping strategies are used.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1364661314000308}, state = {published}, DOI = {10.1016/j.tics.2014.01.013}, author = {Schmid MC; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Article{ ZaretskayaN2014, title = {Introspection, attention or awareness? The role of the frontal lobe in binocular rivalry}, journal = {Frontiers in Human Neuroscience}, year = {2014}, month = {7}, volume = {8}, number = {527}, pages = {1-2}, abstract = {Bistable stimuli are one of the most popular approaches to studying the neural mechanism of conscious visual perception. Such stimuli contain conflicting information, which the visual system cannot integrate into a unified percept. This causes the perceptual state of the observer to change every few seconds between the two interpretations while the physical stimulus remains the same. Binocular rivalry is an example of such perceptual phenomena with ambiguity achieved by presenting one image to one eye and a different image to the other eye. Perceptual changes during binocular rivalry are particularly vivid, and closely resemble a physical image exchange.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fnhum.2014.00527/pdf}, state = {published}, DOI = {10.3389/fnhum.2014.00527}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Narinyan M} } @Article{ KleinvG2014, title = {Stimulus-Specific Adaptation in Field Potentials and Neuronal Responses to Frequency-Modulated Tones in the Primary Auditory Cortex}, journal = {Brain Topography}, year = {2014}, month = {7}, volume = {27}, number = {4}, pages = {599-610}, abstract = {In order to structure the sensory environment our brain needs to detect changes in the surrounding that might indicate events of presumed behavioral relevance. A characteristic brain response presumably related to the detection of such novel stimuli is termed mismatch negativity (MMN) observable in human scalp recordings. A candidate mechanism underlying MMN at the neuronal level is stimulus-specific adaptation (SSA) which has several characteristics in common. SSA is the specific decrease in the response to a frequent stimulus, which does not generalize to an interleaved rare stimulus in a sequence of events. SSA was so far mainly described for changes in the response to simple pure tone stimuli differing in tone frequency. In this study we provide data from the awake rat auditory cortex on adaptation in the responses to frequency-modulated tones (FM) with the deviating feature being the direction of FM modulation. Adaptation of cortical neurons to the direction of FM modulation was stronger for slow modulation than for faster modulation. In contrast to pure tone SSA which showed no stimulus preference, FM adaptation in neuronal data differed sometimes between upward and downward FM. This, however, was not the case in the local field potential data recorded simultaneously. Our findings support the role of the auditory cortex as the source for change-related activity induced by FM stimuli by showing that dynamic stimulus features such as FM modulation can evoke SSA in the rat in a way very similar to FM-induced MMN in the human auditory cortex.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs10548-014-0376-4.pdf}, state = {published}, DOI = {10.1007/s10548-014-0376-4}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; von der Behrens W; Gaese BH} } @Article{ KadjanePBTHHLA2014, title = {Dual-Frequency Calcium-Responsive MRI Agents}, journal = {Chemistry: A European Journal}, year = {2014}, month = {6}, volume = {20}, number = {24}, pages = {7351–7362}, abstract = {Responsive or smart magnetic resonance imaging (MRI) contrast agents are molecular sensors that alter the MRI signal upon changes in a particular parameter in their microenvironment. Consequently, they could be exploited for visualization of various biochemical events that take place at molecular and cellular levels. In this study, a set of dual-frequency calcium-responsive MRI agents are reported. These are paramagnetic, fluorine-containing complexes that produce remarkably high MRI signal changes at the 1H and 19F frequencies at varying Ca2+ concentrations. The nature of the processes triggered by Ca2+ was revealed, allowing a better understanding of these complex systems and their further improvement. The findings indicate that these double-frequency tracers hold great promise for development of novel functional MRI methods.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/chem.201400159/pdf}, state = {published}, DOI = {10.1002/chem.201400159}, author = {Kadjane P{pkadjane}{Department Physiology of Cognitive Processes}; Platas-Iglesias C; Boehm-Sturm P; Truffault V; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Hoehn M; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ EckerT2014, title = {Is there signal in the noise?}, journal = {Nature Neuroscience}, year = {2014}, month = {6}, volume = {17}, number = {6}, pages = {750-751}, abstract = {A study now shows that variability in neuronal responses in the visual system mainly arises from slow fluctuations in excitability, presumably caused by factors of nonsensory origin, such as arousal, attention or anesthesia.}, web_url = {http://www.nature.com/neuro/journal/v17/n6/pdf/nn.3722.pdf}, state = {published}, DOI = {10.1038/nn.3722}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ FroudarakisBECSYSBT2014, title = {Population code in mouse V1 facilitates readout of natural scenes through increased sparseness}, journal = {Nature Neuroscience}, year = {2014}, month = {6}, volume = {17}, number = {6}, pages = {851–857}, abstract = {Neural codes are believed to have adapted to the statistical properties of the natural environment. However, the principles that govern the organization of ensemble activity in the visual cortex during natural visual input are unknown. We recorded populations of up to 500 neurons in the mouse primary visual cortex and characterized the structure of their activity, comparing responses to natural movies with those to control stimuli. We found that higher order correlations in natural scenes induced a sparser code, in which information is encoded by reliable activation of a smaller set of neurons and can be read out more easily. This computationally advantageous encoding for natural scenes was state-dependent and apparent only in anesthetized and active awake animals, but not during quiet wakefulness. Our results argue for a functional benefit of sparsification that could be a general principle governing the structure of the population activity throughout cortical microcircuits.}, web_url = {http://www.nature.com/neuro/journal/v17/n6/pdf/nn.3707.pdf}, state = {published}, DOI = {10.1038/nn.3707}, author = {Froudarakis E; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Cotton RJ; Sinz FH{fabee}{Research Group Computational Vision and Neuroscience}{Research Group Computational Vision and Neuroscience}; Yatsenko D; Saggau P; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ PriesemannWVPLGTNM2014, title = {Spike avalanches in vivo suggest a driven, slightly subcritical brain state}, journal = {Frontiers in Systems Neuroscience}, year = {2014}, month = {6}, volume = {8}, number = {108}, pages = {1-17}, abstract = {In self-organized critical (SOC) systems avalanche size distributions follow power-laws. Power-laws have also been observed for neural activity, and so it has been proposed that SOC underlies brain organization as well. Surprisingly, for spiking activity in vivo, evidence for SOC is still lacking. Therefore we analyzed highly parallel spike recordings from awake rats and monkeys, anaesthetized cats, and also local field potentials from humans. We compared these to spiking activity from two established critical models: the Bak-Tang-Wiesenfeld model, and a stochastic branching model. We found fundamental differences between the neural and the model activity. These differences could be overcome for both models through a combination of three modifications: (1) subsampling, (2) increasing the input to the model (this way eliminating the separation of time scales, which is fundamental to SOC and its avalanche definition), and (3) making the model slightly sub-critical. The match between the neural activity and the modified models held not only for the classical avalanche size distributions and estimated branching parameters, but also for two novel measures (mean avalanche size, and frequency of single spikes), and for the dependence of all these measures on the temporal bin size. Our results suggest that neural activity in vivo shows a mélange of avalanches, and not temporally separated ones, and that their global activity propagation can be approximated by the principle that one spike on average triggers a little less than one spike in the next step. This implies that neural activity does not reflect a SOC state but a slightly sub-critical regime without a separation of time scales. Potential advantages of this regime may be faster information processing, and a safety margin from super-criticality, which has been linked to epilepsy.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00108/pdf}, state = {published}, DOI = {10.3389/fnsys.2014.00108}, author = {Priesemann V; Wibral M; Valderrama M; Pr\"opper R; Le Van Quyen M; Geisel T; Triesch J; Nikolić D; Munk MHJ{munk}{Department Physiology of Cognitive Processes}} } @Article{ MarzoTLE2014, title = {Unilateral electrical stimulation of rat locus coeruleus elicits bilateral response of norepinephrine neurons and sustained activation of medial prefrontal cortex}, journal = {Journal of Neurophysiology}, year = {2014}, month = {6}, volume = {111}, number = {12}, pages = {2570-2588}, abstract = {The brain stem nucleus Locus Coeruleus (LC) is thought to modulate cortical excitability by norepinephrine (NE) release in LC forebrain targets. The effects of LC burst discharge, typically evoked by a strong excitatory input, on cortical ongoing activity are poorly understood. To address this question, we combined direct electrical stimulation of LC (LC-DES) with extracellular recording in LC and medial prefrontal cortex (mPFC), an important cortical target of LC. LC-DES consisting of both, single pulses (0.1 - 0.5 ms, 0.01 - 0.05 mA) or pulse trains (20 - 50 Hz, 50 - 200 ms), evoked short-latency excitatory and inhibitory LC responses bilaterally, as well as a delayed rebound excitation occurring ~100 ms after stimulation offset. The pulse trains, but not single pulses, reliably elicited mPFC activity change, which was proportional to the stimulation strength. The firing rate of ~50% of mPFC units was significantly modulated by the strongest LC-DES. Responses of mPFC putative pyramidal neurons included fast (~100 ms), transient (~100 - 200 ms) inhibition (10% of units) or excitation (13%), and delayed (~500 ms), sustained (~1 s) excitation (26%). The sustained spiking resembled NE-dependent mPFC activity during the delay period of working memory tasks. Concurrently, the low-frequency (0.1-8 Hz) power of the local field potential (LFP) decreased and high-frequency (> 20 Hz) power increased. Overall, the DES-induced LC firing pattern resembled the naturalistic biphasic response of LC-NE neurons to alerting stimuli and was associated with a shift in cortical state that may optimize processing of behaviorally-relevant events.}, web_url = {http://jn.physiology.org/content/111/12/2570.full-text.pdf+html}, state = {published}, DOI = {10.1152/jn.00920.2013}, author = {Marzo A{amarzo}{Department Physiology of Cognitive Processes}; Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Article{ AngelovskiGMEHKAL2014, title = {Investigation of a Calcium-Responsive Contrast Agent in Cellular Model Systems: Feasibility for Use as a Smart Molecular Probe in Functional MRI}, journal = {ACS Chemical Neuroscience}, year = {2014}, month = {5}, volume = {5}, number = {5}, pages = {360–369}, abstract = {Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca2+ may allow tracking neuronal activity independent of brain vasculature, thus avoiding the characteristic limitations of current fMRI techniques. Here we report an in vitro proof-of-principle study with a Ca2+-sensitive, Gd3+-based SCA in an attempt to validate its potential use as a functional in vivo marker. First, we quantified its relaxometric response in a complex 3D cell culture model. Subsequently, we examined potential changes in the functionality of primary glial cells following administration of this SCA. Monitoring intracellular Ca2+ showed that, despite a reduction in the Ca2+ level, transport of Ca2+ through the plasma membrane remained unaffected, while stimulation with ATP induced Ca2+-transients suggested normal cellular signaling in the presence of low millimolar SCA concentrations. SCAs merely lowered the intracellular Ca2+ level. Finally, we estimated the longitudinal relaxation times (T1) for an idealized in vivo fMRI experiment with SCA, for extracellular Ca2+ concentration level changes expected during intense neuronal activity which takes place upon repetitive stimulation. The values we obtained indicate changes in T1 of around 1–6%, sufficient to be robustly detectable using modern MRI methods in high field scanners. Our results encourage further attempts to develop even more potent SCAs and appropriate fMRI protocols. This would result in novel methods that allow monitoring of essential physiological processes at the cellular and molecular level.}, web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn500049n}, state = {published}, DOI = {10.1021/cn500049n}, author = {Angelovski G{goran}{Department Physiology of Cognitive Processes}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Milošević M; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Kadjane P{pkadjane}{Department Physiology of Cognitive Processes}; Andjus P; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ RemediosLK2014, title = {A role of the claustrum in auditory scene analysis by reflecting sensory change}, journal = {Frontiers in Systems Neuroscience}, year = {2014}, month = {4}, volume = {8}, number = {44}, pages = {1-8}, abstract = {The biological function of the claustrum remains speculative, despite many years of research. On the basis of its widespread connections it is often hypothesized that the claustrum may have an integrative function mainly reflecting objects rather than the details of sensory stimuli. Given the absence of a clear demonstration of any sensory integration in claustral neurons, however, we propose an alternative, data-driven, hypothesis: namely that the claustrum detects the occurrence of novel or salient sensory events. The detection of new events is critical for behavior and survival, as suddenly appearing objects may require rapid and coordinated reactions. Sounds are of particular relevance in this regard, and our conclusions are based on the analysis of neurons in the auditory zone of the primate claustrum. Specifically, we studied the responses to natural sounds, their preference to various sound categories, and to changes in the auditory scene. In a test for sound-category preference claustral neurons responded to but displayed a clear lack of selectivity between monkey vocalizations, other animal vocalizations or environmental sounds (Esnd). Claustral neurons were however able to detect target sounds embedded in a noisy background and their responses scaled with target signal to noise ratio (SNR). The single trial responses of individual neurons suggest that these neurons detected and reflected the occurrence of a change in the auditory scene. Given its widespread connectivity with sensory, motor and limbic structures the claustrum could play the essential role of identifying the occurrence of important sensory changes and notifying other brain areas—hence contributing to sensory awareness.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fnsys.2014.00044/pdf}, state = {published}, DOI = {10.3389/fnsys.2014.00044}, author = {Remedios R{ryan}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ GleissK2013_2, title = {Acoustic Noise Improves Visual Perception and Modulates Occipital Oscillatory States}, journal = {Journal of Cognitive Neuroscience}, year = {2014}, month = {4}, volume = {26}, number = {4}, pages = {699-711}, abstract = {Perception is a multisensory process, and previous work has shown that multisensory interactions occur not only for object-related stimuli but also for simplistic and apparently unrelated inputs to the different senses. We here compare the facilitation of visual perception induced by transient (target-synchronized) sounds to the facilitation provided by continuous background noise like sounds. Specifically, we show that continuous acoustic noise improves visual contrast detection by systematically shifting psychometric curves in an amplitude-dependent manner. This multisensory benefit was found to be both qualitatively and quantitatively similar to that induced by a transient and target synchronized sound in the same paradigm. Studying the underlying neural mechanisms using electric neuroimaging (EEG), we found that acoustic noise alters occipital alpha (8–12 Hz) power and decreases beta-band (14–20 Hz) coupling of occipital and temporal sites. Task-irrelevant and continuous sounds thereby have an amplitude-dependent effect on cortical mechanisms implicated in shaping visual cortical excitability. The same oscillatory mechanisms also mediate visual facilitation by transient sounds, and our results suggest that task-related sounds and task-irrelevant background noises could induce perceptually and mechanistically similar enhancement of visual perception. Given the omnipresence of sounds and noises in our environment, such multisensory interactions may affect perception in many everyday scenarios.}, web_url = {http://www.mitpressjournals.org/doi/pdf/10.1162/jocn_a_00524}, state = {published}, DOI = {10.1162/jocn_a_00524}, author = {Gleiss S{sgleiss}{Research Group Physiology of Sensory Integration}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ MusallvRLW2012, title = {Effects of neural synchrony on surface EEG}, journal = {Cerebral Cortex}, year = {2014}, month = {4}, volume = {24}, number = {4}, pages = {1045-1053}, abstract = {It has long been assumed that the surface electroencephalography (EEG) signal depends on both the amplitude and spatial synchronization of underlying neural activity, though isolating their respective contribution remains elusive. To address this, we made simultaneous surface EEG measurements along with intracortical recordings of local field potentials (LFPs) in the primary visual cortex of behaving nonhuman primates. We found that trial-by-trial fluctuations in EEG power could be explained by a linear combination of LFP power and interelectrode temporal synchrony. This effect was observed in both stimulus and stimulus-free conditions and was particularly strong in the gamma range (30–100 Hz). Subsequently, we used pharmacological manipulations to show that neural synchrony can produce a positively modulated EEG signal even when the LFP signal is negatively modulated. Taken together, our results demonstrate that neural synchrony can modulate EEG signals independently of amplitude changes in neural activity. This finding has strong implications for the interpretation of EEG in basic and clinical research, and helps reconcile EEG response discrepancies observed in different modalities (e.g., EEG vs. functional magnetic resonance imaging) and different spatial scales (e.g., EEG vs. intracranial EEG).}, web_url = {http://cercor.oxfordjournals.org/content/24/4/1045.full.pdf+html}, state = {published}, DOI = {10.1093/cercor/bhs389}, author = {Musall S{unone}{Department Physiology of Cognitive Processes}; von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Whittingstall K{kevin}{Department Physiology of Cognitive Processes}} } @Article{ PapanikolaouKPSKPSBSLS2014, title = {Population receptive field analysis of the primary visual cortex complements perimetry in patients with homonymous visual field defects}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2014}, month = {4}, volume = {111}, number = {16}, pages = {E1656–E1665}, abstract = {Injury to the primary visual cortex (V1) typically leads to loss of conscious vision in the corresponding, homonymous region of the contralateral visual hemifield (scotoma). Several studies suggest that V1 is highly plastic after injury to the visual pathways, whereas others have called this conclusion into question. We used functional magnetic resonance imaging (fMRI) to measure area V1 population receptive field (pRF) properties in five patients with partial or complete quadrantic visual field loss as a result of partial V1+ or optic radiation lesions. Comparisons were made with healthy controls deprived of visual stimulation in one quadrant [“artificial scotoma” (AS)]. We observed no large-scale changes in spared-V1 topography as the V1/V2 border remained stable, and pRF eccentricity versus cortical-distance plots were similar to those of controls. Interestingly, three observations suggest limited reorganization: (i) the distribution of pRF centers in spared-V1 was shifted slightly toward the scotoma border in 2 of 5 patients compared with AS controls; (ii) pRF size in spared-V1 was slightly increased in patients near the scotoma border; and (iii) pRF size in the contralesional hemisphere was slightly increased compared with AS controls. Importantly, pRF measurements yield information about the functional properties of spared-V1 cortex not provided by standard perimetry mapping. In three patients, spared-V1 pRF maps overlapped significantly with dense regions of the perimetric scotoma, suggesting that pRF analysis may help identify visual field locations amenable to rehabilitation. Conversely, in the remaining two patients, spared-V1 pRF maps failed to cover sighted locations in the perimetric map, indicating the existence of V1-bypassing pathways able to mediate useful vision.}, web_url = {http://www.pnas.org/content/111/16/E1656.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.1317074111}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Papageorgiou TD; Shao Y{yshao}{Department Physiology of Cognitive Processes}; Krapp E; Papageorgiou E; Stingl K; Bruckmann A; Schiefer U; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Article{ EckerBCSDCSBT2014, title = {State Dependence of Noise Correlations in Macaque Primary Visual Cortex}, journal = {Neuron}, year = {2014}, month = {4}, volume = {82}, number = {1}, pages = {235–248}, abstract = {Shared, trial-to-trial variability in neuronal populations has a strong impact on the accuracy of information processing in the brain. Estimates of the level of such noise correlations are diverse, ranging from 0.01 to 0.4, with little consensus on which factors account for these differences. Here we addressed one important factor that varied across studies, asking how anesthesia affects the population activity structure in macaque primary visual cortex. We found that under opioid anesthesia, activity was dominated by strong coordinated fluctuations on a timescale of 1–2 Hz, which were mostly absent in awake, fixating monkeys. Accounting for these global fluctuations markedly reduced correlations under anesthesia, matching those observed during wakefulness and reconciling earlier studies conducted under anesthesia and in awake animals. Our results show that internal signals, such as brain state transitions under anesthesia, can induce noise correlations but can also be estimated and accounted for based on neuronal population activity.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627314001044}, state = {published}, DOI = {10.1016/j.neuron.2014.02.006}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Cotton RJ; Subramaniyan M; Denfield GH; Cadwell CR; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ CavallariPM2014, title = {Comparison of the dynamics of neural interactions between current-based and conductance-based integrate-and-fire recurrent networks}, journal = {Frontiers in Neural Circuits}, year = {2014}, month = {3}, volume = {8}, number = {12}, pages = {1-23}, abstract = {Models of networks of Leaky Integrate-and-Fire (LIF) neurons are a widely used tool for theoretical investigations of brain function. These models have been used both with current- and conductance-based synapses. However, the differences in the dynamics expressed by these two approaches have been so far mainly studied at the single neuron level. To investigate how these synaptic models affect network activity, we compared the single neuron and neural population dynamics of conductance-based networks (COBNs) and current-based networks (CUBNs) of LIF neurons. These networks were endowed with sparse excitatory and inhibitory recurrent connections, and were tested in conditions including both low- and high-conductance states. We developed a novel procedure to obtain comparable networks by properly tuning the synaptic parameters not shared by the models. The so defined comparable networks displayed an excellent and robust match of first order statistics (average single neuron firing rates and average frequency spectrum of network activity). However, these comparable networks showed profound differences in the second order statistics of neural population interactions and in the modulation of these properties by external inputs. The correlation between inhibitory and excitatory synaptic currents and the cross-neuron correlation between synaptic inputs, membrane potentials and spike trains were stronger and more stimulus-modulated in the COBN. Because of these properties, the spike train correlation carried more information about the strength of the input in the COBN, although the firing rates were equally informative in both network models. Moreover, the network activity of COBN showed stronger synchronization in the gamma band, and spectral information about the input higher and spread over a broader range of frequencies. These results suggest that the second order statistics of network dynamics depend strongly on the choice of synaptic model.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fncir.2014.00012/full#h1}, state = {published}, DOI = {10.3389/fncir.2014.00012}, author = {Cavallari S; Panzeri S{stefano}; Mazzoni A} } @Article{ PanagiotaropoulosKL2014, title = {Subjective visual perception: From local processing to emergent phenomena of brain activity}, journal = {Philosophical Transactions of the Royal Society London B}, year = {2014}, month = {3}, volume = {369}, number = {1641}, pages = {1-13}, abstract = {The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.}, web_url = {http://rstb.royalsocietypublishing.org/content/369/1641/20130534.abstract}, state = {published}, DOI = {10.1098/rstb.2013.0534}, EPUB = {20130534}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ PerrodinKPL2013, title = {Auditory and Visual Modulation of Temporal Lobe Neurons in Voice-Sensitive and Association Cortices}, journal = {Journal of Neuroscience}, year = {2014}, month = {2}, volume = {34}, number = {7}, pages = {2524-2537}, abstract = {Effective interactions between conspecific individuals can depend upon the receiver forming a coherent multisensory representation of communication signals, such as merging voice and face content. Neuroimaging studies have identified face- or voice-sensitive areas (Belin et al., 2000; Petkov et al., 2008; Tsao et al., 2008), some of which have been proposed as candidate regions for face and voice integration (von Kriegstein et al., 2005). However, it was unclear how multisensory influences occur at the neuronal level within voice- or face-sensitive regions, especially compared with classically defined multisensory regions in temporal association cortex (Stein and Stanford, 2008). Here, we characterize auditory (voice) and visual (face) influences on neuronal responses in a right-hemisphere voice-sensitive region in the anterior supratemporal plane (STP) of Rhesus macaques. These results were compared with those in the neighboring superior temporal sulcus (STS). Within the STP, our results show auditory sensitivity to several vocal features, which was not evident in STS units. We also newly identify a functionally distinct neuronal subpopulation in the STP that appears to carry the area's sensitivity to voice identity related features. Audiovisual interactions were prominent in both the STP and STS. However, visual influences modulated the responses of STS neurons with greater specificity and were more often associated with congruent voice-face stimulus pairings than STP neurons. Together, the results reveal the neuronal processes subserving voice-sensitive fMRI activity patterns in primates, generate hypotheses for testing in the visual modality, and clarify the position of voice-sensitive areas within the unisensory and multisensory processing hierarchies.}, web_url = {http://www.jneurosci.org/content/34/7/2524.full.pdf+html}, state = {published}, DOI = {10.1523/JNEUROSCI.2805-13.2014}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MishraMGPSEGP2013, title = {Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes}, journal = {ACS Chemical Neuroscience}, year = {2014}, month = {2}, volume = {5}, number = {2}, pages = {128–137}, abstract = {A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR5) antagonists. In order to directly visualize mGluR5 binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR5 cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.}, web_url = {http://pubs.acs.org/doi/ipdf/10.1021/cn400175m}, state = {published}, DOI = {10.1021/cn400175m}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Mishra R{ritu}{Department High-Field Magnetic Resonance}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Pal R; Sim N; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Goldberg M; Parker D} } @Article{ HagbergMPBMVKDKL2013, title = {Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex}, journal = {Contrast Media & Molecular Imaging}, year = {2014}, month = {1}, volume = {9}, number = {1}, pages = {71–82}, abstract = {Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look–Locker-based quantitative T1 mapping, and T1-weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2–4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cmmi.1535/pdf}, state = {published}, DOI = {10.1002/cmmi.1535}, author = {Hagberg G{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Power A{apower}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Kiselev VG; Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Kub{\`i}ček V; Angelovski G{goran}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ EvrardLB2013, title = {Modular architectonic organization of the insula in the macaque monkey}, journal = {Journal of Comparative Neurology}, year = {2014}, month = {1}, volume = {522}, number = {1}, pages = {64–97}, abstract = {In order to provide a framework for ongoing analyses of the neuronal connections of the insular cortex of the macaque monkey using modern high-resolution methods, we examined its anatomical organization in serial coronal sections stained alternately with Nissl and Gallyas (myelin) techniques. We observed the same 15 distinct architectonic areas in 10 brains. Within the granular, dysgranular, and agranular regions described in prior studies, we identified 4, 4, and 7 distinct areas, respectively. Across brains, these areas have consistent architectonic characteristics, and in flat map reconstructions they display a consistent topological or neighborhood arrangement, despite variations in the size of individual areas between cases. The borders between areas are generally rather sharply defined. Some areas, in particular the dysgranular areas, appear to consistently contain subtle transitions that suggest possible sub-areas or modules within the well-delimited areas. The presence of a distinct granular area that straddles the fundus of the superior limiting sulcus over its entire posterior-to-anterior extent is consistent with the available evidence on interoceptive thalamo-cortical projections, and also with the tensile anchor theory of species-specific cortical gyrification. These observations are consonant with the homeostatic afferent model of processing in the primate insula, and they suggest that discrete modules within insular cortex provide the basis for its polymodal integration of all salient activity relevant to ongoing emotional behavior.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cne.23436/pdf}, state = {published}, DOI = {10.1002/cne.23436}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Bud Craig AD} } @Article{ GleissK2013_3, title = {Oscillatory mechanisms underlying the enhancement of visual motion perception by multisensory congruency}, journal = {Neuropsychologia}, year = {2014}, month = {1}, volume = {53}, pages = {84–93}, abstract = {Multisensory interactions shape every day perception and stimuli in one modality can enhance perception in another even when not being directly task relevant. While the underlying neural principles are slowly becoming evident, most work has focused on transient stimuli and little is known about those mechanisms underlying audio–visual motion processing. We studied the facilitation of visual motion perception by auxiliary sounds, i.e. sounds that by themselves do not provide the specific evidence required for the perceptual task at hand. In our experiment human observers became significantly better at detecting visual random dot motion when this was accompanied by auxiliary acoustic motion rather than stationary sounds. EEG measurements revealed that both auditory and visual motion modulated low frequency oscillations over the respective sensory cortices. Using single trial decoding we quantified those oscillatory signatures permitting the discrimination of visual motion similar to the subject's task. This revealed visual motion-related signatures in low (1–4 Hz) and alpha (8–12 Hz) bands that were significantly enhanced during congruent compared to disparate audio–visual conditions. Importantly, the auditory enhancement of these oscillatory signatures was predictive of the perceptual multisensory facilitation. These findings emphasise the importance of slow and alpha rhythms for perception in a multisensory context and suggest that acoustic motion can enhance visual perception by means of attention or priming-related mechanisms that are reflected in rhythmic activity over parieto-occipital regions.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0028393213003941}, state = {published}, DOI = {10.1016/j.neuropsychologia.2013.11.005}, author = {Gleiss S{sgleiss}{Research Group Physiology of Sensory Integration}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Inproceedings{ BesserveLS2013, title = {Statistical analysis of coupled time series with Kernel Cross-Spectral Density operators}, year = {2014}, pages = {2537-2545}, abstract = {Many applications require the analysis of complex interactions between time series. These interactions can be non-linear and involve vector valued as well as complex data structures such as graphs or strings. Here we provide a general framework for the statistical analysis of these interactions when random variables are sampled from stationary time-series of arbitrary objects. To achieve this goal we analyze the properties of the kernel cross-spectral density operator induced by positive definite kernels on arbitrary input domains. This framework enables us to develop an independence test between time series as well as a similarity measure to compare different types of coupling. The performance of our test is compared to the HSIC test using i.i.d. assumptions, showing improvement in terms of detection errors as well as the suitability of this approach for testing dependency in complex dynamical systems. Finally, we use this approach to characterize complex interactions in electrophysiological neural time series.}, file_url = {fileadmin/user_upload/files/publications/2013/NIPS-2013-Besserve.pdf}, web_url = {http://nips.cc/Conferences/2013/}, editor = {Burges, C.J.C. , L. Bottou, M. Welling, Z. Ghahramani, K.Q. Weinberger}, publisher = {Curran}, address = {Red Hook, NY, USA}, booktitle = {Advances in Neural Information Processing Systems 26}, event_name = {Twenty-Seventh Annual Conference on Neural Information Processing Systems (NIPS 2013)}, event_place = {Lake Tahoe, NV, USA}, state = {published}, ISBN = {78-1-63266-024-4}, author = {Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Sch\"olkopf B{bs}{Department Empirical Inference}} } @Inbook{ PapageorgiouPS2014_2, title = {A Systematic Approach to Visual System Rehabilitation: Population Receptive Field Analysis and Real-time Functional Magnetic Resonance Imaging Neurofeedback Methods}, year = {2014}, month = {5}, pages = {371-402}, abstract = {Visual information transmission flows from the retinal ganglion cells to the lateral geniculate nucleus and then to the primary visual cortex (V1), the chief cortical relay of visual information and in turn, to “higher” extrastriate areas. Beyond area V1, visual processing is distributed across multiple interconnected brain areas, the precise role of which and their interactions are not yet, completely understood. To add to the dynamic complexity of the system, feedback from higher areas and modulation by top-down processes, such as attention are often critical in the formation of visual percepts (Deco and Lee; 2004; Olhausen, 2003; Kastner and Ungerleider, 2000; Mumford, 1994; Hubel and Weisel, 1977).}, web_url = {http://cdn.intechopen.com/pdfs-wm/46090.pdf}, editor = {Papageorgiou, T.D. , G.I. Christopoulos, S.M. Smirnakis}, publisher = {InTech}, address = {Rijeka, Croatia}, booktitle = {Advanced Brain Neuroimaging Topics in Health and Disease: Methods and Applications}, state = {published}, ISBN = {978-953-51-1203-7}, DOI = {10.5772/58258}, author = {Papageorgiou TD; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Poster{ KleinESLS2014, title = {Optogenetic investigation of the LGN koniocellular influence on V1 activity}, year = {2014}, month = {11}, day = {19}, volume = {44}, pages = {816.08}, abstract = {The lateral geniculate nucleus (LGN) of the primate thalamus is organized into parallel parvo-, magno- and konio-cellular projection streams to primary visual cortex (V1). While magno and parvo cells label positive for Parvalbumin and project to layer-4 of V1, konio neurons project to the superficial layers of V1 and are positive for CamKII and Calbindin [1] [2]. Of the three systems, our understanding of the konio pathway and its contribution to vision is still very limited. Here we used optogenetics in anaesthetized macaque monkeys to investigate the influence of koniocellular LGN neurons on V1. To this end we injected the construct AAV5-CamKIIa-ChR2-eYFP into the LGN of two monkeys. Post-mortem histological and immunohistochemical analysis verified that ChR2 expression was predominantly present in the koniocellular system, which is characterized by its expression of CamKII and a focus on the LGN intercalated layers. In earlier experiments optogenetic stimulation that was applied to neurons in the LGN intercalated layers resulted in activation of the superficial layers in V1, but not layer 4, as determined from current-source-density measurements (CSD) from multi-contact laminar recordings in V1. Preliminary analysis of the cortical LFP also showed a power decrease in the beta frequency range (15-30Hz) for the superficial layers during optogenetic stimulation. In additional control experiments in one monkey, we found that electrical micro-stimulation in a parvocellular layer activated layer 4 of V1 similar to visual flicker stimulation. In contrast, electrical microstimulation in the intercalated LGN layers induced activity in superficial layers of V1 similarly to the optogenetic stimulation. In summary, we show for the first time the effective connectivity of the koniocellular LGN projection to V1 and its influence on the LFP. Methodologically, our results demonstrate that both circuit probing approaches, optogenetics and electrical microstimulation, render results with very similar specificity. Reference 1. Hendry, S.H. and T. Yoshioka, A neurochemically distinct third channel in the macaque dorsal lateral geniculate nucleus. Science, 1994. 264(5158): p. 575-577. 2. Casagrande, V.A., et al., The morphology of the koniocellular axon pathway in the macaque monkey. Cereb Cortex, 2007. 17(10): p. 2334-2345.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Shapcott K; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Schmid MC} } @Poster{ LoweZMvLP2014, title = {Different cortical layers in V1 encode different visual information in different frequency bands}, year = {2014}, month = {11}, day = {18}, volume = {44}, pages = {532.19}, abstract = {We previously reported that the activity of primary visual cortex (V1) transmits information about complex naturalistic video stimuli in two distinct frequency bands: a low frequency band (1-24 Hz), and a high frequency (60-100 Hz) gamma oscillation range, with each range carrying its own independent information about the visual stimuli [1]. Here we ask whether these independent frequency channels originate from distinct cortical laminae. We used laminar electrodes with 150 micron spacing spanning the whole cortical depth to record extracellular field potentials from the primary visual cortex of opiate-anaesthetised macaques during presentation of a 2 minute long Hollywood colour movie clip. Using the recorded Local Field Potential (LFP), we computed the Current Source Density (CSD) for each trial. From the time-resolved power of the CSD in each trial, we estimated the mutual information that the power at each frequency carries about which section of the movie is being presented, and how much information there is in frequency bands about different spatial resolutions of changes in luminance. We found, across depth and frequency, two distinct regions carrying large amounts of independent information about the movie stimulus: the low frequency (4-16 Hz) band had high information at depths corresponding to layers 4-6, whereas the high frequency (64-250 Hz) band had high information in layers 1-3. This suggests that different laminae of cortical circuits generate independent information channels that code information in separate frequency ranges. Furthermore, we found the low frequency band contained information about low spatial frequencies changes in luminance (<1 cycle per degree), whilst the high frequency band contained information about finer spatial details (1-6 cycles per degree). This suggests information about these two spatial frequency components arises through two different cortical mechanisms within V1, and information about them is encoded separately in two different frequency bands. References [1] Belitski, A., et al. (2008). J Neuroscience, 28(22), 5696-709.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Lowe SC; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; van Rossum MCW; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ UberoMartinezHPILE2014, title = {Anterograde and retrograde analysis of the connections between the orbital and medial prefrontal cortex and the locus coeruleus in the macaque monkey}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {446.14}, abstract = {Prior dopamine-beta-hydroxylase immunohistochemistry suggested that the projections from the locus coeruleus (LC) to the orbital and medial prefrontal cortex (PFC) are heterogeneous (Lewis & Morrison, J Comp Neurol, 1989, 282:317-30). A tract-tracing corroboration of this heterogeneity is still lacking. In addition, whether areas of PFC that receive direct projections from LC are the same that provide modulatory feedback to LC remains unclear. Here, we examined the distribution of retrograde and anterograde labeling in LC with injections of multiple, differently-colored neuronal tracers in distinct architectonic areas in orbital and medial PFC. On the basis of its connectivity, the orbital and medial PFC was divided into orbital (OPFC) and medial (MPFC) ‘networks’ (Price, ANYAS, 2007, 1121:54-71). Injections of retrograde tracers in PFC produced dense to sparse labeling in the LC core. The distribution of this labeling varied with the location of the injection site, supporting the prior immunohistochemical evidence. In the MPFC network, injections in areas 24, 25, 32, 10, 14c, and the intermediate agranular insula (Iai) produced a moderate to dense labeling in LC, with injections in areas 24, 25 and 32 producing the densest labeling, and with injection in area 10m producing more labeling than injection in area 10o. In the OPFC network, injections in area 13b, 12l, and the posterior median agranular insula (Iapm) produced dense labeling in LC whereas injections in area 11l produced only sparse labeling. The distribution of retrograde labeling in LC revealed a conspicuous overlap of cells labeled from distinct areas, with no obvious internal topography. Despite this conspicuous overlap, no double labeled cells could be observed in cases with injections of differently-colored tracers in distinct areas. This absence of co-localization is consistent with similar recent evidence obtained in rats (Chandler & Waterhouse, Front Behav Neurosci, 2012, 6:1-9) and suggests a complex spatial segregation of LC projecting neurons. The injection of anterograde tracers in PFC produced dense to sparse labeling predominantly in the direct periphery of the LC core. The examination of the distribution of this labeling indicated that the connections between LC and the different areas of OPFC and MPFC are rather reciprocal. In the MPFC network, injections in areas 24, 25, 32, 11m and Iai produced dense labeling whereas injections in 10m and 10o produced moderate and no labeling, respectively. In the OPFC network, injections in area 13l, Iapm, and the medial agranular insula (Iam) produced dense labeling whereas injections in areas 11l produced sparse labeling.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Ubero Martinez M{mubero}{Department Physiology of Cognitive Processes}; Hernandez D{dhernandez}{Department Physiology of Cognitive Processes}; Price JL; Insausti R; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}} } @Poster{ EvrardPL2014, title = {Anterograde and retrograde examination of prefronto-insular connections in the macaque monkey}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {446.11}, abstract = {A recent cyto- and myelo-architectonic analysis demonstrated that the classical agranular, dysgranular and granular ‘sectors’ of the insular cortex in the macaque monkey are divided into consistent and sharply demarcated areas, most of which contain smaller subdivisions or modules (Evrard et al., J Comp Neurol, 2014, 522:64-97). This refined architectonic map readily suggests the existence of a matching modular organization of the connections and functions of the insula. Prior injections of anterograde or retrograde tracers in distinct areas of the orbital and medial ‘networks’ of the prefrontal cortex (OPFC and MPFC) in the macaque monkey labeled small discontinuous ‘patches’ of neurons (Saleem et al., J Comp Neurol, 2008, 506:659-93). In light of the new architectonic map, each of these patches could correspond to a distinct architectonic module. Here, we examined the modular distribution of neurons and axon terminals labeled in the insula with injections of anterograde and retrograde tracers in the distinct OPFC and MPFC network areas. Injections in OPFC areas labeled conspicuous patches of neurons or terminals in both agranular and dysgranular areas. The exact spatial location of each patch adequately matched the location of a distinct architectonic module and varied with the location of the injection site in OPFC. For example, injections in area 13m reproducibly labeled the modules ‘3’ and ‘5’ of the dorsal dysgranular area (Idd3 and Idd5) and the module ‘3’ of the mound dysgranular area (Idm3), whereas injections in area 11l labeled Idm2 and Idm3 as well as Idd4 but not Idd3 and Idd5. Similarly, injections in MPFC areas produced sparser labeling that variably involved Idm2, both modules of the ventral dysgranular area (Idv1 and Idv2), the dorsal and ventral posterior agranular areas (Iapd and Iapv), and the fundal agranular area (Ivfa). The present data demonstrate that each architectonic module recently identified in the macaque insula has distinct connections with distinct OPFC and MPFC areas. This supports the view that the fine architecture of the insula provides the basis for a modular integration of interoceptive and prefrontal activities. Together with the insulo-prefrontal connections, the examination of the connections of each insular module with the rest of the cerebral cortex and with subcortical nuclei will provide a significant insight in the functional organization of the primate insular cortex.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Price JL; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ SalehPLE2014, title = {Insular projections to the midbrain periaqueductal gray in the macaque monkey}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {446.13}, abstract = {We recently demonstrated the presence of the large spindle-shaped von Economo neuron (VEN) in a specific architectonic area (‘VEN-area’) in the anterior insula in the macaque monkey (Evrard et al., Neuron, 2012, 74:482-9). Given its relatively large size and localization in layer 5a, the VEN likely projects to distant brain regions including the midbrain periaqueductal gray (PAG). A prior tracing study demonstrated that distinct areas in the macaque anterior insula project densely to PAG (An et al., J Comp Neurol, 1998, 401:455-79). Here, using previously published (An et al., 1998) and new material, we examined (1) the distribution of neurons retrogradely labeled in the insula with injections of cholera toxin b, fast blue or fluorescent dextran in different columns of PAG, (2) whether any of the architectonic areas projecting to PAG corresponds to the VEN-area, and (3) whether the VEN and its co-mingled companion ‘fork’ cell (FC) project to PAG. Injections in PAG invariably labeled small, discontinuous patches of neurons in the ventral portion of the insula both posterior and anterior to the limen insula. Using a recently refined architectonic map of the macaque insula (Evrard et al., J Comp Neurol, 2014, 522:64-97), we observed that the areal affiliation of these patches consistently varied with the location of the injection site. Injections in the dorsal lateral column of PAG (dlPAG) sparsely labeled the fundal agranular area (Ivfa), and the dorsal and ventral posterior agranular areas (Iapd and Iapv), posterior to the limen, and densely labeled the intermediate agranular area (Iai), anterior to the limen, as reported before by An et al. (1998). Injections in the lateral column of PAG (lPAG) labeled the ‘mound’ dysgranular area (Idm) and the dorsal posterior agranular area (Iapd), posterior to the limen, and the lateral agranular insula (Ial), anterior to the limen. Injections in the ventrolateral column of PAG (vlPAG) produced an intermediate labeling including both Iai and Ial. VENs and fork cells were located preferentially, if not exclusively, in Ial. An analysis of the morphology of the neurons retrogradely labeled in Ial revealed a small subset of VENs and fork cells. The projection of directly adjacent insular areas to different columns of PAG may provide a unique insight in the efferent cortical control of the autonomous system. In this context, the VEN and their companion FC could have a direct and rapid influence on the sympathetic and parasympathetic substrate of emotional behavior and feelings.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Saleh TO; Price JL; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Evrard HC{ervrard}} } @Poster{ MombielaUPILE2014, title = {Projections of the orbital and medial prefrontal cortex to the ventral tegmental area in the macaque monkey}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {446.12}, abstract = {The orbital and medial prefrontal cortex (OMPFC) in macaque monkeys sends discreet glutamatergic projections to the ventral tegmental area (VTA) (Ongür et al., J Comp Neurol, 1998, 401:480-505; Frankle et al., Neuropsychopharmacol, 2006, 31:1627-36). These projections likely provide a mild direct influence on VTA activity, in addition to a stronger indirect influence involving intermediary glutamatergic diencephalic nuclei. On the basis of its connectivity, OMPFC has been divided into orbital ‘sensory’ (OPFC) and medial ‘visceromotor’ (MPFC) networks (Price, ANYAS, 2007, 1121:54-71). Projections to VTA originate from both networks but whether their density varies across areas within a single network and whether they are topographically organized within VTA remain unknown. Here, we examined (1) the distribution of anterograde labeling produced in VTA with injections of biotin dextran amine or fluororuby in distinct architectonic areas in OPFC and MPFC, and (2) the distribution of retrograde labeling produced in PFC with injections of cholera toxin b or fluorescent dextran in VTA. The analysis of the anterograde labeling confirmed prior evidence that PFC contributes only moderate projections to VTA, in contrast with their projections to other targets (e.g. striatum). The density of anterogradely labeled fibers with varicosities in VTA varied with the location of the injection site, so that each network had areas contributing more projections than others. Injections in the medial network produced overall more labeling than injection in the orbital network. Injections in areas 25, 24b, 32, and the intermediate agranular insula (Iai) produced relatively dense labeling. In contrast, injections in areas 10o, 11m and 14c produced sparse or no labeling. In the orbital network, only injections in area 13b and in the posterior median agranular insula (Iapm) produced relatively dense labeling with no major difference between areas. Injections in all the other areas including areas 13l, 11l, 12m, 12r and 12l produced sparse or no labeling. A comparison of the spatial distribution of the labeled fibers in VTA revealed a considerable overlap of the projections from the different areas with only a subtle trend for medial projections to terminate more lateral and rostral than orbital projections. Retrograde tracers injections in VTA supported the heterogeneity of the areal distribution of the cells of origin of PFC projections to VTA. Large injections preferentially labeled areas from which dense labeling was obtained in VTA. Smaller injections tended to label only a subset of these areas supporting the existence of a discreet internal topography within VTA.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Mombiela DH{dhernandez}{Department Physiology of Cognitive Processes}; Ubero M{mubero}{Department Physiology of Cognitive Processes}; Price JL; Insausti R; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}} } @Poster{ PriesemannWVPLTGNM2014, title = {Spiking activity in vivo suggests a slightly sub-critical brain state in rats, cats and monkeys}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {432.14}, abstract = {Neural activity in vitro can show bursts of activity. These bursts are termed neural avalanches and their size distribution f(s) approximates a power law [Beggs & Plenz, 2003]. Since power law distributions are characteristic for self-organized critical (SOC) states [Bak, Tang, Wiesenfeld, 1987], neural activity was proposed to be SOC, too. Moreover, SOC may provide a basis for optimal information processing [Shew & Plenz, 2013]. Evidence for the SOC hypothesis has been obtained for coarse measures of neural activity (LFP, EEG, MEG, BOLD), but surprisingly for spiking activity in vivo evidence for SOC is still missing. Therefore we analyzed highly parallel spike recordings from rats (hippocampus), cats (visual cortex) and monkeys (prefrontal cortex). For all recordings the f(s) were similar (Fig. 1 A-C), but showed fundamental differences to f(s) from a critical spiking model (Fig. 1 D), even under subsampling (Fig. 1 E). The differences between in vivo dynamics and model dynamics could be overcome by decreasing the model’s excitatory synaptic strength, while increasing its external input commensurately (Fig. 1 F). Thereby the model became subcritical and its separation of time scales (STS), which is fundamental to SOC, was eliminated. The match between the subcritical model and the neural activity held for standard and novel avalanche measures (f(s); branching parameter; mean avalanche size; frequency of single events) even when changing the temporal bin size over its full range. In addition, we showed that the same results held for local field potentials recorded in humans. These results suggest that neural activity in vivo is not SOC, but instead reflects a slightly subcritical regime without STS. This regime strikes a balance between optimal information processing and the need to avoid runaway activity. In this regime, avalanches are not temporally separated bursts, but form a mélange. Potential advantages of this regime compared to SOC are faster information processing (due to the lack of STS) and keeping a safety margin from supercriticality, which has been linked to epilepsy.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Priesemann V; Wibral M; Valderrama M; Pr\"opper R; Le Van Quyen M; Triesch J; Geisel T; Nikolić D; Munk M{munk}{Department Physiology of Cognitive Processes}} } @Poster{ WatanabeTKLL2014, title = {Visual backward masking in rats: A behavioral task for studying the neural mechanisms of visual awareness}, year = {2014}, month = {11}, day = {17}, volume = {44}, pages = {436.05}, abstract = {The neural mechanism of visual awareness has been primarily studied by contrasting neural activity between visible and invisible stimuli, in attempt to unveil the necessary and sufficient condition for neural representations to enter conscious vision. Visual illusions that render stimuli invisible (e.g., binocular rivalry, backward masking) are prominent behavioral paradigms. So far, majority of studies on visual awareness have been conducted on human and non-human primates. Although these studies greatly contributed to establishing specific brain region-dependent modulation of neural activity by awareness, the field would benefit from being able to conduct experiments on rodents. This advance would provide access to modern techniques such as optogenetic manipulation and two-photon imaging, etc. Here, for the first time, we report backward masking in rats. Backward masking is a visual illusion in which a target is rendered invisible by a visual mask that follows the target with a brief stimulus onset asynchrony (SOA). We first developed a head-fixed rat spherical treadmill system that is amicable to rats performing visual tasks with low contrast, short duration stimuli, which are required for testing backward masking. Rats were initially trained to discriminate a “go” target (vertical grating: 0.15cpd, 28deg visual angle) and a “no-go” target (horizontal grating: 0.075 cpd, 28deg visual angle) without the visual mask. They responded either by running or staying still on the treadmill during a brief time-window after stimulus presentation and were rewarded with drops of water for running in response to a “go” target and punished with time-out penalty for running in response to a “no-go” target. Duration and contrast of target stimuli were gradually reduced to experimental parameters for the backward masking experiment (duration:16ms, luminance contrast:15%). After achieving threshold performance (d’ >1.5), backward masking experiments were conducted with SOAs at 16, 33, 49, 66, 83, 99, 116 ms. Plaids were used as visual mask (duration:33ms, luminance contrast:95%). In all 5 rats, smaller SOA led to statistically non-significant differences between hit and false-alarm ratio. In contrast, difference between hit and false alarm rate were significant for larger SOAs. Threshold SOAs at which masking occurred varied across rats (range: 33m -66ms). In conclusion, a visual stimulus can be rendered invisible with short SOAs, and hence, backward masking can be used to study the neural correlate of consciousness in rats.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Totah N{ntotah}{Department Physiology of Cognitive Processes}; Kaiser K{kkaiser}{Department Physiology of Cognitive Processes}; L\"owe S{sloewe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ TotahNPLE2014_2, title = {Effects of tonic and phasic norepinephrine release on layer-specific activity in the prefrontal cortex in anesthetized and awake rat}, year = {2014}, month = {11}, day = {16}, volume = {44}, pages = {175.11}, abstract = {Cognitive control relies on functional connectivity between the prefrontal cortex (PFC) and other brain regions. Cortical connections follow a laminar organization, yet little is known about PFC laminar activity. Moreover, cognition is modulated by PFC norepinephrine (NE), which is released in tonic and phasic patterns, but the layer-specific effects of NE on PFC activity are relatively unexplored. We recorded extracellular laminar activity in rat PFC under urethane anesthesia. Tonic and phasic NE were independently manipulated. Tonic NE was increased using the reuptake inhibitor Atomoxetine, ATX, (0.3, 1.0mg/kg), administered acutely (i.p.) or chronically (28 days i.p. diffusion via osmotic pump). Phasic NE release was induced by a brief train (50Hz, 200ms) of mild electric pulses (0.4ms, 30uA) delivered to locus coeruleus (LC). Phasic NE evoked a sustained increase in PFC single unit spiking and population activity (LFP gamma power). The degree of modulation did not differ across different layers. Current source density analysis revealed a current sink in layers 2/3 and 5, suggesting that the cortical activation evoked by phasic NE was mediated via thalamo-cortical afferents. Chronic ATX dampened the PFC response to LC stimulation equally in each layer. Specifically, a smaller proportion of PFC units increased firing rate after LC stimulation (vehicle, 83%; 1.0mg/kg, 34%). In addition, increased NE level resulted in weaker gamma power modulation and lower current sink amplitude in response to NE phasic release. On the other hand, spontaneous activity was increased by ATX. The spontaneous activity enhancement was specific to layers 5,6 (vehicle, 0.9±0.2Hz; 1.0mg/kg, 3.3±0.5Hz). Comparison with acute ATX is ongoing. Given that NE release occurs in response to salient stimuli and decisions, which involve a change in coordinated activity across neurons, we tested the hypothesis that NE altered coordinated activity (spike-gamma LFP phase-locking). Tonic NE increased phase locking after LC stimulation in layers 2/3 and 5 (L2/3: vehicle vs 0.3mg/kg, 1.3±0.5 vs 4.7±0.9; L5: 1.4±0.3 vs 2.8±0.8). Therefore, NE may modulate coordinated activity in thalamocortical recipient layers. Additional analyses of coordinated activity (spike cross-correlations and LFP-LFP synchrony) are underway. Studies in behaving rats will monitor LC and PFC/sensory cortex laminar activity to identify the functional significance of interaction between the NE system and cortex. NE modulation of PFC thalamic input and layer 6 spontaneous activity could effect the output of these layers to sensory cortex and modulate PFC top-down selection of stimuli in sensory cortex.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Neves R{ricardo}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ MoghaddamT2014, title = {Prefrontal cortex and dopamine single neuron spike rates and LFP phase represent time over distinct scales}, year = {2014}, month = {11}, day = {16}, volume = {44}, pages = {230.26}, abstract = {Expectations are generated on multiple timescales. During behavioral planning and working memory utilization, expectations are constructed on the multi-second level (sec), whereas expectations can be externally guided at the sub-second level by rhythmic stimuli (msec). Estimation of multi-second intervals has been associated with monotonic, “climbing” changes in neuron spike rate. On the other hand, sub-second expectations have been associated with rhythmic fluctuations of neuronal excitability in relation to phase of mesoscopic signals. It is not known if changes in gradual spike rate and phase-modulation of neuronal excitability co-occur during multi-second expectations. We studied this question by measuring spike rate, across-trial phase consistency, and phase locked modulations of excitation during a multi-second stimulus expectation task. We recorded single unit spiking and local field potentials from 3 rodent brain regions that have been implicated in time interval estimation, as well as in expectancy and behavioral planning: the prefrontal cortex (PFC), the anterior cingulate cortex (ACC), and the dopamine-producing ventral tegmental area (VTA). A stimulus-evoked phase reset in the PFC, ACC and VTA was observed, which may allow adaptive coding by these neurons and underlie their necessity for behavioral flexibility. In contrast, intrinsic across-trial phase consistency was not observed and phase modulations of excitation did not change in a climbing pattern. These data suggest that expectation over multi-second time intervals is better represented by climbing activity of single dopamine and PFC neurons as compared to mesoscopic signal phase.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Moghaddam B; Totah NKB{ntotah}{Department Physiology of Cognitive Processes}} } @Poster{ InsaustiHULAMAIMEL2014, title = {Comparison of VTA and SN ascending projections to the Hippocampal Formation in the monkey (Macaca fascicularis). An anterograde tracer study}, year = {2014}, month = {11}, day = {15}, volume = {44}, pages = {91.03}, abstract = {The Hippocampal Formation (HF) is the brain system that supports declarative memory in human and nonhuman primates. The HF is made up of dentate gyrus (DG), Cornu Ammonis fields CA3, CA2 and CA1, subiculum (S), presubiculum (PrS), parasubiculum (PaS) and entorhinal cortex (EC). The unidirectional circuit that links all these structures through several synaptic steps ultimately, end up in stable memories, very likely, in the cerebral cortex. This consolidation process takes place once the brainstem activity is cancelled (Logothetis et al., 2012). The HF receives cortical input from polymodal association areas, as well as subcortical brain centers, which are monoaminergic brainstem nuclei. The main centers with direct access to the HF, are dopamine containing cell groups such as the ventral tegmental area (VTA) and the substantia nigra (SN) and adjacent mesencephalic reticular formation, serotonergic (centralis superior and dorsal raphe nuclei), and noradrenergic (Locus coeruleus) as retrograde tracing studies demonstrated. The paths and termination of those brainstem projections to the different HF fields are unknown. In the course of an ongoing study aiming at the study of brainstem projections to the HF, we describe the resulting labeling after deposits into the SN and the in different parts of the VTA. 1) Direct nigro-hipocampal fibers are scarce, but present in all components of the HF in particular rostrally, while VTA are somewhat denser. 2) Both VTA and SN fibers were observed in non-cellular strata of the HF. 3) Both SN and VTA present fibers that change course and adopt a direction in a transversal plane to the main axis of the hippocampus, in stratum radiatum and lacunosum-moleculare, usually orthogonal to the direction of the dendrites. 4) The SN, was observed giving off fibers to the polymorphic cell layer of the DG, which crossed the granule cell layer, into innermost portion of the molecular layer of the DG. Our results are in agreement with retrograde studies in which scarce retrograde labeled neurons were found, and suggest that direct and presumably through modulation of the excitability of the dendritic field of neurons in the HF, they possibly produce an effect on the HF function in memory, as it has been shown already in the monkey (Logothetis et al., 2012). (Supported by Grant BFU 2009-14705, MINECO, Spain)}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Insausti R; Hernandez D{dhernandez}{Department Physiology of Cognitive Processes}; Ubero M{mubero}{Department Physiology of Cognitive Processes}; Legidos M; Arroyo M; Marcos M; Artacho E; Iniguez de Onzono M; Munoz M; Evrard H{evrard}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ BahmaniMLK2014_2, title = {Binocular Flash Suppression in the Primary Visual Cortex of Anesthetized and Awake Macaques}, year = {2014}, month = {10}, volume = {15}, pages = {24}, abstract = {Primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies. However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1. In particular, only a moderate percentage of neurons in V1 were found to modulate in parallel with perception with magnitude substantially smaller than the physical preference of these neurons. It is yet unclear whether these small modulations are rooted from local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. We found that a small but significant modulation was present in both the anesthetized and awake states during the flash suppression presentation. Furthermore, the relative amplitudes of the perceptual modulations were not significantly different in the two states. We suggest that these early effects of perceptual suppression might occur locally in V1, in prior processing stages or within early visual cortical areas in the absence of top-down feedback from higher cognitive stages that are suppressed under anesthesia.}, web_url = {http://www.neuroschool-tuebingen-nena.de/fileadmin/user_upload/Dokumente/neuroscience/Abstractbook_NeNa2014_final.pdf}, event_name = {15th Conference of Junior Neuroscientists of Tübingen (NeNa 2014)}, event_place = {Schramberg, Germany}, state = {published}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ PerrodinKLP2014, title = {The neurobiology of voice processing: What have we learned from neuronal recordings in voice-sensitive cortex?}, year = {2014}, month = {9}, day = {14}, volume = {5}, pages = {99-100}, web_url = {https://www.conftool.com/auditorycortex2014/index.php?page=browseSessions&print=yes&doprint=yes&form_room=2&mode=table&presentations=show}, event_name = {5th International Conference on Auditory Cortex: Towards a Synthesis of Human and Animal Research}, event_place = {Magdeburg, Germany}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ PiesemannWVPLGTNM2014, title = {Do Highly Parallel Spike Recordings from Rats, Cats, and Monkeys Indicate a Self-Organized Critical State?}, year = {2014}, month = {9}, day = {4}, pages = {206-207}, abstract = {The dynamics of highly parallel spike recordings can be characterized in terms of neural avalanches. The avalanche distributions reflect the correlations in activity across neurons, and across time. In vitro, avalanche size distributions f(s) were found to approximate power laws [1]: f(s)∼s−τ. This indicates diverging correlation lengths, and is characteristic for self-organized criticality (SOC) [2], prompting the hypothesis that neural population dynamics may be SOC. Moreover, SOC may provide a basis for optimal information processing [3]. However, evidence for the SOC hypothesis has been obtained only for coarse measures of neural activity (LFP, EEG, BOLD), but surprisingly not for spiking activity in vivo. Therefore we analyzed highly parallel spike recordings from rats (hippocampus), cats (visual cortex) and monkeys (prefrontal cortex). Across all species, the avalanche size distributions f(s) were similar (Fig. 1A-C), but differed fundamentally from f(s) in critical spiking models (Fig. 1D), even when accounting for subsampling (Fig. 1E) (see [4–6]). The differences between in vivo f(s) and model f(s) could be overcome by decreasing the model’s excitatory synaptic strength, while increasing its external input (drive) concomitantly (Fig. 1F). Thereby the model became sub-critical and lost its separation of time scales (STS), which is fundamental to SOC. These results also held for intracranial depth recordings in humans. Our findings indicate that the mammalian brain self-organizes to a slightly subcritical regime without STS. In this regime, avalanches are not temporally separated bursts as for SOC, but form a mélange. This regime may strike a balance between optimal information processing, which has been linked to SOC [3], and the need to avoid the supercritical regime, which has been linked to epilepsy.}, web_url = {http://abstracts.g-node.org/abstracts/1f447f8e-9b32-42ae-852a-e3ad758df1f3}, event_name = {Bernstein Conference 2014}, event_place = {Göttingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2014.0224}, author = {Priesemann V; Wibral M; Valderrama M; Proepper R; Le Van Quyen M; Geisel T; Triesch J; Nikolić D; Munk MHJ{munk}{Department Physiology of Cognitive Processes}} } @Poster{ RamirezVillegasLB2014_2, title = {Dynamical source analysis of hippocampal sharp-wave ripple episodes}, year = {2014}, month = {9}, day = {3}, pages = {106-107}, abstract = {Sharp-wave ripples (SPW-Rs), transient episodes of neural activity combining a sharp wave of dendritic depolarization and a high-frequency oscillation, are a major feature of the cortico-hippocampal communication. Experimental evidence relates these episodes to offline consolidation of memory traces. However, the circuitry dynamics that governs these episodes remains poorly understood. Using multi-site extracellular recordings of the hippocampal CA1, we have previously provided evidence for the existence of differentiated SPW-Rs, whose LFP signatures come in four types that suggest a dynamical coupling between SPWs and ripples[1] (Figure 1a). Here we develop a methodology to extract dynamical components from peri-event activity of the CA1 stratum radiatum (SR) and stratum pyramidale (PL). We hypothesize that SPW-Rs can be approximated by an instantaneous linear superposition of independent sources with different spectral signatures that account for their dynamics. Inspired by the second order blind identification (SOBI) algorithm[2], our approach estimates the spatial spread and spectral signature of these dynamical sources by implementing a Joint Approximate Diagonalization of the cross-spectral density matrix between recording sites. Our analysis reveals that dynamical components with distinct spatial signature can be isolated: a broad-band-spectrum component spanning the gamma and ripple bands, originates in SR; and a second component, with clear spectral peak in the ripple band (80-200Hz), originates in PL (Figure 1b c). Differences between SPW-R subtypes are reflected in the spectra of the second component (ripple). We suggest that differences between SPW-Rs are related to local recurrent dynamics within PL, endowing both pyramidal cells and interneurons. Our preliminary findings illustrate the convenience of our approach for extracting meaningful dynamical components from multi-site LFPs during neuronal events and for unraveling their underlying mechanisms.}, web_url = {http://abstracts.g-node.org/abstracts/f1f1c1d4-d23b-44a3-b48f-cf61e02fd1a8}, event_name = {Bernstein Conference 2014}, event_place = {Göttingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2014.0116}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Poster{ TotahNKLE2014, title = {Effects of Long-Term Administration of Atomoxetine on Attentional Set-Shifting and Activity in the Rat Locus Coeruleus and Prefrontal Cortex}, year = {2014}, month = {7}, day = {8}, volume = {9}, number = {FENS-3019}, abstract = {Norepinephrine (NE) in the medial prefrontal cortex (mPFC) modulates behavioral flexibility. States requiring flexibility correlate with higher activity of NE neurons of the locus coeruleus (LC) and elevated mPFC NE release. NE reuptake transporter (NET) inhibitors are used as medications for attention disorders; however, little is known about the mechanisms mediating their efficacy. Most animal studies have tested the behavioral effects of a single injection of a NE drug. However, chronic administration is more relevant for clinical application. Also, injection handling itself may introduce a confounding stress-associated NE release. We administered Atomoxetine (ATM), a NET inhibitor, over 28 days via an intra-peritoneal (i.p.) implanted osmotic pump. After 11 ? 13 days of drug exposure, we measured set-shifting in an operant task that required a shift from visual cue-guided responding to egocentric space-guided responding. ATM (0.1, 0.3, 1.0 mg/kg, N = 8-9 rats per dose) had no effect on set-shifting compared to vehicle. Other studies reported that repeated i.p. injection of a NET inhibitor (Desipramine) or a single ATM injection (0.1 ? 0.9 mg/kg) enhanced shifting between sensory modalities (odor/touch). The inconsistency may be due to the use of a spatial rule. Salient stimuli elicit phasic LC activation that increases the signal-to-noise ratio of sensory neuron activity, while the role of NE in spatial context has not been described. LC and mPFC activity was recorded in saline- and ATM-exposed rats under urethane anesthesia. The effects of ATM on laminar-specific mPFC unit activity and cortical state (LFP) and LC unit activity will be presented.}, web_url = {http://fens2014.meetingxpert.net/FENS_427/poster_102726/program.aspx}, event_name = {9th FENS Forum of Neuroscience}, event_place = {Milano, Italy}, state = {published}, author = {Totah N{ntotah}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Katakalidis G{gkatakalidis}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ SchuzL2014, title = {Axon Diameters in the Cortical White Matter: an Electron Microscopic Study}, year = {2014}, month = {7}, day = {7}, volume = {9}, number = {FENS-3463}, abstract = {Axon diameters in the cortical white matter are of interest for various reasons: a) to get an impression of the range of conduction velocities, b) to estimate number of fibres in various fibre bundles, c) for comparison with fiber studies in vivo by way of diffusion weighted imaging. We investigated therefore the distribution of diameters of (myelinated) axons in the cortical white matter of human brains and of a macaque with the electron microscope. We took samples a) from the region of the superior longitudinal fascicle, b) from the transition of the white matter between temporal and frontal lobe where the uncinate and the inferior occipitofrontal fascicle merge, and c) from the corpus callosum. All bundles showed similar distributions: the bulk of fibres was relatively thin; the (inner) diameters of myelinated fibers had an average size between 0.5 and 0.8 mm in most samples. The total range of diameters of myelinated fibers was between 0.2 and 9 mm. Thus, a wide range of conduction velocities exists in the various bundles of the cortical white matter. The figure shows an electron microscopic section from the depth of the cortical white matter in the monkey.}, web_url = {http://fens2014.meetingxpert.net/FENS_427/poster_103072/program.aspx/anchor1}, event_name = {9th FENS Forum of Neuroscience}, event_place = {Milano, Italy}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Liewald D{liewald}{Department Physiology of Cognitive Processes}} } @Poster{ LoweMZLP2014, title = {Quantification of the Laminar and Frequency Structure of Information in Primary Visual Cortex}, year = {2014}, month = {7}, day = {7}, volume = {9}, number = {FENS-2860}, abstract = {Aims We previously reported that the activity of primary visual cortex (V1) transmits information about complex naturalistic video stimuli in two distinct frequency bands: a range of low frequency fluctuations below 20 Hz, and a high frequency (50-150 Hz) gamma oscillation range, with each range carrying its own independent information about the visual stimuli [1]. Here we ask whether these independent frequency channels are generated in distinct cortical laminae. Methods We used laminar electrodes with 150 micron spacing spanning the whole cortical depth to record extracellular field potentials from the primary visual cortex of opiate-anaesthetised macaques during presentation of a 2 minute long Hollywood colour movie clip. We then computed the Current Source Density (CSD) for each trial. From the time-resolved power of the CSD in each trial, we estimated the mutual information that the power at each frequency carries about which section of the movie is being presented, and how much information there is in frequency bands about fine and coarse spatial changes in luminance. Results and Conclusions We found, across depth and frequency, two distinct regions carrying large amounts of independent information about the movie stimulus: the low frequency (up to 20Hz) band had high information at depths corresponding to layers 4-6, whereas the 50-150Hz band had high information in layers 1-3. This suggests that different laminae of cortical circuits generate independent information channels that code information in separate frequency ranges.}, web_url = {http://fens2014.meetingxpert.net/FENS_427/poster_102139/program.aspx/anchor102139}, event_name = {9th FENS Forum of Neuroscience}, event_place = {Milano, Italy}, state = {published}, author = {L\"owe S{sloewe}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Logothetis N{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ VanKeulenLE2014, title = {Alerting Effect of the Direct Electrical Stimulation of the Locus Coeruleus on the Acoustic Startle Response in the Rat}, year = {2014}, month = {7}, day = {6}, volume = {9}, number = {FENS-3004}, abstract = {Alerting sensory stimuli activate the noradrenaline (NE) neurons of the Locus Coeruleus (LC) and the associated NE release improves sensory signaling. Impairments of the LC-NE system lead to sensory gating deficits that are widely studied using the Prepulse Inhibition paradigm (PPI) ? a reduction in acoustic startle response produced by a preceding non-alerting stimulus. In order to examine the specific role of LC-NE system in PPI we studied the behavioral startle response and the sensory evoked potential in the medial prefrontal cortex (mPFC) to an acoustic startle pulse (broad band noise, 20ms, 100dB) preceded by either an auditory prepulse (10kHz, 20ms, 70dB) or direct LC stimulation of different frequencies (20, 50 or 100Hz, 50µA, 100ms). Phasic activation of LC 100ms before startle stimulus resulted in PPI, which was proportional to stimulation intensity. The PPI to the highest stimulation frequency (60% startle response reduction) was comparable to standard auditory PPI (73%).The LC stimulation 200ms before startle stimulus was not effective. The auditory prepulse stimulus but not the direct LC stimulation significantly decreased the amplitude of the mPFC evoked potential to startle stimulus. Thus, LC-NE system is critically involved in sensorimotor gating but auditory- and LC stimulation-induced PPI are likely mediated by different neural mechanisms.}, web_url = {http://fens2014.meetingxpert.net/FENS_427/poster_101083/program.aspx}, event_name = {9th FENS Forum of Neuroscience}, event_place = {Milano, Italy}, state = {published}, author = {Van Keulen S{svankeulen}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ SafaaiNELP2014, title = {A dynamical systems model of the effect of Locus Coeruleus firing on single trial cortical state dynamics}, journal = {BMC Neuroscience}, year = {2014}, month = {7}, volume = {15}, number = {Supplement 1}, pages = {58-59}, abstract = {Activity of sensory areas continuously varies reflecting both changes in external sensory stimuli and in internal states of the organism that do not necessarily always have a precise relationship to sensory inputs. An important aim in systems neuroscience is to develop quantitative models that may explain how state-dependent representations are generated and how they can be best interpreted. State-dependent modulations of cortical activity are in part mediated by changes in activity of various subcortical neuromodulatory nuclei. A prominent example is the Locus Coeruleus (LC), which can modulate both ongoing changes of cortical states and their responses to sensory inputs. However, a quantitative model of how the temporal fluctuations of LC firing affect ongoing and stimulus-driven primary cortical dynamics is currently missing. Here we investigated how LC modulates the ongoing cortical states and the sensory information carried by cortical firing using a combination of neurophysiological experiments and data-driven dynamic-system models of cortical state changes. We performed simultaneous recordings of neural activity in primary somatosensory cortex and both ipsilateral and contralateral LC in urethane anaesthetized rats during spontaneous activity and during electrical stimulation of the contralateral hind paw. On the basis of this data, we have constructed a novel data-driven dynamical system model of cortical states dynamics. This model extends and generalizes recent simple effective models [1] by including the effect of firing of LC noradrenergic neurons. We first fitted dynamic systems models of cortical states that either did or did not contain LC-cortical interactions. We found that models omitting the LC noradrenergic input to cortex tend to describe the dynamics of spontaneous activity of S1 cortex reasonably well. However, including ipsilateral (and to a lesser extent contralateral) LC activity as input to the models make the prediction of cortical states and of single trials responses much better. We then investigated which aspects of the LC dynamics help the model to increase cortical state predictability. We found that ipsilateral LC firing activity at low frequencies (< 10 Hz) correlated positively with slow (1-6 Hz) fluctuations of cortical power. The insertion of ipsilateral LC input to the model captured this dynamics by creating additional low frequency (1-6 Hz) state variation of model activity that correlated, both in power and phase, to those observed in real cortical activity. We finally investigated how these dynamical systems models can be used to predict single trial sensory evoked responses and to understand how this dynamics shapes the information representation of sensory stimuli. We derived an explicit mathematical rule predicting the trial-by-trial variability of cortical responses to stimuli arising from LC-modulated cortical state dynamics, and found that subtracting this variability from single trial cortical responses approximately doubles the amount of mutual information about the somatosensory stimuli that could be extracted from cortical responses.}, web_url = {http://www.cnsorg.org/cns-2014}, event_name = {Twenty-Third Annual Computational Neuroscience Meeting (CNS*2014)}, event_place = {Québec City, Canada}, state = {published}, DOI = {10.1186/1471-2202-15-S1-P73}, author = {Safaai H; Neves R{ricardo}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ TotahNPLE2014, title = {Characterization of the Effects of Tonic and Phasic Norepidrine Release on Layer-Specific Prefrontal Cortex and Primary Somatosensory Cortex Activity}, year = {2014}, month = {6}, pages = {117}, abstract = {Cortical connectivity is organized by cortical layer. Cognitive control over perception relies on connectivity between the prefrontal cortex (PFC) and sensory cortex, yet little is known about their laminar interactions. Moreover, cognition and sensory-evoked activity are modulated by norepinephrine (NE), which has a layer-specific distribution of receptors. We recorded extracellular laminar activity in rat PFC and primary somatosensory cortex (S1) under urethane anesthesia. Tonic NE release (minutes to hours) was increased by chronic administration (28 days) of the NE reuptake inhibitor Atomoxetine (0.03, 0.3, 1.0 mg/Kg or vehicle). Phasic NE release (sec) was increased by brief electrical stimulation (30 μA, 0.4 ms biphasic pulse at 50 Hz) of the locus coeruleus (LC), which releases NE in the PFC and S1. Increasing tonic NE had opposing effects on superficial and deep PFC laminar activity. Atomoxetine (ATX) reduced spiking (20 min recording) in PFC layer 2/3 (vehicle: 2.55 0.77 Hz, N = 12 single units; 1.0 mg/Kg ATX: 1.22 0.22 Hz, N = 30 units), while it increased spiking in layer 5 (vehicle: 0.88 0.22 Hz, N = 17 units; 1.0 mg/Kg ATX: 3.26 0.49 Hz, N = 48 units). Increasing phasic NE predominately evoked sustained (about 1 sec) excitation in a similar proportion of units in all PFC layers. The excitatory effect of phasic NE differed in the context of high tonic NE in that, 83% of units exhibited sustained excitation in the vehicle condition (N = 18 units combined across layers), whereas only 34% (N = 65 units) exhibited this pattern in the 1.0 mg/Kg ATX condition. Furthermore, the magnitude of firing rate change evoked by phasic NE release was significantly reduced under high tonic NE (0.3 and 1.0 mg/Kg ATX versus vehicle). Therefore, although tonic NE has a layer-specific modulatory effect on PFC neurons, phasic NE evokes excitation in a layer non-specific manner. Moreover, at high tonic levels of NE, further brief NE increases have a reduced excitatory effect. Given that NE affects population activity oscillations, ongoing analyses focus on spike timing (Fano factor and noise correlations), excitatory population response (current source density), and laminar spike-LFP relations. Additionally, we will report how NE modulates the long-range communication between local PFC and S1 circuits by measuring Granger causality between the LFP signals in individual layers of PFC and S1. We expect NE to modulate communication from PFC output layers to circuits in individual S1 layers. Indeed, this may be one mechanism by which ATX improves cognition in individuals with mental illness.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Totah N{ntotah}{Department Physiology of Cognitive Processes}; Neves R{ricardo}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ AzevedoFLK2014, title = {Dynamics Changes of Bold Functional Connectivity during Natural Viewing in the Awake Macaque Brain}, year = {2014}, month = {6}, pages = {51}, abstract = {The primate brain is a dynamic system interconnected by temporally correlated functional networks. The structure of this correlated activity depends on the brain’s internal state and on stimulus input. In the absence of external stimulation, functional networks of spontaneous activity, i.e. the salience network, the executive control network and the default mode network, can be observed. Their origin and function are not well understood, but they could reflect neural noise within anatomically connected areas or active mechanisms related to perception and awareness. On the other hand, when the brain is being stimulated, a different pattern of activity emerges. Exactly how this patiotemporal transition happens is still unclear. The objective of this study is to characterize the dynamic changes of BOLD based functional connectivity between resting-state and natural-stimuli-driven networks in the awake monkey brain. Due to its high spatial resolution, BOLD-fMRI is a powerful tool to study large-scale correlated brain network activity. We used a paradigm containing sequences of movie-clips with different contexts including natural and artificial environments as well as periods devoid of any visual stimulation (resting) in order to identify the global activation patterns reflecting the interplay between different populations of neurons under these conditions. For our experiments, two macaque monkeys (Macaca mulatta) were trained in a mock scanner to remain headposted and motionless in a custom-made fMRI chair while a RI-compatible periscope presented a movie clip, a gray background (FOV 30 x 23, 60 Hz, eff. res. 530 400 fibers) or nothing. After the behavioral training was completed, the monkeys were scanned under the same conditions in a Bruker 4.7 T vertical MRI scanner with a custom-designed whole-head coil (single-shot GE-EPI, TR 1000 ms, TE 18 ms, 128 64 18 voxels, 1 1 2 mm). Each run lasted 10 min (600 volumes). We collected 30 functional runs of resting state activity (without any visual stimulation) and 30 functional runs of stimulus driven activity (1 min of a natural movie presentation alternated with 1 min of gray background) for each monkey. All the volumes containing artifacts were pre-selected and excluded from the data analysis. For the visual stimulation condition, we selected the scans with strong visual activation based on a generalized linear model (GLM). Functional connectivity data analysis (group-level ICA with 20 components) of the scans devoid of stimulation revealed resting-state networks consistent with previous reports in humans and monkeys (Mantini et al., 2013, J. Neurosci.). Furthermore, preliminary analysis of the scans with visual stimulation revealed components reflecting visually driven networks. Currently, we are employing the eigenvector centrality mapping (ECM), which is a parameter-free effective connectivity method (Lohmann et al., 2010, PLoS ONE) as well as models based dynamic causal modeling (DCM) (Friston et al., 2003, Neuroimage) to delineate differences across stimulation with different contexts and to characterize the physiological mechanisms behind the transition of brain states.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Florin E{eflorin}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ FroudarakisBECSYSBT2014_2, title = {Population Code in Mouse V1 Facilities Read-out of Natural Scenes through Increased Sparseness}, year = {2014}, month = {6}, pages = {69}, abstract = {The neural code is believed to have adapted to the statistical properties of the natural environment. However, the principles that govern the organization of ensemble activity in the visual cortex during natural visual input are unknown. We recorded populations of up to 500 neurons in the mouse primary visual cortex and characterized the structure of their activity, comparing responses to natural movies with those to control stimuli. We found that higher-order correlations in natural scenes induce a sparser code, in which information is encoded by reliable activation of a smaller set of neurons and can be read-out more easily. This computationally advantageous encoding for natural scenes was state-dependent and apparent only in anesthetized and active, awake animals, but not during quiet wakefulness. Our results argue for a functional benefit of sparsification that could be a general principle governing the structure of the population activity throughout cortical microcircuits.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Froudarakis A; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Cotton RJ; Sinz FH{fabee}{Research Group Computational Vision and Neuroscience}{Research Group Computational Vision and Neuroscience}; Yatsenko D; Saggau P; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoNSL2014, title = {Ripple-Triggered Stimulation of the Locus Coeruleus during Post-Learning Sleep Impairs Memory Consolidation}, year = {2014}, month = {6}, pages = {66}, abstract = {Hippocampal ripples, brief high-frequency (150–200 Hz) oscillations occurring during quiet wakefulness or slow wave sleep (SWS), represent simultaneous discharge of a large neuronal population that is synchronized across the entire hippocampus. Learning experience increases frequency of ripple occurrence, which is predictive of memory recall, while ripple suppression impairs hippocampal-dependent learning. Experience-induced replay of neuronal ensembles occurs predominantly during ripples. These observations support the idea that ripples provide a neurophysiological substrate for off-line memory consolidation by facilitating synaptic plasticity within the learning-associated neuronal network. We hypothesized that noradrenaline (NE) release during ripples in subcortical and cortical targets of the Locus Coeruleus (LC) may be beneficial for memory consolidation. Rats implanted with linear electrode arrays for extracellular recording in cortex and hippocampus and a stimulating electrode in LC were trained on a spatial memory task. Neural activity was monitored for 1 h immediately after each learning session. Ripples were detected on-line using a band-pass filtered (150–250 Hz) extracellular voltage signal recorded in the CA1 region of hippocampus by applying a threshold-crossing algorithm. Trains of biphasic electrical pulses (0.4 ms, 0.05 mA) were delivered to LC at each ripple onset. Group 1 received LC stimulation (5 pulses at 20 Hz) that did not produce detectable changes in cortical or hippocampal neural activity. Group 2 received LC stimulation (10–20 pulses at 50–100 Hz) that induced a transient (1–2 s) desynchronization of cortical EEG, during which both thalamocortical sleep spindles and hippocampal ripples were suppressed. Additional control groups included random LC stimulation, stimulation outside of LC, and sham-operated animals. Ripple-triggered LC stimulation produced a spatial memory deficit exclusively in Group 2 rats, when LC stimulation transiently eliminated sleep spindles and ripples. The behavioral performance of none of the other groups differed from intact animals. We conclude that stimulationinduced discharge of LC neurons and concurrent NE release in the projection targets of LC caused a transient brain state change, which was not favorable for off-line hippocampal-cortical communication underlying consolidation of recent memories. The obtained results challenge the original hypothesis on the ripple-coupled NE release for promoting synaptic plasticity within reactivated neuronal assemblies. Yet, the present results further support our recent discovery of a remarkable dichotomy between ripple-associated cortical activation and deactivation of many subcortical regions including thalamus and brain stem neuromodulatory centers (Logothetis, et al., 2012, Nature 491 547–553). Thus, hippocampal ripple events may serve as indicators of a particular brain state that provide low interference for off-line consolidation of the declarative memories. Activation of any competing network during ripples may lead to less efficient consolidation.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Novitskaya Y{ynovitskaya}{Department Physiology of Cognitive Processes}; Sara S; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ CottonFEBST2014, title = {Scaling of Information in Large Sensory Neuronal Populations}, year = {2014}, month = {6}, pages = {60}, abstract = {Although we know a lot about how individual neurons in the brain represent the sensory environment, we are far from understanding how neural populations represent sensory information. Because individual neurons are noisy, pooling the activity of many neurons with similar response properties seems necessary to obtain an accurate representation of the sensory environment. However, it is widely believed that shared noise (or, noise correlations) in the activity of nearby neurons renders such pooling ineffective, profoundly limiting the accuracy of any population code and, ultimately, behavior. This belief is based on model-based extrapolations from correlations measured in individual pairs of neurons, as it has been impossible to record simultaneously from complete neuronal populations. Here, we use a novel 3D high-speed in vivo two-photon microscope to record nearly all of the hundreds of neurons in a small volume of the mouse primary visual cortex and directly measure the amount of information encoded by these local populations. In contrast to previous predictions, we find that the information in a sensory population increases approximately linearly with population size and does not saturate even for several hundred neurons. Moreover, even a decoder ignoring correlations between neurons can decode 80% of the information in the population. Our results suggest that sensory neural populations represent information in a truly distributed manner and pooling of neural activity within local circuits is much more effective than previously anticipated. Thus, the representation in early sensory areas does not appear to be impaired substantially by shared sensory noise and limitations in behavioral performance in psychophysical tasks may need to be attributed to processes downstream of the sensory population.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Cotton RJ; Froudarakis E; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Saggau P; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ EckerBCSDCSBT2014_2, title = {State Dependence of Noise Correlation in Macaque Primary Visual Cortex}, year = {2014}, month = {6}, pages = {64}, abstract = {Shared, trial-to-trial variability in neuronal populations has a strong impact on the accuracy of information processing in the brain. Estimates of the level of such noise correlations are diverse, ranging from 0.01 to 0.4, with little consensus on which factors account for these differences. Here we addressed one important factor that varied across studies, asking how anesthesia affects the population activity structure in macaque primary visual cortex. We found that under opioid anesthesia, activity was dominated by strong coordinated fluctuations on a timescale of 1–2 Hz, which were mostly absent in awake, fixating monkeys. Accounting for these global fluctuations markedly reduced correlations under anesthesia, matching those observed during wakefulness and reconciling earlier studies conducted under anesthesia and in awake animals. Our results show that internal signals, such as brain state transitions under anesthesia, can induce noise correlations, but can also be estimated and accounted for based on neuronal population activity.}, web_url = {http://areadne.org/2014/home.html}, event_name = {AREADNE 2014: Research in Encoding and Decoding of Neural Ensembles}, event_place = {Santorini, Greece}, state = {published}, author = {Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Cotton RJ; Subramaniyan M; Denfield GH; Cadwell CR; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Poster{ GoenseBHSSSLM2014, title = {Novel RF-Coil Assembly to Simultaneously Investigate fMRI and Electrophysiology in Non-Human Primates in a Large Bore Vertical Magnet}, year = {2014}, month = {5}, day = {12}, number = {1348}, abstract = {RF-coil design for combined electrophysiology and fMRI in non-human primates is challenging because any coil design needs to be sufficiently open to allow for electrode access to the brain. Patch antennas allow for a more open design, but since our bore is too small for a 300 MHz traveling wave, we developed an open quadrature transmit coil/antenna placed in-situ. The transmit coil/antenna is capable of producing a sufficiently homogenous B1 field. This device can be used alone in transceiver mode or in combination with dedicated receive arrays which allow for maximum flexibility while maintaining a very high SNR.}, web_url = {http://www.ismrm.org/14/program_files/TP04.htm}, event_name = {Joint Annual Meeting ISMRM-ESMRMB 2014}, event_place = {Milano, Italy}, state = {published}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Hoffmann J{tatum}{Department High-Field Magnetic Resonance}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}} } @Poster{ MalekshahiMPBVC2014, title = {Early and Late Brain Mechanisms Underlying Prediction Error Detection}, journal = {Journal of Cognitive Neuroscience}, year = {2014}, month = {4}, day = {7}, volume = {26}, number = {Supplement}, pages = {159}, abstract = {In the framework of visual cognition and predictive coding models, we tested the hypotheses that visual prediction influences detection of stimuli violating expectation, and that early and late (conscious) behavioral and brain responses to deviant stimuli are related to processing of different aspects of prediction error. To this aim combined recordings of saccadic eye movements and fMRI data were performed on twelve participants performing a visual detection task. Participants were required to detect moving stimuli that were suddenly displaced with respect to their current trajectory (deviant stimuli). Displacement varied in amplitude and orientation. Psychophysical reverse correlation analysis evidenced different perceptual levels of prediction error processing. Analysis of conscious responses revealed reduced detection of visual inputs for stimuli with small deviation from expected behavior with respect to large deviant stimuli as indicated by increased eccentricity of the psychophysical kernel. fMRI data analysis showed that higher-level late conscious processing, mainly associated with cortical activity in fronto-parietal areas as well as subcortical regions such as caudate nucleus and thalamus, seems to be required to detect prediction error and to assess the degree of violation of expectations. Lower-level early processing, associated with dorsal activity in the right angular gyrus, also enables detection of violation of prediction but it does not permit discrimination among large and small deviating stimuli as indicated by almost null eccentricity of psychophysical kernel. These findings highlight at least two primary brain mechanisms, an early and a late stage, subserving detection of visual inputs deviating from perceptual expectations.}, web_url = {https://www.cogneurosociety.org/annual-meeting/previous-meetings/}, event_name = {21st Annual Meeting of the Cognitive Neuroscience Society (CNS 2014)}, event_place = {Boston, MA, USA}, state = {published}, author = {Malekshahi R; Mathews Z; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Birbaumer N; Verschur PFMJ; Caria A} } @Poster{ TotahNPLE2014_3, title = {Characterization of the effects of tonic and phasic norepinephrine release on layer-specific prefrontal cortex and primary somatosensory cortex activity}, year = {2014}, month = {4}, web_url = {http://www.fens.org/Meetings/Brain-Conferences/Controlling-Neurons-Circuits-and-Behaviour/}, event_name = {FENS Spring Brain Conference: Controlling Neurons, Circuits and Behavior}, event_place = {Copenhagen, Denmark}, state = {published}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Neves R{ricardo}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ RamirezVillegasLB2014, title = {Cluster analysis of sharp-wave ripple field potential signatures in the macaque hippocampus}, year = {2014}, month = {3}, volume = {2014}, pages = {199}, abstract = {Sharp-wave ripple complexes (SPW-Rs), transient episodes of neural activity combining a sharp wave of dendritic depolarization and a high-frequency oscillation, are a major feature of the cortico-hippocampal communication during immobility, consummatory behaviors and sleep. Experimental evidence relates these episodes to offline consolidation of memory traces. In order to allow for the wide range of network reconfigurations required by this process, different SPW-R events certainly reflect a large variety of selective interactions both within the hippocampus and with other brain regions. A better understanding of the underlying mechanisms of these interactions thus requires a finer characterization of the SPW-R events and their associated signatures over the entire brain. Using unsupervised-learning artificial neural networks and clustering techniques, we analyzed peri-event multi-channel local field potential (LFP) recordings of the hippocampus of anesthetized macaques, and extracted the electrophysiological characteristics of SPW-R events dynamics. We combined this analysis with neural event-triggered functional magnetic resonance imaging analysis in order to map the activity of the whole brain during SPW-R events. Our primary findings hint upon differentiated SPW-R complexes, whose signatures come in four classes: high frequency oscillations preceding, following or located in the peak of sharp wave dendritic depolarization, as well as high frequency oscillations without noticeable sharp-wave signature. These differentiated SPW-R LFP signatures were highly reproducible both across different animals and experimental sessions. At a larger scale, ripple-triggered fMRI activation map for most of the cerebral cortex and sub-cortical regions during ripples has been described by Logothetis et al., 2012. On top of this, our preliminary results suggest that the classes of SPWR field potential signatures reflect differentiated cortical activation and sub-cortical deactivation maps. In light of these findings, we hypothesize that these distinct patterns of SPW-R in hippocampal LFP mark differentiated brain-wide dynamical events, possibly reflecting several underlying mechanisms of memory function.}, web_url = {http://www.cosyne.org/c/index.php?title=Cosyne_14}, event_name = {Computational and Systems Neuroscience Meeting (COSYNE 2014)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Ramirez-Villegas JF{jramirez}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2014, title = {Insular cortex: Neuroanatomical insight into interoception, emotion and awareness}, year = {2014}, month = {12}, day = {2}, web_url = {http://matarikinetwork.org/wp-content/uploads/2015/02/Brain-and-Mind-Integrative-Neuroscience-Conference-2014-programme.pdf}, event_name = {Matariki Network Conference Brain and Mind Integrative Neuroscience}, event_place = {Dunedin, New Zealand}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Bartels2014_2, title = {Processing of motion, space and visual selection: new insights on human parietal cortex}, year = {2014}, month = {12}, day = {1}, web_url = {http://matarikinetwork.org/wp-content/uploads/2015/02/Brain-and-Mind-Integrative-Neuroscience-Conference-2014-programme.pdf}, event_name = {Matariki Network Conference Brain and Mind Integrative Neuroscience}, event_place = {Dunedin, New Zealand}, state = {published}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ PapanikolaouKLPSLS2014, title = {Organization of human area V5/MT+ and sensitivity to motion coherence after lesions of the primary visual cortex}, year = {2014}, month = {11}, day = {19}, volume = {44}, pages = {772.07}, abstract = {Partial loss of the primary visual cortex (V1) and/or its inputs leads to a scotoma of the contralateral visual hemifield, the extent of which corresponds retinotopically to the region affected. However, some patients have been found to retain a small amount of residual visual sensitivity within the blind field, a phenomenon termed blindsight, suggesting the existence of alternate pathways that transmit information from the retina to cortex effectively bypassing V1. Blindsight has been associated with activity observed in the middle temporal area complex (V5/MT+) following V1 lesions. An important issue is how the properties of area hV5/MT+, like retinotopic organization and sensitivity to motion, change following V1 lesions. We measured responses in human area V5/MT+ in 5 patients with homonymous visual field defects as a result of area V1 or optic radiation lesions using functional magnetic resonance imaging (fMRI). First, we investigated whether the organization of area hV5/MT+ changes following V1 damage. To do so, we used a recent method that estimates population receptive field (pRF) topography in the visual cortex (Lee et al., A new method for estimating population receptive field topography in visual cortex, NeuroImage, 2013). FMRI measurements were obtained during the presentation of a moving bar stimulus while the subjects were fixating. The pRF topography of area hV5/MT+ was compared with that of control subjects stimulated with matching “artificial scotomas”. In addition, we measured the sensitivity of area hV5/MT+ to coherent motion using random dot kinematograms (RDK) for both patients and controls. RDK patches were presented either inside the visual field scotoma or in the contralateral healthy part of the visual field. Subjects were instructed to report the direction of motion of the presented RDK while fixating. In both cases we found responses in hV5/MT+ arising inside the scotoma, independent of area V1 input, suggesting the existence of a functional alternate pathway bypassing area V1. The retinotopic organization of hV5/MT+ differed between patients and controls under the artificial scotoma condition, suggesting a degree of reorganization. The blood oxygen level-dependent (BOLD) response of area hV5/MT+ to RDK coherent motion stimuli also differed between patients and controls, and was dependent on which side was attended. Studying how the properties of visual areas change after injury may allow us to design better rehabilitative strategies in the future.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Lee S{slee}{Department Physiology of Cognitive Processes}; Papageorgiou TD; Schiefer U; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Conference{ BesserveSL2014, title = {Unsupervised identification of neural events in local field potentials}, year = {2014}, month = {11}, day = {15}, volume = {44}, pages = {2.12}, abstract = {Local Field Potentials (LFP) recordings carry information about a large variety of dynamical network mechanisms occurring at multiple scales. While these mechanisms are hypothesized to be instrumental to information processing, identifying them without prior information is challenging. A standard approach to achieve this goal is to extract information from specific frequency bands reported in the literature (such as Theta or Gamma bands). However, the variability of these bands across species, brain structures and individuals is a major difficulty. We propose an unsupervised technique to automatically identify and detect relevant dynamical events. The methodology is based on a Non-negative Matrix Factorization (NMF) of the time varying LFP spectrum that decomposes the signals into a small number of dynamical components with specific spectral signatures. Large transient events in each component are further detected with a statistical test assuming a Gaussian null distribution of time course. We applied this methodology on LFPs recorded from the CA1 subdivision of hippocampus in 3 anesthetized macaques, totalizing 12 recording sessions. In each session, we quantified the stability of the factorization by computing the correlation between the spectral signatures obtained different blocks of LFP data. Setting a threshold on the minimum average correlation to .8, we concluded that one could extract on average 6 stable dynamical components from these signals. The obtained spectral components, clustered across sessions using a graph clustering algorithm, are represented on Figure 1 (left panel), as well as example time courses of components in one session (Figure 1 right panel). The dark rectangles indicate detected dynamical events in each component, among which classical hippocampal sharp-wave and ripple events (first and second component from the top) are well isolated. In sum, our approach offers a principled way to isolate key dynamical events in LFP data without prior frequency band definition and can be applied in a wide range of experimental settings and brain}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2014}, event_name = {44th Annual Meeting of the Society for Neuroscience (Neuroscience 2014)}, event_place = {Washington, DC, USA}, state = {published}, author = {Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Sch\"olkopf B{bs}{Department Empirical Inference}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ ZaidiMSBF2014, title = {Epidural fNIRS as a tool for studying local hemodynamic signals and neuro-vascular coupling}, year = {2014}, month = {10}, day = {14}, volume = {15}, pages = {18}, abstract = {Hemodynamic activity is studied using functional Magnetic Resonance Imaging (fMRI), Intrinsic Signal Optical Imaging (ISOI), and functional Near Infrared Spectroscopy (fNIRS). FNIRS is a non-invasive neuroimaging method that uses a near-infrared light source and detector pair (optode pair), to measure changes in concentrations of oxy-hemoglobin (HbO), deoxy-hemoglobin (HbR) and total hemoglobin (HbT), in a small volume of tissue. The advantages of fNIRS include its portability, metabolic specificity, high temporal resolution, high sensitivity in detecting small substance concentrations, affordability, and low susceptibility to movement artefacts. Given these advantages, fNIRS is a good candidate for use in primates, specifically to measure local hemodynamic signals during electrophysiological measurements. To test the feasibility of using epidural fNIRS with concomitant extracellular electrophysiology, we recorded spontaneous and stimulus induced activity from the primary visual cortex in two anesthetized monkeys. To study the relationship between changes in [HbO] and [HbR], and the underlying neuronal activity, we used system identification techniques. Briefly, our results show that epidural fNIRS has much higher SNR than fMRI, and is a promising tool for studying local hemodynamic signals and neuro-vascular coupling.}, web_url = {http://www.neuroschool-tuebingen-nena.de/fileadmin/user_upload/Dokumente/neuroscience/Abstractbook_NeNa2014_final.pdf}, event_name = {15th Conference of Junior Neuroscientists of Tübingen (NeNa 2014)}, event_place = {Schramberg, Germany}, state = {published}, author = {Zaidi A{azaidi}{Department Physiology of Cognitive Processes}; Munk M{munk}{Department Physiology of Cognitive Processes}; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}; Birbaumer N; Fetz E} } @Conference{ GatysETB2014_2, title = {Synaptic unreliability facilitates information transmission in balanced cortical populations}, year = {2014}, month = {10}, day = {13}, volume = {15}, pages = {11}, abstract = {Cortical neurons fire in a highly irregular manner, suggesting that their input is tightly balanced and changes in presynaptic firing rate are encoded primarily in the variance of the postsynaptic currents. Here we show that such balance has a surprising effect on information transmission: Synaptic unreliability which is ubiquitous in cortex and usually thought to impair neural communication actually increases the information rate. We show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not rely on a threshold nonlinearity.}, web_url = {http://www.neuroschool-tuebingen-nena.de/fileadmin/user_upload/Dokumente/neuroscience/Abstractbook_NeNa2014_final.pdf}, event_name = {15th Conference of Junior Neuroscientists of Tübingen (NeNa 2014)}, event_place = {Schramberg, Germany}, state = {published}, author = {Gatys L; Ecker A{aecker}{Department Physiology of Cognitive Processes}; Tchumatchenko T; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Conference{ Logothetis2014_3, title = {Mechanisms of action of invasive neurostimulation}, year = {2014}, month = {10}, day = {4}, web_url = {http://www.belgianbraincouncil.be/files/bbc2014-abstract-book.pdf}, event_name = {5th Belgian Brain Congress (BBC 2014)}, event_place = {Ghent, Belgium}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ GatysETB2014, title = {Synaptic unreliability facilitates information transmission in balanced cortical populations}, year = {2014}, month = {9}, day = {4}, pages = {21}, abstract = {Cortical neurons fire in a highly irregular manner, suggesting that their input is tightly balanced and changes in presynaptic firing rate are encoded primarily in the variance of the postsynaptic currents. Here we show that such balance has a surprising effect on information transmission: Synaptic unreliability – which is ubiquitous in cortex and usually thought to impair neural communication – actually increases the information rate. We show that the beneficial effect of noise is based on a very general mechanism which contrary to stochastic resonance does not rely on a threshold nonlinearity.}, web_url = {http://abstracts.g-node.org/abstracts/65d2bbbf-5b2d-4570-8200-f994f190e9ca}, event_name = {Bernstein Conference 2014}, event_place = {Göttingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2014.0017}, author = {Gatys LA; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Tchumatchenko T; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}} } @Conference{ Eschenko2014, title = {The role of Locus Coeruleus for sensory processing within the mesocortical dopaminergic pathway}, year = {2014}, month = {7}, day = {6}, volume = {9}, number = {R10101}, abstract = {Salient events evoke burst-like responses of noradrenergic (NE) neurons of the Locus Coeruleus (LC) and dopaminergic (DA) neurons of the ventral tegmental area (VTA). The associated NE and DA release modulates signal processing in the projection targets of LC and VTA, which is beneficial for selection of adaptive behavioral response. In the rat, terminal fields of both LC-NE and VTA-DA neurons converge in the medial prefrontal cortex (mPFC), a cortical area controlling many cognitive capacities. We investigated the role of LC phasic activation for sensory representations in two LC targets by simultaneous electrophysiological recording in LC, VTA and mPFC and pharmacological manipulation of LC activity. Under urhetaine anestesia, noxious stimulation (foot shock, FS) produces a robust short-latency (~20 ms) excitation/inhibition response of LC-NE neurons. Populations of VTA and mPFC neurons also exhibit phasic excitatory and inhibitory responses, yet with longer latencies (~100 ms). Supression of LC spontaneous and evoked activity by iontophoretic injection of clonidine, an alpha2-adrenergic receptor agonist, disinibited a substantial proportion of VTA-DA and mPFC pyramidal neurons regardless of their FS-responsiveness. Furthermore, LC inhibition bidirectionally modulated the VTA-DA and mPFC resposes to noxious stimulation. The ongoing and evoked activity of VTA non-DA neurons was unaffected. These results suggest that depending on the motivational valence of a salient event, the LC-NE system may selectively enhance or supress signalling within different and, possibly, competing mesolimbic and mesocortical pathways. This hypothesis is being currently tested in behaving animals engaiged in a sensory cue-guided reward-motivated operant task.}, web_url = {http://fens2014.meetingxpert.net/FENS_427/poster_100053/program.aspx/anchor100053}, event_name = {9th FENS Forum of Neuroscience}, event_place = {Milano, Italy}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Conference{ Munk2014, title = {Tools for concurrent electrical recording and micro stimulation in high-field MRI}, year = {2014}, month = {7}, day = {1}, web_url = {http://www.nmi.de/fileadmin/PDF/Veranstaltungen/MEA2014_programme_web.pdf}, event_name = {MEA Meeting 2014: 9th International Meeting on Substrate-Integrated Microelectrode Arrays and 1st Tübingen Symposium on Current Topics in Neurotechnology}, event_place = {Reutlingen, Germany}, state = {published}, author = {Munk M{munk}{Department Physiology of Cognitive Processes}} } @Conference{ Perrodin2014, title = {Auditory and audiovisual specificity for processing communication signals in the superior temporal lobe}, year = {2014}, month = {6}, day = {13}, pages = {28}, abstract = {Effective social interactions can depend upon the receiver combining vocal and facial content to form a coherent audiovisual representation of communication signals. Neuroimaging studies have identified face- or voice-sensitive areas in the primate temporal lobe, some of which have been proposed as candidate regions for face-voice integration. However, so far neurons in these areas have been primarily studied in their respective sensory modality. In addition, these higher-level sensory areas are typically not prominent in current models of multisensory processing, unlike early sensory and association cortices. Thus, it was unclear how audiovisual influences occur at the neuronal level within such regions, especially in comparison to classically defined multisensory regions in temporal association cortex. Here I will present data exploring auditory (voice) and visual (face) influences on neuronal responses to vocalizations, that were obtained using extracellular recordings targeting a voice-sensitive region of the anterior supratemporal plane and the neighboring superior-temporal sulcus (STS) in awake rhesus macaques. Our findings suggest that within the superior temporal lobe, neurons in voice-sensitive cortex specialize in the auditory analysis of vocal features while congruency-sensitive visual influences emerge to a greater extent in STS neurons. These results help clarify the audiovisual representation of communication signals at two stages of the sensory pathway in primate superior temporal regions, and are consistent with reversed gradients of functional specificity in unisensory vs multisensory processing along their respective hierarchies.}, web_url = {http://uvtapp.uvt.nl/fsw/spits.ws.frmShowpage?v_page_id=3859096609314761}, event_name = {15th International Multisensory Research Forum (IMRF 2014)}, event_place = {Amsterdam, The Netherlands}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Conference{ PerrodinT2014, title = {Superior Temporal Regions: Slave or Master?}, year = {2014}, month = {6}, day = {13}, pages = {27}, abstract = {While the superior temporal regions (STR) of the primate brain have been reliably implicated in the processing of biologically relevant auditory and visual events, a number of open questions on the functional and behavioral role of audiovisual activity in these regions remain unresolved. This symposium brings together young investigators to present and discuss a variety of perspectives obtained from work in both humans and nonhuman primates, neuronal activity at different spatio-temporal scales, and multiple behavioral contexts. The different studies presented here have a common goal to address the extent to which audiovisual activity in superior temporal regions reflects functional multisensory integration. In particular, they aimed to disentangle whether STR actively relays and gates audiovisual information in a behaviorally relevant manner, or whether it merely represents a multisensory responsive hub supporting crossmodal convergence: Dr. Blank will present human fMRI results and discuss to what extent crossmodal activation of superior temporal regions by congruent prior information is behaviorally relevant to improve speech perception in difficult conditions. Dr. Thelen will present human ERP findings addressing the following questions: How does the STG contribute to audiovisual object memory trace formation and unisensory object recognition? What role does the STG play in multisensory object processing and how does activity within these areas relate to object category and/or semantic contingency? Catherine Perrodin will present extracellular recordings in rhesus macaques that shed light on the role played by neurons at different processing stages in the temporal lobe (STG vs. STS) in the integration of audiovisual communication signals.}, web_url = {http://uvtapp.uvt.nl/fsw/spits.ws.frmShowpage?v_page_id=3859096609314761}, event_name = {15th International Multisensory Research Forum (IMRF 2014)}, event_place = {Amsterdam, The Netherlands}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Thelen A} } @Conference{ Panagiotaropoulos2014, title = {Neural mechanisms of conscious visual perception in the prefrontal cortex: From single units to emergent activity patterns}, year = {2014}, month = {6}, day = {2}, event_name = {Oxford Cortex Symposium: Cortex Club Symposium & Cellular And Systems Neuroscience Cluster Meeting (DPAG)}, event_place = {Oxford, UK}, state = {published}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ OrtizRiosSLR2014, title = {High-resolution fMRI phase-mapping of azimuth space in rhesus monkey auditory cortex}, year = {2014}, month = {6}, pages = {34}, abstract = {Sound localization is one of the most fundamental tasks performed by the auditory system. In mammals, the location of a sound source in azimuth is mainly determined by interaural time and intensity differences between sounds reaching the two ears. Although binaural sound processing in subcortical structures is well understood, much less is known about the representation of space at the cortical level. In humans, the left auditory cortex (AC) shows a predominant response to sounds in the right hemifield, while the right AC responds to sounds in both hemifields (Krumbholz et al., 2007), with contrast between the two hemifields revealing activation along the dorsal stream into parietal cortex. In the monkey, selectivity of neurons in primary AC for positions in contralateral space has been observed, albeit with broad spatial tuning (Middlebrooks et al., 1994). Spatial tuning sharpens significantly in the caudal belt regions (Tian et al., 2001; Recanzone & Beckerman, 2004), but it is not known whether the preferred azimuth positions form a map of auditory space. Here we attempt to bridge studies across human and nonhuman primates by obtaining a comprehensive overview of the cortical representation of azimuth space in the monkey for the first time using phase-mapping functional magnetic resonance imaging (fMRI). Sounds were generated in virtual acoustic space and played back via headphones during fMRI. Stimuli consisted of broad-band noise bursts (0.2-16 kHz, 100 ms duration) moving through azimuth in steps of 30° at a rate of 5° per second. They were presented in a sparse-sampling design as a moving wave analogous to methods used in visual field mapping (Wandell & Winawer, 2011). We acquired high-resolution images oriented along the superior temporal plane in two anesthetized monkeys. We then analyzed the BOLD signal amplitude modulation at the frequency of stimulus presentation (12 cycles per scan) to determine voxel coherence and phase values corresponding to the stimulus cycle. In accordance with prior single-unit studies, a robust contralateral response to azimuth position was observed. The left AC represented mainly the anterior contralateral quadrant, including straight-ahead positions, while the right AC represented both ipsilateral and contralateral space. This hemispheric bias supports previous neuroimaging studies in humans. In addition, it may elucidate the hierarchical processing of space from AC into posterior parietal cortex and the sound localization deficits observed in humans with damage to the right temporo-parietal cortex (Spierer et al., 2009, Rauschecker & Tian, 2000).}, web_url = {https://www.uni-marburg.de/fb13/forschungsgruppen/neurophysik/brainact/downloads/abstracts2014.pdf}, event_name = {4th Joint Spring School Multisensory Perception for Action}, event_place = {Wildbad Kreuth, Germany}, state = {published}, author = {Ortiz Rios M{mortiz}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Conference{ Bartels2014_3, title = {Parietal function in ego-motion}, year = {2014}, month = {6}, pages = {7}, abstract = {Human parietal cortex consists of a number distinct regions that can be delineated from each other using retinotopic mapping. However, very little is known about their function. I will present a series of fMRI studies (some combined with transcranial magnetic stimulation (TMS) ) that each sheds light onto distinct regions within parietal cortex, demonstrating that parietal subdivisions have drastically distinct functional preferences. Most likely I will have time to present four studies: on high-level visual ego-motion cues as induced when humans freely view a movie, on the integration of visual motion with self-induced motion through eye-movements, on the representation of ego-centric space beyond the field of view, and on seeing the wood for the trees (i.e. global vs. local Gestalt perception). If time permits, I may additionally present a new study on cortical colour coding that emphasizes a concept introduced also in the motion studies, namely the influence of feedback on early visual cortex that is consistent with predictive coding.}, web_url = {https://www.uni-marburg.de/fb13/forschungsgruppen/neurophysik/brainact/downloads/abstracts2014.pdf}, event_name = {4th Joint Spring School Multisensory Perception for Action}, event_place = {Wildbad Kreuth, Germany}, state = {published}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2014, title = {Quantitative aspects of cortico-cortical connections, with special reference to the cortical white matter}, year = {2014}, month = {5}, web_url = {http://www.bitlifesciences.com/neurotalk2014/}, event_name = {BIT's 5th Annual World Congress of Neurotalk-2014}, event_place = {Nanjing, China}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2014, title = {Hippocampal–cortical interactions during periods of subcortical silence}, year = {2014}, month = {4}, day = {25}, pages = {19}, abstract = {retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centers involved in sensory processing or potentially mediating procedural learning. Several clinical studies, have demonstrated the phase-dependent synergistic or antagonistic relationship between the neural structures related to declarative and non-declarative (e.g. procedural) memory; Yet our observation demonstrates for the first time that such antagonistic relationship may exist during the “consolidation phase of long-term memory. The down regulation evidently generates conditions of minimal interference between subsystems, enabling consolidation of hippocampus-dependent memory. Importantly, neither the activation maps nor the sequences of up and down-regulation should be thought of indicating a causal relationship between the trigger event and the network activity changes. The state of widespread networks probably depends on a large number of variables (for example, activity changes in individual structures, or changes in inter-structure correlations), a subset of which may be eventually characterized following intensive future experimentation. The outcome of each experimental session may be conceived}, web_url = {http://neuronusforum.pl/previous-editions/}, event_name = {NEURONUS 2014 IBRO & IRUN Neuroscience Forum}, event_place = {Krakow, Poland}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Watanabe2014_2, title = {A Turing Test for Visual Qualia: An Experimental Method to Test Various Hypotheses on Consciousness}, year = {2014}, month = {4}, day = {22}, pages = {120}, abstract = {I propose an experimental method to test various hypotheses on consciousness. Inspired by Sperry’s observation that split-brain patients possess two independent streams of consciousness, the idea is to implement candidate neural mechanisms of visual consciousness onto an artificial hemisphere and test whether subjective experience is evoked in the device’s visual field. In contrast to modern neurosynthetic devices, I show that mimicking interhemispheric connectivity assures that authentic and fine grained subjective experience arises only when a stream of consciousness is generated within the device. It is valid under a widely believed assumption regarding interhemispheric connectivity and neuronal stimulus-invariance, as described below. Interhemispheric connectivity in low/mid-level visual areas is restricted in the sense that cross-hemispheric neuronal projection is observed only in neurons that retinotopically correspond to the vertical meridian. We may say that the retinotopic representation is only stitched together at the boundary of two visual hemifields. Interhemispheric connectivity beyond the parafovea exists only in high-level cortical areas. On the other hand, granularity of visual information decreases in higher visual areas in the form of increased stimulus-invariance. The critical question is whether the informational content in high-level areas is sufficient to support conscious vision. The “Intermediate Level Theory of Consciousness” by Jackendoff states otherwise and claims that it does not play a central role in conscious vision. If this is true, in combination with the hierarchical properties of interhemispheric connectivity, we need to acknowledge that subjective experience and verbal report of bilateral vision arise, not because all necessary information for conscious vision is inter-exchanged between the hemispheres, but because two potentially independent intra-hemispheric streams of consciousness are interlinked. The former scenario is denied because extra-parafoveal visual information represented in low/mid-level visual areas cannot be transmitted over to the other hemisphere in its original resolution. Likewise, under the above assumption, the only possible way we may subjectively experience authentic objects in the device’s visual field is that a stream of consciousness is generated within the artificial hemisphere and is interlinked to our own. Simple influx of information from the artificial to the biological hemisphere would not be sufficient. Hence, we may construct a valid test for machine consciousness and use it to explore the neural correlate of consciousness by means of analysis by synthesis. Interestingly, although fully replacing a cortical hemisphere is something of the far future, a minimal experiment can be conducted with today’s technology, for example, by establishing a brain-machine interface solely between populations of high-level face neurons. If a stream of consciousness is generated within a device, we should be able to construct a case where two objects presented in the device’s visual field are distinguishable by visual experience, but not distinguishable by what is communicated through the brain-machine interface. Finally, I discuss the alternative assumption where high-level visual information is sufficient for conscious vision and show that the proposed test of consciousness can be adapted to cover this case by incorporating knock-out paradigms. Together, I provide an exemplar neural mechanism of subjective bilateral vision that passes the proposed test.}, web_url = {http://www.consciousness.arizona.edu/documents/FinalCCS_BOOKofAbstracts_2014-2.pdf}, event_name = {20th Anniversary Conference Toward a Science of Consciousness (TSC 2014)}, event_place = {Tucson, AZ, USA}, state = {published}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}} } @Conference{ Watanabe2014, title = {A Turing Test for Visual Qualia and the Chaotic Spatiotemporal Fluctuation Hypothesis}, year = {2014}, month = {4}, day = {17}, abstract = {I propose an experimental method to test various hypotheses on consciousness. Inspired by Sperry's observation that split-brain patients possess two independent streams of consciousness, the idea is to implement candidate neural mechanisms of visual consciousness onto an artificial cortical hemisphere and test whether subjective experience is evoked in the device's visual hemifield. In contrast to modern neurosynthetic devices, I show that mimicking interhemispheric connectivity assures that authentic and fine-grained subjective experience arises only when a stream of consciousness is generated within the device. It is valid under a widely believed assumption regarding interhemispheric connectivity and neuronal stimulus- invariance. If consciousness is actually generated within the device, we should be able to construct a case where two objects presented in the device's visual field are distinguishable by visual experience but not by what is communicated through the brain-machine interface. As strange as it may sound, and clearly violating the law of physics, this is likely to be happening in the intact brain, where unified subjective bilateral vision and its verbal report occur without the total interhemispheric exchange of conscious visual information. Together, I present a hypothesis on the neural mechanism of consciousness, “The Chaotic Spatiotemporal Fluctuation Hypothesis” that passes the proposed test for visual qualia and also explains the violation of modern physics. Here, neural activity is divided into two components, the time-averaged activity and the residual temporally fluctuating activity, where the former serves as the content of consciousness (neuronal population vector) and the latter as consciousness itself. The content is “read” into consciousness in the sense that, every local perturbation caused by change in the neuronal population vector creates a spatiotemporal wave in the fluctuation component that that travels through out the system. Deterministic chaos assures that every local difference makes a difference to the whole of the dynamics, as in the butterfly effect, serving as a foundation for the holistic nature of consciousness. Finally, minimal and realistic versions of the proposed test for visual qualia can be conducted on laboratory animals to validate the hypothesis. It deals with two biological hemispheres, which we know already that it contains consciousness. We dissect interhemispheric connectivity and form instead an artificial one that is capable of filtering out the neural fluctuation component. A limited interhemispheric connectivity may be sufficient, which drastically discounts the technological challenge. If the subject is capable of conducting a bilateral stimuli matching task with the full artificial interhemispheric connectivity, but not when the fluctuation component is filtered out, it becomes a strong supporting evidence of the hypothesis.}, web_url = {http://csli-cec.stanford.edu/assets/papers/Watanabe.pdf}, event_name = {Stanford University: Center for the Explanation of Consciousness}, event_place = {Stanford, CA, USA}, state = {published}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}} } @Conference{ Panagiotaropoulos2014_2, title = {Neural mechanisms of conscious visual perception in the prefrontal cortex: From single units to correlations and spatiotemporal patterns}, year = {2014}, month = {4}, day = {9}, abstract = {Until recently the temporal cortex was the only known area where neuronal discharges during subjective visual perception closely matched the respective activity during perception without a subjective component, indicating a robust representation of the content of visual awareness. However, it was not clear whether conscious perception should be uniquely localized in the temporal association cortex. We focused on the next level of the ventral visual stream, the ventrolateral prefrontal cortex (PFC), and found single units that also represent reliably conscious content, suggesting a frontotemporal cortical workspace of conscious access. We also studied whether emergent properties of functional connectivity patterns like the structure of interneuronal firing correlations in the PFC could constrain the population coding accuracy and found a non-detrimental correlation structure during subjective perception. These empirical findings are used to constrain biophysically realistic models in an effort to pin down the dynamic mechanisms of perceptual stability and spontaneous perceptual transitions. The latter could be ascribed to spontaneous fluctuations of intrinsic activity that induce perceptual reorganization. In order to gain a preliminary understanding of these fluctuations in the PFC we used multielectrode (Utah array) recordings and mapped the dynamic spatiotemporal structure of oscillatory activity revealing a dominant travelling wave pattern in the beta (15-30Hz) frequency band.}, web_url = {http://www.ncl.ac.uk/ion/news/events/eventitem.htm?id=extra-ion-seminar-theofanis-panagiotaropoulos}, event_name = {Newcastle University: Extra IoN Seminar}, event_place = {Newcastle, UK}, state = {published}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ SchindlerB2014, title = {Parietal Representations of Egocentric Space include unseen Locations}, year = {2014}, month = {4}, day = {2}, volume = {56}, pages = {229}, abstract = {Our subjective experience links covert visual and egocentric spatial attention seamlessly. However, the latter can extend beyond the visual field, covering all directions relative to our body. Even with closed eyes we can rotate from the computer screen to face the window with little loss of accuracy, and once rotated we are aware of the computer’s updated egocentric position. It appears thus that our egocentric model includes seen and unseen locations. In contrast to visual representations, little is known about unseen egocentric representations in the healthy brain. Parietal cortex appears to be involved in both, because its lesions can lead to deficits in visual attention, but also to a disorder of egocentric spatial awareness, known as hemispatial neglect. In this study, our participants performed a novel egocentric orientation task inside an octagonal room. Once they were familiar with this setup, we exposed our participants to a virtual version of the same paradigm during fMRI recordings. We found egocentric unseen space represented by patterns of voxel activity in parietal cortex, independent of visual information. Intriguingly, the best decoding performances corresponded to brain areas associated with visual covert attention and reaching, as well as to lesion sites associated with spatial neglect.}, web_url = {https://www.teap.de/memory/TeaP_Abstracts_20140219.pdf}, event_name = {56th Conference of Experimental Psychologists (TeaP 2014)}, event_place = {Giessen, Germany}, state = {published}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ Ecker2014, title = {State dependence of noise correlations in primary visual cortex}, year = {2014}, month = {3}, day = {21}, web_url = {http://www.ewcbr.eu/index.php/en/abstracts-112.html}, event_name = {34th European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2014)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Ecker A{aecker}{Department Physiology of Cognitive Processes}} } @Conference{ Eschenko2014_2, title = {Ripple-triggered stimulation of Locus Coeruleus during post-learning sleep impairs memory consolidation}, year = {2014}, month = {3}, day = {17}, abstract = {Hippocampal ripples, brief high-frequency (150-200Hz) oscillations occurring during quiet wakefulness or slow wave sleep (SWS), represent simultaneous discharge of a large neuronal population that is synchronized across the entire hippocampus. Learning experience increases frequency of ripple occurrence, which is predictive of memory recall, while ripple suppression impairs hippocampal-dependent learning. Experience-induced replay of neuronal ensembles occurs predominantly during ripples. These observations support the idea that ripples provide a neurophysiological substrate for ‘off-line’ memory consolidation by facilitating synaptic plasticity within the learning-associated neuronal network. We hypothesized that noradrenaline (NE) release during ripples in subcortical and cortical targets of the Locus Coeruleus (LC) may be beneficial for memory consolidation. Rats implanted with linear electrode arrays for extracellular recording in cortex and hippocampus and a stimulating electrode in LC were trained on a spatial memory task. Neural activity was monitored for 1h immediately after each learning session. Ripples were detected on-line using a band-pass filtered (150-250Hz) extracellular voltage signal recorded in the CA1 region of hippocampus by applying a threshold-crossing algorithm. Trains of biphasic electrical pulses (0.4ms, 0.05mA) were delivered to LC at each ripple onset. Group1 received LC stimulation (5 pulses at 20Hz) that did not produce detectable changes in cortical or hippocampal neural activity. Group2 received LC stimulation (10-20 pulses at 50-100Hz) that induced a transient (1-2s) desynchronization of cortical EEG, during which both thalamocortical sleep spindles and hippocampal ripples were suppressed. Additional control groups included random LC stimulation, stimulation outside of LC, and sham-operated animals. Ripple-triggered LC stimulation produced a spatial memory deficit exclusively in Group2 rats, while behavioral performance of other control rats did not differ from intact animals. The stimulation-induced discharge of LC neurons and concurrent NE release caused a transient state change in the thalamocortical network, which was not favorable for hippocampal-cortical communication. These results challenge the original hypothesis, yet support the findings of our recent fMRI study showing a remarkable dichotomy between ripple-associated cortical activation and deactivation of many subcortical regions including thalamus and brain stem neuromodulatory centers (Logothetis et al., 2012).}, web_url = {http://www.ewcbr.eu/index.php/en/abstracts-112.html}, event_name = {34th European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2014)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2014_2, title = {The functional and effective connectivity of memory-related networks: insights from the neural event triggered BOLD fMRI}, year = {2014}, month = {3}, day = {17}, abstract = {Learning and memory are system properties emerging from the concerted operations of micro- and macro networks at multiple levels of the brain. The consolidation of declarative memory – that entirely depends on hippocampus - is long thought to occur during the slow wave sleep (SWS) by means of the reactivation of neural representations that were temporally stored in hippocampus during the awake state. A large number of studies have suggested that the behavior-dependent electrical changes in the hippocampus may travel back to the cortex by means of the so-called sharp-wave ripple (SPW-R) events. Until recently we had no information related to the effects of SPW-R bursts on different structures of the brain. We developed a new methodology, a neural event triggered BOLD fMRI NET-fMRI), allowing to relate the local brain activity at a recording site to activity in other brain regions, and applied it for mapping brain activity associated with SPW-Rs in non-human primates and rats. We showed that SPW-Rs were tightly associated with robust cortical activations that occur concurrently with extensive activity suppression in subcortical thalamic, associational (e.g. basal ganglia, cerebellum), and midbrain-brainstem neuromodulatory centers. Suppression of thalamic activity might be a strategy that could increase the signal-to-noise ratio of hippocampal-cortical communication. Strong inhibition of the associational subcortical brain structures that are closely involved in the mechanisms of associative learning, such as the basal ganglia and the cerebellar cortex may indicate competition between the fundamentally distinct memory systems. A competition between the hippocampal and pontine regions may similarly reflect antagonistic interactions between procedures related to the redistribution of hippocampal memory traces during SWS (network plasticity), and those occurring during REM (rapid eye movement) sleep phase and involving local increases in plasticity related immediate early gene activity favoring the subsequent synaptic consolidation (local plasticity) in the cortex. The latter procedure, taking place during high cholinergic and theta activity, is associated with the Pontine-Geniculate-Occipital (PGO) waves that are characteristic markers of REM sleep. Thus, NET-fMRI methodology may ultimately reveal the network states that possibly underlie various behaviors and cognitive functions.}, web_url = {http://www.ewcbr.eu/index.php/en/abstracts-112.html}, event_name = {34th European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2014)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Bartels2017, title = {From movies to egocentric representations: visual motion processing in the human brain}, year = {2014}, month = {1}, day = {21}, web_url = {https://medweb4.unige.ch/labnic/news/B&C_Program_Jan2014.pdf}, event_name = {University of Geneva, Departments of Neurosciences and Clinical Neurology: Brain & Cognition Seminar}, event_place = {Geneva, Switzerland}, state = {published}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Book{ QuirogaP2013, title = {Principles of Neural Coding}, year = {2013}, pages = {663}, web_url = {http://www.crcpress.com/product/isbn/9781439853306}, publisher = {CRC Press}, address = {Boca Raton, FL, USA}, state = {published}, ISBN = {978-1-4398-5330-6}, author = {Quian Quiroga R; Panzeri S{stefano}} } @Article{ SchindlerHB2012, title = {Coding of Melodic Gestalt in Human Auditory Cortex}, journal = {Cerebral Cortex}, year = {2013}, month = {12}, volume = {23}, number = {12}, pages = {2987-2993}, abstract = {The perception of a melody is invariant to the absolute properties of its constituting notes, but depends on the relation between them—the melody's relative pitch profile. In fact, a melody's “Gestalt” is recognized regardless of the instrument or key used to play it. Pitch processing in general is assumed to occur at the level of the auditory cortex. However, it is unknown whether early auditory regions are able to encode pitch sequences integrated over time (i.e., melodies) and whether the resulting representations are invariant to specific keys. Here, we presented participants different melodies composed of the same 4 harmonic pitches during functional magnetic resonance imaging recordings. Additionally, we played the same melodies transposed in different keys and on different instruments. We found that melodies were invariantly represented by their blood oxygen level–dependent activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as the primary auditory cortex.}, web_url = {http://cercor.oxfordjournals.org/content/23/12/2987}, state = {published}, DOI = {10.1093/cercor/bhs289}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Herdener M{herdener}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ ChagasTSSBS2013, title = {Functional analysis of ultra high information rates conveyed by rat vibrissal primary afferents}, journal = {Frontiers in Neural Circuits}, year = {2013}, month = {12}, volume = {7}, number = {190}, pages = {1-17}, abstract = {Sensory receptors determine the type and the quantity of information available for perception. Here, we quantified and characterized the information transferred by primary afferents in the rat whisker system using neural system identification. Quantification of “how much” information is conveyed by primary afferents, using the direct method (DM), a classical information theoretic tool, revealed that primary afferents transfer huge amounts of information (up to 529 bits/s). Information theoretic analysis of instantaneous spike-triggered kinematic stimulus features was used to gain functional insight on “what” is coded by primary afferents. Amongst the kinematic variables tested—position, velocity, and acceleration—primary afferent spikes encoded velocity best. The other two variables contributed to information transfer, but only if combined with velocity. We further revealed three additional characteristics that play a role in information transfer by primary afferents. Firstly, primary afferent spikes show preference for well separated multiple stimuli (i.e., well separated sets of combinations of the three instantaneous kinematic variables). Secondly, neurons are sensitive to short strips of the stimulus trajectory (up to 10 ms pre-spike time), and thirdly, they show spike patterns (precise doublet and triplet spiking). In order to deal with these complexities, we used a flexible probabilistic neuron model fitting mixtures of Gaussians to the spike triggered stimulus distributions, which quantitatively captured the contribution of the mentioned features and allowed us to achieve a full functional analysis of the total information rate indicated by the DM. We found that instantaneous position, velocity, and acceleration explained about 50% of the total information rate. Adding a 10 ms pre-spike interval of stimulus trajectory achieved 80–90%. The final 10–20% were found to be due to non-linear coding by spike bursts.}, web_url = {http://www.frontiersin.org/Journal/DownloadFile.ashx?pdf=1&FileId=125135&articleId=56643&Version=1&ContentTypeId=21&FileName=fncir-07-00190.pdf}, state = {published}, DOI = {10.3389/fncir.2013.00190}, author = {Chagas AM; Theis L{lucas}{Research Group Computational Vision and Neuroscience}; Sengupta B{sengupta}{Department Empirical Inference}{Department Physiology of Cognitive Processes}{Research Group Computational Vision and Neuroscience}; St\"uttgen MC; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Schwarz C} } @Article{ BallaGSUSHJHFSPE2013, title = {In vivo visualization of single native pancreatic islets in the mouse}, journal = {Contrast Media & Molecular Imaging}, year = {2013}, month = {12}, volume = {8}, number = {6}, pages = {495-504}, abstract = {The purpose of this study was to investigate the potential of a novel targeted contrast agent (CA) for the in vivo visualization of single native pancreatic islets, the sites of insulin production, in the pancreas of mice using magnetic resonance imaging (MRI). The CA for intravenous administration was composed of the β-cell-specific single-chain antibody fragment, SCA B1, and ferromagnetic carbon-coated cobalt nanoparticles. MRI experiments were performed at 7, 9.4 and 16.4 T in excised organs (pancreas, liver, kidney, spleen), at 7 T in mice fixed in formalin and at 9.4 and 16.4 T in living mice. Image contrast in untreated control animals was compared with images from mice treated with unspecific and specific CA. For the validation of MRI results, selected pancreases were subjected to immunohistochemical staining and numerical contrast simulations were performed. Ex vivo results and the outcome of immunohistochemistry suggest that islets are marked only by the CA containing SCA B1. Strong accumulation of particles was found also in other investigated organs owing to the uptake by the reticuloendothelial system, but the contrast in the MR images is clearly distinguishable from the islet specific contrast in pancreases and numerical predictions. In vivo experiments based on averaged dynamic sampling with 66 × 66 × 100 µm3 and triggered acquisition with 90 × 90 × 200 µm3 nominal resolution resulted in similar particle contrast to in in vitro measurements. The newly developed CA and MRI strategies have the potential to be used for studying mouse diabetes models by visualizing single native pancreatic islets.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cmmi.1580/pdf}, state = {published}, DOI = {10.1002/cmmi.1580}, author = {Balla DZ{ballad}{Department Physiology of Cognitive Processes}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Shajan G{shajang}{Department High-Field Magnetic Resonance}; Ueberberg S; Schneider S; Hardtke-Wolenski M; Jaeckel E; Hoerr V; Faber C; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Pohmann R{rolf}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}} } @Article{ DhingraVermaFUBMPBL2013, title = {New Calcium-Selective Smart Contrast Agents for Magnetic Resonance Imaging}, journal = {Chemistry - A European Journal}, year = {2013}, month = {12}, volume = {19}, number = {52}, pages = {18011–18026}, abstract = {Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca2+ levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca2+ in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca2+-sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca2+ in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd3+-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca2+ chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca2+ present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2–0.8 mM. The determined dissociation constant of the CAs to Ca2+ falls in the range required to sense and report changes in extracellular Ca2+ levels followed by an increase in neural activity. In buffer, with the addition of Ca2+ the increase in relaxivity ranged from 100–157 %, the highest ever known for any T1-based Ca2+-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb3+ analogues, nuclear magnetic relaxation dispersion (NMRD), and 17O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca2+ addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/chem.201300169/pdf}, state = {published}, DOI = {10.1002/chem.201300169}, author = {Dhingra Verma K{kirti}{Department Physiology of Cognitive Processes}; Forg{\'a}cs A; Uh H; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Maier ME; Petoud S; Botta M; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ HerdenerESSLUK2013, title = {Spatial representations of temporal and spectral sound cues in human auditory cortex}, journal = {Cortex}, year = {2013}, month = {12}, volume = {49}, number = {10}, pages = {2822–2833}, abstract = {Natural and behaviorally relevant sounds are characterized by temporal modulations of their waveforms, which carry important cues for sound segmentation and communication. Still, there is little consensus as to how this temporal information is represented in auditory cortex. Here, by using functional magnetic resonance imaging (fMRI) optimized for studying the auditory system, we report the existence of a topographically ordered spatial representation of temporal sound modulation rates in human auditory cortex. We found a topographically organized sensitivity within auditory cortex to sounds with varying modulation rates, with enhanced responses to lower modulation rates (2 and 4 Hz) on lateral parts of Heschl's gyrus (HG) and faster modulation rates (16 and 32 Hz) on medial HG. The representation of temporal modulation rates was distinct from the representation of sound frequencies (tonotopy) that was orientated roughly orthogonal. Moreover, the combination of probabilistic anatomical maps with a previously proposed functional delineation of auditory fields revealed that the distinct maps of temporal and spectral sound features both prevail within two presumed primary auditory fields hA1 and hR. Our results reveal a topographically ordered representation of temporal sound cues in human primary auditory cortex that is complementary to maps of spectral cues. They thereby enhance our understanding of the functional parcellation and organization of auditory cortical processing.}, web_url = {http://www.sciencedirect.com/science/article/pii/S001094521300110X}, state = {published}, DOI = {10.1016/j.cortex.2013.04.003}, author = {Herdener M{herdener}{Department High-Field Magnetic Resonance}; Esposito F; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Schneider P; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Uludag K{kuludag}{Department High-Field Magnetic Resonance}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ LeePLSK2013, title = {A new method for estimating population receptive field topography in visual cortex}, journal = {NeuroImage}, year = {2013}, month = {11}, volume = {81}, pages = {144–157}, abstract = {We introduce a new method for measuring visual population receptive fields (pRF) with functional magnetic resonance imaging (fMRI). The pRF structure is modeled as a set of weights that can be estimated by solving a linear model that predicts the Blood Oxygen Level-Dependent (BOLD) signal using the stimulus protocol and the canonical hemodynamic response function. This method does not make a priori assumptions about the specific pRF shape and is therefore a useful tool for uncovering the underlying pRF structure at different spatial locations in an unbiased way. We show that our method is more accurate than a previously described method (Dumoulin and Wandell, 2008) which directly fits a 2-dimensional isotropic Gaussian pRF model to predict the fMRI time-series. We demonstrate that direct-fit models do not fully capture the actual pRF shape, and can be prone to pRF center mislocalization when the pRF is located near the border of the stimulus space. A quantitative comparison demonstrates that our method outperforms the direct-fit methods in the pRF center modeling by achieving higher explained variance of the BOLD signal. This was true for direct-fit isotropic Gaussian, anisotropic Gaussian, and difference of isotropic Gaussians model. Importantly, our model is also capable of exploring a variety of pRF properties such as surround suppression, receptive field center elongation, orientation, location and size. Additionally, the proposed method is particularly attractive for monitoring pRF properties in the visual areas of subjects with lesions of the visual pathways, where it is difficult to anticipate what shape the reorganized pRF might take. Finally, the method proposed here is more efficient in computation time than direct-fit methods, which need to search for a set of parameters in an extremely large searching space. Instead, this method uses the pRF topography to constrain the space that needs to be searched for the subsequent modeling.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191300520X20X}, state = {published}, DOI = {10.1016/j.neuroimage.2013.05.026}, author = {Lee S{slee}{Department Physiology of Cognitive Processes}; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Article{ BannertB2013, title = {Decoding the Yellow of a Gray Banana}, journal = {Current Biology}, year = {2013}, month = {11}, volume = {23}, number = {22}, pages = {2268–2272}, abstract = {Some everyday objects are associated with a particular color, such as bananas, which are typically yellow. Behavioral studies show that perception of these so-called color-diagnostic objects is influenced by our knowledge of their typical color, referred to as memory color [1,2]. However, neural representations of memory colors are unknown. Here we investigated whether memory color can be decoded from visual cortex activity when color-diagnostic objects are viewed as grayscale images. We trained linear classifiers to distinguish patterns of fMRI responses to four different hues. We found that activity in V1 allowed predicting the memory color of color-diagnostic objects presented in grayscale in naive participants performing a motion task. The results imply that higher areas feed back memory-color signals to V1. When classifiers were trained on neural responses to some exemplars of color-diagnostic objects and tested on others, areas V4 and LOC also predicted memory colors. Representational similarity analysis showed that memory-color representations in V1 were correlated specifically with patterns in V4 but not LOC. Our findings suggest that prior knowledge is projected from midlevel visual regions onto primary visual cortex, consistent with predictive coding theory [3].}, web_url = {http://www.sciencedirect.com/science/article/pii/S0960982213011329}, state = {published}, DOI = {10.1016/j.cub.2013.09.016}, author = {Bannert MM{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ EinevollKLP2013, title = {Modelling and analysis of local field potentials for studying the function of cortical circuits}, journal = {Nature Reviews Neuroscience}, year = {2013}, month = {11}, volume = {14}, number = {11}, pages = {770-785}, abstract = {The past decade has witnessed a renewed interest in cortical local field potentials (LFPs) - that is, extracellularly recorded potentials with frequencies of up to similar to 500 Hz. This is due to both the advent of multielectrodes, which has enabled recording of LFPs at tens to hundreds of sites simultaneously, and the insight that LFPs offer a unique window into key integrative synaptic processes in cortical populations. However, owing to its numerous potential neural sources, the LFP is more difficult to interpret than are spikes. Careful mathematical modelling and analysis are needed to take full advantage of the opportunities that this signal offers in understanding signal processing in cortical circuits and, ultimately, the neural basis of perception and cognition.}, web_url = {http://www.nature.com/nrn/journal/v14/n11/pdf/nrn3599.pdf}, state = {published}, DOI = {10.1038/nrn3599}, author = {Einevoll GT; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Article{ IncePK2013, title = {Neural codes formed by small and temporally precise populations in auditory cortex}, journal = {Journal of Neuroscience}, year = {2013}, month = {11}, volume = {33}, number = {46}, pages = {18277-18287}, abstract = {The encoding of sensory information by populations of cortical neurons forms the basis for perception but remains poorly understood. To understand the constraints of cortical population coding we analyzed neural responses to natural sounds recorded in auditory cortex of primates (Macaca mulatta). We estimated stimulus information while varying the composition and size of the considered population. Consistent with previous reports we found that when choosing subpopulations randomly from the recorded ensemble, the average population information increases steadily with population size. This scaling was explained by a model assuming that each neuron carried equal amounts of information, and that any overlap between the information carried by each neuron arises purely from random sampling within the stimulus space. However, when studying subpopulations selected to optimize information for each given population size, the scaling of information was strikingly different: a small fraction of temporally precise cells carried the vast majority of information. This scaling could be explained by an extended model, assuming that the amount of information carried by individual neurons was highly nonuniform, with few neurons carrying large amounts of information. Importantly, these optimal populations can be determined by a single biophysical marker—the neuron's encoding time scale—allowing their detection and readout within biologically realistic circuits. These results show that extrapolations of population information based on random ensembles may overestimate the population size required for stimulus encoding, and that sensory cortical circuits may process information using small but highly informative ensembles.}, web_url = {http://www.jneurosci.org/content/33/46/18277.full.pdf+html}, state = {published}, DOI = {10.1523/JNEUROSCI.2631-13.2013}, author = {Ince RAA{rince}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ WatanabeBMML2013, title = {Temporal Jitter of the BOLD Signal Reveals a Reliable Initial Dip and Improved Spatial Resolution}, journal = {Current Biology}, year = {2013}, month = {11}, volume = {23}, number = {21}, pages = {2146–2150}, abstract = {fMRI, one of the most important noninvasive brain imaging methods, relies on the blood oxygen level-dependent (BOLD) signal, whose precise underpinnings are still not fully understood [1]. It is a widespread assumption that the components of the hemodynamic response function (HRF) are fixed relative to each other in time, leading most studies as well as analysis tools to focus on trial-averaged responses, thus using or estimating a condition- or location-specific “canonical HRF” [2, 3 and 4]. In the current study, we examined the nature of the variability of the BOLD response and asked in particular whether the positive BOLD peak is subject to trial-to-trial temporal jitter. Our results show that the positive peak of the stimulus-evoked BOLD signal exhibits a trial-to-trial temporal jitter on the order of seconds. Moreover, the trial-to-trial variability can be exploited to uncover the initial dip in the majority of voxels by pooling trial responses with large peak latencies. Initial dips exposed by this procedure possess higher spatial resolution compared to the positive BOLD signal in the human visual cortex. These findings allow for the reliable observation of fMRI signals that are physiologically closer to neural activity, leading to improvements in both temporal and spatial resolution.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0960982213011160}, state = {published}, DOI = {10.1016/j.cub.2013.08.057}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Macke JH{jakob}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ OmerHG2013, title = {Temporally-structured acquisition of multidimensional optical imaging data facilitates visualization of elusive cortical representations in the behaving monkey}, journal = {NeuroImage}, year = {2013}, month = {11}, volume = {82}, pages = {237–251}, abstract = {Fundamental understanding of higher cognitive functions can greatly benefit from imaging of cortical activity with high spatiotemporal resolution in the behaving non-human primate.To achieve rapid imaging of high-resolution dynamicsof cortical representations of spontaneous and evoked activity ,we designed a novel data acquisition protocol for sensory stimulation by rapidly interleaving multiple stimuli in continuous sessions of optical imaging with voltage-sensitive dyes. We also tested a new algorithm for the “temporally structured componentanalysis” (TSCA) of a multidimensional timeseries that was developed for our new data acquisitionprotocol, but was tested only on simulated data (Blumenfeld, 2010). In addition to the raw data, the algorithm incorporates prior knowledge about the temporal structure of the data as well as input from other information. Here we showed thatTSCA can successfully separate functional signal components from other signals referred to as noise. Imaging of responses to multiple visual stimuli, utilizing voltage-sensitive dyes, wasperformed on the visual cortex of awake monkeys. Multiple cortical representations,including orientation and ocular dominance maps as well as thehitherto elusive retinotopic representation of orientation stimuli, were extracted in only 10 secondsof imaging, approximately two orders of magnitude faster than accomplished by conventional methods. Since the approach is rather general, other imaging techniques may also benefit from the same stimulation protocol. This methodology can thus facilitate rapid optical imaging explorations in monkeys, rodents and other specieswith a versatility and speed that were not feasible before.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811913005399}, state = {published}, DOI = {10.1016/j.neuroimage.2013.05.045}, author = {Omer DB{domer}{Department Physiology of Cognitive Processes}; Hildesheim R; Grinvald A} } @Article{ ShaoKPFZ2013, title = {Visual cortex organisation in a macaque monkey with macular degeneration}, journal = {European Journal of Neuroscience}, year = {2013}, month = {11}, volume = {38}, number = {10}, pages = {3456–3464}, abstract = {The visual field is retinotopically represented in early visual areas. It has been suggested that when adult primary visual cortex (V1) is deprived of normal retinal input it is capable of large-scale reorganisation, with neurons inside the lesion projection zone (LPZ) being visually driven by inputs from intact retinal regions. Early functional magnetic resonance imaging (fMRI) studies in humans with macular degeneration (MD) report > 1 cm spread of activity inside the LPZ border, whereas recent results report no shift of the LPZ border. Here, we used fMRI population receptive field measurements to study, for the first time, the visual cortex organisation of one macaque monkey with MD and to compare it with normal controls. Our results showed that the border of the V1 LPZ remained stable, suggesting that the deafferented area V1 zone of the MD animal has limited capacity for reorganisation. Interestingly, the pRF size of non-deafferented V1 voxels increased slightly (~20% on average), although this effect appears weaker than that in previous single-unit recording reports. Area V2 also showed limited reorganisation. Remarkably, area V5/MT of the MD animal showed extensive activation compared to controls stimulated over the part of the visual field that was spared in the MD animal. Furthermore, population receptive field size distributions differed markedly in area V5/MT of the MD animal. Taken together, these results suggest that V5/MT has a higher potential for reorganisation after MD than earlier visual cortex.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1111/ejn.12349/pdf}, state = {published}, DOI = {10.1111/ejn.12349}, author = {Shao Y{yshao}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Fischer MD; Zobor D; J\"agle H; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Article{ RanaGDLS2013, title = {A toolbox for real-time subject-independent and subject-dependent classification of brain}, journal = {Frontiers in Neuroscience}, year = {2013}, month = {10}, volume = {7}, number = {170}, pages = {1-11}, abstract = {There is a recent increase in the use of multivariate analysis and pattern classification in prediction and real-time feedback of brain states from functional imaging signals and mapping of spatio-temporal patterns of brain activity. Here we present MANAS, a generalized software toolbox for performing online and offline classification of fMRI signals. MANAS has been developed using MATLAB, LIBSVM, and SVMlight packages to achieve a cross-platform environment. MANAS is targeted for neuroscience investigations and brain rehabilitation applications, based on neurofeedback and brain-computer interface (BCI) paradigms. MANAS provides two different approaches for real-time classification: subject dependent and subject independent classification. In this article, we present the methodology of real-time subject dependent and subject independent pattern classification of fMRI signals; the MANAS software architecture and subsystems; and finally demonstrate the use of the system with experimental results.}, web_url = {http://journal.frontiersin.org/Journal/10.3389/fnins.2013.00170/pdf}, state = {published}, DOI = {10.3389/fnins.2013.00170}, author = {Rana M; Gupta N; Dalboni Da Rocha JL; Lee S{slee}{Department Physiology of Cognitive Processes}; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}} } @Article{ HelmchenDK2013, title = {Miniaturization of two-photon microscopy for imaging in freely moving animals}, journal = {Cold Spring Harbor Protocols}, year = {2013}, month = {10}, volume = {2013}, number = {10}, pages = {904-913}, abstract = {This article describes the development and application of miniaturized two-photon-excited fluorescence microscopes ("two-photon fiberscopes"). Two-photon fiberscopes have been developed with the aim of enabling high-resolution imaging of neural activity in freely behaving animals. They use fiber optics to deliver laser light for two-photon excitation. Their small front piece typically contains a miniature scanning mechanism and imaging optics. Two-photon fiberscopes can be made sufficiently small and lightweight to be carried by rats and mice and to allow virtually unrestricted movement within a behavioral arena. Typically mounted to the animal's skull above a cranial window, two-photon fiberscopes permit imaging of cells down to at least 250 m below the brain surface (e.g., in rat neocortex). In freely exploring animals, action-potential-evoked calcium transients can be imaged in individual somata of visual cortex neurons bulk-labeled with a calcium indicator. Two-photon fiberscopes thus enable high-resolution optical recording of neural activity with cellular resolution during natural behaviors.}, web_url = {http://cshprotocols.cshlp.org/content/2013/10/pdb.top078147.full}, state = {published}, DOI = {10.1101/pdb.top078147}, author = {Helmchen F; Denk W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ ZaretskayaB2013, title = {Perceptual effects of stimulating V5/hMT+ during binocular rivalry are state specific}, journal = {Current Biology}, year = {2013}, month = {10}, volume = {23}, number = {20}, pages = {R919-R920}, abstract = {Binocular rivalry occurs when two distinct visual stimuli are presented separately to each eye, causing perceptual ambiguity. The conscious state of the observer then alternates between the perceptual dominance of one of the stimuli while the other is suppressed, and vice versa. These vivid changes in perception during constant visual stimulation allow the study of brain processes involved in conscious visual experience. There is abundant electrophysiological as well as fMRI evidence that neural activity in stimulus-selective areas of the temporal lobe correlates with perceptual changes during rivalry [1,2,3]. Yet, almost nothing is known about the causal contribution of these areas to dominance and suppression of their preferred stimulus. We induced binocular rivalry in human observers using moving dots presented to one eye and a static face to the other eye, and applied transcranial magnetic stimulation (TMS) over the motion area V5/hMT+. We show that disrupting activity in V5/hMT+ during rivalry extends periods of motion suppression, with no effect on periods of motion dominance, revealing a state-specific contribution of V5/hMT+ to the competition for awareness in rivalry.}, web_url = {http://download.cell.com/current-biology/pdf/PIIS0960982213011093.pdf}, state = {published}, DOI = {10.1016/j.cub.2013.09.002}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ BuzsakiLS2013, title = {Scaling brain size, keeping timing: evolutionary preservation of brain rhythms}, journal = {Neuron}, year = {2013}, month = {10}, volume = {80}, number = {3}, pages = {751–764}, abstract = {Despite the several-thousand-fold increase of brain volume during the course of mammalian evolution, the hierarchy of brain oscillations remains remarkably preserved, allowing for multiple-time-scale communication within and across neuronal networks at approximately the same speed, irrespective of brain size. Deployment of large-diameter axons of long-range neurons could be a key factor in the preserved time management in growing brains. We discuss the consequences of such preserved network constellation in mental disease, drug discovery, and interventional therapies.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627313009045}, state = {published}, DOI = {10.1016/j.neuron.2013.10.002}, author = {Buzs{\'a}ki G; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Singer W} } @Article{ GottschalkERBPM2013, title = {Comparative in vitro studies of MR imaging probes for metabotropic glutamate subtype-5 receptor targeting}, journal = {Organic & Biomolecular Chemistryi}, year = {2013}, month = {9}, volume = {11}, number = {36}, pages = {6131-6141}, abstract = {A series of magnetic resonance imaging probes has been evaluated to target selectively the metabotropic glutamate receptor subtype 5 (mGluR5). Eight imaging probes based on the contrast agent [Gd·DOTA], previously derived by linking it to a series of specific and selective mGluR5 antagonists, have been extensively tested for their functionality in vitro. The Nuclear Magnetic Relaxation Dispersion (NMRD) profiles of selected probes have been examined via field-cycling relaxometry in the presence and absence of a model protein. The properties of the targeted contrast agents were evaluated using a primary astrocyte model, as these cells mimic the in vivo situation effectively. The probes were non-toxic (up to 200 μM) to these mGluR5 expressing primary cells. Cellular proton longitudinal relaxation rate enhancements of up to 35% were observed by MRI at 200 μM of probe concentration. The antagonistic effect of all compounds was tested using an assay measuring changes of intracellular calcium levels. Furthermore, treatment at two different temperatures (4 °C vs. 37 °C) and of an mGluR5-negative cell line provided further insight into the selectivity and specificity of these probes towards cell surface mGluR5. Finally, two out of eight probes demonstrated an antagonistic effect as well as significant enhancement of receptor mediated cellular relaxation rates, strongly suggesting that they would be viable probes for the mapping of mGluR5 by MRI in vivo.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2013/ob/c3ob41297k}, state = {published}, DOI = {10.1039/C3OB41297K}, author = {Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Rolla GA; Botta M; Parker D; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}} } @Article{ PanagiotaropoulosKL2013, title = {Desynchronization and rebound of beta oscillations during conscious and unconscious local neuronal processing in the macaque lateral prefrontal cortex}, journal = {Frontiers in Psychology}, year = {2013}, month = {9}, volume = {4}, number = {603}, pages = {1-10}, abstract = {Accumulating evidence indicates that control mechanisms are not tightly bound to conscious perception since both conscious and unconscious information can trigger control processes, probably through the activation of higher-order association areas like the prefrontal cortex. Studying the modulation of control-related prefrontal signals in a microscopic, neuronal level during conscious and unconscious neuronal processing, and under control-free conditions could provide an elementary understanding of these interactions. Here we performed extracellular electrophysiological recordings in the macaque lateral prefrontal cortex (LPFC) during monocular physical alternation (PA) and binocular flash suppression (BFS) and studied the local scale relationship between beta (15–30 Hz) oscillations, a rhythmic signal believed to reflect the current sensory, motor, or cognitive state (status-quo), and conscious or unconscious neuronal processing. First, we show that beta oscillations are observed in the LPFC during resting state. Both PA and BFS had a strong impact on the power of this spontaneous rhythm with the modulation pattern of beta power being identical across these two conditions. Specifically, both perceptual dominance and suppression of local neuronal populations in BFS were accompanied by a transient beta desynchronization followed by beta activity rebound, a pattern also observed when perception occurred without any underlying visual competition in PA. These results indicate that under control-free conditions, at least one rhythmic signal known to reflect control processes in the LPFC (i.e., beta oscillations) is not obstructed by local neuronal, and accordingly perceptual, suppression, thus being independent from temporally co-existing conscious and unconscious local neuronal representations. Future studies could reveal the additive effects of motor or cognitive control demands on prefrontal beta oscillations during conscious and unconscious processing.}, web_url = {http://www.frontiersin.org/Journal/DownloadFile.ashx?pdf=1&FileId=72588&articleId=58465&Version=1&ContentTypeId=21&FileName=fpsyg-04-00603.pdf}, state = {published}, DOI = {10.3389/fpsyg.2013.00603}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ SigalaSSCE2013, title = {Modeling and simulating the adaptive electrical properties of stochastic polymeric 3D networks}, journal = {Modelling and Simulation in Materials Science and Engineering}, year = {2013}, month = {9}, volume = {21}, number = {7}, pages = {1-17}, abstract = {Memristors are passive two-terminal circuit elements that combine resistance and memory. Although in theory memristors are a very promising approach to fabricate hardware with adaptive properties, there are only very few implementations able to show their basic properties. We recently developed stochastic polymeric matrices with a functionality that evidences the formation of self-assembled three-dimensional (3D) networks of memristors. We demonstrated that those networks show the typical hysteretic behavior observed in the 'one input-one output' memristive configuration. Interestingly, using different protocols to electrically stimulate the networks, we also observed that their adaptive properties are similar to those present in the nervous system. Here, we model and simulate the electrical properties of these self-assembled polymeric networks of memristors, the topology of which is defined stochastically. First, we show that the model recreates the hysteretic behavior observed in the real experiments. Second, we demonstrate that the networks modeled indeed have a 3D instead of a planar functionality. Finally, we show that the adaptive properties of the networks depend on their connectivity pattern. Our model was able to replicate fundamental qualitative behavior of the real organic 3D memristor networks; yet, through the simulations, we also explored other interesting properties, such as the relation between connectivity patterns and adaptive properties. Our model and simulations represent an interesting tool to understand the very complex behavior of self-assembled memristor networks, which can finally help to predict and formulate hypotheses for future experiments.}, web_url = {http://iopscience.iop.org/0965-0393/21/7/075007/pdf/0965-0393_21_7_075007.pdf}, state = {published}, DOI = {10.1088/0965-0393/21/7/075007}, EPUB = {075007}, author = {Sigala R{sigala}{Department Physiology of Cognitive Processes}; Smerieri A; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Camorani P; Erokhin V} } @Article{ GambinoETBLM2013, title = {Multimodal contrast agents for in vivo neuroanatomical analysis of monosynaptic connections}, journal = {Biomaterials}, year = {2013}, month = {9}, volume = {34}, number = {29}, pages = {7135–7142}, abstract = {We developed and examined the applicability of two multimodal paramagnetic contrast agents for the longitudinal in vivo investigations of the brain projections. The classical dextran based neuroanatomical tracer was conjugated with mono- and bimetal Gd3+ complexes and an optical reporter. Relaxometric studies of both tracer molecules were performed in vitro followed by in cellulo MR and microscopy investigations. Finally, tracers were injected into the motor cortex of the rat brain; uptake and transporting properties were compared by MRI. The advantage of the multimodal approach was taken and histological studies were performed on the same animals. The histology results confirm the MRI studies demonstrating that the applied tracers labelled anterogradely the regions known for their connections with the motor cortex of the rat brain. (C) 2013 Elsevier Ltd. All rights reserved.}, web_url = {http://www.sciencedirect.com/science/article/pii/S014296121300656X}, state = {published}, DOI = {10.1016/j.biomaterials.2013.05.064}, author = {Gambino G{ggambino}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Tei L; Botta M; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}} } @Article{ PlacidiBKHBKRTLA2013, title = {Aryl-Phosphonate Lanthanide Complexes and Their Fluorinated Derivatives: Investigation of Their Unusual Relaxometric Behavior and Potential Application as Dual Frequency 1H/19F MRI Probes}, journal = {Chemistry - A European Journal}, year = {2013}, month = {8}, volume = {19}, number = {35}, pages = {11644–11660}, abstract = {A series of low molecular weight lanthanide complexes were developed that have high 1H longitudinal relaxivities (r1) and the potential to be used as dual frequency 1H and 19F MR probes. Their behavior was investigated in more detail through relaxometry, pH-potentiometry, luminescence, and multinuclear NMR spectroscopy. Fitting of the 1H NMRD and 17O NMR profiles demonstrated a very short water residence lifetime (<10 ns) and an appreciable second sphere effect. At lower field strengths (20 MHz), two of the complexes displayed a peak in r1 (21.7 and 16.3 mM−1 s−1) caused by an agglomeration, that can be disrupted through the addition of phosphate anions. NMR spectroscopy revealed that at least two species are present in solution interconverting through an intramolecular binding process. Two complexes provided a suitable signal in 19F NMR spectroscopy and through the selection of optimized imaging parameters, phantom images were obtained in a MRI scanner at concentrations as low as 1 mM. The developed probes could be visualized through both 1H and 19F MRI, showing their capability to function as dual frequency MRI contrast agents.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/chem.201300763/pdf}, state = {published}, DOI = {10.1002/chem.201300763}, author = {Placidi MP{matteo}{Department Physiology of Cognitive Processes}; Botta M; K{\'a}lm{\'a}n FK; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Baranyai Z; Krenzer A; Rogerson AK; T{\'o}th I; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ SimGPEPM2014, title = {Responsive MR-imaging probes for N-methyl-D-aspartate receptors and direct visualisation of the cell-surface receptors by optical microscopy}, journal = {Chemical Science}, year = {2013}, month = {8}, volume = {4}, number = {8}, pages = {3148-3153}, abstract = {A series of N-methyl-D-aspartate (NMDA) receptor-targeted MRI contrast agents has been developed, based on the known competitive NMDA antagonist, 3,4-diamino-3-cyclobutene-1,2-dione. Their use as responsive MR imaging probes has been evaluated in vitro and two contrast agents showed 170–176% enhancements in relaxation rate, following incubation with a neuronal cell line model. A derivative of the lead compound was prepared containing a biotin moiety, and both the specificity and reversibility of binding to the NMDA cell surface receptors demonstrated using confocal microscopy.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2013/sc/c3sc50903f}, state = {published}, DOI = {10.1039/C3SC50903F}, author = {Sim N; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Pal R; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Parker D; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}} } @Article{ GleissK2013, title = {Eccentricity dependent auditory enhancement of visual stimulus detection but not discrimination}, journal = {Frontiers in Integrative Neuroscience}, year = {2013}, month = {7}, volume = {7}, number = {52}, pages = {1-8}, abstract = {Sensory perception is enhanced by the complementary information provided by our different sensory modalities and even apparently task irrelevant stimuli in one modality can facilitate performance in another. While perception in general comprises both, the detection of sensory objects as well as their discrimination and recognition, most studies on audio–visual interactions have focused on either of these aspects. However, previous evidence, neuroanatomical projections between early sensory cortices and computational mechanisms suggest that sounds might differentially affect visual detection and discrimination and differentially at central and peripheral retinal locations. We performed an experiment to directly test this by probing the enhancement of visual detection and discrimination by auxiliary sounds at different visual eccentricities and within the same subjects. Specifically, we quantified the enhancement provided by sounds that reduce the overall uncertainty about the visual stimulus beyond basic multisensory co-stimulation. This revealed a general trend for stronger enhancement at peripheral locations in both tasks, but a statistically significant effect only for detection and only at peripheral locations. Overall this suggests that there are topographic differences in the auditory facilitation of basic visual processes and that these may differentially affect basic aspects of visual recognition.}, web_url = {http://www.frontiersin.org/Journal/DownloadFile.ashx?pdf=1&FileId=72214&articleId=56991&Version=1&ContentTypeId=21&FileName=fnint-07-00052.pdf}, state = {published}, DOI = {10.3389/fnint.2013.00052}, author = {Gleiss S{sgleiss}{Research Group Physiology of Sensory Integration}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ CalcinaghiWJSKWFBMW2013, title = {Multimodal Imaging in Rats Reveals Impaired Neurovascular Coupling in Sustained Hypertension}, journal = {Stroke}, year = {2013}, month = {7}, volume = {44}, number = {7}, pages = {1957-1964}, abstract = {BACKGROUND AND PURPOSE: Arterial hypertension is an important risk factor for cerebrovascular diseases, such as transient ischemic attacks or stroke, and represents a major global health issue. The effects of hypertension on cerebral blood flow, particularly at the microvascular level, remain unknown. METHODS: Using the spontaneously hypertensive rat (SHR) model, we examined cortical hemodynamic responses on whisker stimulation applying a multimodal imaging approach (multiwavelength spectroscopy, laser speckle imaging, and 2-photon microscopy). We assessed the effects of hypertension in 10-, 20-, and 40-week-old male SHRs and age-matched male Wistar Kyoto rats (CTRL) on hemodynamic responses, histology, and biochemical parameters. In 40-week-old animals, losartan or verapamil was administered for 10 weeks to test the reversibility of hypertension-induced impairments. RESULTS: Increased arterial blood pressure was associated with a progressive impairment in functional hyperemia in 20- and 40-week-old SHRs; baseline capillary red blood cell velocity was increased in 40-week-old SHRs compared with age-matched CTRLs. Antihypertensive treatment reduced baseline capillary cerebral blood flow almost to CTRL values, whereas functional hyperemic signals did not improve after 10 weeks of drug therapy. Structural analyses of the microvascular network revealed no differences between normo- and hypertensive animals, whereas expression analyses of cerebral lysates showed signs of increased oxidative stress and signs of impaired endothelial homeostasis upon early hypertension. CONCLUSIONS: Impaired neurovascular coupling in the SHR evolves upon sustained hypertension. Antihypertensive monotherapy using verapamil or losartan is not sufficient to abolish this functional impairment. These deficits in neurovascular coupling in response to sustained hypertension might contribute to accelerate progression of neurodegenerative diseases in chronic hypertension.}, web_url = {http://stroke.ahajournals.org/content/44/7/1957.abstract}, state = {published}, DOI = {10.1161/STROKEAHA.111.000185}, author = {Calcinaghi N; Wyss MT; Jolivet R; Singh A; Keller AL{akeller}{Department Physiology of Cognitive Processes}; Winnik S; Fritschy JM; Buck A; Matter CM; Weber B{bweber}{Department Physiology of Cognitive Processes}} } @Article{ WallaceGSRNK2013, title = {Rats maintain an overhead binocular field at the expense of constant fusion}, journal = {Nature}, year = {2013}, month = {6}, volume = {498}, number = {7452}, pages = {65–69}, abstract = {Fusing left and right eye images into a single view is dependent on precise ocular alignment, which relies on coordinated eye movements. During movements of the head this alignment is maintained by numerous reflexes. Although rodents share with other mammals the key components of eye movement control, the coordination of eye movements in freely moving rodents is unknown. Here we show that movements of the two eyes in freely moving rats differ fundamentally from the precisely controlled eye movements used by other mammals to maintain continuous binocular fusion. The observed eye movements serve to keep the visual fields of the two eyes continuously overlapping above the animal during free movement, but not continuously aligned. Overhead visual stimuli presented to rats freely exploring an open arena evoke an immediate shelter-seeking behaviour, but are ineffective when presented beside the arena. We suggest that continuously overlapping visual fields overhead would be of evolutionary benefit for predator detection by minimizing blind spots.}, web_url = {http://www.nature.com/nature/journal/v498/n7452/pdf/nature12153.pdf}, state = {published}, DOI = {10.1038/nature12153}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Rulla S{rulla}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ LippertTKO2013_2, title = {Asymmetric Multisensory Interactions of Visual and Somatosensory Responses in a Region of the Rat Parietal Cortex}, journal = {PLoS ONE}, year = {2013}, month = {5}, volume = {8}, number = {5}, pages = {1-13}, abstract = {Perception greatly benefits from integrating multiple sensory cues into a unified percept. To study the neural mechanisms of sensory integration, model systems are required that allow the simultaneous assessment of activity and the use of techniques to affect individual neural processes in behaving animals. While rodents qualify for these requirements, little is known about multisensory integration and areas involved for this purpose in the rodent. Using optical imaging combined with laminar electrophysiological recordings, the rat parietal cortex was identified as an area where visual and somatosensory inputs converge and interact. Our results reveal similar response patterns to visual and somatosensory stimuli at the level of current source density (CSD) responses and multi-unit responses within a strip in parietal cortex. Surprisingly, a selective asymmetry was observed in multisensory interactions: when the somatosensory response preceded the visual response, supra-linear summation of CSD was observed, but the reverse stimulus order resulted in sub-linear effects in the CSD. This asymmetry was not present in multi-unit activity however, which showed consistently sub-linear interactions. These interactions were restricted to a specific temporal window, and pharmacological tests revealed significant local intra-cortical contributions to this phenomenon. Our results highlight the rodent parietal cortex as a system to model the neural underpinnings of multisensory processing in behaving animals and at the cellular level.}, web_url = {http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0063631&representation=PDF}, state = {published}, DOI = {10.1371/journal.pone.0063631}, EPUB = {e63631}, author = {Lippert MT{mlippert}{Department Physiology of Cognitive Processes}; Takagaki K; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Ohl FW} } @Article{ KapoorKKLP2013, title = {Development of Tube Tetrodes and a Multi-Tetrode Drive for deep structure electrophysiological recordings in the macaque brain}, journal = {Journal of Neuroscience Methods}, year = {2013}, month = {5}, volume = {216}, number = {1}, pages = {43–48}, abstract = {Understanding the principles that underlie information processing by neuronal networks requires simultaneous recordings from large populations of well isolated single units. Twisted wire tetrodes (TWTs), typically made by winding together four ultrathin wires (diameter–12 to 25 microns), are ideally suited for such population recordings. They are advantageous over single electrodes; both with respect to quality of isolation as well as the number of single units isolated and have therefore been used extensively for superficial cortical recordings. However, their limited tensile strength poses a difficulty to their use for recordings in deep brain areas. We therefore developed a method to overcome this limitation and utilize tetrodes for electrophysiological recordings in the inferotemporal cortex of rhesus macaque. We fabricated a novel, stiff tetrode called the tube tetrode (TuTe) and developed a multi-tetrode driving system for advancing up to 5 TuTes through a ball and socket chamber to precise locations in the temporal lobe of a rhesus macaque. The signal quality acquired with TuTes was comparable to conventional TWTs and allowed excellent isolation of multiple single units. We describe here a simple method for constructing TuTes, which requires only standard laboratory equipment. Further, our TuTes can be easily adapted to work with other microdrives commonly used for electrophysiological investigation in the macaque brain and produce minimal damage to the cortex along its path because of their ultrathin diameter. The tetrode development described here could allow studying neuronal populations in deep lying brain structures previously difficult to reach with the current technology.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0165027013001222}, state = {published}, DOI = {10.1016/j.jneumeth.2013.03.017}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Krampe E{krampe}{Department Physiology of Cognitive Processes}; Klug A{klug}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}} } @Article{ BalduzziOB2012, title = {Metabolic cost as an organizing principle for cooperative learning}, journal = {Advances in Complex Systems}, year = {2013}, month = {5}, volume = {16}, number = {02n03}, pages = {1-18}, abstract = {This article investigates how neurons can use metabolic cost to facilitate learning at a population level. Although decision-making by individual neurons has been extensively studied, questions regarding how neurons should behave to cooperate effectively remain largely unaddressed. Under assumptions that capture a few basic features of cortical neurons, we show that constraining reward maximization by metabolic cost aligns the information content of actions with their expected reward. Thus, metabolic cost provides a mechanism whereby neurons encode expected reward into their outputs. Further, aside from reducing energy expenditures, imposing a tight metabolic constraint also increases the accuracy of empirical estimates of rewards, increasing the robustness of distributed learning. Finally, we present two implementations of metabolically constrained learning that confirm our theoretical finding. These results suggest that metabolic cost may be an organizing principle underlying the neural code, and may also provide a useful guide to the design and analysis of other cooperating populations.}, web_url = {http://www.worldscientific.com/doi/abs/10.1142/S0219525913500124}, state = {published}, DOI = {10.1142/S0219525913500124}, author = {Balduzzi D{balduzzi}; Ortega PA{portega}{Research Group Sensorimotor Learning and Decision-Making}; Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Article{ SubramaniyanEBT2013, title = {Macaque Monkeys Perceive the Flash Lag Illusion}, journal = {PLoS ONE}, year = {2013}, month = {3}, volume = {8}, number = {3}, pages = {1-10}, abstract = {Transmission of neural signals in the brain takes time due to the slow biological mechanisms that mediate it. During such delays, the position of moving objects can change substantially. The brain could use statistical regularities in the natural world to compensate neural delays and represent moving stimuli closer to real time. This possibility has been explored in the context of the flash lag illusion, where a briefly flashed stimulus in alignment with a moving one appears to lag behind the moving stimulus. Despite numerous psychophysical studies, the neural mechanisms underlying the flash lag illusion remain poorly understood, partly because it has never been studied electrophysiologically in behaving animals. Macaques are a prime model for such studies, but it is unknown if they perceive the illusion. By training monkeys to report their percepts unbiased by reward, we show that they indeed perceive the illusion qualitatively similar to humans. Importantly, the magnitude of the illusion is smaller in monkeys than in humans, but it increases linearly with the speed of the moving stimulus in both species. These results provide further evidence for the similarity of sensory information processing in macaques and humans and pave the way for detailed neurophysiological investigations of the flash lag illusion in behaving macaques.}, web_url = {http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0058788&representation=PDF}, state = {published}, DOI = {10.1371/journal.pone.0058788}, EPUB = {e58788}, author = {Subramaniyan M; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Berens P{berens}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ NgLK2012, title = {EEG phase patterns reflect the selectivity of neural firing}, journal = {Cerebral Cortex}, year = {2013}, month = {2}, volume = {23}, number = {2}, pages = {389-398}, abstract = {Oscillations are pervasive in encephalographic signals and supposedly reflect cognitive processes and sensory representations. While the relation between oscillation amplitude (power) and sensory–cognitive variables has been extensively studied, recent work reveals that the dynamic oscillation signature (phase pattern) can carry information about such processes to a greater degree than amplitude. To elucidate the neural correlates of oscillatory phase patterns, we compared the stimulus selectivity of neural firing rates and auditory-driven electroencephalogram (EEG) oscillations. We employed the same naturalistic sound stimuli in 2 experiments, one recording scalp EEGs in humans and one recording intracortical local field potentials (LFPs) and single neurons in macaque auditory cortex. Using stimulus decoding techniques, we show that stimulus selective firing patterns imprint on the phase rather than the amplitude of slow (theta band) oscillations in LFPs and EEG. In particular, we find that stimuli which can be discriminated by firing rates can also be discriminated by phase patterns but not by oscillation amplitude and that stimulus-specific phase patterns also persist in the absence of increases of oscillation power. These findings support a neural basis for stimulus selective and entrained EEG phase patterns and reveal a level of interrelation between encephalographic signals and neural firing beyond simple amplitude covariations in both signals.}, web_url = {http://cercor.oxfordjournals.org/content/23/2/389.full.pdf+html}, state = {published}, DOI = {10.1093/cercor/bhs031}, author = {Ng BSW{benedict}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ VibhuteEVMLA2012, title = {Synthesis and characterization of pH-sensitive, biotinylated MRI contrast agents and their conjugates with avidin}, journal = {Organic & Biomolecular Chemistry}, year = {2013}, month = {2}, volume = {11}, number = {8}, pages = {1294-1305}, abstract = {Responsive or smart contrast agents (SCAs) provide new opportunities in magnetic resonance imaging (MRI) to examine a number of physiological and pathological events. However, their application in vivo remains challenging. Therefore, much research is focused on the optimization of their properties, to enable their use in additional imaging modalities, pre-targeted delivery, or to increase the local concentration of the agent. The key feature in the SCA synthetic modification is the retention of their physicochemical properties related to the specific MR response. Here, we report the preparation and characterization of pH sensitive SCAs appended with a phosphonate pendant arm and either an aliphatic (GdL1) or aromatic linker (GdL2). The longitudinal relaxivity of GdL1 and GdL2 increases by 146% and 31%, respectively, while the pH decreases from 9 to 5. These two SCAs were converted to the biotinylated systems GdL3 and GdL4 and their interaction with avidin was investigated. The binding affinity with avidin was assessed with a fluorescence displacement assay and with MRI phantom experiments in a 3T MRI scanner. The fluorometric assay and MRI E-titrations revealed a 3 : 1 binding mode of GdL3–4 to avidin with the binding affinity as high as that of the parent avidin–biotin complex. The high binding affinity was confirmed with MRI by a competitive assay. The avidin–GdL3–4 complexes thus obtained exhibit changes in both r1 and r2 that are pH dependent. The results reveal a new pathway for the modification and improvement of SCAs to make them more suitable for in vivo application.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2013/ob/c2ob26555a}, state = {published}, DOI = {10.1039/C2OB26555A}, author = {Vibhute SM{svibhute}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Verbić T; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Article{ PanagiotaropoulosKLD2013, title = {A Common Neurodynamical Mechanism Could Mediate Externally Induced and Intrinsically Generated Transitions in Visual Awareness}, journal = {PLoS ONE}, year = {2013}, month = {1}, volume = {8}, number = {1}, pages = {1-10}, abstract = {The neural correlates of conscious visual perception are commonly studied in paradigms of perceptual multistability that allow multiple perceptual interpretations during unchanged sensory stimulation. What is the source of this multistability in the content of perception? From a theoretical perspective, a fine balance between deterministic and stochastic forces has been suggested to underlie the spontaneous, intrinsically driven perceptual transitions observed during multistable perception. Deterministic forces are represented by adaptation of feature-selective neuronal populations encoding the competing percepts while stochastic forces are modeled as noise-driven processes. Here, we used a unified neuronal competition model to study the dynamics of adaptation and noise processes in binocular flash suppression (BFS), a form of externally induced perceptual suppression, and compare it with the dynamics of intrinsically driven alternations in binocular rivalry (BR). For the first time, we use electrophysiological, biologically relevant data to constrain a model of perceptual rivalry. Specifically, we show that the mean population discharge pattern of a perceptually modulated neuronal population detected in electrophysiological recordings in the lateral prefrontal cortex (LPFC) during BFS, constrains the dynamical range of externally induced perceptual transitions to a region around the bifurcation separating a noise-driven attractor regime from an adaptation-driven oscillatory regime. Most interestingly, the dynamical range of intrinsically driven perceptual transitions during BR is located in the noise-driven attractor regime, where it overlaps with BFS. Our results suggest that the neurodynamical mechanisms of externally induced and spontaneously generated perceptual alternations overlap in a narrow, noise-driven region just before a bifurcation where the system becomes adaptation-driven.}, web_url = {http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=EF29256D0A77BD57133469DBE40B96AA?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0053833&representation=PDF}, state = {published}, DOI = {10.1371/journal.pone.0053833}, EPUB = {e53833}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Deco G} } @Article{ PawlakGSGK2013, title = {Changing the responses of cortical neurons from sub- to suprathreshold using single spikes in vivo}, journal = {eLife}, year = {2013}, month = {1}, volume = {2}, pages = {1-18}, abstract = {Action Potential (APs) patterns of sensory cortex neurons encode a variety of stimulus features, but how can a neuron change the feature to which it responds? Here, we show that in vivo a spike-timing-dependent plasticity (STDP) protocol—consisting of pairing a postsynaptic AP with visually driven presynaptic inputs—modifies a neurons' AP-response in a bidirectional way that depends on the relative AP-timing during pairing. Whereas postsynaptic APs repeatedly following presynaptic activation can convert subthreshold into suprathreshold responses, APs repeatedly preceding presynaptic activation reduce AP responses to visual stimulation. These changes were paralleled by restructuring of the neurons response to surround stimulus locations and membrane-potential time-course. Computational simulations could reproduce the observed subthreshold voltage changes only when presynaptic temporal jitter was included. Together this shows that STDP rules can modify output patterns of sensory neurons and the timing of single-APs plays a crucial role in sensory coding and plasticity.}, web_url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552422/pdf/elife00012.pdf}, state = {published}, DOI = {10.7554/eLife.00012}, EPUB = {e00012}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sprekeler H; Gerstner W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Article{ GhazanfarMK2013, title = {Monkeys are perceptually tuned to facial expressions that exhibit a theta-like speech rhythm}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2013}, month = {1}, volume = {110}, number = {5}, pages = {1959-1963}, abstract = {Human speech universally exhibits a 3- to 8-Hz rhythm, corresponding to the rate of syllable production, which is reflected in both the sound envelope and the visual mouth movements. Artificial perturbation of the speech rhythm outside the natural range reduces speech intelligibility, demonstrating a perceptual tuning to this frequency band. One theory posits that the mouth movements at the core of this speech rhythm evolved through modification of ancestral primate facial expressions. Recent evidence shows that one such communicative gesture in macaque monkeys, lip-smacking, has motor parallels with speech in its rhythmicity, its developmental trajectory, and the coordination of vocal tract structures. Whether monkeys also exhibit a perceptual tuning to the natural rhythms of lip-smacking is unknown. To investigate this, we tested rhesus monkeys in a preferential-looking procedure, measuring the time spent looking at each of two side-by-side computer-generated monkey avatars lip-smacking at natural versus sped-up or slowed-down rhythms. Monkeys showed an overall preference for the natural rhythm compared with the perturbed rhythms. This lends behavioral support for the hypothesis that perceptual processes in monkeys are similarly tuned to the natural frequencies of communication signals as they are in humans. Our data provide perceptual evidence for the theory that speech may have evolved from ancestral primate rhythmic facial expressions.}, web_url = {http://www.pnas.org/content/110/5/1959.full.pdf+html}, state = {published}, DOI = {10.1073/pnas.1214956110}, author = {Ghazanfar AA{asifg}{Department Physiology of Cognitive Processes}; Morrill RJ; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ SchindlerB2012, title = {Parietal Cortex Codes for Egocentric Space beyond the Field of View}, journal = {Current Biology}, year = {2013}, month = {1}, volume = {23}, number = {2}, pages = {177–182}, abstract = {Our subjective experience links covert visual and egocentric spatial attention seamlessly. However, the latter can extend beyond the visual field, covering all directions relative to our body. In contrast to visual representations [1, 2, 3 and 4], little is known about unseen egocentric representations in the healthy brain. Parietal cortex appears to be involved in both, because lesions in it can lead to deficits in visual attention, but also to a disorder of egocentric spatial awareness, known as hemispatial neglect [5 and 6]. Here, we used a novel virtual reality paradigm to probe our participants’ egocentric surrounding during fMRI recordings. We found that egocentric unseen space was represented by patterns of voxel activity in parietal cortex, independent of visual information. Intriguingly, the best decoding performances corresponded to brain areas associated with visual covert attention and reaching, as well as to lesion sites associated with spatial neglect.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0960982212014406}, state = {published}, DOI = {10.1016/j.cub.2012.11.060}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ ZaretskayaAB2012, title = {Parietal Cortex Mediates Conscious Perception of Illusory Gestalt}, journal = {Journal of Neuroscience}, year = {2013}, month = {1}, volume = {33}, number = {2}, pages = {523-531}, abstract = {Grouping local elements into a holistic percept, also known as spatial binding, is crucial for meaningful perception. Previous studies have shown that neurons in early visual areas V1 and V2 can signal complex grouping-related information, such as illusory contours or object-border ownerships. However, relatively little is known about higher-level processes contributing to these signals and mediating global Gestalt perception. We used a novel bistable motion illusion that induced alternating and mutually exclusive vivid conscious experiences of either dynamic illusory contours forming a global Gestalt or moving ungrouped local elements while the visual stimulation remained the same. fMRI in healthy human volunteers revealed that activity fluctuations in two sites of the parietal cortex, the superior parietal lobe and the anterior intraparietal sulcus (aIPS), correlated specifically with the perception of the grouped illusory Gestalt as opposed to perception of ungrouped local elements. We then disturbed activity at these two sites in the same participants using transcranial magnetic stimulation (TMS). TMS over aIPS led to a selective shortening of the duration of the global Gestalt percept, with no effect on that of local elements. The results suggest that aIPS activity is directly involved in the process of spatial binding during effortless viewing in the healthy brain. Conscious perception of global Gestalt is therefore associated with aIPS function, similar to attention and perceptual selection.}, web_url = {http://www.jneurosci.org/content/33/2/523.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.2905-12.2013}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Anstis S; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ PehrsonBTM2013, title = {The influence of NMDA and GABAA receptors and glutamic acid decarboxylase (GAD) activity on attention}, journal = {Psychopharmacology}, year = {2013}, month = {1}, volume = {225}, number = {1}, pages = {31-39}, abstract = {Rationale Attention dysfunction is the hallmark of cognitive deficits associated with major psychiatric illnesses including schizophrenia. Cognitive deficits of schizophrenia have been attributed to reduced function of the N-methyl-d-aspartate (NMDA) receptor or reduced expression of the gamma-aminobutyric acid (GABA)-synthesizing enzyme glutamic acid decarboxylase-67, which presumably leads to attenuated neurotransmission at GABAA receptors. Objective The present study used a rodent model to compare the inhibition of NMDA and GABAA receptors, and GAD activity on attention. We tested the impact of inhibiting these proteins brain wide or in the anterior cingulate cortex (ACC), a prefrontal cortex region critical for attentional processing. Methods Rats were trained on the three choice serial reaction time task (3-CSRT), an attention test. The impact of systemic or intra-ACC injection of drugs on performance was measured in well-trained rats. Results Reducing GABAA receptor function within the ACC with the direct antagonist SR95531 (1 or 3 ng/side) or brain wide using systemic injection of the benzodiazepine inverse agonist FG7142 (5 mg/kg) impaired accuracy and increased omissions. Systemic or intra-ACC inhibition of NMDA receptors using MK-801 (at 3 mg/kg or 3 μg, respectively) also impaired performance. Inhibition of GAD with 3-mercaptopropionic acid, even at high doses, had no effect on 3-CSRT accuracy or omissions when administered systemically or within the ACC. Conclusions These data demonstrate that, while tonic stimulation of NMDA and GABAA receptors within the ACC are critical for attentional performance, reduction in GAD activity may have little functional significance and is not indicative of reduced GABA neurotransmission.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs00213-012-2792-z.pdf}, state = {published}, DOI = {10.1007/s00213-012-2792-z}, author = {Pehrson AL; Bondi CO; Totah NKB{ntotah}{Department Physiology of Cognitive Processes}; Moghaddam B} } @Inproceedings{ BalduzziB2012, title = {Towards a learning-theoretic analysis of spike-timing dependent plasticity}, year = {2013}, month = {4}, pages = {2465-2473}, abstract = {This paper suggests a learning-theoretic perspective on how synaptic plasticitybenefits global brain functioning. We introduce a model, the selectron, that (i)arises as the fast time constant limit of leaky integrate-and-fire neurons equippedwithspikingtimingdependentplasticity(STDP)and(ii)isamenabletotheoreticalanalysis. We show that the selectron encodes reward estimates into spikes and thatan error bound on spikes is controlled by a spiking margin and the sum of synapticweights. Moreover, the efficacy of spikes (their usefulness to other reward maxi-mizing selectrons) also depends on total synaptic strength. Finally, based on ouranalysis, we propose a regularized version of STDP, and show the regularizationimproves the robustness of neuronal learning when faced with multiple stimuli.}, file_url = {fileadmin/user_upload/files/publications/2012/NIPS-2012-Balduzzi.pdf}, web_url = {http://nips.cc/Conferences/2012/}, editor = {Bartlett, P. , F.C.N. Pereira, L. Bottou, C.J.C. Burges, K.Q. Weinberger}, publisher = {Curran}, address = {Red Hook, NY, USA}, booktitle = {Advances in Neural Information Processing Systems 25}, event_name = {Twenty-Sixth Annual Conference on Neural Information Processing Systems (NIPS 2012)}, event_place = {Lake Tahoe, Nevada, USA}, state = {published}, ISBN = {978-1-627-48003-1}, author = {Balduzzi D{balduzzi}{Department Empirical Inference}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}} } @Inbook{ PanagiotaropoulosL2013, title = {Multistable Visual Perception as a Gateway to the Neuronal Correlates of Phenomenal Consciousness: The Scope and Limits of Neuroscientific Analysis}, year = {2013}, month = {3}, pages = {119-144}, abstract = {This chapter focuses on the neuronal correlates of multistable perception as a method that could provides significant insights into the neuronal correlates of consciousness. It describes the current state of knowledge on the contribution of cortical and subcortical areas in subjective visual perception as measured by the presentation of multistable stimulus configurations, mainly binocular rivalry, coupled with invasive and noninvasive recordings of neurophysiological signals. The findings from these experiments apparently support the view that correlates of subjective visual perception are found across different primary and secondary sensory and associational cortical and subcortical areas. This chapter ensures that the neuroscientific method, assisted by phenomenological psychophysics and computational neuroscience, has potentially unlimited power, constrained only by the experimental methods used in revealing the neuronal correlates of cognitive processes.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/9781118329016.ch4/summary}, editor = {Albertazzi, L.}, publisher = {Wiley-Blackwell}, address = {Chichester, UK}, booktitle = {Handbook of Experimental Phenomenology: Visual Perception of Shape, Space and Appearance}, state = {published}, ISBN = {978-1-119-95468-2}, DOI = {10.1002/9781118329016.ch4}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Inbook{ MazzoniLP2013, title = {Information Content of Local Field Potentials}, year = {2013}, pages = {411-430}, abstract = {The LFPs is a broadband signal that captures variations of neural population activity over a wide range of time scales. The range of time scales available in LFPs is particularly interesting from the neural coding point of view because it opens up the possibility to investigate whether there are privileged time scales for information processing, a question that has been hotly debated over the last one or two decades.It is possible that information is represented by only a small number of specific frequency ranges, each carrying a separate contribution to the information representation. To shed light on this issue, it is important to quantify the information content of each frequency range of neural activity, and understand which ranges carry complementary or similar information.}, web_url = {http://www.crcnetbase.com/doi/abs/10.1201/b14756-24}, editor = {Quian Quiroga, R. , S. Panzeri}, publisher = {CRC Press}, address = {Boca Raton, FL, USA}, booktitle = {Principles of Neural Coding}, state = {published}, ISBN = {978-1-4398-5330-6}, DOI = {10.1201/b14756-24}, author = {Mazzoni A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Inbook{ Ince2013, title = {Open-Source Software for Studying Neural Codes}, year = {2013}, pages = {597-606}, abstract = {In this chapter we first outline some of the popular computing environments used for analysing neural data, followed by a brief discussion of 'software carpentry', basic tools and skills from software engineering that can be of great use to computational scientists. We then introduce the concept of open-source software and explain some of its potential benefits for the academic community before giving a brief directory of some freely available open source software packages that address various aspects of the study of neural codes. While there are many commercial offerings that provide similar functionality, we concentrate here on open source packages, which in addition to being available free of charge, also have the source code available for study and modification.}, web_url = {http://www.crcnetbase.com/doi/abs/10.1201/b14756-35}, editor = {Quian Quiroga, R. , S. Panzeri}, publisher = {CRC Press}, address = {Boca Raton, FL, USA}, booktitle = {Principles of Neural Coding}, state = {published}, ISBN = {978-1-4398-5330-6}, DOI = {10.1201/b14756-35}, author = {Ince RAA{rince}{Department Physiology of Cognitive Processes}} } @Inbook{ WhittingstallL2013, title = {Physiological Foundations of Neural Signals}, year = {2013}, pages = {3-14}, abstract = {One of the central goals in neuroscience is to understand the function of neural circuits in the brain and how they are related to behavior. As a result, a great effort has been dedicated to developing techniques which enable the recording of the brain’s electrical activity at different spatial scales. This consists of measures ranging from the localized spiking activity of individual neurons and/ or their local field potential (LFP), all the way up to more global measures such as the electroencephalogram (EEG). When recorded in a well-controlled experimental paradigm, the assumption is that modulations in these measured signals reflect changes in cortical processing. This information can then be used to better understand the neural mechanisms underlying specific cognitive functions (e.g., memory, learning, perception, etc.). However, each recording method is limited in the sense that the signals in which they measure are not representative of all the processes that occur in the brain, making it difficult to isolate specific neural events. The complex structural and functional architecture of the brain can thus lead to a biased interpretation of such signals depending on the manner in which they are acquired (e.g., EEG vs. LFP). Knowledge of the physiological properties giving rise to neural signals is therefore essential for better interpreting the neural correlates of a particular cognitive function, and reconciling results obtained across different recording modalities.}, web_url = {http://www.crcnetbase.com/doi/abs/10.1201/b14756-3}, editor = {Quian Quiroga, R. , S. Panzeri}, publisher = {CRC Press}, address = {Boca Raton, FL, USA}, booktitle = {Principles of Neural Coding}, state = {published}, ISBN = {978-1-4398-5330-6}, DOI = {10.1201/b14756-3}, author = {Whittingstall K{kevin}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoBMEBOL2013, title = {BOLD responses associated with hippocampal ripples in the rat brain}, year = {2013}, month = {11}, day = {13}, volume = {43}, number = {863.09}, abstract = {Hippocampal ripples, brief high-frequency oscillations, occur during behavioral states that are not associated with active sensory processing. The ripple event represents a simultaneous burst of a large neuronal population that is synchronized across the entire hippocampus. Reactivation of neuronal ensembles that were active during learning predominantly occurs during ripples. The number of ripples is increased after learning and this increase is predictive for memory recall. Ripple suppression is unfavorable for memory consolidation. Ripples have been suggested to provide a neurophysiological substrate for ‘off-line’ memory consolidation by facilitating synaptic plasticity within the learning-associated neuronal ensembles. The neuronal activity in other brain regions that is time-locked to hippocampal ripples may underlie a cross-regional information transfer. We exploited the methodology allowing simultaneous extracellular recording combined with fMRI. An anesthetized rat was fixed in the MRI scanner and MRI-compatible linear electrode array was placed with electrode contacts in cortex, hippocampus, and thalamus using a custom-made movable drive. Spontaneous whole-brain BOLD activity was acquired along with multi-site electrophysiological recording. The ripple events were detected and classified off-line using a custom software. The time series of BOLD responses were extracted for each voxel according to the event-triggered design, where the ripple onset was used as an event, and the statistical maps were generated indicating the voxels with positive and negative BOLD responses. The voxels were subsequently grouped according to the anatomical brain regions by co-registration of the functional images with the digital rat brain atlas. The positive BOLD response was detected within the direct proximity to the ripple recording site in the CA1 region of hippocampus. The most of the hippocampal volume was also co-activated. In addition, a number of cortical regions including sensory and associative cortices contained a substantial proportion of voxels showing positive BOLD responses. Several brain regions consistently showed negative BOLD responses. These included many of the thalamic nuclei, neuromodulatory nuclei of the midbrain and brain stem and cerebellum. The fMRI findings were further confirmed by electrophysiological recordings in multiple brain areas. Our results identify a brain network that possibly supports hippocampal-dependent memory consolidation. Besides, hippocampal ripples may cause a transient inhibition within competing functional networks to enable more efficient intra brain region communication.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Evrard H{evrard}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ KelirisSPLS2013, title = {Estimation of average single-unit receptive field size by fMRI}, year = {2013}, month = {11}, day = {13}, volume = {43}, number = {824.16}, abstract = {Receptive fields (RF) are a fundamental property characterizing sensory neurons. In the visual domain, numerous electrophysiological and computational studies established the spatio-temporal characteristics of RFs and modeled early visual neurons in primates as Gabor filters with well-defined properties. Recently functional magnetic resonance imaging (fMRI) techniques have been introduced to estimate aggregate (voxel-based) “population” receptive field (pRF) sizes in humans (Dumoulin SO, Wandell BA, 2008). Population receptive field estimates are a function of: 1) the receptive field properties of single units belonging to a voxel, and 2) the scatter in the location of receptive field centers across units. In this study, we estimate RF sizes by exploiting the spatial-frequency selectivity of visual RFs modeled as Gabor functions. Blood oxygen level dependent (BOLD) measurements were collected from humans fixating in the center of band-limited white noise stimuli presented in a block-design (12 seconds ON, 20 seconds OFF). In different blocks, we modulated the spatial frequency content of the stimuli by changing the size of the pixels of the white noise. We found that the BOLD signal amplitude in retinotopic visual cortex changes dramatically with different stimulation conditions in a way consistent with the spatial frequency sensitivity of the Gabor RF models. We modeled the BOLD signal of each voxel as a sum of Gabors with homogeneous orientation distribution followed by a compressive non-linearity and fit this model to our data. The standard deviation of the Gaussian envelope of the Gabor function provides an estimate of RF size. Estimates obtained this way were compared to pRF estimates derived from additional experiments with moving bar stimuli. RF size estimates obtained with our method increased linearly with eccentricity as expected, but were significantly smaller in comparison to standard pRF measurements (Dumoulin SO, Wandell BA, 2008). The reason is that our method is not sensitive to the receptive field scatter that happens between units belonging to the same voxel. Similar experiments performed in anesthetized macaques provided RF size estimates comparable to electrophysiological measurements of single-unit RFs. We conjecture that our method estimates for the fist time average single-unit RF sizes in the human.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Keliris GA{george}{Department Physiology of Cognitive Processes}; Shao Y{yshao}{Department Physiology of Cognitive Processes}; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis M{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Poster{ SafaviPKLB2013_2, title = {Coupling between spiking activity and beta band spatio-temporal patterns in the macaque PFC}, year = {2013}, month = {11}, day = {12}, volume = {43}, number = {586.09}, abstract = {Previous analysis of Local Field Potentials (LFPs) recorded from the inferior convexity of the macaque prefrontal cortex (PFC) revealed a dominant travelling wave pattern in the beta band (15-30 Hz) propagating along the ventral-dorsal plane. We hypothesized that propagating rhythmic activity reflects the intrinsic dynamics of the underlying neural populations which might be instrumental to information processing and sensory integration. Here, we investigated the relationship between multi-unit spiking activities (MUA) and LFPs in the same area of the PFC. We first computed spike-field coherence for each channel of the array. Many recording sites (typical example in Fig 1A) exhibited a distinctive peak in the beta frequency range both for resting state (spontaneous activity) and during visual stimulation with dynamic movie stimuli. We extracted the instantaneous phases in the beta band using Hilbert transform. We then computed the phase locking of spikes in each channel to a common LFP reference channel. The results exemplified on Fig 1 B, showed that many recording sites exhibited locking of spikes to the same phase of remote beta band LFP. This result was observed for many LFP reference channels, suggesting action potentials in all channels are synchronized to a common phenomenon. We used complex Singular Value Decomposition (SVD) of the spike-phase locking matrix to capture the dominant underlying spatio-temporal pattern of beta oscillations associated to spiking activity across the array. The dominant pattern estimated from the first eigen-mode of SVD exhibits a phase gradient along the ventral-dorsal plane (Fig 1 C), suggesting that MUA across the array are synchronized to the global travelling wave pattern previously observed along this direction in the LFP signal. This new result suggests MUA is synchronized to large scale ongoing travelling wave patterns in the beta band both during stimulation and spontaneous activity. Further information theoretic analysis will address how this mechanism serves distributed sensory encoding and processing in this area.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}} } @Poster{ PerrodinKLP2013, title = {Audio-visual interactions in neurons from voice-sensitive auditory cortex and the superior-temporal sulcus}, year = {2013}, month = {11}, day = {11}, volume = {43}, number = {453.09}, abstract = {During social communication, vocal and facial cues combine to form a coherent audiovisual percept. While electrophysiology studies have described crossmodal interactions at various sensory processing stages, it remains unclear how audiovisual influences occur at the neuronal level in face- or voice-sensitive areas. Here, we characterize visual influences from facial content on neuronal responses to vocalizations from a voice-sensitive region in the anterior supratemporal plane (aSTP) and the anterior superior-temporal sulcus (STS). We hypothesized that the STS, a typical multisensory region, would show greater specificity in visual-auditory interactions, while the aSTP would be mainly involved in auditory analysis, such as distinguishing between voice-identity or call-type features. Using dynamic face and voice stimuli, we recorded individual single neurons from both regions in the right hemisphere of two awake Rhesus macaques. To test the specificity of visual influences to behaviorally relevant stimuli, we included a set of audiovisual control stimuli, in which a voice was paired with a mismatched visual facial context. Within the aSTP we found an interesting division of neural sensitivity to vocal features: the sensitivity to call-type or speaker-identity was supported by two functionally distinct neuronal subpopulations within this area. In contrast, neurons in the STS were less sensitive to these vocal features. Multisensory response modulation was observed in both regions, while evoked responses to visual stimuli were more prevalent in the STS. Moreover, visual influences in the STS were modulated by speaker-related features and were reduced during stimulation with incongruent voice-face pairs. In contrast, visual influences in the aSTP showed little specificity for audio-visual congruency. Our results thus show that voice-sensitive cortex specializes in auditory analysis via a division of neuronal sensitivity while congruency-sensitive visual influences emerge to a greater extent in the STS. Together, our results highlight the transformation of audio-visual representations of communication signals across successive levels of the multisensory processing hierarchy in the primate temporal lobe.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ OrtizSLR2013, title = {High-resolution fMRI phase-mapping of azimuth space in rhesus monkey auditory cortex}, year = {2013}, month = {11}, day = {11}, volume = {43}, number = {353.12}, abstract = {Sound localization is one of the most fundamental tasks performed by the auditory system. In mammals, the location of a sound source in azimuth is mainly determined by interaural time and intensity differences between sounds reaching the two ears. Although binaural sound processing in subcortical structures is well understood, much less is known about the representation of space at the cortical level. In humans, the left auditory cortex (AC) shows a predominant response to sounds in the right hemifield, while the right AC responds to sounds in both hemifields (Krumbholz et al., 2007), with contrast between the two hemifields revealing activation along the dorsal stream into parietal cortex. In the monkey, selectivity of neurons in primary AC for positions in contralateral space has been observed, albeit with broad spatial tuning (Middlebrooks et al., 1994). Spatial tuning sharpens significantly in the caudal belt regions (Tian et al., 2001; Recanzone & Beckerman, 2004), but it is not known whether the preferred azimuth positions form a map of auditory space. Here we attempt to bridge studies across human and nonhuman primates by obtaining a comprehensive overview of the cortical representation of azimuth space in the monkey for the first time using phase-mapping functional magnetic resonance imaging (fMRI). Sounds were generated in virtual acoustic space and played back via headphones during fMRI. Stimuli consisted of broad-band noise bursts (0.2-16 kHz, 100 ms duration) moving through azimuth in steps of 30° at a rate of 5° per second. They were presented in a sparse-sampling design as a moving wave analogous to methods used in visual field mapping (Wandell & Winawer, 2011). We acquired high-resolution images oriented along the superior temporal plane in two anesthetized monkeys. We then analyzed the BOLD signal amplitude modulation at the frequency of stimulus presentation (12 cycles per scan) to determine voxel coherence and phase values corresponding to the stimulus cycle. In accordance with prior single-unit studies, a robust contralateral response to azimuth position was observed. The left AC represented mainly the anterior contralateral quadrant, including straight-ahead positions, while the right AC represented both ipsilateral and contralateral space. This hemispheric bias supports previous neuroimaging studies in humans. In addition, it may elucidate the hierarchical processing of space from AC into posterior parietal cortex and the sound localization deficits observed in humans with damage to the right temporo-parietal cortex (Spierer et al., 2009, Rauschecker & Tian, 2000).}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Poster{ LakshminarasimhanLK2013, title = {Stimulus-dependent gamma-frequency shifting in the macaque v1}, year = {2013}, month = {11}, day = {10}, volume = {43}, number = {259.15}, abstract = {The phase of spikes in the gamma cycle has previously been shown to be modulated by stimulus orientation in macaque V1 (Vinck et al. 2010, Womelsdorf et al. 2012). These studies suggested that such stimulus-dependent phase shifts selectively facilitate the impact of neurons that fire earlier in the gamma cycle, on their targets. However, such phase coding schemes implicitly depend on the generation of a consistent gamma oscillation frequency across stimulus conditions. To test this, we examined whether the stimulus orientation and the eye of presentation affected the peak gamma frequency in V1. Two macaque monkeys were trained to passively fixate on a central spot, while one of two orthogonally oriented gratings was presented monocularly through a mirror stereoscope for a period of one second. In different trials either the eye of presentation or the orientation, were changed. Local field potential (LFP) signals recorded from 168 sites across multiple sessions were found to exhibit significant coherence with concurrently recorded single-unit spikes in the gamma frequency range. The power spectral density of each of those LFPs was fit as the sum of a power function and a gaussian function, and the center of the gaussian was taken as the peak gamma frequency. We found that, across sites the peak frequency varied between 30 Hz and 45 Hz in both monkeys. Moreover, within each site there was a significant shift in the peak frequency both with orientation (median shift ~1.99Hz) as well as the eye of presentation (median shift ~0.89Hz). There was no systematic relationship between the direction of shift and stimulus preference. Given that the orientation-dependent phase shifts reported earlier were of a very small magnitude (only a few degrees), it follows that such frequency changes could be detrimental for phase-shift coding schemes that rely on entrainment of multiple cortical areas to a single ‘clock-like’ signal. Alternatively, neural mechanisms implementing phase computations could be relatively invariant to frequency changes by using more intricate signal properties like instantaneous phase.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Lakshminarasimhan K; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ ShaoKSPLS2013, title = {Population receptive field measurements in the visual cortex of macaque monkeys with and without retinal lesions}, year = {2013}, month = {11}, day = {9}, volume = {43}, number = {64.01}, abstract = {Visual receptive fields have dynamic properties and it has been reported that receptive field organization can change following chronic visual deprivation. We used 4.7 Tesla functional magnetic resonance imaging (fMRI) to study the visual cortex of two healthy adult macaque monkeys, and two monkeys with binocular central retinal lesions. FMRI experiments were performed under light remifentanyl induced anesthesia (Logothetis et al. Nat. Neurosci. 1999). Standard moving horizontal/vertical bar stimuli and expanding ring stimuli were presented to the subjects and the population receptive field (pRF) method (Dumoulin and Wandell, Neuroimage 2008) was used to measure retinotopic maps and pRF sizes in early visual areas. In general, there is good agreement between maps obtained by fMRI and previous results obtained by anatomical and physiological methods. FMRI pRF sizes and electrophysiology measurements in healthy animals show similar trends. For the monkeys with a photocoagulation induced retinal lesion, a former study has shown that the fMRI defined lesion projection zone (LPZ) border in V1 did not shift following the lesion (Smirnakis et al. Nature 2005). We reanalyzed these data using pRF methods and suggest that pRF size in the non-deafferented V1 showed little, if any, change on average. However, voxels inside the LPZ of areas V2/V3 do show visual modulation over time following the lesion, suggesting that area V2/V3 has more capacity for plasticity than area V1. Further investigation using fMRI and standard electrophysiology methods is in progress.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Shao Y{yshao}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Schmid MC; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Poster{ ZaidiRRS2013, title = {Subject independent pattern classification of overt and covert movements from fNIRS signals}, year = {2013}, month = {11}, day = {9}, volume = {43}, number = {79.21}, abstract = {Several studies have reported on the feasibility of using Near Infra-Red Spectroscopty (NIRS) for developing brain-computer interface (BCI) devices as an alternate mode of communication and environmental control for the disabled, including its application in neurofeedback training. In the present study, we report the development of a real-time Support Vector Machine (SVM) based pattern classification and neurofeedback system using multi-channel NIRS. We used left versus right hand movement execution and movement imageries for training and testing the classifier. Subjects performed hand movements similar to clenching a ball. We conducted three experiments to test the robustness of our classifier system, training the classifier on movement imagery and testing on movement execution, or vice versa. In the first two experiments, activations in the motor cortex during motor execution and movement imagery were used to develop subject-specific models. The classifiers implemented an adaptive bias-correction algorithm. We obtained high classification accuracies establishing the robustness of the classifier. The third experiment focused on real-time binary classification of movement execution and movement imagery using a subject-independent classifier that was trained on movement execution data from four subjects. The average online classification accuracies for subject-independent classification of new, untrained subjects were approximately 63% for movement imagery and 80% for movement execution. We also performed offline analysis to identify the spatial patterns of activation and the classifier parameters. This method of classification has applications towards rehabilitation of stroke patients that have improper activation patterns in their motor cortex. Furthermore, the capability of our system to successfully classify activation patterns from both motor imagery and motor execution supports earlier reports that their underlying neural patterns have common}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Zaidi AD{azaidi}{Department Physiology of Cognitive Processes}; Robinson N; Rana M; Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}} } @Poster{ OrtizSLR2013_2, title = {High‐resolution fMRI phase‐mapping of azimuth space in rhesus monkey auditory cortex}, year = {2013}, month = {11}, day = {8}, pages = {74}, abstract = {^Sound localization is one of the most fundamental tasks performed by the auditory system. In mammals, the location of a sound source in azimuth is mainly determined by interaural time and intensity differences between sounds reaching the two ears. Although binaural sound processing in subcortical structures is well understood, much less is known about the representation of space at the cortical level. In humans, the left auditory cortex (AC) shows a predominant response to sounds in the right hemifield, while the right AC responds to sounds in both hemifields (Krumbholz et al., 2007), with contrast between the two hemifields revealing activation along the dorsal streaminto parietal cortex. In the monkey, selectivity of neurons in primary AC for positions in contralateral space has been observed, albeit with broad spatial tuning (Middlebrooks et al., 1994). Spatial tuning sharpens significantly in the caudal belt regions (Tian et al., 2001; Recanzone &Beckerman, 2004), but it is not known whether the preferred azimuth positions forma map of auditory space. Here we attempt to bridge studies across human and nonhuman primates by obtaining a comprehensive overviewof the cortical representation of azimuth space in the monkey for the first time using phase mapping functional magnetic resonance imaging (fMRI). Sounds were generated in virtual acoustic space and played back via headphones during fMRI. Stimuli consisted of broad band noise bursts (0.2 16 kHz, 100 ms duration) moving through azimuth in steps of 30° at a rate of 5° per second. They were presented in a sparse sampling design as a moving wave analogous to methods used in visual field mapping (Wandell &Winawer, 2011). We acquired high resolution images oriented along the superior temporal plane in two anesthetized monkeys. We then analyzed the BOLD signal amplitude modulation at the frequency of stimulus presentation (12 cycles per scan) to determine voxel coherence and phase values corresponding to the stimulus cycle. In accordance with prior single unit studies, a robust contralateral response to azimuth position was observed. The left AC represented mainly the anterior contralateral quadrant, including straight ahead positions, while the right AC represented both ipsilateral and contralateral space. This hemispheric bias supports previous neuroimaging studies in humans. In addition, it may elucidate the hierarchical processing of space fromAC into posterior parietal cortex and the sound localization deficits observed in humans with damage to the right temporo parietal cortex (Spierer et al., 2009, Rauschecker &Tian, 2000).}, web_url = {http://www.med.upenn.edu/apan/assets/user-content/documents/Archived.APAN.2013.pdf}, event_name = {Tucker‐Davis Technologies Symposium on Advances and Perspectives in Auditory Neurophysiology (APAN 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Poster{ PerrodinKLP2013_2, title = {Visual modulation of neurons in voice‐sensitive auditory cortex and the superior‐temporal sulcus}, year = {2013}, month = {11}, day = {8}, pages = {77}, abstract = {Effective social interactions can depend upon the receiver combining vocal and facial content to form a coherent audiovisual representation of communication signals. Neuroimaging studies have identified face- or voice-sensitive areas in the primate brain, some of which have been proposed as candidate regions for face-voice integration. However, it was unclear how audiovisual influences occur at the neuronal level within such regions and in comparison to classically defined multisensory regions in temporal association cortex. Here, we characterize visual influences from facial content on neuronal responses to vocalizations from a voice-sensitive region in the anterior supratemporal plane (STP) and the anterior superior-temporal sulcus (STS). Using dynamic face and voice stimuli, we recorded individual units from both regions in the right hemisphere of two awake Rhesus macaques. To test the specificity of visual influences to behaviorally relevant stimuli, we included a set of audiovisual control stimuli, in which a voice was paired with a mismatched visual facial context. Within the STP, our results show auditory sensitivity to various vocal features, which was not evident in STS units. We newly identify a functionally distinct neuronal subpopulation in the STP that carries the area’s sensitivity to voice-identity related characteristics. Audio-visual interactions were prominent in both areas, with direct crossmodal convergence being more prevalent in the STS. Moreover, visual influences modulated the responses of STS neurons with greater specificity, such as being more often associated with congruent voice-face stimulus pairings than STP neurons. Our results show that voice-sensitive cortex specializes in auditory analysis of vocal features while congruency-sensitive visual influences emerge to a greater extent in the STS. Together, our results highlight the transformation of audio-visual representations of communication signals across successive levels of the multisensory processing hierarchy in the primate temporal lobe.}, web_url = {http://www.med.upenn.edu/apan/assets/user-content/documents/Archived.APAN.2013.pdf}, event_name = {Tucker‐Davis Technologies Symposium on Advances and Perspectives in Auditory Neurophysiology (APAN 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ GottschalkSPEPM2013, title = {Towards functional NMDA-receptor MR-imaging: Novel probes based on competitive antagonists}, journal = {Molecular Imaging and Biology}, year = {2013}, month = {11}, volume = {15}, number = {Supplement 1}, pages = {S642}, abstract = {For neuroimaging techniques such as positron emission tomography and optical imaging brain receptor-targeting is a widely used concept, either using probes based on receptor antagonists or agonist. So far, applying competitive binding approaches for brain functional magnetic resonance imaging (fMRI) has not been demonstrated. Our idea was therefore to develop responsive MRI contrast agents (CAs) based on competitive antagonists to the N-methyl-D-aspartate (NMDA) receptor, an ionotropic glutamate receptor that plays an important role in controlling synaptic plasticity and memory function.[1] Ultimately, such CAs would allow to monitor glutamate activity at NMDA receptors (NMDARs) and thus neuronal activity itself. For such a CA to be responsive, release of glutamate from the pre-synapse will detach the CA from the receptor, in turn leading to a reduction in image contrast, followed by a restoration of equilibrium and again binding of the CA to the receptor. It has been shown, that these events happen over a period of a few seconds allowing data acquisition with modern fast MR-techniques.[2] Here we report the in vitro evaluation of a series of NMDAR targeted CAs, that are based on established competitive NMDAR-antagonists[3] coupled to DOTA-derived gadolinium chelates (Fig. 1A). Cellular labeling, cytotoxicity, receptor binding and reversibility were studied on the NMDAR-expressing (shown by immunofluorescence) neuronal cell line model NSC-34. Binding affinity in cultured cells (Fig. 1B) showed that two of the compounds (Gd.L2 and Gd.L4) increased the cellular relaxation rate R1,cell up to 170±11% and 176±4% of control, respectively (200 µM, 45min., 37°C). MRI-measurements were done on a 3T human whole body scanner. No cytotoxic effects with the concentrations used (24h incubation) were seen. Receptor binding and reversibility were demonstrated using a modified version of Gd.L4, with a trans-substituted biotin moiety appended to the macrocyclic core (Gd.L5, Fig. 1C). Cell-surface binding was visualized after adding an AvidinAlexaFluor® 488 conjugate, which binds with high specificity to the biotin moiety, while the receptor-binding moiety of the CA binds to the receptor on the cell membrane. Live cell confocal microscopy showed labeling of the cell membrane by Gd.L5 (green) in a pit-like manner and co-localization with a cell membrane specific marker (red, Figure 1D). Furthermore, a glutamate wash (1 mM) demonstrated that Gd.L5 is removed from the cell surface (Fig. 1E). In conclusion, we were able to identify two promising novel NMDAR-targeted MRI contrast agents. These CAs are based on the structures of competitive antagonists to NMDAR and we were able to demonstrate specific receptor binding and reversibility, which is essential for functional measurements of receptor-activity. Thus, our results indicate the possibility of using MRI for brain functional measurements based on competitive binding approaches.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-013-0703-2.pdf}, event_name = {Sixth Annual World Molecular Imaging Congress (WMIC 2013)}, event_place = {Savannah, GA, USA}, state = {published}, DOI = {10.1007/s11307-013-0703-2}, author = {Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Sim N; Pal R; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Parker S; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}} } @Poster{ GunduzPLA2013, title = {Synthesis of High Affinity Contrast Agents for Targeted MR Neuroimaging}, year = {2013}, month = {9}, day = {3}, abstract = {Magnetic resonance imaging (MRI) has become one of the essential noninvasive diagnostic techniques for soft tissues and diseases. Contrast agents have been developed to produce additional contrast and increase the signal intensity for MRI [1]. Here we report on the synthesis development of target specific contrast agents for MR neuroimaging. Monomeric and dendrimeric targeted contrast agents (TCA) were synthesized taking advantage of the highly specific interaction of the protein avidin with its ligand biotin [2]. The classical monomeric CAs have disadvantages such as non-specificity, fast renal excretion, low contrast efficiency and therefore they require a high dosage. To overcome this problem, we use multivalent, highly-branched dendrimeric molecules that are capable of carrying large number of CAs and hence the MRI amplification [3]. The TCAs are additionally labeled with a fluorescent dye, for to achieve their multimodal detection by means of optical and MR-based techniques. Upon their preparation, the biotinylated TCAs are suitable for labeling genetically engineered cell surface receptors that contain avidin. [4]. The preliminary experiments showed that TCAs bind specifically to avidin-coated beads (Figure 1). Their further characterization ensures exciting progress in neuroimaging enabling high resolution MRI of specific neuronal populations.}, web_url = {http://www.cim.unito.it/website/documenti/COST_TD1004_Athens_2013/Athens_2013_Book_of_Abstracts_final.pdf}, event_name = {COST TD1004 Action: Theranostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging: Guided Drug Delivery}, event_place = {Athens, Greece}, state = {published}, author = {G\"und\"uz S{sgunduz}; Power A{apower}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Poster{ SafaviPKLB2013, title = {Analyzing locking of spikes to spatio-temporal patterns in the macaque prefrontal cortex}, year = {2013}, month = {9}, pages = {43-44}, abstract = {Previous analysis of LFPs recorded from the macaque inferior convexity of the Prefrontal Cortex with Utah arrays revealed a dominant travelling wave in the beta band propagating along the ventral-dorsal plane [1, 2]. We hypothesized that propagating rhythmic activity reflects the intrinsic dynamics of the underlying neural populations which might be instrumental to information processing functions such as sensory integration. Here, we investigated the relationship between multi-unit spiking activities and LFPs in the same area of the Prefrontal Cortex. We computed spike-field coherence for each channel of the array. The results showed that many recording sites exhibited a distinctive peak in the beta frequency range both for spontaneous activity and during visual stimulation (A). Then we computed the beta band phase locking of spikes for each channel to a common LFP reference channel. The results showed that many recording sites exhibited locking of spikes to the same phase of remote beta band LFP (B). This result was observed for many LFP reference channels, suggesting spikes in all channels are synchronized to a common phenomenon. To characterize this phenomenon, we developed a new methodology inspired by spike triggered analysis to capture the dominant underlying spatio-temporal pattern of beta oscillations associated to spiking activity. The dominant spatio-temporal pattern estimated by matrix factorization, exhibits a phase gradient along the ventral-dorsal plane (C), suggesting that multi-unit activities across the array are synchronized to the global travelling wave previously observed along this direction in the LFP signal. Our result suggests spikes are synchronized to large scale travelling wave in the beta band. We postulate this reflects an endogenous mechanism for the large scale coordination of population activity. Further information theoretic analysis will address how this mechanism serves distributed sensory encoding and processing in this area.}, web_url = {https://portal.g-node.org/abstracts/bc13/#/doi/nncn.bc2013.0018}, event_name = {Bernstein Conference 2013}, event_place = {Tübingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2013.0018}, author = {Safavi S{ssafavi}{Department Physiology of Cognitive Processes}; Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}} } @Poster{ Besserve2013, title = {Characterization of different types of sharp-wave ripple signatures in the CA1 of the macaque hippocampus}, year = {2013}, month = {9}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Besserve M{besserve}{Department Physiology of Cognitive Processes}} } @Poster{ BahmaniLK2013_2, title = {Effects of binocular flash suppression in awake and anesthetized macaque}, year = {2013}, month = {9}, pages = {127-128}, abstract = {The primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies (Lehky, 1988; Blake, 1989; Polonsky et al., 2000; Tong and Engel, 2001). However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1 (Leopold and Logothetis, 1996; Sheinberg and Logothetis, 1997). In particular, only a moderate percentage of neurons in V1 was modulated in parallel with perception and the magnitude of their modulation was substantially smaller than the physical preference of these neurons (Keliris et al., 2010). It is yet unclear whether these small modulations are rooted in local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of awake and anesthetized macaque monkeys during the paradigm of binocular flash suppression. The results showed that the pattern of perceptual modulation of neurons in V1 under the conditions of general anesthesia is almost identical to those recorded from awake monkeys. This suggests a role of local processes in V1 in perceptual suppression. Alternatively, these modulations could be caused by feedback from higher areas independent of conscious state.}, web_url = {https://portal.g-node.org/abstracts/bc13/#/doi/nncn.bc2013.0124}, event_name = {Bernstein Conference 2013}, event_place = {Tübingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2013.0124}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ PropperMO2013, title = {Memory load modulates spiking activity in prefrontal cortex}, year = {2013}, month = {9}, pages = {172-173}, abstract = {While short-term memory is an essential requirement for behavior, knowledge about its neural code remains limited. In particular, how the brain organizes maintenance of multiple items at the same time has received little attention in this context. We trained two macaque monkeys to perform well in a memory task with load 1 and then, without further training had them memorize one to four visual sample stimuli presented sequentially over a period of 900 ms. Behavioral performance was above chance for all load conditions from the first session on. After a 3 second delay, the monkeys had to decide whether a newly presented test stimulus was part of the memorized set or not. During all subsequent sessions in which the monkey performed with load > 1, we recorded multi-unit activity and LFPs in prefrontal cortex using up to 16 micro-tetrodes. We performed spike sorting with a new algorithm (bayes optimal template matching) and analyzed rate modulations across task time: preliminary results show the firing rate of most sorted single units is significantly modulated during stimulus presentations and delay, compared to the level of baseline activity. Separating units from the compound tetrode multi-unit signal provides additional information: many multi-units exhibit no significant (Friedman test, p<0.05) rate modulation for different memory loads, while we find multiple load-selective single units after sorting the respective spikes. Most selective sorted units modulate their firing rate during the first second of the delay period. For the majority of these units, the rate during this period is increased compared to the baseline activity. Later in the delay period, the selective units exhibit no preference towards an increase in firing rate. These results suggest an active memory encoding phase shortly after the stimulus presentation. We are now starting to assess single trial classification performance and include analyses of LFP oscillations and correlations between units.}, web_url = {https://portal.g-node.org/abstracts/bc13/#/doi/nncn.bc2013.0180}, event_name = {Bernstein Conference 2013}, event_place = {Tübingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2013.0180}, author = {Pr\"opper R; Munk MHJ{munk}{Department Physiology of Cognitive Processes}; Obermayer K} } @Poster{ LiLK2013_2, title = {Parallel processes may underly pattern motion perception}, year = {2013}, month = {9}, pages = {128-129}, abstract = {Local measurements by small receptive fields induce ambiguous and noisy one-dimensional motion estimation. This problem can be overcome by selective integration or pooling over time and space to reconstruct the global pattern (Adelson & Movshon, 1982). However, it remains unclear if the local signals from intersections could influence the global pattern motion perception. Many studies used multiple apertures in order to investigate motion integration over space (Alais, Van der Smagt, Van den Berg, & Van de Grind, 1998; Maruya, Amano, & Nishida, 2010; Mingolla, Todd, & Norman, 1992; Takahashi, 2004), but none took this issue into consideration. Here we developed a novel stimulus and try to answer this question. We used a mask with multiple transparent apertures over a moving plaid. The plaid consisted of two overlapping moving gratings with directions 135° apart. The apertures were small (0.4°) and were placed in locations that allowed either only single contours (AP1) or intersections (AP2) to pass through. We hypothesized that if motion integration takes place only at higher stages with larger receptive fields, the probability of coherent pattern motion perception would not be affected by the relative ratios of the aperture types. Our results indicate that motion perception is largely affected by the ratio of aperture types. We conjecture that parallel processes at different stages are involved in motion integration.}, web_url = {https://portal.g-node.org/abstracts/bc13/#/doi/nncn.bc2013.0125}, event_name = {Bernstein Conference 2013}, event_place = {Tübingen, Germany}, state = {published}, DOI = {10.12751/nncn.bc2013.0125}, author = {Li Q{qinglinli}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ vankeulenLE2013, title = {Suppression of noradrenergic and dopaminergic neurotransmission differentially affects detection of behaviorally relevant auditory stimuli}, year = {2013}, month = {9}, abstract = {Both central noradrenergic (NE) and dopaminergic (DA) neuromodulatory systems are involved in processing of behaviorally relevant sensory stimuli. The brain stem nucleus Locus Coeruleus (LC) is activated by sensory stimulation and associated NE release in the LC forebrain targets modulates feed-forward sensory processing. The DA neurons of the midbrain ventral tegmental area (VTA) are responsive to reward-predicting stimuli and associated DA release facilitates reorganization of their neural representations. The specific contribution of NE and DA transmission for sensory processing in the higher-order cortical areas like the medial Prefrontal Cortex (mPFC) is less understood. We trained rats to detect a reward predicting frequency modulated target sound out of a sequence of pure tones (8, 12, 14 and 16 kHz) in the operant chamber. Four frequency modulation magnitudes were used: 0, 5, 30 and 100%. After reaching the learning criterion, the rats were implanted with bilateral chronic cannulas in the VTA and/or LC. The rat performance was tested after injection of Clonidine, an alpha2-noradrenergic-Agonist, into LC (25ng, 500nl) or U69593, a Kappa-Opioid-Agonist, into VTA (320ng, 500nl). Preliminary results indicated that decreased DA transmission within the VTA-mPFC pathway by U69593-infusion increased the reaction time regardless of the magnitude of frequency modulation of the target sound. Suppression of LC activity by clonidine-infusion impaired only detection of sounds with 5% frequency modulation. Our results suggest that DA release in the mPFC is critical for executive control of signal detection regardless of the signal detection threshold, while NE release is important for lowering the detection threshold.}, web_url = {https://sites.google.com/site/salletjerome/liens-links/mcc2013_paris}, event_name = {Motivational & Cognitive Control (MCC 2013): Neural Circuits for Adaptive Control of Behavior}, event_place = {Paris, France}, state = {published}, author = {van Keulen S{svankeulen}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ vanKeulenLE2013_2, title = {Suppression of noradrenergic and dopaminergic neurotransmission differentially affects detection of behaviorally relevant auditory stimuli}, year = {2013}, month = {9}, web_url = {http://www.ebbs2013.com/}, event_name = {45th Meeting of the European Brain and Behavior Society (EBBS 2013)}, event_place = {München, Germany}, state = {published}, author = {van Keulen S{svankeulen}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ BahmaniLK2013, title = {Effects of binocular flash suppression in the anesthetized macaque}, journal = {Perception}, year = {2013}, month = {8}, volume = {42}, number = {ECVP Abstract Supplement}, pages = {145}, abstract = {The primary visual cortex (V1) was implicated as an important candidate for the site of perceptual suppression in numerous psychophysical and imaging studies (Lehky, 1988; Blake, 1989; Polonsky et al., 2000; Tong and Engel, 2001). However, neurophysiological results in awake monkeys provided evidence for competition mainly between neurons in areas beyond V1 (Leopold and Logothetis, 1996; Sheinberg and Logothetis, 1997). In particular, only a moderate percentage of neurons in V1 was modulated in parallel with perception and the magnitude of their modulation was substantially smaller than the physical preference of these neurons (Keliris et al., 2010). It is yet unclear whether these small modulations are rooted in local circuits in V1 or influenced by higher cognitive states. To address this question we recorded multi-unit spiking activity and local field potentials in area V1 of anesthetized macaque monkeys during the paradigm of binocular flash suppression. The results showed that the pattern of perceptual modulation of neurons in V1 under the conditions of general anesthesia is almost identical to those recorded from awake monkeys. This suggests a role of local processes in V1 in perceptual suppression. Alternatively, these modulations could be caused by feedback from higher areas independent of conscious state.}, web_url = {http://pec.sagepub.com/content/42/1_suppl.toc}, event_name = {36th European Conference on Visual Perception (ECVP 2013)}, event_place = {Bremen, Germany}, state = {published}, DOI = {10.1177/03010066130420S101}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ LiLK2013, title = {Pattern motion signals from V1 receptive fields}, journal = {Perception}, year = {2013}, month = {8}, volume = {42}, number = {ECVP Abstract Supplement}, pages = {145}, abstract = {Local measurements by small receptive fields (RFs) in V1 are thought to induce ambiguous and noisy one-dimensional motion estimation. This necessitates integration at higher brain stages for computation of global pattern motion. Electrophysiological evidence from monkeys viewing plaid stimuli is consistent with this hypothesis finding a small percentage of cells in V1 responding to pattern motion but the percentage is increasing in higher motion responsive areas MT and MST. We conjectured that a subset of V1 RFs residing on specific stimulus features could directly respond to the pattern motion thus biasing motion integration at higher stages. We used a novel stimulus to mimic V1 RF responses to plaids. It comprised of a mask with multiple transparent apertures (0.4°) over a moving plaid. The aperture locations were chosen in advance to be of two types: AP1 were chosen to “see” only single grating components at any given time while AP2 were chosen to “see” only grating intersections. We manipulated the percentage of these two types in different trials to test how they influence motion perception. We found that the motion perception of subjects changes sigmoidally from 100% transparent when all apertures are AP1 to 100% coherent when all apertures are AP2.}, web_url = {http://pec.sagepub.com/content/42/1_suppl.toc}, event_name = {36th European Conference on Visual Perception (ECVP 2013)}, event_place = {Bremen, Germany}, state = {published}, DOI = {10.1177/03010066130420S101}, author = {Li Q{qinglinli}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ ChicharroKP2013, title = {Assessing the role of synchronization and phase coherence in neural communication comparing cortical recordings and integrate-and-fire network models}, journal = {BMC Neuroscience}, year = {2013}, month = {7}, volume = {14}, number = {Supplement 1}, pages = {187-188}, abstract = {Cognitive functions likely require that the routes of neural communication can be flexibly modulated. A proposed mechanism for modulating the effective strength of the connections in the neural dynamics relies on band specific neural synchronization and phase relations [1]. Evidence of the modulation of neuronal interactions through the phase relation of rhythmic activity in the gamma band was provided in [2]. Further evidence based on the analysis of a network of integrate-and fire neurons [3] has shown that the phase relation also modulates information transfer and is not specific of the gamma band. Here we combine the study of experimental recordings of local field potentials (LFP's) and multiple-unit activity (MUA) together with model data to better understand the origins of the phase-dependent modulation of interactions. Recordings include spontaneous activity and natural stimulus-driven activity in the monkey visual cortex V1 [4], as well as natural-stimulus driven activity in monkey auditory cortex [5]. Simulations were obtained extending the recurrent network of integrate-and-fire neurons used in [6] to model the connectivity between two different brain areas. We address some open questions regarding the generation, generality, and mechanistic nature of the phase-dependent modulation. We obtained, for any frequency band, the instantaneous power in each area (reflecting the local neural synchronization), and the instantaneous phases. We analyzed how the power correlation is modulated by the phase relation with a 1ms resolution, in contrast to the hundreds of milliseconds in [2]. We found that this modulation is accompanied by changes in the magnitude of the power of each area separately. Accordingly, we evaluated the role of the power determining the degree of phase coherence and thus the existence of a preferred phase relation. We found that the optimal phase relation associated with maximal power correlation always corresponds to the preferred phase relation for large powers. These results are not frequency band specific and were reproduced with model data, using both unidirectional and bidirectional connections, as well as both excitatory-excitatory and excitatory-inhibitory connections. Our analysis suggests that the degree of local neural synchronization that determines the power of a given rhythm in each of the interacting areas plays a role to be considered together with the one of the phase relations as part of the mechanisms that modulate dynamically the effective strength of the connections.}, web_url = {http://www.biomedcentral.com/1471-2202/14/S1/P306}, event_name = {Twenty-Second Annual Computational Neuroscience Meeting (CNS*2013)}, event_place = {Paris, France}, state = {published}, DOI = {10.1186/1471-2202-14-S1-P306}, author = {Chicharro D; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Panzeri S{stefano}} } @Poster{ BarbieriMLPB2013_2, title = {Input dependence of local field potential spectra: experiment vs theory}, journal = {BMC Neuroscience}, year = {2013}, month = {7}, volume = {14}, number = {Supplement 1}, pages = {38-39}, abstract = {How sensory stimuli are encoded in neuronal activity is a major challenge for understanding perception. A prominent effect of sensory stimulation is to elicit oscillations in EEG and Local Field Potential (LFP) recordings over a broad range of frequencies. Belitski et al. [1] recorded LFPs and spiking activity in the primary visual cortex of anaesthetized macaques presented with naturalistic movies and found that the power of the gamma and low-frequency bands of LFP carried largely independent information about visual stimuli, while the information carried by the spiking activity was largely redundant with that carried by the gamma-band LFPs. To understand better how different frequency bands of the LFP are controlled by sensory input, we computed analytically the power spectrum of the LFP of a theoretical model of V1 (a network composed of two populations of neurons - excitatory and inhibitory), subjected to time-dependent external inputs modelling inputs from the LGN, as a function of the parameters characterizing single neurons, synaptic connectivity, as well as parameters characterizing the statistics of external inputs. Our model consists in a two populations network of excitatory and inhibitory leaky integrate-and-fire neurons. Standard analytical methods using the Fokker-Planck formalism can be used to compute average firing rates of both populations in the asynchronous state of the network, as well as the region of parameters for which this state is stable ([2,3]). The power spectrum of the global activity and the LFP (sum of average excitatory and inhibitory currents onto pyramidal cells of the network) can also be computed in a network of finite size ([2]). Using linear response theory we then calculated the response of the network to a dynamic input ([4]). The final result was an equation giving the LFP power spectrum as a function of the intrinsic parameters of the network and of the parameters characterizing the dynamic input. We then used the analytical expression of the LFP power to fit the experimental data of [1]. The data consists in LFP recordings from primary visual cortex of monkeys, during the presentation of a movie that last several minutes. In order to capture the LFP power changes during the movie presentation, the LFP traces were divided into 2 seconds non-overlapping scenes. We then fitted the LFP power of all the scenes with the same network parameters, but with input parameters free to vary scene-by-scene. We used a simplex method repeatedly applied for different initial conditions. The parameter set that was selected was the one that minimized the reduced chisquare, among sets for which the asynchronous state was stable. The model provided excellent fits of the data. The fitting procedure permitted to extract the values of the firing rates of the excitatory and inhibitory populations and the parameters characterizing the external input for most of the scenes of the movie. These outcomes could be then correlated with experimental firing rates and the features of the movie itself, such as temporal and spatial contrast as well as orientation. We found a significant correlation both between firing rates extracted from fit and the multi-unit activity recorded during the movie and between the parameters characterizing the external input and the features of the movie. These results show how an analytical approach can be used to estimate the key parameters underlying changes in the LFP spectral dynamics.}, web_url = {http://www.biomedcentral.com/1471-2202/14/S1/P41}, event_name = {Twenty-Second Annual Computational Neuroscience Meeting (CNS*2013)}, event_place = {Paris, France}, state = {published}, DOI = {10.1186/1471-2202-14-S1-P41}, author = {Barbieri A; Mazzoni A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Brunel N} } @Poster{ MazzoniYNpD2013, title = {Spike timing in rat somatosensory cortex contributes to behavior}, journal = {BMC Neuroscience}, year = {2013}, month = {7}, volume = {14}, number = {Supplement 1}, pages = {76}, abstract = {The precise spike timing of sensory neurons carries more information about stimuli than the number of spikes counted over longer time windows [1-3]. However, the behavioral relevance of this extra information remains to be assessed. To investigate whether precise timing contributes to behavior, we considered spike trains recorded extracellularly in the rat somatosensory cortex during a texture discrimination task [4,5]. We analyzed the spike trains following the contact of the whiskers with the texture and we measured the information carried about texture by post-touch spike times and spike counts. This analysis is technical challenging because it is difficult to quantify the information content of precise patterns of spike that extend over relatively long time windows with the relatively little number of trials available in behavioral experiments. To address this challenge, we reduced the dimensionality of the response space by decomposing single trial spike train densities into Principal Components (PCs), selecting the most informative PC as the "temporal template" to interpret neural responses, and finally measuring the information about the presented texture carried by the projection of each trial relative to this template. We compared the so -measured spike timing information with the information carried by spike counts and we found that spike times carried more than 60% more texture information than spike counts. Next, we reasoned that if a neuronal coding mechanism contributes to behavior, then the code would be found to transmit less stimulus information in error trials, i.e. trials in which the rat made the wrong choice. We found that the texture information carried both by spike counts and spike patterns decreased significantly when we included error trials in the analysis, but the effect was much more pronounced for patterns (30% information decrease) than for counts (~15% information decrease). These differences between spike pattern and spike count codes hold for both primary and secondary somatosensory cortex, suggesting that spike timing could contribute to behavior at different stages of the sensory processing. Taken together, these results indicate that in the somatosensory cortex the time at which spikes occur, not just the number of spikes, makes a crucial contribution to tactile perception.}, web_url = {http://www.biomedcentral.com/1471-2202/14/S1/P109}, event_name = {Twenty-Second Annual Computational Neuroscience Meeting (CNS*2013)}, event_place = {Paris, France}, state = {published}, DOI = {10.1186/1471-2202-14-S1-P109}, author = {Mazzoni A; Yanfang Z; Notaro G{gnotaro}; Panzeri S{stefano}; Diamond ME} } @Poster{ DwarakanathK2013, title = {Seeing ghosts - Disentangling cross - modal top - down predictive control by actively manipulating arbitrarily learned associations}, year = {2013}, month = {6}, day = {4}, volume = {14}, number = {72}, web_url = {http://www.jmfs.org/media/files/Poster%20Presentations%20IMRF%202013.pdf}, event_name = {14th International Multisensory Research Forum (IMRF 2013)}, event_place = {Jerusalem, Israel}, state = {published}, author = {Dwarakanath A{adwarakanath}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Poster{ GoenseBL2013, title = {Decreased Cerebral Blood Volume and Flow in Areas with Negative BOLD Indicates the Mechanism for Negative BOLD May Be Stimulus- and Area-Specific}, year = {2013}, month = {4}, day = {25}, volume = {21}, pages = {3131}, abstract = {In earlier work, we showed increased CBV in regions with negative BOLD responses. This seems to disagree with work in cats where CBV was decreased in areas with negative BOLD. Here, we used a full-field checkerboard stimulus and show decreased CBV and CBF in areas that show negative BOLD responses. However, this type of negative BOLD signals occurred in peripheral V1 and extrastriate visual cortex. Our results suggest that different mechanisms for negative BOLD exist and that these may be area-dependent.}, file_url = {fileadmin/user_upload/files/publications/2013/ISMRM-2013-2341.pdf}, web_url = {http://www.ismrm.org/13/tp14.htm}, event_name = {21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Bohraus Y{ybohraus}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ HagbergKMPMLS2013, title = {19F-Lanthanide Complexes: T1 - and T2 - Dependent Signal Gain Using Gradient Echoes}, year = {2013}, month = {4}, day = {23}, volume = {21}, pages = {2681}, abstract = {19F-labelled compounds have unique benefits for biological applications but are hampered by low sensitivity. Lanthanide-complexes that shorten the 19F T1 and T2 relaxation times can boost the SNR in spoiled gradient echo sequences (FLASH). We investigated the MRI signal systematically for a wide range of T1 and T2 times for FLASH and balanced steady state free precession (tFISP). For long T2 times the tFISP signal is always greater, and for short relaxation times the signal gain depends on the duration of encoding and spoiling. None of the available compounds had ‘ideal’ relaxation times that gives the highest possible signal. Our results can be used to design better 19F contrast agents tailored to a specific MRI sequence.}, file_url = {fileadmin/user_upload/files/publications/2013/ISMRM-2013-1891.pdf}, web_url = {http://www.ismrm.org/13/tp07.htm}, event_name = {21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Keliris A{abrud}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Placidi M{Matteo}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ deAzevedoALK2013, title = {Effeccts of Visual Attention on Neural Processing in Rhesus' V1 by Simultaneous Electrophysiology and Bold-FMRI}, year = {2013}, month = {3}, day = {16}, web_url = {http://nwg.glia.mdc-berlin.de/media/pdf/conference/Program2013.pdf}, event_name = {10th Göttingen Meeting of the German Neuroscience Society, 34th Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {de Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Azevedo LC{lazevedo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris G{george}{Department Physiology of Cognitive Processes}} } @Poster{ EschenkoBOL2013, title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia}, year = {2013}, month = {3}, abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was first implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s base line sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.}, web_url = {http://www.ewcbr.eu/files/2013/Abstracts/Eschenko.pdf}, event_name = {33rd European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2013)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ BarbieriMLPB2013, title = {Input dependence of local field potential spectra: experiment vs theory}, year = {2013}, month = {3}, number = {I-30}, web_url = {http://www.cosyne.org/c/index.php?title=Cosyne_13}, event_name = {Computational and Systems Neuroscience Meeting (COSYNE 2013)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Barbieri F; Mazzoni A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Brunel N} } @Thesis{ Vibhute2013, title = {Synthetic Modifications of Responsive MRI Contrast Agents: Development of Multifunctional Conjugates for Novel Class of fMRI [Synthetische Modifizierung von Intelligenten MRI Kontrastmitteln:Entwicklung von Multifunktionalen Verbindungen für eine neuartige Klasse von fMRI}, year = {2013}, month = {4}, web_url = {https://publikationen.uni-tuebingen.de/xmlui/handle/10900/49893}, state = {published}, type = {PhD}, author = {Vibhute SM{svibhute}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2013, title = {Anatomical and Functional Organization of the Primate Insular Cortex}, year = {2013}, month = {11}, day = {28}, abstract = {The insula exerts a crucial role in processing interoceptive and emotional states, and in interdependently engendering subjective feelings of self-awareness and empathy. One major problem in understanding how this occurs is that little is known about the insula’s anatomical organization, including its architecture and hodology. We re-examined the architecture of the macaque insula and found that each of its three classical “sectors” contains several smaller, reproducibly distinct and sharply delimited areas including 8 agranular areas, 4 dysgranular areas and 4 granular areas. Each area appears to be subdivided into smaller sub-areas organized in a series of anteroposterior stripes. Using intra- and extra-insular injections of neuronal tracers, (1) we confirmed the existence of smaller areas and of a stripe-like hodological pattern and (2) we observed that each area harbours a complex but highly organized topography. On the basis of this and other works, we proposed a new working model of the primate insular organization that resonates to some extent with models recently proposed on the basis of human imaging studies. We are currently completing the analysis of our tract-tracing to test and refine our model. Finally, using careful anatomical examination, we found that one specific area of the macaque insula contains von Economo neurons (VENs), an atypical form of projection neurons previously thought to occur only in humans and great apes among primates and known to be particularly vulnerable in the behavioural variant of frontotemporal lobe dementia. In connexion with our other studies, this finding offers new and much needed opportunities to investigate the primal connections and physiology of a neuron and brain area that could be crucial for human self- awareness, social cognition, and related neuropsychiatric disorders.}, web_url = {http://www.cin.uni-tuebingen.de/news-events/browse-all-events/detail/view/338/page/1/conference-cin-symposium-2013.html}, event_name = {CIN Symposium 2013}, event_place = {Tübingen, Germany}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2013_2, title = {Network analyses of fMRI Data}, year = {2013}, month = {11}, day = {22}, event_name = {ESMRMB-Lectures on Magnetic Resonance, Advanced methods for acquisition and analysis of fMRI data}, event_place = {Tübingen, Germany}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Munk2013, title = {Electrophysiological correlates of the BOLD response}, year = {2013}, month = {11}, day = {20}, event_name = {ESMRMB-Lectures on Magnetic Resonance, Advanced methods for acquisition and analysis of fMRI data}, event_place = {Tübingen, Germany}, state = {published}, author = {Munk M{munk}{Department Physiology of Cognitive Processes}} } @Conference{ Keliris2013_2, title = {Measuring average neuronal receptive field sizes with fMRI and how it can be used to study plasticity and reorganization}, year = {2013}, month = {11}, day = {20}, event_name = {ESMRMB-Lectures on Magnetic Resonance, Advanced methods for acquisition and analysis of fMRI data}, event_place = {Tübingen, Germany}, state = {published}, author = {Keliris G{george}{Department Physiology of Cognitive Processes}} } @Conference{ Munk2013_2, title = {Pharmacology and Neuromodulation of neurovascular coupling}, year = {2013}, month = {11}, day = {20}, event_name = {ESMRMB-Lectures on Magnetic Resonance, Advanced methods for acquisition and analysis of fMRI data}, event_place = {Tübingen, Germany}, state = {published}, author = {Munk M{munk}{Department Physiology of Cognitive Processes}} } @Conference{ Panagiotaropoulos2013, title = {Spatiotemporal patterns of sub-threshold oscillatory activity in the inferior convexity of the macaque prefrontal cortex}, year = {2013}, month = {11}, day = {14}, abstract = {Despite significant progress in understanding functional parcellation of the primate prefrontal cortex (PFC) it is currently unknown whether an intrinsic mechanism could dynamically coordinate activity between these functionally specialized sub-regions. Such a mechanism could be reflected in spatially organized rhythmic activity that is mesoscopically observed as complex, rhythmic spatio-temporal patterns. In order to identify such spatio-temporal patterns in the default state of the prefrontal cortical network we recorded from the inferior convexity of the macaque PFC during anesthesia using multi-electrode (Utah) arrays. The power spectrum and spatial coherence of oscillatory activity exhibited a distinctive peak in the beta (15-30 Hz) frequency range of local field potentials (LFP's) during resting state but also during sensory stimulation with dynamic movie stimuli, revealing a dominant rhythm in the PFC. We observed consistent phase gradients in the beta band that formed complex, dynamic patterns, suggesting propagation of oscillatory activity across the cortical surface. These spatio-temporal patterns were subsequently clustered using a graph cut algorithm based on a measure of phase shift invariant similarity. Our analysis revealed a dominant travelling wave pattern in the beta band, propagating along the ventral-dorsal plane and replaced by less frequent, less dominant patterns both in the absence of visual stimulation (spontaneous activity) and during stimulation with movie clips. By estimating mutual information, we found that the amplitude of this wave conveyed sensory information during the presentation of several movies. These findings suggest that spatiotemporal phenomena are suggestive of highly coordinated activity in the PFC, a cortical area known to be involved in associative functions. In particular, traveling waves of oscillatory neural activity are modulated by sensory input and could provide a functional substrate for coordinating activity across different subregions of the PFC.}, web_url = {http://www.caltech.edu/content/cns-seminar-3}, event_name = {California Institute of Technology: Computation & Neural Systems Seminar}, event_place = {Pasadena, CA, USA}, state = {published}, author = {Panagiotaropoulos T{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ Kerr2013_3, title = {What are they looking at? Imaging activity in the freely moving rodent from the eye to the cortex}, year = {2013}, month = {11}, day = {13}, volume = {43}, number = {790.06}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ PapanikolaouKPSKPSLS2013, title = {Human area V5/MT+ organization changes following lesions of the primary visual cortex}, year = {2013}, month = {11}, day = {12}, volume = {43}, number = {602.07}, abstract = {Damage of the primary visual cortex (V1) and/or its inputs leads to a visual field loss (scotoma) in the corresponding, homonymous, region of the contralateral visual hemifield. The resulting visual field defect often involves the whole hemifield (hemianopia) or one quadrant (quadrantanopia). However, some patients have been found to retain a small amount of residual visual sensitivity within the blind field, a phenomenon termed blindsight, suggesting that there are alternate pathways that effectively bypass V1 and transmit visual information directly to extrastriate visual cortex. Blindsight has been associated with activity observed in the middle temporal area complex (V5/MT+) following V1 lesions. An important issue is how the organization of area V5/MT+, including how it covers the visual field, changes following V1 lesions. We used the population receptive field (pRF) method (Dumoulin SO, Wandell BA, Population receptive field estimates in human visual cortex, Neuroimage 39, 2008) to study the organization of human area V5/MT+ after V1 injury in adulthood. Functional magnetic resonance imaging (fMRI) measurements were obtained during the presentation of a moving bar stimulus while the subjects were fixating. We mapped the retinotopic organization of area V5/MT+ in 5 patients with approximate quadrantanopia and compared them to control subjects stimulated with matching “artificial scotomas”. We investigated i) whether area hV5/MT+ remains responsive following the V1 lesion, ii) whether it retains its retinotopic organization, and iii) whether hV5/MT+ organization changes by recruiting inputs from intact portions of area V1, or from the contralateral hV5/MT+. In three patients we found responses in hV5/MT+ arising inside the scotoma, independent of area V1 input, suggesting the existence of a functional alternate pathway bypassing area V1. hV5/MT+ of the other patients responded only to locations outside of the perceptual scotoma. The retinotopic organization of V5/MT+ for all 5 patients was different than that seen in controls stimulated with the “artificial scotoma.” Specifically, the pRF center distribution was shifted across the horizontal meridian towards locations outside the visual field scotoma for all patients. PRF size distributions differed between patients and controls under the artificial scotoma condition, with some subjects having larger pRFs on average, while others smaller. Finally, changes were observed in the retinotopic organization of the contra-lesional area hV5/MT+, likely mediated via trans-callosal connections.}, web_url = {http://www.sfn.org/annual-meeting/neuroscience-2013}, event_name = {43rd Annual Meeting of the Society for Neuroscience (Neuroscience 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Papageorgiou GT; Shao Y{yshao}{Department Physiology of Cognitive Processes}; Krapp E; Papageorgiou E; Schiefer U; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Conference{ KikuchiAMWP2013, title = {Cortical oscillations and spiking activity associated with Artificial Grammar Learning in the monkey auditory cortex}, year = {2013}, month = {11}, day = {8}, web_url = {http://www.med.upenn.edu/apan/assets/user-content/documents/Archived.APAN.2013.pdf}, event_name = {Tucker‐Davis Technologies Symposium on Advances and Perspectives in Auditory Neurophysiology (APAN 2013)}, event_place = {San Diego, CA, USA}, state = {published}, author = {Kikuchi Y; Attaheri A; Milne A; Wilson B; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Conference{ Kapoor2013_2, title = {Development and use of tube tetrodes for electrophysiological investigation of deep lying brain structures of the macaque}, year = {2013}, month = {10}, day = {31}, pages = {20}, abstract = {A major approach of investigation in systems neuroscience has been to study the activity of single neurons (units) in relation to a sensory input or a behavioral act. One tool, which has been consistently employed for this purpose is the microelectrode. Recent advances in microelectrode technology have permitted recording the activity of several neurons simultaneously, therefore allowing the study of information processing at the level of neuronal populations. Twisted wire tetrodes (TWTs), have played an instrumental role in this advance because of their ability to record multiple single units and the isolation quality of the recorded single units. However, their limited tensile strength has hindered their use for electrophysiological recordings in deep lying structures of the macaque brain. We therefore developed a simple method for conferring strength to conventional TWTs, and call them Tube Tetrodes (TuTes). TuTes can be built using standard laboratory equipment and are very cost efficient. Further, their ultrathin diameter minimizes the tissue damage along their path. We also developed a multi-tetrode drive to independently control and advance up to 5 TuTes to the inferotemporal cortex of a rhesus macaque. Electrophysiological activity recorded with these TuTes from a macaque engaged in a simple behavioral task demonstrates that the signal quality recorded from them is comparable to conventional TWTs. Finally, these TuTes could be easily adapted to work with other microdrives commonly used for electrophysiology.}, web_url = {http://www.ru.nl/dondersdiscussions/previous-events/dd2013/}, event_name = {Donders Discussions 2013}, event_place = {Nijmegen, The Netherlands}, state = {published}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}} } @Conference{ Zaretskaya2013, title = {Causal contributions of parietal cortex to perceptual selection and spatial binding}, year = {2013}, month = {10}, day = {11}, web_url = {http://www.cin.uni-tuebingen.de/news-events/browse-all-events/detail/view/338/page/1/3rd-nips-cin-joint-symposium.html}, event_name = {3rd NIPS-CIN Joint Symposium}, event_place = {Okazaki, Japan}, state = {published}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}} } @Conference{ Evrard2013_2, title = {The Primate Insular Cortex: A neuroanatomical insight intointeroception, emotion and self-awareness}, year = {2013}, month = {10}, day = {10}, web_url = {http://www.cin.uni-tuebingen.de/news-events/browse-all-events/detail/view/338/page/1/3rd-nips-cin-joint-symposium.html}, event_name = {3rd NIPS-CIN Joint Symposium}, event_place = {Okazaki, Japan}, state = {published}, author = {Evrard H{evrard}{Department Physiology of Cognitive Processes}} } @Conference{ Dwarakanath2013, title = {Is seeing believing? The role of predictive coding in perception}, year = {2013}, month = {10}, day = {2}, volume = {14}, pages = {19}, web_url = {http://www.cin.uni-tuebingen.de/fileadmin/content/05_News_%26_Events/Conferences/Conference_130930_NeNa_2013.pdf}, event_name = {14th Conference of Junior Neuroscientists of Tübingen (NeNa 2013)}, event_place = {Schramberg, Germany}, state = {published}, author = {Dwarakanath A{adwarakanath}} } @Conference{ Logothetis2013_3, title = {Studying Large-Scale Brain Networks: Electrical Stimulation & Neural-Event-Triggered fMRI}, year = {2013}, month = {9}, day = {27}, abstract = {The brain is "the" example of an adaptive, complex system. It is characterized by ultra-high structural complexity and massive connectivity, both of which change and evolve in response to experience. Information related to sensors and effectors is processed in both a parallel and a hierarchical fashion. The connectivity between different hierarchical levels is bidirectional, and its effectiveness is continuously controlled by specific associational and neuromodulatory centers. In the study of such systems one major problem is the adequate definition for an elementary operational unit (often called an "agent"), because any such module can be a complex system in its own right and may be recursively decomposed into other sets of units. A second difficulty arises from the synergistic organization of complex systems and of the brain in particular. Synergy here refers to the fact that the behavior of an integral, aggregate, whole system cannot be trivially reduced to, or predicted from, the components themselves. Localizing and comprehending the neural mechanisms underlying our cognitive capacities demands the combination of multimodal methodologies, i.e. it demands concurrent study of components and networks; one way of doing this, is to combine invasive methods which afford direct access to the brain’s electrical activity at the microcircuit level with global imaging technologies such as magnetic resonance imaging (MRI). In my talk, I'll discuss two such methodologies: Direct Electrical Stimulation and fMRI (DES-fMRI) and Neural-Event-Triggered fMRI (NET-fMRI).}, web_url = {http://lpp.psycho.univ-paris5.fr/event.php?id=238}, event_name = {INC Seminar: Laboratoire Psychologie de la Perception}, event_place = {Paris, France}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Logothetis2013, title = {Studying Large-Scale Brain Networks: Electrical Stimulation & Neural-Event-Triggered fMRI}, year = {2013}, month = {9}, day = {15}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Conference{ Kapoor2013, title = {Development and use of tube tetrodes for electrophysiological investigation of deep lying brain structures of the macaque}, year = {2013}, month = {9}, day = {14}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Kapoor V{vishal}{Department Physiology of Cognitive Processes}} } @Conference{ Ortiz2013, title = {High-resolution fMRI phase-mapping of azimuth space in rhesus monkey auditory cortex}, year = {2013}, month = {9}, day = {14}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}} } @Conference{ Keliris2013, title = {Receptive field mapping using fMRI: what can it tells us about functional organization}, year = {2013}, month = {9}, day = {14}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Keliris G{george}{Department Physiology of Cognitive Processes}} } @Conference{ Perrodin2013, title = {Visual modulation of neurons in voice-sensitive and association cortices}, year = {2013}, month = {9}, day = {13}, web_url = {http://www.neuroschool-tuebingen-cogni.de/index.php?id=374}, event_name = {Networks! 2013: 4th German Neurophysiology PhD Meeting}, event_place = {Tübingen, Germany}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}} } @Conference{ VibhuteMLA2013, title = {Development of Ca2+ Responsive Contrast Agents for fMRI}, year = {2013}, month = {9}, day = {3}, abstract = {Magnetic resonance imaging (MRI) using contrast agents has been widely employed in diagnostic imaging and biomedical research. For this purpose, Gd3+ based complexes are commonly utilized. Recently, responsive (smart) contrast agents (SCAs) are being developed in order to aid better understanding of biological processes [1] They are able to report physiological or pathophysiological changes by altering the MR signal they produce. However the routine in vivo use of SCA is hampered due to challenges such as lack of tools to localize or quantify the agents, low MR signal, non-specific delivery etc. To overcome these challenges, one of the meaningful strategies is to conjugate SCA to various functional molecules such as dendrimers, nanoparticles, delivery vectors or fluorescent tags. The essential requirement when coupling SCAs to functional molecules is retaining their crucial physico-chemical properties in terms of MRI activity. Hence, the overall objective of our approach was to develop synthetic strategies in which modified DO3A chelator is appended with different linkers for further functionalization. Diverse synthetic strategies were successfully developed using liquid, as well as solid phase chemistry [2]. The SCA were modified and they still robustly response to Ca2+. The newly developed strategies open pathways to improve in vivo applicability of DO3A-based SCAs and to serve as better in vivo reporters in future fMRI experiments.}, web_url = {http://www.cim.unito.it/website/documenti/COST_TD1004_Athens_2013/Athens_2013_Book_of_Abstracts_final.pdf}, event_name = {COST TD1004 Action: Theranostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging: Guided Drug Delivery}, event_place = {Athens, Greece}, state = {published}, author = {Vibhute SM{svibhute}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Conference{ Kerr2013_4, title = {Rats! What are they looking at?}, year = {2013}, month = {8}, day = {30}, web_url = {http://www.caesar.de/978.html}, event_name = {3rd International caesar Conference "Chasing the Neuronal Ensemble II": Center of Advanced European Studies and Research}, event_place = {Bonn, Germany}, state = {published}, author = {Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Conference{ Greenberg2013, title = {Action Potential Detection and Model Fitting for in Vivo Fluorescent Calcium Sensors}, year = {2013}, month = {8}, day = {29}, web_url = {http://www.caesar.de/978.html}, event_name = {3rd International caesar Conference "Chasing the Neuronal Ensemble II": Center of Advanced European Studies and Research}, event_place = {Bonn, Germany}, state = {published}, author = {Greenberg D{david}{Research Group Neural Population Imaging}} } @Conference{ Ecker2013, title = {State dependence of noise correlations in macaque primary visual cortex}, year = {2013}, month = {7}, day = {18}, abstract = {The structure and magnitude of noise correlations in the monkey visual system has been subject to intense debate over the last couple of years. We previously found that neural responses to repeated presentations of the same visual stimulus were close to independent in V1 of awake, fixating monkeys (average rsc: 0.01). Other labs, in contrast, found average levels of correlations up to an order of magnitude higher. Although a number of possible explanations for this discrepancy have been put forward, only few of them have been directly addressed. We tested one of our original hypotheses, that fluctuations of global brain state under anesthesia may induce positive correlations between neurons, which are absent during wakefulness. We performed multi-tetrode recordings in V1 of opiod-anesthetized monkeys under conditions otherwise identical to our previous awake recordings. Activity in anesthetized monkey V1 was dominated by strong coordinated fluctuations involving nearly every active neuron. These state fluctuations evolve on a timescale of 1–2 Hz, substantially slower than what would be expected from shared sensory noise, and resemble up and down states, which have been described for many other types of anesthetics before. During wakefulness, in contrast, such state fluctuations were absent. We further found that after accounting for the brain state under anesthesia the level of noise correlations was reduced to that during wakefulness. Our results highlight an important caveat of neural population recordings under anesthesia: if not properly accounted for, state fluctuations, which are not present in awake animals, are the primary source of correlated variability.}, web_url = {http://www.gnt.ens.fr/~sostojic/cns2013_workshop.html}, event_name = {CNS 2013 Workshop on Functional Role of Correlations: Theory and Experiment}, event_place = {Paris, France}, state = {published}, author = {Ecker A{aecker}{Department Physiology of Cognitive Processes}} } @Conference{ LogothetisEMASEBO2013, title = {Studying large-scale brain networks: electrical stimulation and neural-event-triggered fMRI}, journal = {BMC Neuroscience}, year = {2013}, month = {7}, volume = {14}, number = {Supplement 1}, pages = {1}, abstract = {The brain is "the" example of an adaptive, complex system. It is characterized by ultra-high structural complexity and massive connectivity, both of which change and evolve in response to experience. Information related to sensors and effectors is processed in both a parallel and a hierarchical fashion. The connectivity between different hierarchical levels is bidirectional, and its effectiveness is continuously controlled by specific associational and neuromodulatory centers. In the study of such systems one major problem is the adequate definition for an elementary operational unit (often called an "agent"), because any such module can be a complex system in its own right and may be recursively decomposed into other sets of units. A second difficulty arises from the synergistic organization of complex systems and of the brain in particular. Synergy here refers to the fact that the behavior of an integral, aggregate, whole system cannot be trivially reduced to, or predicted from, the components themselves. Localizing and comprehending the neural mechanisms underlying our cognitive capacities demands the combination of multimodal methodologies, i.e. it demands concurrent study of components and networks; one way of doing this, is to combine invasive methods which afford us direct access to the brain's electrical activity at the microcircuit level with global imaging technologies such as magnetic resonance imaging (MRI). In my talk, I'll discuss two such methodologies: Direct Electrical Stimulation and fMRI (DES-fMRI) and Neural-Event-Triggered fMRI (NET-fMRI). DES-fMRI can be used in hopes of gaining insight into the functional or effective connectivity underlying DES-induced behaviors. Yet, our first findings suggest that DES has an important limitation: It clearly demarcates all monosynaptic targets of a stimulated site, but it largely fails to reveal polysynaptic cortico-cortical connectivity. NET-fMRI, on the other hand, appears to offer great potential for mapping whole-brain activity that is associated with individual local events. In the second part of my talk, I'll describe the characteristic states of widespread cortical and subcortical networks that are associated with the occurrence of hippocampal sharp waves and ripples; the brief aperiodic episodes associated with memory consolidation.}, web_url = {http://www.biomedcentral.com/1471-2202/14/S1/A1}, event_name = {Twenty-Second Annual Computational Neuroscience Meeting (CNS*2013)}, event_place = {Paris, France}, state = {published}, DOI = {10.1186/1471-2202-14-S1-A1}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Augath M{mark}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}} } @Conference{ Angelovski2013, title = {Visualization of biological processes using responsive MRI contrast agents}, year = {2013}, month = {6}, day = {28}, pages = {7}, abstract = {Magnetic resonance imaging (MRI) has evolved into a powerful tool in modern biomedical research. Its signal specificity can be further improved using contrast agents and their application has largely contributed to the MRI development. The aim of our group is to develop new measurement techniques that would enable visualization of neuronal activity and better understanding of brain function by using responsive (or 'smart') agents. These are biochemical markers that alter their MR signal upon a certain biochemical event due to changes in their microenvironment. Calcium is an excellent marker tightly linked to brain activation, which has typically been the preferred target for a number of optical imaging methods. To accomplish our goals, we synthesize and study smart MRI contrast agents, complexes that respond to differing concentrations of endogenous Ca2+ by altering their magnetic properties. Over the past years we have reported a number of Gd3+ chelates linked to modified Ca2+ chelators that act as smart MRI contrast agents.[1] Some of the agents exhibited remarkable sensitivity towards Ca2+, and their physicochemical characteristics were found to be superior to any other previously described Ca2+-sensitive MRI agents.[2] In parallel, we developed a series of fluorine-containing complexes with a range of paramagnetic and diamagnetic ions. They exhibit high proton longitudinal relaxivities while displaying an increase in 19F relaxation rates which are favorable for 19F MRI experiments.[3] Subsequently, the complexes that contain a Ca2+ chelator in between the paramagnetic and fluorine-containing moieties are prepared and they are capable of reporting the changes in Ca2+ concentrations simultaneously by 1H and 19F MRI. Extensive studies revealed mechanisms which underly the intramolecular changes triggered by Ca2+, and are responsible for the alternation of the MRI signals at both frequencies.[4] A new generation of dual-frequency probes suitable for both 1H and 19F MRI opens novel perspectives for successful assessment of Ca2+ in living organisms. The ability to observe its concentration changes in a non-invasive fashion would be of paramount importance for MRI methodology advancements and biomedical research in general. The presentation will give a brief overview of smart MRI contrast agents recently studied and reported by our group.}, web_url = {http://eprints.ugd.edu.mk/8532/1/ICSECS8-Book_of_Abstrcts.pdf}, event_name = {8th International Conference of the Chemical Societies of the South-East European Countries (ICOSECS 2013)}, event_place = {Beograd, Serbia}, state = {published}, author = {Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Conference{ Schuz2013, title = {Network structure of the cerebral cortex: observations on the grey and white matter in mice, monkeys and humans}, year = {2013}, month = {6}, day = {24}, web_url = {https://www.uni-salzburg.at/fileadmin/multimedia/PhD%20Program%20Imaging%20the%20Mind/documents/2193722.PDF}, event_name = {Second Annual DK+ "Imaging the Mind" Summer School: "Aspects of functional and structural brain connectivity"}, event_place = {Salzburg, Austria}, state = {published}, author = {Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Conference{ Watanabe2013, title = {Is the primary visual cortex modulated by visual awareness?}, year = {2013}, month = {6}, day = {5}, abstract = {The role of V1 in visual awareness and attention has been a matter of intense debate due to its unique position in the visual hierarchy, the entrance stage of visual processing in cortex. Using a two-by-two factorial functional magnetic resonance imaging design with binocular suppression, we found that the visibility or invisibility of a visual target led to only non-significant BOLD effects in the human primary visual cortex, while directing attention toward and away from the target had much larger and robust effects across all subjects. The difference in the lower level limit of BOLD activation between attention and awareness illustrates dissociated neural correlates of the two processes. Our results agree with previously reported V1 BOLD effects on attention while they invite a reconsideration of the functional role of V1 in visual awareness.}, web_url = {http://www.psy.gla.ac.uk/events/index.php?id=1578}, event_name = {University of Glasgow: Seminar Series in Psychology}, event_place = {Glasgow, UK}, state = {published}, author = {Watanabe M{watanabe}{Department Physiology of Cognitive Processes}} } @Conference{ HuberGIKTM2013, title = {Cerebral Blood Volume Changes in Negative BOLD Regions During Visual Stimulation in Humans at 7T}, year = {2013}, month = {4}, day = {26}, volume = {21}, pages = {1638}, abstract = {Based on recent studies in monkeys (Goense, J, et al., Neuron, in press), the changes in cerebral blood volume (CBV) were investigated in human brain regions that show negative BOLD responses during a visual task. Therefore a CBV-sensitive VASO method was implemented that can account for BOLD and inflow contaminations at 7T. In regions with negative BOLD responses, significant CBV decreases can be seen. This CBV decrease is dominated by voxels that include the cortical surface at the transition region between grey matter and cerebrospinal fluid, while many voxels in deeper layers show a CBV increase.}, file_url = {fileadmin/user_upload/files/publications/2013/ISMRM-2013-0847.pdf}, web_url = {http://www.ismrm.org/13/session84.htm}, event_name = {21st Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2013)}, event_place = {Salt Lake City, UT, USA}, state = {published}, author = {Huber L; Goense J{jozien}{Department Physiology of Cognitive Processes}; Ivanov D; Krieger SN; Turner R; Moeller HE} } @Conference{ Bartels2013, title = {Perceptual selection and grouping: A common function of parietal cortex}, year = {2013}, month = {3}, day = {25}, volume = {55}, pages = {25}, web_url = {https://www.teap.de/memory/Abstractband_55_2013_wien.pdf}, event_name = {55. Tagung Experimentell Arbeitender Psychologen (TeaP 2013)}, event_place = {Wien, Austria}, state = {published}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Conference{ DwarakanathK2013_2, title = {Disentangling cross-modal top-down predictive control by actively manipulating arbitrarily learned associations}, year = {2013}, month = {3}, day = {15}, pages = {135}, abstract = {Various studies have characterised the brain as an efficient coding system, thereby describing sensory processing as being optimised to the incoming statistics of natural stimuli. A key framework in this respect is that of predictive coding, which asserts that the brain actively predicts an upcoming sensory stimulus via top-down control mechanisms rather than passively registering it. This top-down control involves the propagation of a prediction to the primary sensory area where the error signal between the prediction and the incoming stimulus is calculated and propagated to higher areas for refinement of the prediction. Accurate predictions hence lead to a decrease in activity in early sensory areas, a presumed signature of predictive coding which several studies used to confirm the theory. However many studies used high level stimuli such as speech, for which subjects have strong and innate priors and which come with potentially confounding contextual variables and changes in attention. To account for such confounding effects in tests of predictive coding, we designed non-contextual priors consisting of arbitrary associations of random perceptual features. We used visual stimuli consisting of Gabor patches of six orientations (from 0° to 165°) paired with pseudo-natural acoustic soundscapes created by filtering a natural sound in six frequency bands (128 Hz to 8192 Hz, logarithmic steps). For each subject one orientation was randomly associated with one frequency band, and the subject was exposed to short presentations (1.5s) of these pairs for 15min. Subsequently we tested the impact of this learned predictive association on stimulus recognition in supra-, subliminal and occluded conditions using a 2AFC task. Stimuli were rendered subliminal using each subjects contrast detection threshold and occluded stimuli were masked to 50% by white pixel noise. During the test phase we presented stimuli both as pairs by preserving the previous pairing (control phase) and by pairing sounds with different orientations in order to see whether the acoustic predictor changes the perceived orientation. Responses were analysed by calculating bias and d’ for each trial type and a shift in the 50% response bias was taken as evidence for a predictive effect on perceptual decisions. The important finding is that in the test condition we found a shift of the bias towards the orientation predicted by the sound in subliminal, catch and occluded trials. Our results hence provide evidence for predictive coding and top-down biasing in the context of arbitrary audio-visual associations.}, web_url = {https://www.nwg-goettingen.de/2013/default.asp?id=4}, event_name = {10th Göttingen Meeting of the German Neuroscience Society, 34th Göttingen Neurobiology Conference}, event_place = {Göttingen, Germany}, state = {published}, author = {Dwarakanath A{adwarakanath}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Conference{ Munk2013_3, title = {Task Dependent Changes in Oscillatory Coupling during Visuomotor Integration and Memory}, year = {2013}, month = {3}, abstract = {Given the connectivity of its inputs, the neocortex is the largest part of the brain which is mainly self referencing. This bears several consequences for the organization of neuronal activity. One relatively simple consequence is that ongoing activity is best predicted by correlating it to other cortical activity. In contrast, stimulus-related activity which is mediated by subcortical inputs may only contribute a small fraction to the total activity measured. Such a system design can be considered an advantage, because high degrees of freedom for the dynamical evolvement of brain activity require relative independence from external signals. As the output of cortical neurons is highly sensitive to the timing of the many inputs, relative timing of neuronal activity e.g. determined by the phase relation of oscillatory processes may play an important role for integrating and propagating activity through the cortex. By analyzing field potentials recorded simultaneously in multiple cortical areas during a visuomotor task that requires multiple subsequent steps of sensorimotor integration, we found that oscillations occur in many of the recorded sites and persist almost invariably throughout the task, often beginning before the monkey actually started the actual visuomotor transformation. In contrast, signal correlation across sites, as revealed by time resolved coherence or cross-correlation, increased only during particular epochs during which precise coordination between visual cue and motor output is needed. In contrast, during much less transient behavior like short term memory of static objects, in which it is assumed that highly persistent signals like sustained neuronal firing and/or oscillations carry information across the memory delay, it is not straight forward to find signals which really bridge the gap and therefore provide a potential mechanism for memory maintenance, even in prefrontal cortex. We therefore devised a bootstrapping method with which we analyzed differential effects of behavioral performance or the memorized stimuli on the occurrence of oscillations. With these methods it is more feasible to track continuing oscillatory signals, even if their frequency changes over time. We found that in the high gamma-frequency (60-95 Hz) band there is more or less continuously activity which bridges the memory delay and from which several times during the delay oscillatory processes emerge which rapidly reduced their frequency. In our study, performance and stimulus related oscillatory processes reduced their frequency into the beta-frequency (15-30 Hz) range at the time when the monkey had to compare test stimuli and the content of short-term memory in order to generate a behavioral response. There is growing evidence that cortical oscillations occur in rather continuous form and adapt more their frequency or coupling to the dynamics of task-related processes. Future work will have to show how the dynamical changes of oscillations can modulate the spiking output of neuronal populations which determines signal transmission and ultimately behavior.}, web_url = {http://www.ewcbr.eu/files/2013/Abstracts/Munk.pdf}, event_name = {33rd European Winter Conference on Brain Research and European Brain and Behaviour Society (EWCBR/EBBS 2013)}, event_place = {Brides-les-Bains, France}, state = {published}, author = {Munk MHJ{munk}{Department Physiology of Cognitive Processes}} } @Conference{ Panagiotaropoulos2013_2, title = {Neuronal correlates of visual consciousness in the primate brain: From single units to spatiotemporal patterns}, year = {2013}, month = {1}, day = {28}, web_url = {http://www.sussex.ac.uk/lifesci/neuroscience/seminars/?id=17580}, event_name = {University of Sussex: Sussex Neuroscience Seminars}, event_place = {Brighton, UK}, state = {published}, author = {Panagiotaropoulos F{theofanis}{Department Physiology of Cognitive Processes}} } @Conference{ Munk2013_4, title = {Neur(on)al Coding in Prefrontal Cortex during Visual Memory}, year = {2013}, month = {1}, day = {18}, abstract = {As natural environments constantly change, the storage of behaviorally relevant information in short-term memory requires dynamical neuronal representations. Although such representations need to be flexible, they also need to code reliably and specifically. This appears incompatible with the broad selectivity profiles of many cortical neurons suggesting that accurate representations are based on ensembles rather than single neurons. Ensembles of neurons need to organize in a way that they can effectively encode and maintain information. This requires that the activity of distributed populations of neurons is coordinated in a way that allows for receiving (sensitivity), maintaining (stability) and relaying information (emission of effective spike patterns) upon recall for readout and the generation of behavior. At the neuronal level, almost nothing is known how encoding works except that everybody tends to believe that the synaptic activation of certain pre-assigned units or circuits reflects how e.g. PFC encodes information that needs to be stored. But, what is the role of the activity that is already in place when new sensory information arrives? If populations are responsible for encoding and maintaining information, then mere changes in activity are unlikely to represent the relevant mechanism, because this would require a very intelligent switch in each individual cell to change from transient activation to sustained firing. Then one would be stuck to explain how this switch would be operated in all involved cells simultaneously. If however, as has been postulated for many decades, reverberating activity was responsible for (at least) stabilizing the trace and maybe also for further maintenance, then a more dynamic scheme would be feasible in which the selection of contributing neurons could depend on their ability to synchronize their firing with the respective reverberating activities. Whether reverberations are always or sometimes expressed as oscillations at a local scale is not clear, but we have evidence that oscillations at various frequencies accompany all phases of working memory being correlated, both, with behavioral performance and memory content. We also have evidence for ensembles of neurons, which are distributed over columns of PFC being several millimeters apart, to become coactivated in a stimulus-selective or even -specific way during encoding, stabilization and retrieval. This coactivation has been investigated on a time scale of hundreds of milliseconds, aiming at a measure based on firing rate, while temporally more precise patterns of spike firing have been shown to coexist in the same data sets.}, web_url = {http://www.bccn-heidelberg-mannheim.de/pub/seminarspub_basic_for.php?a=0300000700000000000000000000000300000000100005101000400}, event_name = {Bernstein Center for Computational Neuroscience}, event_place = {Heidelberg, Germany}, state = {published}, author = {Munk M{munk}{Department Physiology of Cognitive Processes}} } @Article{ TuressonLH2012, title = {Category-selective phase coding in the superior temporal sulcus}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, year = {2012}, month = {11}, volume = {109}, number = {47}, pages = {19438-19443}, abstract = {Object perception and categorization can occur so rapidly that behavioral responses precede or co-occur with the firing rate changes in the object-selective neocortex. Phase coding could, in principle, support rapid representation of object categories, whereby the first spikes evoked by a stimulus would appear at different phases of an oscillation, depending on the object category. To determine whether object-selective regions of the neo-cortex demonstrate phase coding, we presented images of faces and objects to two monkeys while recording local field potentials (LFP) and single unit activity from object-selective regions in the upper bank superior temporal sulcus. Single units showed preferred phases of firing that depended on stimulus category, emerging with the initiation of spiking responses after stimulus onset. Differences in phase of firing were seen below 20 Hz and in the gamma and high-gamma frequency ranges. For all but the <20-Hz cluster, phase differences remained category-specific even when controlling for stimulus-locked activity, revealing that phase-specific firing is not a simple consequence of category-specific differences in the evoked responses of the LFP. In addition, we tested for firing rate-to-phase conversion. Category-specific differences in firing rates accounted for 30–40% of the explained variance in phase occurring at lower frequencies (<20 Hz) during the initial response, but was limited (<20% of the explained variance) in the 30- to 60-Hz frequency range, suggesting that gamma phase-of-firing effects reflect more than evoked LFP and firing rate responses. The present results are consistent with theoretical models of rapid object processing and extend previous observations of phase coding to include object-selective neocortex.}, web_url = {http://www.pnas.org/content/109/47/19438}, state = {published}, DOI = {10.1073/pnas.1217012109}, author = {Turesson HK{hjalmar}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Hoffman KL{kari}{Department Physiology of Cognitive Processes}} } @Article{ GoenseML2012_2, title = {High-Resolution fMRI Reveals Laminar Differences in Neurovascular Coupling between Positive and Negative BOLD Responses}, journal = {Neuron}, year = {2012}, month = {11}, volume = {76}, number = {3}, pages = {629–639}, abstract = {The six cortical layers have distinct anatomical and physiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, as well as laminar differences in neurovascular coupling.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627312008549}, state = {published}, DOI = {10.1016/j.neuron.2012.09.019}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Merkle H{hellmut}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ LogothetisEMASEBO2012, title = {Hippocampal-cortical interaction during periods of subcortical silence}, journal = {Nature}, year = {2012}, month = {11}, volume = {491}, number = {7425}, pages = {547–553}, abstract = {Hippocampal ripples, episodic high-frequency field-potential oscillations primarily occurring during sleep and calmness, have been described in mice, rats, rabbits, monkeys and humans, and so far they have been associated with retention of previously acquired awake experience. Although hippocampal ripples have been studied in detail using neurophysiological methods, the global effects of ripples on the entire brain remain elusive, primarily owing to a lack of methodologies permitting concurrent hippocampal recordings and whole-brain activity mapping. By combining electrophysiological recordings in hippocampus with ripple-triggered functional magnetic resonance imaging, here we show that most of the cerebral cortex is selectively activated during the ripples, whereas most diencephalic, midbrain and brainstem regions are strongly and consistently inhibited. Analysis of regional temporal response patterns indicates that thalamic activity suppression precedes the hippocampal population burst, which itself is temporally bounded by massive activations of association and primary cortical areas. These findings suggest that during off-line memory consolidation, synergistic thalamocortical activity may be orchestrating a privileged interaction state between hippocampus and cortex by silencing the output of subcortical centres involved in sensory processing or potentially mediating procedural learning. Such a mechanism would cause minimal interference, enabling consolidation of hippocampus-dependent memory.}, web_url = {http://www.nature.com/nature/journal/v491/n7425/full/nature11618.html}, state = {published}, DOI = {10.1038/nature11618}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Augath M{mark}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Besserve M{besserve}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}} } @Article{ KayserIP2012, title = {Analysis of slow (theta) oscillations as a potential temporal reference frame for information coding in sensory cortices}, journal = {PLoS Computational Biology}, year = {2012}, month = {10}, volume = {8}, number = {10}, pages = {1-13}, abstract = {While sensory neurons carry behaviorally relevant information in responses that often extend over hundreds of milliseconds, the key units of neural information likely consist of much shorter and temporally precise spike patterns. The mechanisms and temporal reference frames by which sensory networks partition responses into these shorter units of information remain unknown. One hypothesis holds that slow oscillations provide a network-intrinsic reference to temporally partitioned spike trains without exploiting the millisecond-precise alignment of spikes to sensory stimuli. We tested this hypothesis on neural responses recorded in visual and auditory cortices of macaque monkeys in response to natural stimuli. Comparing different schemes for response partitioning revealed that theta band oscillations provide a temporal reference that permits extracting significantly more information than can be obtained from spike counts, and sometimes almost as much information as obtained by partitioning spike trains using precisely stimulus-locked time bins. We further tested the robustness of these partitioning schemes to temporal uncertainty in the decoding process and to noise in the sensory input. This revealed that partitioning using an oscillatory reference provides greater robustness than partitioning using precisely stimulus-locked time bins. Overall, these results provide a computational proof of concept for the hypothesis that slow rhythmic network activity may serve as internal reference frame for information coding in sensory cortices and they foster the notion that slow oscillations serve as key elements for the computations underlying perception.}, web_url = {http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1002717}, state = {published}, DOI = {10.1371/journal.pcbi.1002717}, EPUB = {e1002717}, author = {Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Ince RAA{rince}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Article{ vanGrootelvv2012, title = {Experimental test of spatial updating models for monkey eye-head gaze shifts}, journal = {PLoS ONE}, year = {2012}, month = {10}, volume = {7}, number = {10}, pages = {1-18}, abstract = {How the brain maintains an accurate and stable representation of visual target locations despite the occurrence of saccadic gaze shifts is a classical problem in oculomotor research. Here we test and dissociate the predictions of different conceptual models for head-unrestrained gaze-localization behavior of macaque monkeys. We adopted the double-step paradigm with rapid eye-head gaze shifts to measure localization accuracy in response to flashed visual stimuli in darkness. We presented the second target flash either before (static), or during (dynamic) the first gaze displacement. In the dynamic case the brief visual flash induced a small retinal streak of up to about 20 deg at an unpredictable moment and retinal location during the eye-head gaze shift, which provides serious challenges for the gaze-control system. However, for both stimulus conditions, monkeys localized the flashed targets with accurate gaze shifts, which rules out several models of visuomotor control. First, these findings exclude the possibility that gaze-shift programming relies on retinal inputs only. Instead, they support the notion that accurate eye-head motor feedback updates the gaze-saccade coordinates. Second, in dynamic trials the visuomotor system cannot rely on the coordinates of the planned first eye-head saccade either, which rules out remapping on the basis of a predictive corollary gaze-displacement signal. Finally, because gaze-related head movements were also goal-directed, requiring continuous access to eye-in-head position, we propose that our results best support a dynamic feedback scheme for spatial updating in which visuomotor control incorporates accurate signals about instantaneous eye- and head positions rather than relative eye- and head displacements.}, web_url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047606}, state = {published}, DOI = {10.1371/journal.pone.0047606}, EPUB = {e47606}, author = {van Grootel TJ{vangrootel}{Department Physiology of Cognitive Processes}; van der Willigen RF; van Opstal AJ} } @Article{ InceMBLP2011, title = {A novel test to determine the significance of neural selectivity to single and multiple potentially correlated stimulus features}, journal = {Journal of Neuroscience Methods}, year = {2012}, month = {9}, volume = {210}, number = {1}, pages = {49–65}, abstract = {Mutual information is a principled non-linear measure of dependence between stochastic variables, which is widely used to study the selectivity of neural responses to external stimuli. Here we define and develop a set of novel statistical independence tests based on mutual information, which quantify the significance of neural selectivity to either single features or to multiple, potentially correlated stimulus features like those often present in naturalistic stimuli. If the values of different features are correlated during stimulus presentation, it is difficult to establish if one feature is genuinely encoded by the response, or if it instead appears to be encoded only as a side effect of its correlation with another genuinely represented feature. Our tests provide a way to disambiguate between these two possibilities. We use realistic simulations of neural responses tuned to one or more correlated stimulus features to investigate how limited sampling bias correction procedures affect the statistical power of such independence tests, and we characterize the regimes in which the distribution of information values under the null hypothesis can be approximated by simple distributions (Chi-square or Gaussian). Finally, we apply these tests to experimental data to determine the significance of tuning of the band limited power (BLP) of the gamma [30–100 Hz] frequency range of the primary visual cortical local field potential to multiple correlated features during presentation of naturalistic movies. We show that gamma BLP carries significant, genuine information about orientation, space contrast and time contrast, despite the strong correlations between these features.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0165027011006893}, state = {published}, DOI = {10.1016/j.jneumeth.2011.11.013}, author = {Ince RAA{rince}{Department Physiology of Cognitive Processes}; Mazzoni A; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Article{ KelirisMHLSE2012, title = {A smart 19F and 1H MRI probe with self-immolative linker as a versatile tool for detection of enzymes}, journal = {Contrast Media & Molecular Imaging}, year = {2012}, month = {9}, volume = {7}, number = {5}, pages = {478–483}, abstract = {Here we report on a dual-modal 19F and 1H MRI paramagnetic probe with a self-immolative linker, Gd–DOMF–Gal. The enzymatic conversion of this probe by β-galactosidase resulted in a simultaneous turning on of the fluorine signal and changed ability of the Gd3+ complex to modulate the 1H MR signal intensity of the surrounding water molecules. A versatile imaging platform for monitoring a variety of enzymes by 19F and 1H MRI using this molecular design is proposed.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cmmi.1470/pdf}, state = {published}, DOI = {10.1002/cmmi.1470}, author = {Keliris A{abrud}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}} } @Article{ GleissK2012, title = {Audio-visual detection benefits in the rat}, journal = {PLoS ONE}, year = {2012}, month = {9}, volume = {7}, number = {9}, pages = {1-8}, abstract = {Human psychophysical studies have described multisensory perceptual benefits such as enhanced detection rates and faster reaction times in great detail. However, the neural circuits and mechanism underlying multisensory integration remain difficult to study in the primate brain. While rodents offer the advantage of a range of experimental methodologies to study the neural basis of multisensory processing, rodent studies are still limited due to the small number of available multisensory protocols. We here demonstrate the feasibility of an audio-visual stimulus detection task for rats, in which the animals detect lateralized uni- and multi-sensory stimuli in a two-response forced choice paradigm. We show that animals reliably learn and perform this task. Reaction times were significantly faster and behavioral performance levels higher in multisensory compared to unisensory conditions. This benefit was strongest for dim visual targets, in agreement with classical patterns of multisensory integration, and was specific to task-informative sounds, while uninformative sounds speeded reaction times with little costs for detection performance. Importantly, multisensory benefits for stimulus detection and reaction times appeared at different levels of task proficiency and training experience, suggesting distinct mechanisms inducing these two multisensory benefits. Our results demonstrate behavioral multisensory enhancement in rats in analogy to behavioral patterns known from other species, such as humans. In addition, our paradigm enriches the set of behavioral tasks on which future studies can rely, for example to combine behavioral measurements with imaging or pharmacological studies in the behaving animal or to study changes of integration properties in disease models.}, web_url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045677}, state = {published}, DOI = {10.1371/journal.pone.0045677}, EPUB = {e45677}, author = {Gleiss S{sgleiss}{Research Group Physiology of Sensory Integration}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ MaierPTK2012, title = {Introduction to research topic – binocular rivalry: a gateway to studying consciousness}, journal = {Frontiers in Human Neuroscience}, year = {2012}, month = {9}, volume = {6}, number = {263}, pages = {1-3}, abstract = {In 1593, Neapolitan polymath Giambattista della Porta publicly lamented that he was unable to improve his impressive productivity (he had published in areas as diverse as cryptography, hydraulics, pharmacology, optics, and classic fiction). Della Porta was trying to read two books simultaneously by placing both volumes side-by-side, and using each eye independently. To his great surprise, his setup allowed him to only read one book at a time. This discovery arguably marks the first written account of binocular rivalry (Wade, 2000) – a perceptual phenomenon that more than 400 years later still both serves to intrigue as well as to illuminate the limits of scientific knowledge. At first glance, binocular rivalry is an oddball. In every day vision, our eyes receive largely matching views of the world. The brain combines the two images into a cohesive scene, and concurrently, perception is stable. However, when showing two very different images (such as two different books) to each eye, the brain resolves the conflict by adopting a “diplomatic” strategy. Rather than mixing the views of the two eyes into an insensible visual percept, observers perceive a dynamically changing series of perceptual snapshots, with one eye’s view dominating for a few seconds before being replaced by its rival from the other eye. With prolonged viewing of a rivalrous stimulus, one inevitably experiences a sequence of subjective perceptual reversals, separated by random time intervals, and this process continues for as long as the sensory conflict is present.}, web_url = {http://www.frontiersin.org/Human_Neuroscience/10.3389/fnhum.2012.00263/full}, state = {published}, DOI = {10.3389/fnhum.2012.00263}, author = {Maier A{amaier}{Department Physiology of Cognitive Processes}; Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Tsuchiya N; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Article{ DhingraVermaMEBML2012, title = {Magnetic-Field-Dependent 1H Relaxivity Behavior of Biotin/Avidin-Based Magnetic Resonance Imaging Probes}, journal = {ChemPlusChem}, year = {2012}, month = {9}, volume = {77}, number = {9}, pages = {758–769}, abstract = {One major challenge in noninvasive mapping of various molecular targets is their inherently low in vivo concentration coupled with the insensitivity of imaging modalities, such as the widely used magnetic resonance imaging (MRI). Development of agents with high sensitivity and specificity is of paramount importance for structural and functional noninvasive imaging. The design, synthesis, and physiochemical characterization of two gadolinium-based contrast agents (CAs) for MRI, the sensitivity of which was optimized by exploiting the well-established biotin–avidin amplification strategies, are reported. The relaxivity of these agents showed a large increase if bound to avidin; specifically, the first compound showed an approximately 1000 % increase in transverse proton relaxivity (r2p), whereas the second compound had an approximately 250 % r2p increase. The increase in r2p was magnetic field independent in the range of 1.5–16.4 T whereas the longitudinal proton relaxivity (r1p) showed strong field dependence. The CAs were further characterized by measuring luminescence lifetimes and emission spectral changes upon addition of avidin to their Eu3+ analogues. The difference in relaxation rate behavior of both complexes was explained on the basis of hydration number modulation and the “global/internal motion concept”. The association constant of these CAs with avidin was found to be in the range of approximately 1015 M−1, which shows that the coupling of biotin to Gd-DO3A did not affect its affinity for binding to avidin (DO3A=1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid).}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/cplu.201200064/pdf}, state = {published}, DOI = {10.1002/cplu.201200064}, author = {Dhingra Verma K{kirti}{Department Physiology of Cognitive Processes}; Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MagriMLP2011, title = {Optimal Band Separation of Extracellular Field Potentials}, journal = {Journal of Neuroscience Methods}, year = {2012}, month = {9}, volume = {210}, number = {1}, pages = {66–78}, abstract = {Local Field Potentials (LFPs) exhibit a broadband spectral structure that is traditionally partitioned into distinct frequency bands which are thought to originate from different types of neural events triggered by different processing pathways. However, the exact frequency boundaries of these processes are not known and, as a result, the frequency bands are often selected based on intuition, previous literature or visual inspection of the data. Here, we address these problems by developing a rigorous method for defining LFP frequency bands and their boundaries. The criterion introduced for determining the boundaries delimiting the bands is to maximize the information about an external correlate carried jointly by all bands in the partition. The method first partitions the LFP frequency range into two bands and then successively increases the number of bands in the partition. We applied the partitioning method to LFPs recorded from primary visual cortex of anaesthetized macaques, and we determined the optimal band partitioning that describes the encoding of naturalistic visual stimuli. The first optimal boundary partitioned the LFP response at 60 Hz into low and high frequencies, which had been previously found to convey independent information about the natural movie correlate. The second optimal boundary divided the high-frequency range at approximately 100 Hz into gamma and high-gamma frequencies, consistent with recent reports that these two bands reflect partly distinct neural processes. A third important boundary was at 25 Hz and it split the LFP range below 50 Hz into a stimulus-informative and a stimulus-independent band.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0165027011006613}, state = {published}, DOI = {10.1016/j.jneumeth.2011.11.005}, author = {Magri C{cmagri}{Department Physiology of Cognitive Processes}; Mazzoni A; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Article{ ErokhinBGCPRRSS2012, title = {Stochastic hybrid 3D matrix: learning and adaptation of electrical properties}, journal = {Journal of Materials Chemistry}, year = {2012}, month = {9}, volume = {22}, number = {43}, pages = {22881-22887}, abstract = {Memristive devices are electronic elements with memory properties. This feature marks them out as possible candidates for mimicking synapse properties. Development of systems capable of performing simple brain operations demands a high level of integration of elements and their 3D organization into networks. Here, we demonstrate the formation and electrical properties of stochastic polymeric matrices. Several features of the network revealed similarities with those of the nervous system. In particular, applying different training protocols, we obtained two kinds of learning comparable to the “baby” and “adult” learning in animals and humans. To mimic “adult” learning, multi-task training was applied simultaneously resulting in the formation of few parallel pathways for a given task, modifiable by successive training. To mimic “baby” learning (imprinting), single task training was applied at one time, resulting in the formation of multiple parallel signal pathways, scarcely influenced by successive training.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2012/jm/c2jm35064e}, state = {published}, DOI = {10.1039/C2JM35064E}, author = {Erokhin V; Berzina T; Gorshkov K; Camorani P; Pucci A; Ricci L; Ruggeri G; Sigala R{sigala}{Department Physiology of Cognitive Processes}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Article{ BerensECMBT2012, title = {A Fast and Simple Population Code for Orientation in Primate V1}, journal = {Journal of Neuroscience}, year = {2012}, month = {8}, volume = {32}, number = {31}, pages = {10618-10626}, abstract = {Orientation tuning has been a classic model for understanding single-neuron computation in the neocortex. However, little is known about how orientation can be read out from the activity of neural populations, in particular in alert animals. Our study is a first step toward that goal. We recorded from up to 20 well isolated single neurons in the primary visual cortex of alert macaques simultaneously and applied a simple, neurally plausible decoder to read out the population code. We focus on two questions: First, what are the time course and the timescale at which orientation can be read out from the population response? Second, how complex does the decoding mechanism in a downstream neuron have to be to reliably discriminate between visual stimuli with different orientations? We show that the neural ensembles in primary visual cortex of awake macaques represent orientation in a way that facilitates a fast and simple readout mechanism: With an average latency of 30–80 ms, the population code can be read out instantaneously with a short integration time of only tens of milliseconds, and neither stimulus contrast nor correlations need to be taken into account to compute the optimal synaptic weight pattern. Our study shows that—similar to the case of single-neuron computation—the representation of orientation in the spike patterns of neural populations can serve as an exemplary case for understanding the computations performed by neural ensembles underlying visual processing during behavior.}, web_url = {http://www.jneurosci.org/content/32/31/10618.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.1335-12.2012}, author = {Berens P; Ecker AS{aecker}{Department Physiology of Cognitive Processes}; Cotton RJ; Ma WJ; Bethge M{mbethge}{Research Group Computational Vision and Neuroscience}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Article{ NgSK2012, title = {A precluding but not ensuring role of entrained low-frequency oscillations for auditory perception}, journal = {Journal of Neuroscience}, year = {2012}, month = {8}, volume = {32}, number = {35}, pages = {12268-12276}, abstract = {Oscillatory activity in sensory cortices reflects changes in local excitation–inhibition balance, and recent work suggests that phase signatures of ongoing oscillations predict the perceptual detection of subsequent stimuli. Low-frequency oscillations are also entrained by dynamic natural scenes, suggesting that the chance of detecting a brief target depends on the relative timing of this to the entrained rhythm. We tested this hypothesis in humans by implementing a cocktail-party-like scenario requiring subjects to detect a target embedded in a cacophony of background sounds. Using EEG to measure auditory cortical oscillations, we find that the chance of target detection systematically depends on both power and phase of theta-band (2–6 Hz) but not alpha-band (8–12 Hz) oscillations before target. Detection rates were higher and responses faster when oscillatory power was low and both detection rate and response speed were modulated by phase. Intriguingly, the phase dependency was stronger for miss than for hit trials, suggesting that phase has a inhibiting but not ensuring role for detection. Entrainment of theta range oscillations prominently occurs during the processing of attended complex stimuli, such as vocalizations and speech. Our results demonstrate that this entrainment to attended sensory environments may have negative effects on the detection of individual tokens within the environment, and they support the notion that specific phase ranges of cortical oscillations act as gatekeepers for perception.}, web_url = {http://www.jneurosci.org/content/32/35/12268.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.1877-12.2012}, author = {Ng BS-W{benedict}; Schroeder T{tschroeder}{Research Group Physiology of Sensory Integration}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ FischerZKSSJLS2012, title = {Detailed functional and structural characterization of a macular lesion in a rhesus macaque}, journal = {Documenta Ophthalmologica}, year = {2012}, month = {8}, volume = {125}, number = {3}, pages = {179-194}, abstract = {Animal models are powerful tools to broaden our understanding in disease mechanisms and to develop future treatment strategies. Here we present detailed structural and functional findings of a rhesus macaque suffering from a naturally occurring bilateral macular dystrophy (BMD), partial optic atrophy and corresponding reduction of central V1 signals in visual fMRI experiments when compared to data in a healthy macaque (CTRL) of similar age. Fluorescence and indocyanine green angiography showed reduced macular vascularization with significantly larger foveal avascular zones (FAZ) in the affected animal (FAZBMD = 8.85 mm2 vs. FAZCTRL = 0.32 mm2). Optical coherence tomography showed bilateral thinning of the macula within the FAZ (total retinal thickness, TRTBMD = 174 ± 9 μm) and partial optic nerve atrophy when compared to control (TRTCTRL = 303 ± 45 μm). Segmentation analysis revealed that inner retinal layers were primarily affected (inner retinal thickness, IRTBMD = 33 ± 9 μm vs. IRTCTRL = 143 ± 45 μm), while the outer retina essentially maintained its thickness (ORTBMD = 141 ± 7 μm vs. ORTCTRL = 160 ± 11 μm). Accordingly, a strong central reduction in the multifocal electroretinography and a specific attenuation of cone-derived signals in Ganzfeld electroretinography was found, whereas rod function remained normal. We provided detailed characterization of a primate macular disorder. This study aims to stimulate awareness and further investigation in primates with macular disorders eventually leading to the identification of a primate animal model and facilitating the preclinical development of therapeutic strategies.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs10633-012-9340-3}, state = {published}, DOI = {10.1007/s10633-012-9340-3}, author = {Fischer MD; Zobor D; Keliris GA{george}{Department Physiology of Cognitive Processes}; Shao Y{yshao}{Department Physiology of Cognitive Processes}; Seeliger MW; Haverkamp S; J\"agle H; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}} } @Article{ Logothetis2012, title = {Intracortical recordings and fMRI: An attempt to study operational modules and networks simultaneously}, journal = {NeuroImage}, year = {2012}, month = {8}, volume = {62}, number = {2}, pages = {962–969}, abstract = {The brain can be envisaged as a complex adaptive system. It is characterized by a very high structural complexity and by massive connectivity, both of which change and evolve in response to experience. Information related to sensors and effectors is processed in both a parallel and a hierarchical fashion; the connectivity between different hierarchical levels is bidirectional, and its effectiveness is continuously controlled by specific associational and neuromodulatory centers. When questions are addressed at the level of a distributed, large-scale whole system such as that underlying perception and cognition, it is not clear what should be considered as an elementary operational unit because the behavior of integral, aggregate systems is always emergent and most often remains unpredicted by the behaviors of single cells. To localize and comprehend the neural mechanisms underlying our perceptual or cognitive capacities, concurrent studies of microcircuits, of local and long-range interconnectivity between small assemblies, and of the synergistic activity of larger neuronal populations are called for. In other words, multimodal methodologies that include invasive neuroscientific methods as well as global neuroimaging techniques are required, such as the various functional aspects of magnetic resonance imaging. These facts were the driving force behind the decision to begin animal-MRI in my lab. The wonderful idea of the editors of NeuroImage to publish a Special Issue commemorating 20 years of functional fMRI provides me with the opportunity of sharing not only our first moments of frustration with the readers, but also our successful results.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191200050X}, state = {published}, DOI = {10.1016/j.neuroimage.2012.01.033}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ BiessmannMLMM2012, title = {Improved decoding of neural activity from fMRI signals using non-separable spatiotemporal deconvolutions}, journal = {NeuroImage}, year = {2012}, month = {7}, volume = {61}, number = {4}, pages = {1031–1042}, abstract = {The goal of most functional Magnetic Resonance Imaging (fMRI) analyses is to investigate neural activity. Many fMRI analysis methods assume that the temporal dynamics of the hemodynamic response function (HRF) to neural activation is separable from its spatial dynamics. Although there is empirical evidence that the HRF is more complex than suggested by space–time separable canonical HRF models, it is difficult to assess how much information about neural activity is lost when assuming space–time separability. In this study we directly test whether spatiotemporal variability in the HRF that is not captured by separable models contains information about neural signals. We predict intracranially measured neural activity from simultaneously recorded fMRI data using separable and non-separable spatiotemporal deconvolutions of voxel time series around the recording electrode. Our results show that abandoning the spatiotemporal separability assumption consistently improves the decoding accuracy of neural signals from fMRI data. We compare our findings with results from optical imaging and fMRI studies and discuss potential implications for classical fMRI analyses without invasive electrophysiological recordings.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811912003965}, state = {published}, DOI = {10.1016/j.neuroimage.2012.04.015}, author = {Biessmann F{fbiessma}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; M\"uller KR{klaus}; Meinecke FC} } @Article{ Bartels2012, title = {Oxytocin and the Social Brain: Beware the Complexity}, journal = {Neuropsychopharmacology}, year = {2012}, month = {7}, volume = {37}, number = {8}, pages = {1795–1796}, abstract = {Love, or in more functional–biological terms, social attachment or bonding, is the evolutionary key to the existence of species like humans: our babies’ survival depends entirely on parental care, which in turn provides the opportunity to transmit a vast amount of knowledge from one generation to the next. It is therefore no surprise that the brain's mechanisms that evolved to ensure parent–child bonding are powerful and under genetic control.}, web_url = {http://www.nature.com/npp/journal/v37/n8/pdf/npp201271a.pdf}, state = {published}, DOI = {10.1038/npp.2012.71}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ ValverdeSalzmannBLS2012, title = {Color Blobs in Cortical Areas V1 and V2 of the New World Monkey Callithrix jacchus, Revealed by Non-Differential Optical Imaging}, journal = {Journal of Neuroscience}, year = {2012}, month = {6}, volume = {32}, number = {23}, pages = {7881-7894}, abstract = {Color vision is reserved to only few mammals, such as Old World monkeys and humans. Most Old World monkeys are trichromats. Among them, macaques were shown to exhibit functional domains of color-selectivity, in areas V1 and V2 of the visual cortex. Such color domains have not yet been shown in New World monkeys. In marmosets a sex-linked dichotomy results in dichromatic and trichromatic genotypes, rendering most male marmosets color-blind. Here we used trichromatic female marmosets to examine the intrinsic signal response in V1 and V2 to chromatic and achromatic stimuli, using optical imaging. To activate the subsystems individually, we used spatially homogeneous isoluminant color opponent (red/green, blue/yellow) and hue versus achromatic flicker (red/gray, green/gray, blue/gray, yellow/gray), as well as achromatic luminance flicker. In contrast to previous optical imaging studies in marmosets, we find clearly segregated color domains, similar to those seen in macaques. Red/green and red/gray flicker were found to be the appropriate stimulus for revealing color domains in single-condition maps. Blue/gray and blue/yellow flicker stimuli resulted in faint patch-patterns. A recently described multimodal vessel mapping approach allowed for an accurate alignment of the functional and anatomical datasets. Color domains were tightly colocalized with cytochrome oxidase blobs in V1 and with thin stripes in V2. Thus, our findings are in accord with 2-Deoxy-d-glucose studies performed in V1 of macaques and studies on color representation in V2. Our results suggest a similar organization of early cortical color processing in trichromats of both Old World and New World monkeys.}, web_url = {http://www.jneurosci.org/content/32/23/7881.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.4832-11.2012}, author = {Valverde Salzmann MF{valverde}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Article{ PanagiotaropoulosDKL2012, title = {Neuronal Discharges and Gamma Oscillations Explicitly Reflect Visual Consciousness in the Lateral Prefrontal Cortex}, journal = {Neuron}, year = {2012}, month = {6}, volume = {74}, number = {5}, pages = {924–935}, abstract = {Neuronal discharges in the primate temporal lobe, but not in the striate and extrastriate cortex, reliably reflect stimulus awareness. However, it is not clear whether visual consciousness should be uniquely localized in the temporal association cortex. Here we used binocular flash suppression to investigate whether visual awareness is also explicitly reflected in feature-selective neural activity of the macaque lateral prefrontal cortex (LPFC), a cortical area reciprocally connected to the temporal lobe. We show that neuronal discharges in the majority of single units and recording sites in the LPFC follow the phenomenal perception of a preferred stimulus. Furthermore, visual awareness is reliably reflected in the power modulation of high-frequency (>50 Hz) local field potentials in sites where spiking activity is found to be perceptually modulated. Our results suggest that the activity of neuronal populations in at least two association cortical areas represents the content of conscious visual perception.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627312003807}, state = {published}, DOI = {10.1016/j.neuron.2012.04.013}, author = {Panagiotaropoulos TI{theofanis}{Department Physiology of Cognitive Processes}; Deco G; Kapoor V{vishal}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ SultanAHMORT2017, title = {Unravelling cerebellar pathways with high temporal precision targeting motor and extensive sensory and parietal networks}, journal = {Nature Communications}, year = {2012}, month = {6}, volume = {3}, number = {924}, pages = {1-10}, abstract = {Increasing evidence has implicated the cerebellum in providing forward models of motor plants predicting the sensory consequences of actions. Assuming that cerebellar input to the cerebral cortex contributes to the cerebro-cortical processing by adding forward model signals, we would expect to find projections emphasising motor and sensory cortical areas. However, this expectation is only partially met by studies of cerebello–cerebral connections. Here we show that by electrically stimulating the cerebellar output and imaging responses with functional magnetic resonance imaging, evoked blood oxygen level-dependant activity is observed not only in the classical cerebellar projection target, the primary motor cortex, but also in a number of additional areas in insular, parietal and occipital cortex, including sensory cortical representations. Further probing of the responses reveals a projection system that has been optimized to mediate fast and temporarily precise information. In conclusion, both the topography of the stimulation effects and its emphasis on temporal precision are in full accordance with the concept of cerebellar forward model information modulating cerebro-cortical processing.}, web_url = {http://www.nature.com/articles/ncomms1912.pdf}, state = {published}, DOI = {10.1038/ncomms1912}, author = {Sultan F; Augath M{mark}{Department Physiology of Cognitive Processes}; Hamodeh S; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Thier P} } @Article{ vonPfostlLZGZSLR2012, title = {Effects of lactate on the early visual cortex of non-human primates, investigated by pharmaco-MRI and neurochemical analysis}, journal = {NeuroImage}, year = {2012}, month = {5}, volume = {61}, number = {1}, pages = {98–105}, abstract = {In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811912002698}, state = {published}, DOI = {10.1016/j.neuroimage.2012.02.082}, author = {von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Li J{juan}{Department Physiology of Cognitive Processes}; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}; Zhang X{xiaozhe}{Department Physiology of Cognitive Processes}; Serr N{nserr}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}} } @Article{ EvrardFL2012_2, title = {Von economo neurons in the anterior insula of the macaque monkey}, journal = {Neuron}, year = {2012}, month = {5}, volume = {74}, number = {3}, pages = {482–489}, abstract = {The anterior insular cortex (AIC) and its unique spindle-shaped von Economo neuron (VEN) emerged within the last decade as having a potentially major role in self-awareness and social cognition in humans. Invasive examination of the VEN has been precluded so far by the assumption that this neuron occurs among primates exclusively in humans and great apes. Here, we demonstrate the presence of the VEN in the agranular anterior insula of the macaque monkey. The morphology, size, laminar distribution, and proportional distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. This finding sheds new light on the phylogeny of the VEN and AIC. Most importantly, it offers new and much-needed opportunities to investigate the primal connections and physiology of a neuron that could be crucial for human self-awareness, social cognition, and related neuropsychiatric disorders.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627312002267}, state = {published}, DOI = {10.1016/j.neuron.2012.03.003}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Forro T{tforro}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MishraJEL2012, title = {Synthesis and in Vitro Evaluation of a Biotinylated Dextran-Derived Probe for Molecular Imaging}, journal = {ACS Chemical Neuroscience}, year = {2012}, month = {4}, volume = {3}, number = {4}, pages = {268–273}, abstract = {Herein we report the design, synthesis, and in vitro evaluation of a gadolinium-containing biotinylated dextran-derived molecular imaging probe as a prospective neuroanatomical tracer by means of magnetic resonance imaging (MRI). The probe was effectively taken up by cultured differentiated murine neuroblastoma cells and significantly enhanced the contrast in T1- and T2-weighted MR images of labeled cells under physiological conditions. A significant longitudinal relaxation rate enhancement in the presence of avidin was observed allowing the verification of the results in the end of noninvasive longitudinal MRI connectivity studies by post-mortem histology. The in vitro results indicate that the probe has the potential to be used in vivo to identify the organization of global neuronal networks in the brain with MRI.}, web_url = {http://pubs.acs.org/doi/pdf/10.1021/cn200112v}, state = {published}, DOI = {10.1021/cn200112v}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Joshi R{raju}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ FischerLBB2011, title = {Visual Motion Responses in the Posterior Cingulate Sulcus: A Comparison to V5/MT and MST}, journal = {Cerebral Cortex}, year = {2012}, month = {4}, volume = {22}, number = {4}, pages = {865-876}, abstract = {Motion processing regions apart from V5+/MT+ are still relatively poorly understood. Here, we used functional magnetic resonance imaging to perform a detailed functional analysis of the recently described cingulate sulcus visual area (CSv) in the dorsal posterior cingulate cortex. We used distinct types of visual motion stimuli to compare CSv with V5/MT and MST, including a visual pursuit paradigm. Both V5/MT and MST preferred 3D flow over 2D planar motion, responded less yet substantially to random motion, had a strong preference for contralateral versus ipsilateral stimulation, and responded nearly equally to contralateral and to full-field stimuli. In contrast, CSv had a pronounced preference to 2D planar motion over 3D flow, did not respond to random motion, had a weak and nonsignificant lateralization that was significantly smaller than that of MST, and strongly preferred full-field over contralateral stimuli. In addition, CSv had a better capability to integrate eye movements with retinal motion compared with V5/MT and MST. CSv thus differs from V5+/MT+ by its unique preference to full-field, coherent, and planar motion cues. These results place CSv in a good position to process visual cues related to self-induced motion, in particular those associated to eye or lateral head movements.}, web_url = {http://cercor.oxfordjournals.org/content/22/4/865.full.pdf+html}, state = {published}, DOI = {10.1093/cercor/bhr154}, author = {Fischer E{efischer}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; B\"ulthoff HH{hhb}{Department Human Perception, Cognition and Action}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ Scholkopf2012, title = {A Kernel Two-Sample Test}, journal = {Journal of Machine Learning Research}, year = {2012}, month = {3}, volume = {13}, pages = {723−773}, abstract = {We propose a framework for analyzing and comparing distributions, which we use to construct statistical tests to determine if two samples are drawn from different distributions. Our test statistic is the largest difference in expectations over functions in the unit ball of a reproducing kernel Hilbert space (RKHS), and is called the maximum mean discrepancy (MMD). We present two distribution-free tests based on large deviation bounds for the MMD, and a third test based on the asymptotic distribution of this statistic. The MMD can be computed in quadratic time, although efficient linear time approximations are available. Our statistic is an instance of an integral probability metric, and various classical metrics on distributions are obtained when alternative function classes are used in place of an RKHS. We apply our two-sample tests to a variety of problems, including attribute matching for databases using the Hungarian marriage method, where they perform strongly. Excellent performance is also obtained when comparing distributions over graphs, for which these are the first such tests.}, web_url = {http://jmlr.csail.mit.edu/papers/v13/gretton12a.html}, state = {published}, author = {Gretton A{arthur}{Department Empirical Inference}; Borgwardt K{karsten}{Department Empirical Inference}; Rasch M{rasch}{Department Physiology of Cognitive Processes}; Sch\"olkopf B{bs}{Department Empirical Inference}; Smola A{smola}} } @Article{ FischerBLB2012, title = {Human Areas V3A and V6 Compensate for Self-Induced Planar Visual Motion}, journal = {Neuron}, year = {2012}, month = {3}, volume = {73}, number = {6}, pages = {1228-1240}, abstract = {Little is known about mechanisms mediating a stable perception of the world during pursuit eye movements. Here, we used fMRI to determine to what extent human motion-responsive areas integrate planar retinal motion with nonretinal eye movement signals in order to discard self-induced planar retinal motion and to respond to objective (“real”) motion. In contrast to other areas, V3A lacked responses to self-induced planar retinal motion but responded strongly to head-centered motion, even when retinally canceled by pursuit. This indicates a near-complete multimodal integration of visual with nonvisual planar motion signals in V3A. V3A could be mapped selectively and robustly in every single subject on this basis. V6 also reported head-centered planar motion, even when 3D flow was added to it, but was suppressed by retinal planar motion. These findings suggest a dominant contribution of human areas V3A and V6 to head-centered motion perception and to perceptual stability during eye movements.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627312001407}, state = {published}, DOI = {10.1016/j.neuron.2012.01.022}, author = {Fischer E{efischer}{Department Physiology of Cognitive Processes}; B\"ulthoff HH{hhb}{Department Human Perception, Cognition and Action}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Article{ LivZZLR2011, title = {Measuring multiple neurochemicals and related metabolites in blood and brain of the rhesus monkey by using dual microdialysis sampling and capillary hydrophilic interaction chromatography-mass spectrometry}, journal = {Analytical and Bioanalytical Chemistry}, year = {2012}, month = {3}, volume = {402}, number = {8}, pages = {2545-2554}, abstract = {In vivo measurement of multiple functionally related neurochemicals and metabolites (NMs) is highly interesting but remains challenging in the field of basic neuroscience and clinical research. We present here an analytical method for determining five functionally and metabolically related polar substances, including acetylcholine (quaternary ammonium), lactate and pyruvate (organic acids), as well as glutamine and glutamate (amino acids). These NMs are acquired from samples of the brain and the blood of non-human primates in parallel by dual microdialysis, and subsequently analyzed by a direct capillary hydrophilic interaction chromatography (HILIC)–mass spectrometry (MS) based method. To obtain high sensitivity in electrospray ionization (ESI)–MS, lactate and pyruvate were detected in negative ionization mode whereas the other NMs were detected in positive ionization mode during each HILIC-MS run. The method was validated for linearity, the limits of detection and quantification, precision, accuracy, stability and matrix effect. The detection limit of acetylcholine, lactate, pyruvate, glutamine, and glutamate was 150 pM, 3 μM, 2 μM, 5 nM, and 50 nM, respectively. This allowed us to quantitatively and simultaneously measure the concentrations of all the substances from the acquired dialysates. The concentration ratios of both lactate/pyruvate and glutamine/glutamate were found to be higher in the brain compared to blood (p < 0.05). The reliable and simultaneous quantification of these five NMs from brain and blood samples allows us to investigate their relative distribution in the brain and blood, and most importantly paves the way for future non-invasive studies of the functional and metabolic relation of these substances to each other.}, web_url = {http://www.springerlink.com/content/m75q3716w21h6u5g/fulltext.pdf}, state = {published}, DOI = {10.1007/s00216-011-5427-z}, author = {Li J{juan}{Department Physiology of Cognitive Processes}; von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Zhang X{xiaozhe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}} } @Article{ LiebeHLR2012, title = {Theta coupling between V4 and prefrontal cortex predicts visual short-term memory performance}, journal = {Nature Neuroscience}, year = {2012}, month = {3}, volume = {15}, number = {3}, pages = {456-462}, abstract = {Short-term memory requires communication between multiple brain regions that collectively mediate the encoding and maintenance of sensory information. It has been suggested that oscillatory synchronization underlies intercortical communication. Yet, whether and how distant cortical areas cooperate during visual memory remains elusive. We examined neural interactions between visual area V4 and the lateral prefrontal cortex using simultaneous local field potential (LFP) recordings and single-unit activity (SUA) in monkeys performing a visual short-term memory task. During the memory period, we observed enhanced between-area phase synchronization in theta frequencies (3–9 Hz) of LFPs together with elevated phase locking of SUA to theta oscillations across regions. In addition, we found that the strength of intercortical locking was predictive of the animals' behavioral performance. This suggests that theta-band synchronization coordinates action potential communication between V4 and prefrontal cortex that may contribute to the maintenance of visual short-term memories.}, web_url = {http://www.nature.com/neuro/journal/v15/n3/full/nn.3038.html}, state = {published}, DOI = {10.1038/nn.3038}, author = {Liebe S{sliebe}{Department Physiology of Cognitive Processes}; Hoerzer GM; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rainer G{gregor}{Department Physiology of Cognitive Processes}} } @Article{ MamedovEEBL2011, title = {Dual-functional probes towards in vivo studies of brain connectivity and plasticity}, journal = {Chemical Communications}, year = {2012}, month = {2}, volume = {48}, number = {22}, pages = {2755-2757}, abstract = {A Gd3+ based paramagnetic dextran conjugate has been developed, which enables the tracking of neuroanatomical connectivity in the brain by both MR and optical imaging. Cell studies and subsequent in vivo experiments in rodents demonstrate efficient internalisation and transport properties of the new tracer molecule.}, web_url = {http://pubs.rsc.org/en/Content/ArticleLanding/2012/CC/c1cc15991g}, state = {published}, DOI = {10.1039/C1CC15991G}, author = {Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ BrasseletPLK2012, title = {Neurons with stereotyped and rapid responses provide a reference frame for relative temporal coding in primate auditory cortex}, journal = {Journal of Neuroscience}, year = {2012}, month = {2}, volume = {32}, number = {9}, pages = {2998-3008}, abstract = {The precise timing of spikes of cortical neurons relative to stimulus onset carries substantial sensory information. To access this information the sensory systems would need to maintain an internal temporal reference that reflects the precise stimulus timing. Whether and how sensory systems implement such reference frames to decode time-dependent responses, however, remains debated. Studying the encoding of naturalistic sounds in primate (Macaca mulatta) auditory cortex we here investigate potential intrinsic references for decoding temporally precise information. Within the population of recorded neurons, we found one subset responding with stereotyped fast latencies that varied little across trials or stimuli, while the remaining neurons had stimulus-modulated responses with longer and variable latencies. Computational analysis demonstrated that the neurons with stereotyped short latencies constitute an effective temporal reference for relative coding. Using the response onset of a simultaneously recorded stereotyped neuron allowed decoding most of the stimulus information carried by onset latencies and the full spike train of stimulus-modulated neurons. Computational modeling showed that few tens of such stereotyped reference neurons suffice to recover nearly all information that would be available when decoding the same responses relative to the actual stimulus onset. These findings reveal an explicit neural signature of an intrinsic reference for decoding temporal response patterns in the auditory cortex of alert animals. Furthermore, they highlight a role for apparently unselective neurons as an early saliency signal that provides a temporal reference for extracting stimulus information from other neurons.}, web_url = {http://www.jneurosci.org/content/32/9/2998.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.5435-11.2012}, author = {Brasselet R{rbrasselet}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}} } @Article{ EschenkoMPS2011, title = {Noradrenergic Neurons of the Locus Coeruleus Are Phase Locked to Cortical Up-Down States during Sleep}, journal = {Cerebral Cortex}, year = {2012}, month = {2}, volume = {22}, number = {2}, pages = {426-435}, abstract = {Nonrapid eye movement (NREM) sleep is characterized by periodic changes in cortical excitability that are reflected in the electroencephalography (EEG) as high-amplitude slow oscillations, indicative of cortical Up/Down states. These slow oscillations are thought to be involved in NREM sleep-dependent memory consolidation. Although the locus coeruleus (LC) noradrenergic system is known to play a role in off-line memory consolidation (that may occur during NREM sleep), cortico–coerulear interactions during NREM sleep have not yet been studied in detail. Here, we investigated the timing of LC spikes as a function of sleep-associated slow oscillations. Cortical EEG was monitored, along with activity of LC neurons recorded extracellularly, in nonanesthetized naturally sleeping rats. LC spike-triggered averaging of EEG, together with phase-locking analysis, revealed preferential firing of LC neurons along the ascending edge of the EEG slow oscillation, correlating with Down-to-Up state transition. LC neurons were locked best when spikes were shifted forward ∼50 ms in time with respect to the EEG slow oscillation. These results suggest that during NREM sleep, firing of LC neurons may contribute to the rising phase of the EEG slow wave by providing a neuromodulatory input that increases cortical excitability, thereby promoting plasticity within these circuits.}, web_url = {http://cercor.oxfordjournals.org/content/22/2/426.full.pdf+html}, state = {published}, DOI = {10.1093/cercor/bhr121}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Magri C{cmagri}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Sara SJ} } @Article{ TuriGSVMW2011, title = {Quantifying additive evoked contributions to the event-related potential}, journal = {NeuroImage}, year = {2012}, month = {2}, volume = {59}, number = {3}, pages = {2607–2624}, abstract = {Event-related potentials (ERPs) are widely used in basic neuroscience and in clinical diagnostic procedures. In contrast, neurophysiological insights from ERPs have been limited, as several different mechanisms led to ERPs. Apart from stereotypically repeated responses (additive evoked responses), these mechanisms are asymmetric amplitude modulations and phase-resetting of ongoing oscillatory activity. Therefore, a method is needed that differentiates between these mechanisms and moreover quantifies the stability of a response. We propose a constrained subspace independent component analysis that exploits the multivariate information present in the all-to-all relationship of recordings over trials. Our method identifies additive evoked activity and quantifies its stability over trials. We evaluate identification performance for biologically plausible simulation data and two neurophysiological test cases: Local field potential (LFP) recordings from a visuo-motor-integration task in the awake behaving macaque and magnetoencephalography (MEG) recordings of steady-state visual evoked fields (SSVEFs). In the LFPs we find additive evoked response contributions in visual areas V2/4 but not in primary motor cortex A4, although visually triggered ERPs were also observed in area A4. MEG-SSVEFs were mainly created by additive evoked response contributions. Our results demonstrate that the identification of additive evoked response contributions is possible both in invasive and in non-invasive electrophysiological recordings.}, web_url = {http://www.sciencedirect.com/science/article/pii/S105381191101010X}, state = {published}, DOI = {10.1016/j.neuroimage.2011.08.078}, author = {Turi G; Gotthardt S; Singer W; Vuong TA; Munk M{munk}{Department Physiology of Cognitive Processes}; Wibral M} } @Article{ CavusogluBYU2011, title = {Retinotopic maps and hemodynamic delays in the human visual cortex measured using arterial spin labeling}, journal = {NeuroImage}, year = {2012}, month = {2}, volume = {59}, number = {4}, pages = {4044–4054}, abstract = {Cortical representations of the visual field are organized retinotopically, such that nearby neurons have receptive fields at nearby locations in the image. Many studies have used blood oxygenation level-dependent (BOLD) fMRI to non-invasively construct retinotopic maps in humans. The accuracy of the maps depends on the spatial extent of the metabolic and hemodynamic changes induced by the neural activity. Several studies using gradient-echo MRI at 1.5 T and 3 T showed that most of the BOLD signal originates from veins, which might lead to a spatial displacement from the actual site of neuronal activation, thus reducing the specificity of the functional localization. In contrast to BOLD signal, cerebral blood flow (CBF) as measured using arterial spin labeling (ASL) is less or not at all affected by remote draining veins, and therefore spatially and temporally more closely linked to the underlying neural activity. In the present study, we determined retinotopic maps in the human brain using CBF as well as using BOLD signal in order to compare their spatial relationship and the temporal delays of each imaging modality for visual areas V1, V2, V3, hV4 and V3AB. We tested the robustness and reproducibility of the maps across different sessions, calculated the overlap as well as signal delay times across visual areas. While area boundaries were relatively well preserved, we found systematic differences of response latencies between CBF and the BOLD signal between areas. In summary, CBF data obtained using ASL allows reliable retinotopic maps to be constructed; this approach is, therefore, suitable for studying visual areas especially in close proximity to large veins where the BOLD signal is spatially inaccurate.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811911012201}, state = {published}, DOI = {10.1016/j.neuroimage.2011.10.056}, author = {Cavusoglu M{mustafa}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Yesilyurt B{baris}{Department High-Field Magnetic Resonance}; Uludag K{kuludag}{Department High-Field Magnetic Resonance}} } @Article{ CariadVLERBB2012, title = {Species-specific response to human infant faces in the premotor cortex}, journal = {NeuroImage}, year = {2012}, month = {2}, volume = {60}, number = {2}, pages = {884–893}, abstract = {The human infant face represents an essential source of communicative signals on the basis of which adults modulate their interactions with infants. Behavioral studies demonstrate that infants' faces activate sensitive and attuned responses in adults through their gaze, face expression, voice, and gesture. In this study we aimed to identify brain responses that underlie adults' general propensity to respond to infant faces. We recorded fMRI during adults' (non-parents) processing of unfamiliar infant faces compared to carefully matched adult faces and infrahuman mammal infant and adult faces. Human infant faces activated several brain systems including the lateral premotor cortex, supplementary motor area, cingulate cortex, anterior insula and the thalamus. Activation of these brain circuits suggests adults' preparation for communicative behavior with infants as well as attachment and caregiving. The same brain regions preferentially responded to human infant faces when compared to animal infant faces, indicating species-specific adult brain responses. Moreover, results of support vector machine based classification analysis indicated that these regions allowed above chance-level prediction of brain state during perception of human infant faces. The complex of brain responses to human infant faces appears to include biological mechanisms that underlie responsiveness and a caring inclination toward young children which appear to transcend adult's biological relationship to the baby.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811911014704}, state = {published}, DOI = {10.1016/j.neuroimage.2011.12.068}, author = {Caria A; de Falco S; Venuti P; Lee S{slee}{Department Physiology of Cognitive Processes}; Esposito G; Rigo P; Birbaumer N; Bornstein MH} } @Article{ KayserR2012, title = {Suppressive Competition: How Sounds May Cheat Sight}, journal = {Neuron}, year = {2012}, month = {2}, volume = {73}, number = {4}, pages = {627–629}, abstract = {In this issue of Neuron, Iurilli et al. (2012) demonstrate that auditory cortex activation directly engages local GABAergic circuits in V1 to induce sound-driven hyperpolarizations in layer 2/3 and layer 6 pyramidal neurons. Thereby, sounds can directly suppress V1 activity and visual driven behavior.}, web_url = {http://www.sciencedirect.com/science/article/pii/S0896627312001262}, state = {published}, DOI = {10.1016/j.neuron.2012.02.001}, author = {Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Remedios R{ryan}{Research Group Physiology of Sensory Integration}} } @Article{ EschenkoENBML2011, title = {Tracing of noradrenergic projections using manganese-enhanced MRI}, journal = {NeuroImage}, year = {2012}, month = {2}, volume = {59}, number = {4}, pages = {3252–3265}, abstract = {We examined the applicability of manganese-enhanced MRI (MEMRI) to the in vivo tracing of diffuse neuromodulatory projections by means of simultaneous iontophoretic injections of an extremely low, non-toxic concentration of MnCl2 (10 mM) and fluorescent dextran in the locus coeruleus (LC) in the rat. We validated the use of the iontophoretic injection by reproducing previously reported results from pressure injections of MnCl2 in primary somatosensory cortex. Twenty four hours after injection in LC, Mn2 + labeling was detected in major cortical and subcortical targets of LC projections including predominantly ipsilateral primary motor and somatosensory cortices, hippocampus and amygdala. Although the injections were in most cases centered in the core of LC, the pattern of Mn2 + labeling greatly varied across rats. In addition, despite a certain degree of overlap of the labeling obtained with both MEMRI and classical tracing, MEMRI tracing consistently failed to reliably label not only several minor but also major targets of LC, notably the thalamus. The lack of Mn2 + labeling in thalamus possibly reflected a weaker functional connectivity within coeruleothalamic projections that could not be predicted by anatomical tracing. Inversely, a number of brain regions, particularly contralateral motor cortex, that were not or only sparsely labeled with fluorescent dextran were strongly labeled by Mn2 +. This discrepancy could be partly due to both the activity-dependent and transsynaptic nature of Mn2 + transport. The overall labeling produced using MEMRI with iontophoretic injections in LC indicates that the Mn2 + imaging of highly diffuse projections is in principle feasible. However, the labeling pattern of each individual case needs to be carefully interpreted particularly before submitting data for group analysis or in the case of longitudinal examination of discrete changes in functional connectivity under various physiological or behavioral conditions.}, web_url = {http://www.sciencedirect.com/science/article/pii/S1053811911013127}, state = {published}, DOI = {10.1016/j.neuroimage.2011.11.031}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Neves RM{ricardo}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ StoewerGKBLDS2012, title = {An Analysis Approach for High-Field fMRI Data from Awake Non-Human Primates}, journal = {PLoS One}, year = {2012}, month = {1}, volume = {7}, number = {1}, pages = {1-13}, abstract = {fMRI experiments with awake non-human primates (NHP) have seen a surge of applications in recent years. However, the standard fMRI analysis tools designed for human experiments are not optimal for analysis of NHP fMRI data collected at high fields. There are several reasons for this, including the trial-based nature of NHP experiments, with inter-trial periods being of no interest, and segmentation artefacts and distortions that may result from field changes due to movement. We demonstrate an approach that allows us to address some of these issues consisting of the following steps: 1) Trial-based experimental design. 2) Careful control of subject movement. 3) Computer-assisted selection of trials devoid of artefacts and animal motion. 4) Nonrigid between-trial and rigid within-trial realignment of concatenated data from temporally separated trials and sessions. 5) Linear interpolation of inter-trial intervals and high-pass filtering of temporally continuous data 6) Removal of interpolated data and reconcatenation of datasets before statistical analysis with SPM. We have implemented a software toolbox, fMRI Sandbox (http://code.google.com/p/fmri-sandbox/), for semi-automated application of these processing steps that interfaces with SPM software. Here, we demonstrate that our methodology provides significant improvements for the analysis of awake monkey fMRI data acquired at high-field. The method may also be useful for clinical applications with subjects that are unwilling or unable to remain motionless for the whole duration of a functional scan.}, web_url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029697}, state = {published}, DOI = {10.1371/journal.pone.0029697}, EPUB = {e29697}, author = {Stoewer S{stoewer}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Duncan J; Sigala N{natasha}{Department Physiology of Cognitive Processes}} } @Article{ BorchersHLK2012, title = {Direct electrical stimulation of human cortex: the gold standard for mapping brain functions?}, journal = {Nature Reviews Neuroscience}, year = {2012}, month = {1}, volume = {13}, number = {1}, pages = {63-70}, abstract = {Despite its clinical relevance, direct electrical stimulation (DES) of the human brain is surprisingly poorly understood. Although we understand several aspects of electrical stimulation at the cellular level, surface DES evokes a complex summation effect in a large volume of brain tissue, and the effect is difficult to predict as it depends on many local and remote physiological and morphological factors. The complex stimulation effects are reflected in the heterogeneity of behavioural effects that are induced by DES, which range from evocation to inhibition of responses — sometimes even when DES is applied at the same cortical site. Thus, it is a misconception that DES — in contrast to other neuroscience techniques — allows us to draw unequivocal conclusions about the role of stimulated brain areas.}, web_url = {http://www.nature.com/nrn/journal/v13/n1/pdf/nrn3140.pdf}, state = {published}, DOI = {10.1038/nrn3140}, author = {Borchers S{svenja}; Himmelbach M; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Karnath HO} } @Article{ GoenseWL2012, title = {Neural and BOLD responses across the brain}, journal = {Wiley Interdisciplinary Reviews: Cognitive Science}, year = {2012}, month = {1}, volume = {3}, number = {1}, pages = {75–86}, abstract = {Functional Magnetic Resonance Imaging (fMRI) has quickly grown into one of the most important tools for studying brain function, especially in humans. Despite its prevalence, we still do not have a clear picture of what exactly the blood oxygenation level dependent (BOLD) signal represents or how it compares to the signals obtained with other methods (e.g., electrophysiology). We particularly refer to single neuron recordings and electroencephalography when we mention ‘electrophysiological methods’, given that these methods have been used for more than 50 years, and have formed the basis of much of our current understanding of brain function. Brain function involves the coordinated activity of many different areas and many different cell types that can participate in an enormous variety of processes (neural firing, inhibitory and excitatory synaptic activity, neuromodulation, oscillatory activity, etc.). Of these cells and processes, only a subset is sampled with electrophysiological techniques, and their contribution to the recorded signals is not exactly known. Functional imaging signals are driven by the metabolic needs of the active cells, and are most likely also biased toward certain cell types and certain neural processes, although we know even less about which processes actually drive the hemodynamic response. This article discusses the current status on the interpretation of the BOLD signal and how it relates to neural activity measured with electrophysiological techniques.}, web_url = {http://onlinelibrary.wiley.com/doi/10.1002/wcs.153/pdf}, state = {published}, DOI = {10.1002/wcs.153}, author = {Goense J{jozien}{Department Physiology of Cognitive Processes}; Whittingstall K{kevin}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Article{ MishraGEP2011, title = {Responsive imaging probes for metabotropic glutamate receptors}, journal = {Chemical Science}, year = {2012}, month = {1}, volume = {3}, number = {1}, pages = {131-135}, abstract = {The design, synthesis and evaluation of eight contrast agents for metabotropic glutamate receptors is reported. Each of the contrast agents contains a selective mGluR5 binding moiety linked to a ‘DOTA’-derived gadolinium complex. The potential of these systems was evaluated in vitro for application as responsive MR imaging probes. The targeting moieties mGluR5 antagonists based on aromatic alkyne and dipyridyl/heterobiaryl amide derivatives integrated in a modular fashion, involving linkage to the macrocyclic DOTA ligand to allow specific binding to the mGluR5 receptors. Signal intensity enhancements of up to 27% were observed by MRI in primary astrocyte suspensions and the reversibility of probe binding to the receptor sites, induced by added glutamate, was demonstrated using optical emission and the antagonistic activity of complexes was defined by calcium binding assays.}, web_url = {http://pubs.rsc.org/en/content/articlepdf/2011/sc/c1sc00418b}, state = {published}, DOI = {10.1039/C1SC00418B}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Parker D} } @Article{ MagriSMPL2011, title = {The Amplitude and Timing of the BOLD Signal Reflects the Relationship between Local Field Potential Power at Different Frequencies}, journal = {Journal of Neuroscience}, year = {2012}, month = {1}, volume = {32}, number = {4}, pages = {1395-1407}, abstract = {There is growing evidence that several components of the mass neural activity contributing to the local field potential (LFP) can be partly separated by decomposing the LFP into nonoverlapping frequency bands. Although the blood oxygen level-dependent (BOLD) signal has been found to correlate preferentially with specific frequency bands of the LFP, it is still unclear whether the BOLD signal relates to the activity expressed by each LFP band independently of the others or if, instead, it also reflects specific relationships among different bands. We investigated these issues by recording, simultaneously and with high spatiotemporal resolution, BOLD signal and LFP during spontaneous activity in early visual cortices of anesthetized monkeys (Macaca mulatta). We used information theory to characterize the statistical dependency between BOLD and LFP. We found that the alpha (8–12 Hz), beta (18–30 Hz), and gamma (40–100 Hz) LFP bands were informative about the BOLD signal. In agreement with previous studies, gamma was the most informative band. Both increases and decreases in BOLD signal reliably followed increases and decreases in gamma power. However, both alpha and beta power signals carried information about BOLD that was largely complementary to that carried by gamma power. In particular, the relationship between alpha and gamma power was reflected in the amplitude of the BOLD signal, while the relationship between beta and gamma bands was reflected in the latency of BOLD with respect to significant changes in gamma power. These results lay the basis for identifying contributions of different neural pathways to cortical processing using fMRI.}, web_url = {http://www.jneurosci.org/content/32/4/1395.full.pdf+html}, state = {published}, DOI = {10.1523/​JNEUROSCI.3985-11.2012}, author = {Magri C{cmagri}{Department Physiology of Cognitive Processes}; Schridde U{schridde}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Inproceedings{ Logothetis2012_4, title = {What We Can and What We Can’t Do with fMRI}, year = {2012}, month = {10}, day = {12}, pages = {7-14}, abstract = {Functional activation of the brain can be detected with magnetic resonance imaging (MRI) by directly measuring tissue perfusion, blood-volume changes, or changes in the concentration of oxygen. The latter blood oxygenation level–dependent (BOLD) contrast mechanism (Logothetis, 2003; Logothetis and Wandell, 2004; Logothetis, 2008) is currently the mainstay of human neuroimaging. The interpretation of fMRI signals in brain research, and by extension, the utility of fMRI, critically depends on factors such as signal specificity and spatial and temporal resolution. Signal specificity ensures that the generated maps reflect actual neural changes, whereas spatial and temporal resolution determine our ability to discern the elementary units of the activated networks and the time course of various neural events.}, web_url = {https://www.sfn.org/Careers-and-Training/Career-Tools-and-Resources/Short-Courses/2012-Short-Course-II}, event_name = {Society for Neuroscience: 2012 Short Course II MRI and Advanced Imaging in Animals and Humans}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Inproceedings{ BiessmannMLMM2012_2, title = {Non-separable Spatiotemporal Brain Hemodynamics Contain Neural Information}, year = {2012}, pages = {140-147}, abstract = {The goal of many functional Magnetic Resonance Imaging (fMRI) studies is to infer neural activity from hemodynamic signals. Classical fMRI analysis approaches assume a canonical hemodynamic response function (HRF), which is identical in every voxel. Canonical HRFs imply space-time separability. Many studies explored the relevance of non-separable HRFs. These studies were focusing on the relationship between stimuli or electroencephalographic data and fMRI data. It is not clear from these studies whether non-separable spatiotemporal dynamics of fMRI signals contain neural information. This study provides direct empirical evidence that non-separable spatiotemporal deconvolutions of multivariate fMRI time series predict intracortical neural signals better than standard canonical HRF models. Our results demonstrate that there is more neural information in fMRI signals than detected by most analysis methods.}, web_url = {http://link.springer.com/content/pdf/10.1007%2F978-3-642-34713-9_18.pdf}, editor = {Langs, G. , I. Rish, M. Grosse-Wentrup, B. Murphy}, publisher = {Springer}, address = {Berlin, Germany}, series = {Lecture Notes in Computer Science ; 7263}, booktitle = {Machine Learning and Interpretation in Neuroimaging}, event_name = {NIPS Workshop on Machine Learning and Interpretation in Neuroimaging (MLINI 2011)}, event_place = {Sierra Nevada, Spain}, state = {published}, ISBN = {978-3-642-34712-2}, DOI = {10.1007/978-3-642-34713-9_18}, author = {Biessmann F{fbiessma}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; M\"uller K-R{klaus}{Department Empirical Inference}; Meinecke FC} } @Inbook{ SitaramLB2012, title = {BCIs That Use Brain Metabolic Signals}, year = {2012}, month = {5}, pages = {301-314}, abstract = {Most brain-computer interfaces (BCIs) currently under development use the brain's electrical signals. Nevertheless, nonelectrical metabolic signals also have potential for use in BCI development. Two methods currently available for measuring brain metabolic activity that are of greatest immediate interest for BCI development are: functional near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI). fNIRS has the advantages of being noninvasive and inexpensive. fMRI has the advantages of being noninvasive and providing very high spatial resolution. This chapter focuses on BCIs based on fNIRS and fMRI methods. It reviews the fundamental principles underlying their use, the factors important in their use for BCIs, the kinds of BCI applications that are most promising, and possible future directions and challenges.}, web_url = {http://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780195388855.001.0001/acprof-9780195388855-chapter-018}, editor = {Wolpaw, J. , E. Winter Wolpaw}, publisher = {Oxford University Press}, address = {Oxford, UK}, booktitle = {Brain–Computer Interfaces: Principles and Practice}, state = {published}, ISBN = {978-019993268-9}, DOI = {10.1093/acprof:oso/9780195388855.003.0018}, author = {Sitaram R{rsitaram}{Department Physiology of Cognitive Processes}{Department Physiology of Cognitive Processes}; Lee S{slee}{Department Physiology of Cognitive Processes}; Birbaumer N} } @Inbook{ PanzeriI2012, title = {Information-Theoretic Approaches to Pattern Analysis}, year = {2012}, month = {1}, pages = {565-598}, web_url = {http://mitpress.mit.edu/catalog/item/default.asp?ttype=2&tid=12661}, editor = {Kriegskorte, N. , G. Kreiman}, publisher = {MIT Press}, address = {Camridge, MA, USA}, booktitle = {Visual population codes: toward a common multivariate framework for cell recording and functional imaging}, state = {published}, ISBN = {978-0-262-01624-7}, author = {Panzeri S{stefano}; Ince RAA} } @Inbook{ MishraDMSEBCL2011, title = {Biocytin-based contrast agents for molecular imaging: an approach to developing new in vivo neuroanatomical tracers for MRI}, year = {2012}, volume = {1}, pages = {181-204}, abstract = {One of the most striking characteristic of the brain is its profuse neuronal connectivity. Not surprisingly, the function of the nervous system critically depends on the spatiotemporal pattern of intercommunication between different regions of the brain. Both macro- and microscopic aspects of the wiring diagrams of brain circuits are relevant and need to be understood in order to cope with the complexity of the brain function. In this way, for instance, the long-range connections that carry the functional specification of cortical territories need to be studied together with the detailed microcircuits inside a cortical column. Moreover, the temporal dimension of these wiring diagrams must be investigated since neuronal networks are dynamic structures exhibiting context-dependent changes in synaptic weights (Canals et al., 2009) and numbers (Chklovskii et al., 2004). Investigations over the last decades strongly suggest that stimulus or task related neural activity is distributed over large parts of the brain, covering different cortical and sub-cortical areas. For a detailed understanding of brain function, it is of prime importance to understand the organization of the neuronal connections. To chart the anatomical connections between the various components of brain networks, the neuronal tract tracing technique has been proved to be very useful. Thus, experimental tools that allow the exploration of brain circuits at diverse organizational levels are mandatory for the understanding of brain intercommunication and information processing.}, web_url = {http://www.intechopen.com/articles/show/title/biocytin-based-contrast-agents-for-molecular-imaging-an-approach-to-developing-new-in-vivo-neuroanat}, editor = {Bright, P.}, publisher = {InTech}, address = {Rijeka, Croatia}, booktitle = {Neuroimaging - Methods}, state = {published}, ISBN = {978-953-51-0097-3}, DOI = {10.5772/23806}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Mishra R{ritu}{Department High-Field Magnetic Resonance}; Canals S{canals}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Engelmann J{joern}{Department High-Field Magnetic Resonance}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}; Dhingra K{kirti}{Department Physiology of Cognitive Processes}} } @Inbook{ BartelsGL2011, title = {Functional Magnetic Resonance Imaging}, year = {2012}, pages = {410-469}, abstract = {Functional magnetic resonance imaging (fMRI) allows the non-invasive measurement of neural activity nearly everywhere in the brain. The structural predecessor, MRI, was invented in the early 1970s (Lauterbur, 1973) and has been used clinically since the mid-1980s to provide high-resolution structural images of body parts, including rapid successions of images for example of the beating heart. However, it was the advent of blood oxygenation level dependent (BOLD) functional imaging developed first by Ogawa et al. (1990) that made the method crucial especially for the human neurosciences, leading to a vast expansion of both the method of fMRI as well as the field of human neurosciences. fMRI is now a mainstay of neuroscience research and by far the most widespread method for investigations of neural function in the human brain as it is entirely harmless, relatively easy to use, and the data are relatively straightforward to analyze. It is therefore no surprise that fMRI has provided a wealth of information about the functional organization of the human brain. While many publications initially confirmed knowledge derived from invasive animal experiments or from clinical studies, it is now frequently fMRI that opens up a new field of investigation that is then later followed up by invasive methods. It is important to note that fMRI does not measure electrical or neurochemical activity directly. Physically, it relies on decay time-constants of water protons, which are affected by brain tissue and the concentration of deoxyhemoglobin.}, web_url = {http://ebooks.cambridge.org/chapter.jsf?bid=CBO9780511979958&cid=CBO9780511979958A083&tabName=Chapter}, editor = {Brette, R. , A. Destexhe}, publisher = {Cambridge University Press}, address = {Cambridge, UK}, booktitle = {Handbook for Neural Activity Measurement}, state = {published}, ISBN = {978-0-521-51622-8}, DOI = {10.1017/CBO9780511979958.011}, author = {Bartels A{abartels}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Inbook{ 7051, title = {Local Field Potentials, BOLD, and Spiking Activity: Relationsships and Physiological Mechanisms}, year = {2012}, pages = {599-624}, abstract = {Extracellular voltage fluctuations (local field potentials, LFPs) reflecting neural mass action are ubiquitous across species and brain regions. Numerous studies have characterized the properties of LFP signals in the cortex to study sensory and motor computations as well as cognitive processes like attention, perception and memory. In addition, its extracranial counterpart – the electroencephalogram – is widely used in clinical applications. However, the link between LFP signals and the underlying activity of local populations of neurons is still largely elusive. For the LFP to aid our understanding of cortical computation, however, we need to know as precisely as possible what aspects of neural mass action it reflects. In this chapter, we examine recent advances and results regarding the origin, the feature selectivity and the spatial resolution of the local field potential and discuss its relationship to local spiking activity as well as the BOLD signal used in fMRI. We place particular focus on the gamma-band of the local field potential since it has long been implicated to play an important role in sensory processing. We conclude that in contrast to spikes, the local field potential does not measure the output of the computation performed by a cortical circuit, but are rather indicative of the synaptic and dendritic processes, as well as the dynamics of cortical computation.}, web_url = {https://mitpress.mit.edu/books/visual-population-codes}, web_url2 = {http://precedings.nature.com/documents/5216/version/1}, editor = {Kriegeskorte, N. , G. Kreiman}, publisher = {MIT Press}, address = {Cambridge, MA, USA}, booktitle = {Visual population codes: toward a common multivariate framework for cell recording and functional imaging}, state = {published}, ISBN = {978-0-26201-624-7}, author = {Berens P{berens}{Research Group Computational Vision and Neuroscience}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Tolias AS{atolias}{Department Physiology of Cognitive Processes}} } @Inbook{ 6030, title = {Multisensory Influences on Auditory Processing: Perspectives from fMRI and Electrophysiology}, year = {2012}, pages = {99-114}, abstract = {In this review, we discuss some of the results of early multisensory influences on auditory processing, and provide evidence that sensory integration occurs distributed and across several processing stages. In particular, we discuss some of the methodological aspects relevant for studies seeking to localize and characterize multisensory influences, and emphasize some of the recent results pertaining to speech and voice integration.}, web_url = {http://www.crcnetbase.com/doi/abs/10.1201/b11092-9}, editor = {Murray, M. M. , M. T. Wallace}, publisher = {CRC Press}, address = {Boca Raton, FL, USA}, series = {Frontiers in Neuroscience}, booktitle = {The neural bases of multisensory processes}, state = {published}, ISBN = {978-1-439-81217-4}, DOI = {10.1201/b11092-9}, author = {Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Petkov C{chrisp}{Department Physiology of Cognitive Processes}; Remedios R{ryan}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ JankowskaMLA2013, title = {A novel approach towards Ca2+-responsive MRI probes}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1234}, abstract = {Calcium, present in high concentrations in the brain, plays an important role in neuronal signalling, e.g. through the transfer of charges between synapses, or triggering the release of neurotransmitters. It has been previously demonstrated that the concentration of Ca2+ changes significantly during neural activity.[1] However, used techniques are highly invasive and can only cover a small area of the brain at any moment with limited tissue penetration. Magnetic Resonance Imaging (MRI) on the other hand is non-invasive and allows the mapping of the whole brain at unlimited depths. To measure neural activity through changes in Ca2+ concentration using MRI, responsive contrast agents have been designed.[2] Recent reports of a system based on 3,2-hydroxypyridinone (3,2-HOPO) have demonstrated its attractive features as a contrast agent enabling this system to supersede current probes.[3] It exhibits high relaxivity values and a thermodynamic stability comparable with commercial agents. Moreover, it also has negligible interactions with interfering endogenous ions, despite the high number of coordinated water molecules. To the best of our knowledge there are currently no responsive probes based on this system. Therefore, we focused on the fusion of a 3,2-HOPO MR probe with a Ca2+ chelator. We show for the first time a facile synthesis to obtain a new HOPO-based MR-reporter without specialized equipment[3] and the introduction of a Ca2+ responsive moiety. We present the performance of this novel Ca2+ responsive probe from in vitro to more biologically realistic conditions. 1. Nicholson, C., et al., Calcium and potassium changes in extracellular micro-environment of cat cerebellar cortex. Journal of Neurophysiology, 1978. 41(4): p. 1026-1039. 2. Que, E.L. and C.J. Chang, Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Jankowska K{karolina}{Department Physiology of Cognitive Processes}; Maier ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Angelovski G{goran}{Department Physiology of Cognitive Processes}} } @Poster{ AngelovskiAM2012, title = {Characterization of a Calcium-responsive MR-Agent in Cellular Model Systems}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1663}, abstract = {Introduction Calcium is an essential metal ion for life. In the brain, essential intracellular signaling processes are known to depend on Ca2+ influx from the extracellular space. Any substantial fluctuation in extracellular Ca2+ concentrations is likely to have important functional effects. Hence, the ability to non-invasively observe these changes in Ca2+ concentrations using MRI would be of paramount importance for biological research. Our recently developed smart contrast agent (SCA) showed remarkable longitudinal relaxivity changes upon interaction with Ca2+ in buffer and biologically relevant solutions, such as a model of an extracellular matrix[1]. Presently, our goal is to study the potential MR-response of our SCA in cellular model systems, as well as to characterize its physiological effects on cells and intracellular Ca2+. Methods We have designed a model system that mimics living tissues in regards to density and partially occupied (extracellular) volume by using monodisperse polystyrene microspheres. Furthermore, growing fibroblast cells (3T3) as 3D culture embedded in an extracellular matrix gel (Matrigel) were used. Microspheres were mixed or cells were perfused with a cell culture medium containing SCA. Next, we manipulated the extracellular Ca2+ concentration and determined T1 with inversion recovery experiments in an NMR spectrometer at physiological temperature. Furthermore, we monitored changes in intracellular Ca2+ and ATP-induced Ca2+ transients upon the addition of SCA to primary glial cells (conventional 2D culture of astrocytes) and checked for concentration dependence in experimental perfusion chambers. For these experiments, we used laser scanning confocal microscopy imaging using Ca2+ sensitive fluorescent probes. Results and conclusions Inversion recovery experiments revealed a change in T1 of a few milliseconds upon the alteration of Ca2+ concentrations that were comparable to changes induced during neural activity. Physiological experiments using confocal fluorescence microscopy showed that SCA reduces intracellular Ca2+ concentration upon its addition and influences ATP-induced Ca2+ transients in astrocytes. However, the response to ATP recovers after waiting for 10 minutes. Moreover, SCA is not toxic at the applied concentrations (up to 1.8 mM) and its presence does not interfere significantly with intracellular Ca2+ signaling. Overall, the 3D cellular model demonstrates that the T1-response of our SCA to extracellular Ca2+ fluctuations would be sufficient to allow the development of an entirely new in vivo fMRI method that is not based on the BOLD signal.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Angelovski G{goran}{Department Physiology of Cognitive Processes}; Andjus P; Milosevic M} } @Poster{ MishraGSEP2012, title = {Development of responsive imaging probes for metabotropic glutamate receptors}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1677}, abstract = {In spite of decades of work by neuroscientists, understanding how our brain functions is still a milestone question. A range of techniques, such as electrical measurements with single or multiple electrodes, pharmacological testing, non-invasive computational methods and BOLD fMRI is being used to address this fundamental issue. None of these techniques provides complete understanding. To achieve a better appreciation of brain function and dysfunction, a multimodal approach is required that can combine the advantages of each technique. We propose the development of a new measurement technique. Our objective is to develop glutamate (Glu) responsive contrast agents (RCAs) to image changes in different parts of the brain upon neural activation. Glutamate is abundantly present in the mammalian central nervous system, and plays a critical role in mediating excitatory signals through both G-proteincoupled metabotropic receptors and ligand-gated ionotropic receptors present on postsynaptic neuronal cells. The metabotropic Glu receptor subtype 5 (mGluR5) is known to be actively involved in transducing excitatory signals via G-protein coupled secondary messengers between neurons through Glu. In this work, we have developed two series of Glu-RCAs containing various specific mGluR5 antagonists (based on aromatic alkyne and dipyridyl/heterobiaryl amide)[1] to exploit their potential application as responsive MR imaging probes. 1) The first set of molecules is derived from GdDOTA where antagonists were integrated into these structures in a modular fashion. 2) The second set of molecules is derived from trans 1,3-N,N-DO2A where 2nd-N of macrocycle was appended with a lumophore to allow visualization using luminescence methods and 4th-N was incorporated with antagonists to target the receptors. The biocompatibility of these Glu-RCAs was evaluated on mGluR5 expressing primary astrocytes. In vitro MR relaxivity measurements showed a significant (~40%) increase in relaxation rate in the presence of high abundance of mGluR5 in cortical primary astrocytes cell suspensions[2]. The reversibility of probe binding to the receptor sites, induced by added Glu, was demonstrated using optical emission, and the antagonistic activity of complexes was defined by calcium binding assays. The lumophore coupled RCAs are being evaluated using in cellulo luminescence measurements assays under appropriate physiological conditions.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Mishra A{anuragrk}{Department Physiology of Cognitive Processes}; Gottschalk S{sgott}{Department High-Field Magnetic Resonance}; Sim N; Engelmann J{joerm}; Parker D} } @Poster{ HagbergMPBM2013, title = {Diffusion of conventional and calcium sensitive MRI contrast agents in the rat cerebral cortex}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1544}, abstract = {Calcium sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an in vivo MRI based method capable of determining diffusion properties of conventional and calcium sensitive agents. Simulations and experiment demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value, and for calcium sensitive contrast agents. Sprague-Dawley rats (N=19, 220-300g) were used as approved by the local authorities in compliance with guidelines EUVD 86/609/EEC. Physiological signs were monitored throughout the experiment and remained within physiological limits. Surgery was performed after anesthesia (2.0%isoflurane, Forene, urethane (1.5 g/kg, i.p.) and xylocain (locally)). A burr hole was made above the primary sensory cortex (S1) and a guiding cannula was implanted and fixed prior to positioning in a stereotaxic holder and insertion of a glass capillary (tip: OD: 21-30μm, ID: 6-10μm) in the center of S1. The glass capillary was connected to an injection pump via 6.5m long fused silica tubes and the rat positioned in the center of a 7T Bruker Biospec 70/30 scanner (BGA-9S, Helmholtz RF volume transmission coil, 2cm single loop receiving surface coil). Biodistribution and diffusion of the contrast agents were imaged continuously before, during and after a 1.1±0.3µl slow bolus infusion, with a rate of 32±9nl/min by a T1-weighted RARE sequence (TE/TR 9/290ms) and by quantitative mapping of T1 times by a Look-Locker inversion recovery sequence with a single-shot EPI read out (11.5/8000ms; TI1=35ms, TIdelay=250ms, total of 18 LL images). Data analysis consisted of estimation of the Gadolinium concentration from the images and non-linear fitting of the diffusion equation (Figure). The D* values observed for conventional and responsive contrast agents[1-3] in vivo by MRI were in agreement with model predictions for extra-cellular diffusion and previous findings using other measurement techniques[4], the only exception being Dextran10k (Table 1). This compound has been used both as an extra-cellular tracer for diffusion measurements, and as a neuroanatomical connectivity tracer. The MRI method described is based on long observation times (up to 20h) and assessed both extra-cellular diffusion and intra-cellular transport across extended brain regions of Dextran10k. The apparent diffusion coefficient determined for the calcium sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady-state, hereby enabling quantitative sensing of the local calcium concentration.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Power A{apower}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Merckle H; Dhingra K{kirti}{Department Physiology of Cognitive Processes}; Kubicek V; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ KelirisMHLSE2012_2, title = {Dual 1H/19F MR imaging approach for detection of enzyme activity}, journal = {Molecular Imaging and Biology}, year = {2012}, month = {11}, volume = {14}, number = {Supplement 2}, pages = {S1235}, abstract = {Numerous processes taking place in living organism demand the action of enzymes. These catalysts serve as indicators of diseases and are used as markers of gene expression. Hence, a development of imaging probes allowing noninvasive in vivo mapping of enzyme activity by means of Magnetic Resonance Imaging (MRI) would provide a powerful means for assaying the efficacy of gene therapies and diseases diagnostics. Several mono-modal enzyme-responsive MRI probes have been reported over the years. Nevertheless, dual-modality imaging has recently attracted much attention as the way to facilitate visualization of enzyme activity in vivo by combining the benefits of different imaging techniques. In this line, we now demonstrate a smart dual-modal 1H/19F MRI probe, Gd-DOMF-Gal, sensing the activity of beta-galactosidase (marker enzyme used for revealing gene expression) as a prototype of a novel class of probes for specific detection of enzymes. In its molecular design we explored the use of a self-immolative linker that was inserted between the imaging reporters (Gd3+-chelate and a fluorine-bearing unit) and an enzyme recognizable moiety. The enzymatic activation of the probe resulted in a decomposition of the self-immolative spacer with release of imaging moieties leading to alternations in 1H/19F MRI signal intensities. Accordingly, as shown in the representative images (Fig.1, left) of phantoms filled with solutions of Gd-DOMF-Gal and samples treated with beta-galactosidase in phosphate buffer (PBS), no 19F MRI signal was detected for intact probe (intramolecular relaxation enhancement of fluorine relaxation times by paramagnetic gadolinium), whereas a 19F MRI signal of increasing intensity was observed after enzymatic conversion [1]. The corresponding proton T1 map (Fig.1, right) acquired during the same imaging session on a 7T scanner (∼25°C) prior to 19F measurements displayed a significantly longer T1 in the samples pre-incubated with beta-galactosidase. The longitudinal relaxivity (r1) of Gd-DOMF-Gal in PBS was found to be 6.7±0.6 mM-1s-1 and 5.1±0.5 mM-1s-1 for the cleaved complex (300 MHz,∼25°C), whereas at 123 MHz the r1 values were found to be 9.6±0.1 mM-1s-11 and 7.0±0.1 mM-11s-1, respectively. To explore the effect of buffer composition on relaxivity we also determined the r1 values at 123 MHz (∼25°C) in HEPES buffer (does not coordinate to gadolinium center) where the relative change in relaxivity Δr1 of 46% between Gd-DOMF-Gal and cleaved complex was higher than Δr1 obtained in PBS buffer (27%) [1]. In order to increase probe sensitivity, we have now introduced structural modifications and synthesized derivatives of Gd-DOMF-Gal with an increased number of fluorine per molecule. Here, we will present the rationale for our molecular design and MR evaluation of the enzymatic conversion of 1H/19F probes under in vitro conditions and in a cellular model. With this approach that explores the use of self-immolative spacers we will also extend in the future the application of the proposed model for the detection of other enzymes.}, web_url = {http://link.springer.com/content/pdf/10.1007%2Fs11307-012-0598-3.pdf}, event_name = {Fifth Annual World Molecular Imaging Congress (WMIC 2012)}, event_place = {Dublin, Ireland}, state = {published}, DOI = {10.1007/s11307-012-0598-3}, author = {Keliris A{abrud}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}; Engelmann J{joern}{Department High-Field Magnetic Resonance}} } @Poster{ AzevedoALK2012_2, title = {Effects of spatial attention on neural processing in rhesus’ V1: a simultaneous electrophysiology and fMRI study}, year = {2012}, month = {11}, pages = {19}, abstract = {Attention is a cognitive function thought to enhance our ability to select, process, and perceive only a behaviorally relevant fraction of the immense sensory input impinging on our receptors (Knudsen, 2007). Early electrophysiological studies in primates demonstrate that attention can modulate substantially the firing rate of single cells in extrastriate visual areas but has no or little impact in the primary visual cortex (Moran & Desimone, 1985). In contrast, attention has been linked to strong bloodoxygenlevel-dependent (BOLD) signal modulations in human subjects (Gandhi et al., 1999). Our goal is to understand how selective visual spatial attention modulates the neuronal activity in primary visual cortex (V1) and how these effects are reflected in the different signals (single unit activity, local field potentials, and BOLD). To this end, we have trained two rhesus macaques to perform an orientation-change detection task in high field fMRI scanners (4.7T, 7T) while we can simultaneously acquire highresolution fMRI maps and electrophysiological signals. Preliminary results suggest that attention modulates the BOLD and electrophysiological signals in distinct ways. We are currently trying to address the layer specificity of the effects by using MRI compatible multicontact probes and implanted RF coils that provide ultra-high resolution maps of the fMRI activations.}, web_url = {http://www.danielabalslev.dk/workshop/Abstract_booklet.pdf}, event_name = {ERNI-HSF Science Meeting: Orienting of Attention: Neural Implementation, Underlying Mechanisms and Clinical Implications}, event_place = {Tübingen, Germany}, state = {published}, author = {Azevedo F{fazevedo}{Department Physiology of Cognitive Processes}; Azevedo L{lazevedo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ AzevedoALK2012, title = {Effects of visual attention on neural processing in Rhesus' V1 by simultaneous electrophysiology and BOLD-fMRI}, year = {2012}, month = {11}, volume = {13}, pages = {36}, abstract = {Attention is a cognitive function thought to enhance our ability to select, process, and perceive only a behaviorally relevant fraction of the immense sensory input impinging on our receptors (Knudsen, 2007). Early electrophysiological studies in primates demonstrate that attention can modulate substantially the firing rate of single cells in extrastriate visual areas but has no or little impact in the primary visual cortex (Moran & Desimone, 1985). In contrast, attention has been linked to strong bloodoxygen-level-dependent (BOLD) signal modulations in human subjects (Gandhi et al., 1999). Our goal is to understand how selective visual spatial attention modulates the neuronal activity in primary visual cortex (V1) and how these effects are reflected in the different signals (single unit activity, local field potentials, and BOLD). To this end, we have trained two rhesus macaques to perform an orientation-change detection task in high field fMRI scanners (4.7T, 7T) while we can simultaneously acquire high-resolution fMRI maps and electrophysiological signals. Preliminary results suggest that attention modulates the BOLD and electrophysiological signals in distinct ways.We are currently trying to address the layer specificity of the effects by using MRI compatible multicontact probes and implanted RF coils that provide ultra-high resolution maps of the fMRI activations.}, web_url = {http://www.neuroschool-tuebingen-nena.de/}, event_name = {13th Conference of the Junior Neuroscientists of Tübingen (NeNA 2012)}, event_place = {Schramberg, Germany}, state = {published}, author = {Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Azevedo LAC{lazevedo}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris G{george}{Department Physiology of Cognitive Processes}} } @Poster{ OrtizSALR2012_2, title = {Functional neuroimaging of sound motion in the macaque dorsal stream}, year = {2012}, month = {11}, pages = {43}, abstract = {The macaque ventral intraparietal area (VIP), located in the fundus of the intraparietal sulcus (IPS), is considered a polymodal association area that responds to visual, tactile, vestibular and auditory stimuli. VIP receives projections from multiple visual areas and from auditory regions in the posterior superior temporal (pST) cortex. In humans, several studies have reported activation of the pST and IPS to sound source motion confirming the existence of a dorsal processing stream for spatial aspects of sound in humans. In order to bridge the gap between single-unit recordings in monkeys and neuroimaging studies in humans, we used high-resolution fMRI in monkeys to further investigate these results. First, we created a virtual acoustic space environment using binaural sound recording techniques with miniature microphones inserted into a macaque head cast. We validated the acoustics of the technique and by measuring saccadic eye movements during playback to sound sources we were able to confirm a behavioral response to different locations. We then performed fMRI to identify cortical areas sensitive to sound motion in azimuth of the left and right hemifields. Preliminary results showed that all moving sounds activated areas MT, MST and the IPS. Contrasting left and right sound-motion conditions against center yielded greater activation in contralateral VIP. These results suggest that interaural information induced by lateralized sounds is processed along a dorsal cortical processing stream comprising VIP in the respective contralateral hemisphere.}, web_url = {http://www.danielabalslev.dk/workshop/Abstract_booklet.pdf}, event_name = {ERNI-HSF Science Meeting: Orienting of Attention: Neural Implementation, Underlying Mechanisms and Clinical Implications}, event_place = {Tübingen, Germany}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Augath M{mark}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Poster{ SchindlerB2012_2, title = {Parietal cortex codes for egocentric space beyond the field of view}, year = {2012}, month = {11}, pages = {50}, abstract = {Our subjective experience links covert visual- and egocentric spatial attention seamlessly. However, the latter can extend beyond the visual field, covering all directions relative to our body. In contrast to visual representations, only little is known about unseen egocentric representations in the healthy brain. Parietal cortex appears involved in both, as lesions in it can lead to deficits in visual attention, but also to a disorder of egocentric spatial awareness, known as hemi-spatial neglect. Here, we used a novel virtual reality paradigm to probe our participants’ egocentric surrounding during fMRI recordings. We found that egocentric unseen space was encoded by patterns of voxel activity in parietal cortex. Intriguingly, the brain regions with best decoding performances comprised two areas known to be involved in visual covert attention and reaching as well as a region in inferior parietal cortex that coincided with a lesion site associated with spatial neglect.}, web_url = {http://www.danielabalslev.dk/workshop/Abstract_booklet.pdf}, event_name = {ERNI-HSF Science Meeting: Orienting of Attention: Neural Implementation, Underlying Mechanisms and Clinical Implications}, event_place = {Tübingen, Germany}, state = {published}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ ZaretskayaAB2012_2, title = {Parietal cortex mediates perceptual grouping across space}, year = {2012}, month = {11}, pages = {57}, abstract = {One of the key real-world challenges to our visual system is posed by cluttered scenes and occluded objects. To make sense of such scenes, local elements belonging to the same object need to be perceptually grouped, also referred to as spatial binding problem. However, it remains unknown how and where in the brain the local information is grouped together to give rise to a holistic percept. In the current study we addressed this question with a novel bistable motion stimulus developed by Anstis and Kim (2011) that consists of four pairs of dots coherently moving on a circular path. The stimulus causes perception to alternate spontaneously between two interpretations: local dot motion and global motion of two imaginary squares. Using functional magnetic resonance imaging (fMRI), we found that activity in the right parietal cortex correlated specifically with global as compared to local perception periods. To test for a causal role of parietal function in perceptual grouping, we used transcranial magnetic stimulation (TMS) to temporarily disrupt activity in two subregions of the parietal cortex. TMS over one of the subregions - the right anterior intraparietal sulcus (IPS) - specifically affected the global percept durations without affecting the local ones. Our results provide causal evidence that IPS may play a crucial role in perceptual grouping of local elements into a holistic percept, suggesting it to be a common anatomical locus of attention, perceptual grouping and perceptual selection processes.}, web_url = {http://www.danielabalslev.dk/workshop/Abstract_booklet.pdf}, event_name = {ERNI-HSF Science Meeting: Orienting of Attention: Neural Implementation, Underlying Mechanisms and Clinical Implications}, event_place = {Tübingen, Germany}, state = {published}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Anstis S; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ ViswanathZvRL2012, title = {The role of adenosine in the neurovascular coupling of the BOLD signal in early visual cortex of non-human primates}, year = {2012}, month = {11}, volume = {13}, pages = {48}, abstract = {In this study, CPX, an antagonist of adenosine was used to determine the role of adenosine in uncoupling the vascular and neuronal response observed by the BOLD signal after a strong visual stimulation in primary visual cortex (V1). We systemically and locally applied CPX and pharmacologically manipulated the sensory response in the early visual cortex of anaesthetized macaques. Pharmacological magnetic resonance imaging (phMRI) in combination with electrophysiology was used to determine the impact of CPX on V1. Results were obtained from recordings of the BOLD and electrophysiological activity during the injections. Systemic application of CPX resulted in a disruption of the visual modulation in the BOLD signal. Local applications of CPX resulted in a decrease in the power of low LFP and an increase in the power of MUA. In addition it resulted in a decrease in the CV and FF. No significant changes were observed in the BOLD signal after systemic application of phosphate buffered saline, which was used as a control. The results show that we indeed observe dissociation between the vascular and the neuronal activity during adenosinergic modulation. Apparently adenosine reduces functional hyperaemia, which is reflected by the reduction in BOLD signal, while underlying neuronal activity is increased, indicated by an increase in MUA. Further studies have to be conducted using simultaneous sampling of neurochemicals and phMRI to fully elucidate the functional role of adenosine for the vascular and neuronal interplay in V1.}, web_url = {http://www.neuroschool-tuebingen-nena.de/}, event_name = {13th Conference of the Junior Neuroscientists of Tübingen (NeNA 2012)}, event_place = {Schramberg, Germany}, state = {published}, author = {Viswanath S{sviswanath}{Department Physiology of Cognitive Processes}; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ HagbergMPKMLS2012, title = {19F-Lanthanide complexes: T1- and T2-dependent signal gain using gradient echoes}, year = {2012}, month = {10}, day = {29}, web_url = {http://cordis.europa.eu/news/rcn/133149_en.html}, event_name = {ENCITE Symposium "Red hot MRI: In vivo 19F imaging"}, event_place = {Nijmegen, The Netherlands}, state = {published}, author = {Hagberg GE{ghagberg}{Department High-Field Magnetic Resonance}; Mamedov I{ilgar}{Department Physiology of Cognitive Processes}; Placidi M{Matteo}{Department Physiology of Cognitive Processes}; Keliris A{abrud}{Department High-Field Magnetic Resonance}; Merkle H{hellmut}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Scheffler K{scheffler}{Department High-Field Magnetic Resonance}} } @Poster{ MombielaMAMALUGLCLI2012, title = {Brainstem afferents to the hippocampal formation: Comparative immunohistochemical study in the Macaca fascicularis monkey}, year = {2012}, month = {10}, day = {17}, volume = {42}, number = {916.24}, abstract = {The synaptic plasticity of the Hippocampal Formation (HF, which includes the dentate gyrus -DG-, CA3, CA2, CA1, subiculum, pre-parasubiculum and the entorhinal cortex -EC) is strongly influenced by neurotransmiters (presumably Dopaminergic -DA, Ventral Tegmental Area-VTA; Noradrenergic -NA, Locus Coeruleus-LC and Serotoninergic -5-HT, Raphe Nuclei- RN, respectively), (Otmakhova and Lisman, 1996; Katsuki et al., 1997), although the anatomical basis of the chemical modulation of memory in the HF is far from being understood. The neuroanatomical connections between the brainstem and in the HF in the nonhuman primate are still unclear. Previous tracer studies showed retrogradely labeled neurons in the brainstem areas including the VTA, LC and RN, after deposits in the hippocampus (Amaral and Cowan, 1980), as well as in the EC (Insausti et al., 1987). In order to characterize the neurochemical nature of those projections, as well as their topographic and laminar differences, we studied comparatively the distribution on those substances in the HF using immunohistochemical techniques. Immunohistochemistry for each DA (Tyrosine Hydroxylase, TH), NA (Dopamine Beta Hydroxylase -DBH-, and 5-HT) as well as double-immunohistochemical techniques using Alexa 488 (5-HT detection) and Alexa 568 (TH or DBH labeling) disclosed that: • The polymorphic layer of the DG had fibers with the three neurotransmitters, whereas the molecular layer showed only TH and 5-HT immunolabeling, without double-stained processes. • The pyramidal layer of CA3 showed denser 5-HT fiber labeling than TH; CA1 showed only scattered TH and 5-HT fibers, without double labeling profiles. • The subiculum and presubiculum showed fibers immunoreactive for TH, SER and BHD in the molecular layer. No double-labeled TH-5HT or DBH-5HT fibers were seen. • The superficial layers of the rostral EC (I and II) displayed TH- or 5-HT-labelled processes, while the most lateral subdivisions of EC (ELR/ELc) had TH- or DBH-positive fibers; they did not show co-localization. The preferential location of these positive fibers in ELR/ELc is significant, as this portion of the EC receives abundant unimodal and polymodal sensory input and innervates the body and tail of the hippocampus, and therefore it might be an important step for the monoaminergic modulation memory consolidation. Our preliminary anatomical results suggest that the HF function may be modulated independently by monoaminergic neurotransmitters.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=21e8c0d9-7629-46c2-ad26-9754d4be2d40&cKey=a6a0f24f-75d9-4dc4-a640-a7eafd0a4c45&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Mombiela DH; Munoz M; Arroyo-Jimenez M; Mohedano-Moriano A; Artacho-Perula E; Legidos-Garcia E; Ubero M{mubero}{Department Physiology of Cognitive Processes}; Gonzalez-Fuentes J; Lagartos-Donate M; Cebada-Sanchez S; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Insausti R} } @Poster{ TotahM2012, title = {Theta oscillations in the rat medial prefrontal cortex, but not the anterior cingulate or ventral tegmental area, are phase entrained to an attended but not unattended stimulus}, year = {2012}, month = {10}, day = {17}, volume = {42}, number = {913.13}, abstract = {The phase entrainment of local field potential (LFP) oscillations to the timing of a stimulus may improve attentional selection by increasing neuronal excitability at the time of stimulus onset. Studies in humans and monkeys have demonstrated phase entrainment to rhythmically presented stimuli, whereas other studies have demonstrated phase entrainment to the onset of non-rhythmic, but attended stimuli. These studies support the idea that the brain may intrinsically generate phase entrainment in expectation of a task-relevant stimulus in order to improve attentional selection. While this idea has been investigated using humans and monkeys as subjects, it has not been studied in the rat. Therefore, we recorded LFP in the rat from brain regions that have been implicated in expectancy and preparatory attention: the medial prefrontal cortex (mPFC), the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA). We employed a well-characterized rodent preparatory attention task that requires the rat to anticipate a brief visual stimulus, which would appear at 1 of 3 randomly selected locations on each trial. Phase entrainment to the stimulus onset was measured by performing Rayleigh’s Z test on the distribution of phase angles across all trials, for each subject (n=8 rats for PFC and ACC and n=14 rats for VTA). We assessed phase entrainment between 4 - 50 Hz and only found significant entrainment of ~ 5 Hz oscillations. Across subjects, the excitatory LFP troughs of 5 Hz oscillations were locked to the stimulus onset. Furthermore, this entrainment was only observed in the mPFC, not in the ACC or in the VTA. The 5 Hz entrainment in mPFC was not observed when the rat selected the incorrect stimulus location suggesting a critical linkage between phase entrainment and attention task behavior. At the time of stimulus onset, correct and incorrect trials involved similar motor preparation, motor execution, and reward expectation. Therefore, we suggest that low-frequency oscillations may be a cross-species neurophysiological mechanism for attentional selection of expected stimuli. Selection of an expected stimulus may be implemented by enhancing neuronal excitability at the time of stimulus onset.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=a7c3e65d-d195-4860-ade1-97e8648d7912&cKey=522a21af-ad2c-477e-b9ac-b0c0f451ded8&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Totah NK{ntotah}{Department Physiology of Cognitive Processes}; Moghaddam B} } @Poster{ EschenkoBOL2012, title = {BOLD responses evoked by electrical stimulation of Locus Coeruleus in rats under anesthesia}, year = {2012}, month = {10}, day = {16}, volume = {42}, pages = {674.15}, abstract = {We performed a whole-brain fMRI imaging in the rat under urethane anesthesia and studied BOLD responses induced by electrical stimulation of the brain stem noradrenergic nucleus Locus Coeruleus (LC). The rat was implanted with a MRI-compatible custom-made iridium electrode into LC under electrophysiological guidance. A 7T (300 MHz) magnet with a 30-cm horizontal bore (Bruker BioSpec 70/30, Ettlingen, Germany) equipped with a 20cm inner diameter gradient (Bruker BGA-20S Ettlingen, Germany) was used for MRI scanning. The experimental paradigm consisted of 6s baseline sampling, followed by 4s of unilateral LC stimulation and 10s of post-stimulus sampling. Biphasic square pulses (0.05-0.4mA) were delivered to LC at 20-100Hz either continuously for 4s or grouped in 100-500ms trains. These stimulation parameters were efficient in eliciting LC burst firing bilaterally. We also collected BOLD responses induced by peripheral sensory stimulation in the same animal and using the same experimental design (6/4/10s). For visual stimulation we used a luminance flicker presented to both eyes at 16Hz and delivered via fiber optic cables. A mild electrical stimulation (1-5mA) of a forepaw was used as somatosensory stimulation. The fMRI images were collected with spatial resolution of 0.4x0.4x1.0mm and temporal resolution of 1s. BOLD maps were generated by using GLM with standard (HRF-convolved boxcar functions) or neural regressors. We observed a remarkable dichotomy between BOLD responses of cortical and subcortical structures. Specifically, LC stimulation produced positive BOLD responses in the majority of structures belonging to metencephalon, mesencephalon and diencephalon, while negative BOLD responses in the entire neocortex. The robust neuronal activation in thalamic projections of LC was further confirmed by electrophysiological recordings. The cortical inhibition as a result of LC stimulation and associated NE release in cortical targets of LC has been reported in earlier studies. The peripheral sensory stimulation evoked both sensory-specific and non-specific activation/deactivation pattern. Strikingly, the regions of non-specific BOLD responses were common for both sensory modalities and largely overlapped with brain regions that showed responses to LC stimulation. We hypothesize that sensory stimulation activates modality-specific sensory pathways along with LC-NE system; and the LC co-activation produces the observed non-specific BOLD responses.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=56e5a2a5-ea9a-475f-a0a5-90bc1015fd1b&cKey=24dcc369-8c88-4e2b-9178-d2498997deed&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}; Beyerlein M{bayo}{Department Physiology of Cognitive Processes}; Oeltermann A{axel}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ SawinskiGWK2012, title = {Combining ocular videography and 2-photon imaging in freely moving rats}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.29}, abstract = {Accurately recording eye movements is essential to understanding how an animal moves its eyes to establish vision. Rodents are a commonly used as a model for the mammalian visual system, but it is not known how they move their eyes during free movement. We describe here a custom-built ocular videography system light enough to be carried_in combination with a head-mount two-photon microscope (Sawinski et al., 2009)on the head of a freely moving rat. Each camera, complete with mounting arm and infrared (IR) illumination weighs 1.8 g, with outer dimensions of the camera about 2.5×1×1 cm³. Rats comfortably carry 2 cameras, one recording the movements of each eye. The off-the-shelf monochrome camera chips (Aptina) are capable of recording 752×480 pixel images at a maximum frame rate of 60 Hz, and have a wide wavelength range which allows IR illumination. Using a 45° IR reflector that is transparent to visible light allows the cameras to be positioned in a way that minimizes disturbance to the animal’s visual field. The optics consist of a plano-convex lens (focal length f=9 mm) and a visible-light reflector. The lens is mounted in reverse orientation favoring a more planar image plane. The image size is 1.3×0.9 cm² at a working distance of about 1 cm. Inbuilt illumination from an IR LED (850nm) provides consistent image quality during normal exploratory behaviors and jumping. Image quality and resolution is good enough to identify the fine detail of the edge of the iris, which can be used for the detection of ocular torsion (rotation of the eye around the optical axis). Cabling is minimal, as the camera chip can be controlled with a two-wire serial interface and is able to transmit image data over a twisted pair using low-voltage differential signaling (LVDS). To reduce rotational stiffness we have built 2 m long custom cables by twisting enameled 50 µm dia. copper wires. While the wire resistance is less critical for LVDS signaling (even though the impedance is lower than required due to small wire separation) the voltage-level-wise sensitive two-wire serial communication required galvanic separation of the ground connection of the mobile cameras power supply and the external signal decoding board. The signals are then decoded on a custom-built decoding board using a standard LVDS deserializer (12bit) and an additional two-wire serial bus buffer. Signals are then transmitted via a USB interface. In combination with the miniature two-photon microscope, the eye-cameras are deployed in combination with a fully optical head-orientation detection system consisting of 6 IR LEDs mounted on the animal’s head with the miniaturized cameras, and a set of 4 external overhead cameras.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=d1e3e411-5ec5-471e-ba5b-08c8049a76fa&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Sawinski J{jsaw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Wallace DJ{dhw}{Research Group Neural Population Imaging}; Kerr J{jkerr}{Research Group Neural Population Imaging}} } @Poster{ ZaretskayaB2012, title = {Conscious perception of global motion is related to higher-level motion regions}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {672.18}, abstract = {The processing of motion in the primate brain is distributed across multiple regions of the cerebral cortex. The two well-studied visual areas MT and MST have been linked to conscious perception and decision-making related to simple flow stimuli as well as to integration of component plaid motion into a coherently moving pattern. However, it is unclear whether processing and perception of other types of global motion, which require large-scale integration of the local signals, is related to activity of the same areas. In the current study we used fMRI to investigate neural responses to a bi-stable visual motion stimulus. The stimulus consisted of four pairs of dots, each pair coherently moving on a circular path. Perception alternated spontaneously between two states: local dot motion in each of the four quadrants of the visual field or global planar motion of two illusory squares spanning all four visual quadrants [1]. Importantly, these alternations were purely perceptual and involved no stimulus manipulation. We localized visual areas that are known to respond to visual movement (V3a, V6, V7, MT, MST, IPS1-4, and the recently described cingulate sulcus visual area (CSv) [2,3]) individually in each subject. We then investigated responses of these areas to global and local perceptual states of our subjects, while they viewed the bistable stimulus and reported their perception. We found that activity of two of the areas, CSv and IPS4, specifically correlated with global, but not the local perceptual states, while V6 showed a trend in the opposite direction. Interestingly, neither V5/MT, nor MST, nor any other motion-responsive region differentiated between global and local perceptual states. Our results suggest that CSv and IPS4 may be involved in the computation of global motion by large-scale integration of similar motion directions, or by spatial binding between distant loci in the visual field, respectively. Importantly, these results imply a certain 'blindness' of V5/MT and of MST to vivid changes in the conscious perception of large-scale motion stimuli. The perception of global, large-scale motion may therefore be mediated by higher-level motion-processing regions with larger receptive fields, such as by areas CSv and IPS4.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=7764a0cc-8b09-401e-b3fa-a74ce61fb559&cKey=f7d13c88-f677-42d2-971b-2e2341868c80&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Zaretskaya N{nataliya}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ KwonWFB2012, title = {Effects of visual attention on BOLD signal variance}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {673.14}, abstract = {The responses of sensory neurons are noisy, and laboratory studies typically deal with this variability by averaging responses to many stimulus presentations. Recently, it has been observed that the noise signals carry important information about the brain activity, especially by observing the trial-to-trial noise correlation of spiking activity across populations of neurons (Ecker et al. 2010). The trial-to-trial fluctuations in the responses of pairs of neuron are affected by attention, and this has influence on behavior (Cohen et al. 2009, Mitchell et al. 2009). In particular, it was found that attention decreased the noise correlation of neural responses in V4, indicating a more efficient encoding or an increase of information content. Yet the results of these electrophysiology studies left it unclear whether such effects would also occur elsewhere in the cortex, and whether similar effects can be observed in the BOLD signal. In the present study we asked human participants to perform a difficult, attention-demanding task on a complex visual motion display during a prolonged period of time, alternated by equally long periods of visual stimulation without any task. Brain activity was recorded using fMRI. We then analyzed changes in the mean BOLD signal during both conditions, as well as the signal variance within the time-series of each condition. During attention, the BOLD signal variance decreased in several regions, including V5/MT, the temporal parietal junction, and in additional medial-frontal regions. Mean BOLD signal increased in early visual cortex, V5/MT, and in the parieto-frontal attention network. The results demonstrate firstly that the variance of BOLD activity can be altered by visual attention. Secondly they show that there is only a partial overlap between regions whose BOLD signal increases and those whose BOLD signal variance changes. This suggests that changes in variance and in net amplitude may reflect distinct brain processes related to attention.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=13aef0ee-194c-4c83-b6c3-a2f957eb924e&cKey=91cf697d-26cb-4c3f-b36a-de798b0687fb&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Kwon S{soyoung}{Department Physiology of Cognitive Processes}; Watanabe M{watanabe}{Department Physiology of Cognitive Processes}; Fischer E{efischer}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ WallaceSGNRK2012, title = {Eye movements in rats maintain an overhead binocular field at the expense of binocular fusion}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.28}, abstract = {How much does an unrestrained rat move its eyes, and what are the characteristics of these movements? Though many elements of rat vision have been well studied, such as their perception of depth and color, their visual acuity, and the physiology of neurons in the retina, thalamus and visual cortex, this essential element in understanding their visual sense has not been studied to date in unrestrained animals. To study this aspect of rat vision, we recorded eye movements in freely moving rats using a custom-built miniaturized ocular-videography system. A large fraction of the movements were found to be disconjugate and not consistent with the maintenance of a common point of fixation for both eyes, with the line of gaze of the two eyes regularly pointing in substantially different directions. Saccade-like conjugate movements, while forming the majority of movements seen in head-restrained animals, were only a small fraction of the movements observed in unrestrained animals. The asymmetrical movements of the two eyes implies substantial variability in the correspondence of the left and right eye images, and this, together with the lack of a common point of fixation for both eyes, precludes binocular fusion (fusion of left and right eye images into a single visual percept) and stereoscopic binocular vision using the mechanism described for other animals such as cats and primates. Movements of the two eyes were continuous while the animal was moving, but reduced to near stationary when the animal stopped moving its head, reflecting the strong influence of the vestibulo-ocular system in the rat. Horizontal movements of the eyes (movements in the rostral-caudal axis) were strongly related to head pitch, nose up pitch resulting in convergent movements of the two eyes and nose down pitch divergent movements. Vertical movements were strongly related to head roll, with roll to the right resulting in dorsally-directed movement of the right eye and ventrally directed movement of the left. Combined analysis of eye and head movements showed that the eye movements stabilize the animal’s horizon by moving and rotating the eyes in a way that counteracts the perturbations of the orientation of the horizontal axis of the retina caused by movements of the head. In addition, these movements also keep the visual fields of the two eyes strongly overlapping above the animal the vast majority of the time, which may be of substantial evolutionary benefit for a small ground dwelling animal. We suggest that the selective pressure on the rat has led to its visual system being rather more specialized to maximize overhead surveillance at the expense of binocular fusion and stereoscopic vision.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=59f3b1cb-6e31-4c11-9b39-58d10b46cc64&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Wallace DJ{dhw}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Rulla S{rulla}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ UberoMartinezMMAMAHLGLCALI2012, title = {Frontal cortex afferents to the ventral tegmental area in the Macaca fascicularis monkey}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {701.02}, abstract = {The prefrontal cortico-midbrain pathway is thought to play an important role in the regulation of the firing pattern in the ventral tegmental area (VTA) neurons. The understanding of the mechanisms that underlie the regulation of the midbrain dopamine neurons is critical to elucidate the reward system as well as certain pathological conditions such as drug addiction or schizophrenia. Descending prefrontal cortex (PFC) projections to the VTA have been primarily documented in the rodent brain (Maurice et al., 1999; Sesack and Carr, 2002). Furthermore, several anatomical studies based on the use of anterograde tracers in the nonhuman primate, have shown labeled fibers in the VTA that originated in the medial frontal cortex and anterior cingulate cortex (areas 25, 32 and 24), orbitofrontal cortex (areas 11 and 14) and dorsolateral prefrontal cortex (area 9 and 46) (Chiba et al., 2001; Frankle et al., 2006). In order to complete the study of the direct inputs from the PFC to the VTA, the retrograde tracer 3% Fast Blue (FB) was placed in the mesencephalic ventral and dorsal tegmentum in Macaca fascicularis monkey, including the ventral tegmental area. We analyzed three cases injected with FB through a Hamilton syringe in the ventral mesencephalon. A magnetic resonance (MR) examination to localize the stereotaxic coordinates of the injection site was performed in all the animals used in this study. After 2 weeks survival, animals were deeply anesthetized and perfused through the heart with 4% paraformaldehyde. Several additional cases with 3H-aminoacid injections reported previously (Insausti and Amaral, 2008) were also available for analysis under dark field illumination. Our preliminary results showed labeled neurons in the deep layers of principally, the medial frontal and orbitofrontal cortices, including areas 24, 32 and 25, and the orbitofrontal cortex (areas 11, 13, 12 and 14). Comparatively, the dorsolateral prefrontal (area 10, 9, 46 and 6) cortex displayed far fewer labeled neurons. Most of the labeled neurons were situated at the level of the medial part of caudal area 9 and rostral area 6. The anterograde tracer experiments (5 cases with 3H-aminoacid deposits placed in the orbitofrontal cortex, and 3 cases in the medial frontal cortex) confirmed the existence of these projections, thus ruling out the contamination by fibers of passage at the retrograde tracer injection sites. Our data suggest that the influence of medial frontal and orbitofrontal cortices on the dopaminergic ascending projections is much higher than from the dorsolateral prefrontal cortex.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=ff0663fa-12f6-425a-81bf-96bf5e58a914&cKey=47b9fccc-06cf-4307-9eca-0e9745695ec8&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Ubero Martinez M{mubero}{Department Physiology of Cognitive Processes}; Mohedano-Moriano A; Munoz M; Arroyo-Jimenez MM; Marcos P; Artacho-Perula E; Hernandez-Mombiela D{dhernandez}{Department Physiology of Cognitive Processes}; Legidos-Garcia ME; Gonzalez-Fuentes J; Lagartos-Donate MJ; Cebada-Sanchez S; Amaral DG; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Insausti R} } @Poster{ NevesvLE2012, title = {Locus coeruleus noradrenergic system mediates the transient cortical activation evoked by nociceptive stimulation}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {674.16}, abstract = {It is well-established that electrical or pharmacological activation of several nuclei in the reticular formation elicits cortical arousal which is reflected in the EEG as low amplitude and high frequency, or ‘desynchronized’, activity pattern. Among the ascending reticular activating system (ARAS) is the noradrenergic locus coeruleus (LC), which is critically involved in regulation of the sleep-wake cycle. Local activation of LC, as well as stimulation of its afferents, has been reported to induce cortical desynchronization. Interestingly, several nuclei of the ARAS have been shown to have either anatomical connections with LC or their activation showed impact on activity of LC neurons. Therefore, we hypothesized that the LC is a primary hub component in the ARAS. In order to test this hypothesis, we stimulated LC directly, by applying brief (100-200ms) trains of electrical pulses, or indirectly, by electrical stimulation of contralateral limb paw and simultaneously recorded local field potential (LFP) from multiple cortical and subcortical brain regions in urethane anesthetized rats. Both stimulation paradigms evoked transient (1-2 sec) desynchronization of the cortical LFP in all recorded sites, which were characterized by decreased LFP signal power within low frequency (1-8 Hz) and increased in high frequency range (>20 Hz). Foot shock evoked LFP desynchronization was completely abolished in all recording sites including the hid paw representation of the primary somatosensory cortex after bilateral, but not unilateral, selective inhibition of LC neurons by means of local iontophoretic injection of α2-agonist clonidine. Cortical desynchronization to nociceptive stimulation is used as an indicator of efficiency of analgesic treatment. Furthermore, clonidine is known to possess antinociceptive properties when used as additive in anesthetics. Therefore, our results demonstrate that LC is tightly involved in mediating nociception. The well-known antinociceptive property of α2-agonists in the peripheral nervous system is likely due to decreased levels of noradrenaline as result of the activation of presynaptic negative feedback of α2-receptors. The brain regions that mediate LC-dependent cortical desynchronization are yet to be identified.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=56e5a2a5-ea9a-475f-a0a5-90bc1015fd1b&cKey=33130b78-33dd-44aa-a810-e21f9e3e6496&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Neves RM{ricardo}{Department Physiology of Cognitive Processes}; van Keulen S{svankeulen}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ GreenbergWSNRK2012, title = {Optical tracking of head movements, eye movements and ocular torsion incorporated into a miniaturized two-photon microscope}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {569.27}, abstract = {The miniaturized two photon (2P) microscope or ‘fiberscope’ allows imaging during free movement, requiring continuous tracking of the head and eyes to determine visual input. We developed a 2P-compatible, all-optical system for head and eye tracking in rodents. Head tracking with 6 DOF employed infrared LEDs mounted on the microscope and imaged by multiple overhead cameras, while miniaturized camera systems with specialized, custom-built optics and electronics were used to image the eyes (see accompanying poster for details). Calibration procedures based on the Tsai camera model realistically incorporated radial lens distortion, and for custom-built camera systems decentering and thin-prism distortions as well. To detect eye movements, we directly compared 3D geometric models of the eye and pupil to each observed image, minimizing an objective function over eye rotation angles and pupil dilation radii. We found that this approach, which detected the 2D pupil boundary and 3D eye rotation simultaneously in a single step, was more robust than previous methods with an intermediate stage of 2D feature detection, allowing our system to operate effectively at lower contrast. Since the pupil-iris boundary deviated slightly from a perfect circle, with an uneven, crenellated appearance on a fine spatial scale, we also detected ocular torsion by measuring rotation of this rough boundary through 3D space. The eye tracker was self-calibrating in that animals were not required to fixate a presented target, aiding the use of this system in rodents where such training is impossible. Finally, based on the appearance of the eyeball-eyelid boundary we defined anatomically based coordinate axes and baseline pupil positions that were consistent across animals, even when the location and orientation of eye tracking cameras varied. Together, these tracking systems and analysis methods allowed stimulus presentation monitors and other environmental features to be mapped continuously onto each pupil plane, and gaze vectors for each eye to be projected into the animal’s environment.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c2acba4a-3c88-400b-8cf8-710fdf9d735b&cKey=d565ef28-d831-42fa-b72e-f0a377971f43&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Greenberg DS{david}{Research Group Neural Population Imaging}; Wallace D{dhw}{Research Group Neural Population Imaging}; Sawinski J{jsaw}{Research Group Neural Population Imaging}; Notaro G{gnotaro}; Rulla S{rulla}{Research Group Neural Population Imaging}; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ KleinEPBLS2012, title = {Optogenetics in the macaque thalamus}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {610.09}, abstract = {Optogenetics is a potentially powerful tool to manipulate and map specific neural circuits. The few studies that have so far implemented this method in primates focused on the neocortex. Here, we transduced cells in multiple thalamic nuclei of one rhesus macaque with a DNA construct encoding the microbial proton-pump ArchT and the green fluorescent protein (GFP). A constitutively active promoter (CAG) was used to ensure high-level protein expression. Adeno associated virus (AAV2 or AAV5) was used to deliver the gene. Electrophysiological recordings were carried out under anesthesia six to eight weeks after the AAV injections. Continuous illumination with green light (532 nm) through an optic fiber (110 µm diameter) placed in the injected thalamic regions markedly and reliably reduced the local ongoing spiking activity (60% on average) with fast recovery to baseline firing after light offset. Post-mortem stereological microscope examination indicated that ~25% of the neurons in the thalamic injection sites were GFP-labeled and exhibited the typical large soma size and radial dendritic arborization characteristic of thalamocortical projection (TC) neurons. We also found dense GFP-labeled axon terminals in layers 3-4 in the cortical targets of the injected thalamic regions. In the TC soma, the GFP labeling was mostly localized at membrane sites with no accumulation in the cytoplasm and cell nucleus. Based on morphological analysis there was no obvious GFP labeling in local interneurons or in the glia. However, besides the apparently healthy TC neurons, we also observed a small percentage (~5%) of round GFP-labeled formations that had roughly the same diameter as the TC dendrite arborization (~85 µm) but no recognizable neuropil or perikaryal morphology. These formations could be the remains of cells that degenerated after overexpressing the construct. These results show that AAV vectors can be used in the monkey thalamus for intra-neuronal delivery of opsin-encoding DNA sequences and reliable manipulation of neuronal activity. While further characterization of the extent and specificity of gene expression is necessary, intrathalamic injections of AAV vectors could provide the much-needed tool to examine separately and in great physiological and anatomical detail the intricately mingled components of the primate thalamocortical circuitry.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=d1660f1a-fad3-4ea9-9013-b825af0501e8&cKey=b7d911d7-bd0e-429b-8bba-af65c26a7388&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Power AT{apower}{Department Physiology of Cognitive Processes}; Boyden ES; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Schmid M{mschmid}} } @Poster{ PawlakGSGK2012, title = {Spike-timing dependent plasticity changes responses of cortical neurons from sub- to supra-threshold in vivo}, year = {2012}, month = {10}, day = {16}, volume = {42}, number = {572.01}, abstract = {A broad range of visual stimuli generate synaptic input to visual cortex neurons, whereas only a small selection of stimuli generates action potential output from the neuron, that informs downstream targets of the sensory event - but whether plasticity rules can predictably change the spiking response of a neuron by changing a subthreshold response into a suprathreshold response, although proposed, is unclear. Here, we show that a brief spike-timing dependent plasticity (STDP) protocol consisting of close timing of postsynaptic action potentials (APs) and presynaptic inputs derived from visual stimulation can convert subthreshold responses into suprathreshold responses and restructure the neuron's suprathreshold receptive field. This reorganization of spiking responses was paralleled by a change in the time course of the subthreshold voltages and was abolished when muscarinic acetylcholine receptors were blocked. Computational simulations, based on in vitro STDP data, could reproduce the subthreshold membrane potential changes reported here, only when temporal jitter, based on in vivo data, was included during pairing at the presynaptic input stage. Together this shows that timing based plasticity rules, using 10’s postsynaptic spikes, has a functional impact on the spiking response patterns of sensory neurons in vivo by changing suprathreshold tuning properties of the visual cortex neurons.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=080529e4-b28c-45c0-9c78-317a4cb68dcb&cKey=3d077755-c40b-4ec1-b4e7-b44858c81c44&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Pawlak V{vpawlak}{Research Group Neural Population Imaging}; Greenberg DS{david}{Research Group Neural Population Imaging}; Sprekeler H; Gerstner W; Kerr JND{jkerr}{Research Group Neural Population Imaging}} } @Poster{ BesserveBML2012, title = {Centrality of the Mammalian Functional Brain Network}, year = {2012}, month = {10}, day = {15}, volume = {42}, number = {507.20}, abstract = {Brain networks are characterized by strong recurrence, and widespread connectivity. As a consequence it is inherently difficult to tell apart local processing and interactions between structures. This is a major obstacle to the identification of a modular organization of the brain. However, complex network analysis enables to attack the problem from a different angle. Specifically, such analysis may consider directly the whole brain as a network and then characterize its topology. In this work, we use this framework to identify the polysynaptic topology of functional brain networks with a high spatial resolution. We first estimated network connectivity from fMRI signals by computing statistical dependency measures between pairs of voxels. Then, assuming that a restricted set of core regions relay information to the whole network, we developed a statistical test to characterize the structure of this high dimensional network using the concept of eigenvector centrality [1]. We applied these techniques to fMRI recordings in 6 humans during resting state and 4 monkeys during anesthesia. Eigenvector centrality measures based on correlation enabled us to identify a robust set of central areas that was similar in both species, involving cortical (precuneus, medial prefrontal cortex) and subcortical structures (hippocampus). Further graph theoretic analysis based on random walks allowed clustering these regions into robust groups with dedicated subnetworks of influence and to identify their hierarchical organization (clusters of central regions in human are shown in the figure below). In sum, centrality revealed a synthesis of the complex topology of functional networks in a consistent restricted set of core regions in monkey and human brains. Further work will investigate the temporal dynamics of these regions, and their influence on the activity of the whole network will be validated by experimental manipulation.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8ff77860-91b7-47e0-a97d-694a5dca70cc&cKey=4224f8d4-0be1-4676-a1e6-0c99c64ac3f9&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Besserve M{besserve}{Department Empirical Inference}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Murayama Y{yusuke}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ SchindlerHB2012_2, title = {Coding of melodic Gestalt in human auditory cortex}, year = {2012}, month = {10}, day = {15}, volume = {42}, number = {462.09}, abstract = {A melody consists of a temporal sequence of pitches. Its ‘Gestalt’ is invariant to absolute pitch but depends on the relation between pitches [[unable to display character: –]] the relative pitch profile. Consequently, a melody can be recognised regardless of the instrument used to play it and it even retains its identity after transposition to a different key, which involves a global change of all pitches in the melodic sequence. In contrast, a change in a melody’s temporal pitch order is usually accompanied with a change in its relative pitch profile and therefore also affects its melodic ‘Gestalt’. Pitch processing is assumed to occur in the auditory cortex. It is however still unknown whether early auditory regions are capable of integrating pitches over time and whether the resulting representations are invariant with respect to the key of their presentation. Here, we exposed participants to different melodies composed of the same four harmonic pitches during fMRI recordings. Additionally, we presented the same melodies transposed to different keys or played on different instruments. We found that melodies were invariantly represented by their BOLD activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as primary auditory cortex.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=0f42e296-1480-4f47-95c9-e286ef58741f&cKey=56eb3b16-1831-48e4-9a55-3948b9e6c5c9&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Schindler A{aschindler}{Department Physiology of Cognitive Processes}; Herdener M{herdener}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ vanGrootelMMKMLK2012, title = {Longitudinal fMRI study of cortical development in young monkeys}, year = {2012}, month = {10}, day = {15}, volume = {42}, number = {464.14}, abstract = {In typical adult visual processing, low-level visual features are integrated into a global construct that enables the recognition of an object. Behaviorally, young primates are impaired at integrating global form and motion cues. Also the neural machinery to support global processing is not fully developed. However, earlier studies using single-unit electrophysiology show that neuronal response properties are relatively mature compared to behavioral capability. Behavioral sensitivity to global stimuli continues to improve for months or years beyond the time that neuronal responses are adult-like. To understand this discrepancy, we used a larger scale method to investigate cortical development, functional MRI. We tracked the development of BOLD activation in striate and extra-striate cortex of macaque monkeys (Macaca mulatta) longitudinally over 2-3 years. The animals were imaged at 4.7T while anesthetized and paralyzed. To segregate dorsal and ventral stream activity, we used stationary and dynamic Glass pattern stimuli. These have comparable local features (dipoles) but different global forms (concentric or radial) and responses were compared to random-dipole patterns having the same overall statistics. We analyzed responses to a variety of spatial and spatio-temporal stimuli using multi-voxel pattern analysis (MVPA). We determined how classification accuracy depended on the cumulative number of voxels from different cortical areas using a support vector machine (SVM). In young monkeys (age < 2 years), we observed high classification accuracies in primary visual cortex (V1) when Glass patterns were present or absent (stimulus vs. blank) but lower accuracy for static vs. dynamic patterns. Only 2/10 imaging sessions yielded accuracies significantly higher than chance for the same contrast in extrastriate area MT of young monkeys. These same comparisons consistently produced high classification accuracy in animals older than 2 years. These results indicate that BOLD signal differences can be measured at young ages with a Glass pattern stimulus. However, signals related to pattern type are not distinguished reliably until older ages. These results complement our earlier findings showing late onset of activation patterns in extrastriate cortex (Kourtzi et al., 2006, Mag Res Imaging).}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=3ae52744-f560-4589-9308-6e400b244399&cKey=f3a45ca9-c1f1-4fe8-9bef-bfb9853d8db2&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {van Grootel TJ{vangrootel}{Department Physiology of Cognitive Processes}; Meeson A; Munk MHJ{munk}{Department Physiology of Cognitive Processes}; Kourtzi Z{zoe}{Department Physiology of Cognitive Processes}; Movshon JA{tony}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Kiorpes L{kiorpes}{Department Physiology of Cognitive Processes}} } @Poster{ PerrodinKLP2012, title = {Visual influences on neurons in voice-sensitive cortex}, year = {2012}, month = {10}, day = {15}, volume = {42}, number = {366.18}, abstract = {The brains of human and nonhuman primates are thought to contain brain regions that have specialized for processing voice and face content. Although voice- and face-sensitive regions have been primarily studied in their respective sensory modalities, recent human functional magnetic resonance imaging (fMRI) studies have suggested that cross-modal interactions occur in these regions. Here, we investigated whether, and how, neuronal spiking activity in a voice region is modulated by visual (face) stimulation. Using fMRI-guided electrophysiology, we targeted neurons in a voice-sensitive region in the right supra-temporal plane of two rhesus macaques. We used dynamic faces and voices for stimulation, including congruent and incongruent audiovisual pairs. Different stimuli by monkey and human callers were organized in a multifactorial design, to analyze the impact of the following factors on neuronal audiovisual influences: caller species, familiarity, and identity, and call type. Within this voice-sensitive region, we obtained recordings from 149 auditory responsive units, 45% of which demonstrated visual influences. The majority of the visual modulation was characterized by audiovisual responses that significantly deviated from the sum of the responses to both unimodal stimuli (i.e., non-additive multisensory influences). Contrasting monkey ‘coo’ calls with human-mimicked ‘coos’ revealed qualitatively similar, but quantitatively different audiovisual processing of conspecific relative to heterospecific voices; human calls elicited more sub-additive interactions than monkey calls. The call type and speaker identity factors interacted and significantly impacted upon both the direction and amplitude of the visual influences. Finally, familiar voices consistently elicited stronger audiovisual influences than unfamiliar voices, despite auditory responses being similar. Lastly, we compared the specificity of audiovisual interactions and the reliability of neuronal responses across congruent and incongruent audiovisual pairs. In some cases, we found neurons to be differentially affected by voice-face congruency, e.g., neurons were most sensitive to violating the congruency of a conspecific voice/face pairing as caused by substituting the monkey face with a human face. In conclusion, our study links to human fMRI studies on cross-sensory influences in voice/face regions, and the results describe the nature of the visual influences on neuronal responses in a voice-sensitive region in the primate brain. The results also help to characterize the stimulus feature-dependent influences on the cross-modal effects into this region.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=b012820a-b1ec-488f-8d44-68830bc3b213&cKey=4104b857-4524-4a2f-8a26-37f1c3fc0d7a&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ ValverdeSalzmannBLS2012_2, title = {Color blobs in visual areas V1 and V2 of the common marmoset}, year = {2012}, month = {10}, day = {14}, volume = {52}, number = {261.11}, abstract = {Color vision is reserved to only few mammals, such as Old World monkeys and humans. Most Old World monkeys are trichromats. Among them, macaques were shown to exhibit functional domains of color-selectivity, in areas V1 and V2 of the visual cortex. Such color domains have not yet been shown in New World monkeys. In marmosets a sex-linked dichotomy results in dichromatic and trichromatic genotypes, rendering most male marmosets color-blind. Here we used trichromatic female marmosets to examine the intrinsic signal response in V1 and V2 to chromatic and achromatic stimuli, using optical imaging. In order to activate the visual subsystems individually, we used spatially homogeneous isoluminant color opponent (red/green, blue/yellow) and hue versus achromatic flicker (red/gray, green/gray, blue/gray, yellow/gray), as well as achromatic luminance flicker. In contrast to previous optical imaging studies in marmosets, we find clearly segregated color domains, similar to those seen in macaques. Red/green and red/gray flicker were found to be the appropriate stimulus for revealing color domains in single condition maps (see figure). Blue/gray and blue/yellow flicker stimuli resulted in faint patch-patterns. A recently described multimodal vessel mapping approach allowed for an accurate alignment of the functional and anatomical datasets. Color domains were tightly colocalized with cytochrome oxidase blobs in V1 and with thin stripes in V2. Thus, our findings are in accord with 2-Deoxy-D-glucose studies performed in V1 of macaques and studies on color representation in V2. Our results suggest a similar organization of early cortical color processing in trichromats of both, Old World and New World monkeys.}, file_url = {fileadmin/user_upload/files/publications/2012/Neuroscience-2012-Valverde.pdf}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=84193aad-2bac-4c16-b075-86ba04f67615&cKey=4666bcb8-f47e-4d26-bd5e-b78d1015a381&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Valverde Salzmann MF{valverde}{Department Physiology of Cognitive Processes}{Department High-Field Magnetic Resonance}; Bartels A{abartels}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Sch\"uz A{schuez}{Department Physiology of Cognitive Processes}} } @Poster{ KuGLB2012, title = {Facial expression and identity encoding in macaques revealed by fMRI adaptation}, year = {2012}, month = {10}, day = {14}, volume = {42}, number = {263.22}, abstract = {fMRI has revealed a face processing network in the macaque brain that encompasses regions in the superior temporal sulcus (STS), the lateral and ventral temporal cortex, the medial temporal lobe and in the prefrontal cortex (Tsao and Livingstone 2008; Ku, Tolias et al. 2011). However, the functionality of each individual face-responsive patch is largely unknown. In humans fMRI evidence suggests that the middle STS is important for facial expression encoding, while the ventral temporal cortex is primarily involved in identity encoding (Haxby, Hoffman et al. 2002). This is consistent with single unit studies showing facial expression selective cells in the STS and identity encoding neurons in LTG in monkeys. However, there is no equivalent evidence indicating such a functional segregation in terms of BOLD responses to face stimuli. In order to examine whether there is a similar response pattern in monkeys and to further identify more candidate brain regions which might be also important in encoding these two aspects of faces, we scanned two awake and five anesthetized monkeys at 7Tesla. Using an adaptation paradigm we found that STS was sensitive to changing facial expressions independent of changing of identities in all awake and anesthetized monkeys. In brain regions not covered in the awake monkeys, the same contrast revealed that the medial orbital frontal cortex (area 47/12 ) of four anesthetized monkeys was also sensitive to changing facial expressions. In addition, we found that the anterior hippocampus of the two awake and three anesthetized monkeys was sensitive to changing identities. The results suggest differential selectivities for the encoding of facial expressions and of identities across a network of regions in the monkey.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=eeec6d3c-40a5-417d-b51c-1e1f644b54f0&cKey=2e031589-b220-48f5-9df2-f754124ef8a5&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Ku S-P{shihpi}{Department Physiology of Cognitive Processes}; Goense JBG{jozien}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ EvrardC2012, title = {Modular architectonic parcellation of the insula in the macaque monkey}, year = {2012}, month = {10}, day = {14}, volume = {42}, number = {266.03}, abstract = {We examined the anatomical organization of the insular cortex of the cynomolgus macaque monkey in serial coronal sections stained alternately with Nissl and Gallyas (myelin) techniques, supplemented in some cases with immunohistochemical staining techniques. We observed the same 23 distinct cytoarchitectonic areas in 12 brains. Within the granular, dysgranular, and agranular regions described in prior studies, we identified 4, 11, and 8 distinct areas, respectively. Across brains, these areas have consistent architectonic characteristics, and in flat map reconstructions they display a consistent topological or neighborhood arrangement, despite variations in the size of individual areas between cases. The borders between areas are generally sharply defined, yet particular borders can have a transitional appearance (in part because they are obliquely oriented in coronal sections), which helps explain the more vague conclusions made in earlier studies. The presence of a distinct granular area that straddles the fundus of the superior limiting sulcus over its entire posterior-to-anterior extent is consistent with the available evidence on interoceptive thalamo-cortical projections, and also with the tensile anchor theory of species-specific cortical gyrification. These observations are consonant with the homeostatic afferent model of processing in the primate insula, and they suggest that discrete modules within insular cortex provide the basis for its polymodal integration of all salient activity relevant for ongoing emotional behavior.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=8479cbde-191e-4d2a-81ca-35a040a2470b&cKey=95b15055-11b1-4cc2-84c2-e6399639f02a&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Craig AD} } @Poster{ BannertB2012, title = {Predicting memory color from neural responses to achromatic images of color-diagnostic objects}, year = {2012}, month = {10}, day = {14}, volume = {42}, number = {261.10}, abstract = {Some objects that we deal with on a daily basis are associated with an object-specific color [[unable to display character: –]] such as yellow for bananas, red for strawberries, green for lettuce, etc. Such objects are referred to as color-diagnostic and their associated color as their memory color (Hering, 1920). Psychophysical evidence shows that achromatic , i.e. grayscale, images of color-diagnostic objects elicit percepts that are differentially biased towards their memory color (Hansen, Olkkonen, Walter, & Gegenfurtner, 2006; Olkkonen, Hansen, & Gegenfurtner, 2008). This phenomenon suggests some form of learned and automatic association between colors and particular objects. In the present study we tested whether neural responses to color-diagnostic objects convey color-specific information, even when the objects were presented achromatically to subjects who were naïve to the purpose of the study. We first collected fMRI data while participants viewed grayscale images of 8 different color-diagnostic objects (4 colors, 2 per color). We then recorded responses to chromatic stimulation with red, green, blue, and yellow abstract color stimuli that contained no object information. All object and color stimuli were set to equiluminance for each subject individually. To analyze the data, we applied a whole-brain searchlight procedure by training linear support vector machine classifiers to distinguish between local voxel patterns associated with the four colors. They were then tested on patterns elicited by color-diagnostic achromatic objects to predict their correct memory colors. At the group level, we found significant decoding accuracy in a large cluster covering foveal regions of early visual cortex. In some but not all individual subjects, smaller clusters were also evident in the fusiform gyrus. Our results suggest that memory color and color signals evoked by chromatic stimulation share a common neural mechanism in early visual cortex. Retinotopic mapping in combination with classification techniques will be used to clarify the contribution of individual visual areas to this mechanism.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=84193aad-2bac-4c16-b075-86ba04f67615&cKey=70e8a431-7b35-4472-97f5-a1bcb918f1d4&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Bannert MM{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ BohrausLG2012, title = {High-resolution CMRO2 in gray matter of macaque visual cortex}, year = {2012}, month = {10}, day = {13}, volume = {42}, number = {95.03}, abstract = {Commonly used fMRI signals measure local vascular and neural changes, with the former underlying a certain degree of spatiotemporal blurring. To minimize the latter, methods can be used that are less sensitive to partial volume effects. One such methodology capitalizes on high resolution, voxel-by-voxel CMRO2 measurements. Here we combined such measurements with so-called calibrated BOLD methodology to acquire CBF and BOLD maps during visual stimulation. Calibration was done by estimating a normalization factor (M) assessed in hypercapnia conditions, reflecting the upper limit of BOLD signal-changes. Quantitative description and interpretation of the data was done by using a model with parameters α, relating relative changes of CBV to CBF according to Grubb’s law (α=0.38), and β linking blood oxygenation to relaxivity (β=1.5). To improve the model, α was selected to account for changes in venous CBV only (α=0.23), i.e. to account for CBV-changes that are relevant to the BOLD signal, rather than to total CBV alterations. Alternatively, the model was compared to a more detailed model and showed highest accuracy with α=0.14 & β=0.91. We determined the CMRO2 in anesthetized macaques at 7T & high resolution to separate the visually induced percent changes in CMRO2 (%CMRO2) in gray matter from white matter and vessel signals. We subsequently repeated the calculations using the aforementioned α & β parameters in order to reassess the robustness of the results. CBF and BOLD signals were acquired simultaneously with a triple-echo sequence. The %CMRO2 changes, M and n (ratio of fractional CBF to CMRO2) were calculated in V1 and V2. At a resolution of 1x1x3 mm3, the average %CMRO2 was 12±5% (mean ± sem) with M=0.29 ± 0.05. The coupling constant n was 2.1 ± 0.4. Similar values were obtained for α=0.23. The calibration constant M slightly increased using α=0.14 & β=0.91 but remained consistent with the value of 0.3-0.4 in gray matter at 7T. %CMRO2 changes & n were not very sensitive to the choice of parameters. For resolution of 0.5x0.5x3mm3 the results suggested higher %CMRO2 changes in gray matter than in white matter with a possible peak in layer IV, being the main input layer in macaque monkey. CBF and BOLD percent changes during visual stimulation and hypercapnic challenge were increased at a resolution of 0.5x0.5x3mm3 compared to 1x1x3 mm3. In conclusion, using the calibrated BOLD method, we found high-resolution %CMRO2 changes of 12-14% and coupling ratios of 1.8-2.1, and demonstrated differences in %CMRO2 measured in gray and white matter. The reported results were found to be robust and insensitive to changes in the α & β parameters at high field.}, web_url = {http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=c8bd9447-7936-4f8b-9392-60945d74cc56&cKey=f12ea640-cb2c-4319-8798-038d5a69d738&mKey=70007181-01c9-4de9-a0a2-eebfa14cd9f1}, event_name = {42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Bohraus Y{ybohraus}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}} } @Poster{ PerrodinKLP2012_4, title = {Visual influences on neurons in voice-sensitive cortex}, year = {2012}, month = {10}, day = {12}, pages = {64}, abstract = {The brains of human and nonhuman primates are thought to contain brain regions that have specialized for processing voice and faces. Although voice- and face-sensitive regions have been primarily studied in their respective sensory modalities, recent human functional magnetic resonance imaging (fMRI) studies have suggested that cross-modal interactions occur in these regions. Here, we investigated whether, and how, neuronal activity in a voice region is modulated by visual (face) stimulation. Using fMRI-guided electrophysiology, we targeted neurons in a voice-sensitive region in the right supra-temporal plane of two rhesus macaques. We used dynamic faces and voices of different human and monkey individuals for stimulation, including congruent and incongruent audiovisual pairs. We observed robust non-additive visual influences of facial information on the auditory responses of neurons in this voice-sensitive region. In accordance with previous studies, the direction of the audiovisual interactions seemed primarily determined by the phase of visually-evoked theta oscillations at auditory stimulus onset. Yet, we found that, in addition, speaker-related stimulus features such as caller familiarity and identity and call type, studied within a multifactorial experimental design, differentially modulated the crossmodal effects. In particular, familiar voices consistently elicited larger audiovisual influences than unfamiliar voices, despite auditory responses being similar. Finally, we found neurons to be differentially sensitive to stimulus congruency: the specificity of audiovisual influences was disrupted when violating the congruency of a conspecific voice/face pairing by substituting the monkey face with a human face. In conclusion, our results describe the nature of the visual influences on neuronal responses in a voice-sensitive region in the primate brain. This study links to human fMRI studies on multisensory influences in voice/face regions, provides insights on the neuronal cross-modal effects in these regions and hypothesizes that neurons at facesensitive regions might show comparable multisensory influences from the auditory domain.}, web_url = {http://www.apan.jhu.edu/APAN2012_Abstracts.pdf}, event_name = {Tucker-Davis Symposium on Advances and Perspectives in Auditory Neurophysiology (APAN 2012)}, event_place = {New Orleans, LA, USA}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ KleinEPBLS2012_2, title = {Optogenetics in the macaque thalamus}, year = {2012}, month = {10}, web_url = {http://www.brainresearchconference.com/}, event_name = {7th Brain Research Conference “Optogenetics and Pharmacogenetics in Neuronal Function and Dysfunction”}, event_place = {New Orleans, LA, USA}, state = {accepted}, author = {Klein C{cklein}{Department Physiology of Cognitive Processes}; Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Power AT{apower}{Department Physiology of Cognitive Processes}; Boyden ES; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Schmid MC{mschmid}} } @Poster{ LiFLK2012, title = {Multi-Stable Visual Motion Perception}, journal = {Frontiers in Computational Neuroscience}, year = {2012}, month = {9}, day = {14}, volume = {Conference Abstract: Bernstein Conference 2012}, pages = {190}, abstract = {Perceptual multi-stability is established when the brain fails to reach a single interpretation of the input from the external world. This issue intrigued scientific minds for more than two hundred years. This phenomenon has been found in vision (Leopold & Logothetis, 1999), audition (Repp, 2007), olfaction (Zhou & Chen, 2009) and speech (Warren & Gregory, 1958). Crucial features are similar within and across modalities (Schwarts et al., 2012). In the visual modality, a number of ambiguous visual patterns have been described such as the Necker cube, motion plaids, and binocular rivalry. Multi-stable stimuli can provide unique insights into visual processing, as changes in perception are decoupled from changes in the stimulus. Understanding of how multi-stable perception occurs might help one to understand visual perception in general. A key question in multi-stable perception is what the brain processes are responsible in the identification and alternation of the percepts. Some investigators suggest that both top-down and bottom-up processes are involved (García Pérez, 1989) but others argue that multi-stable perception does not need high-level processing but happens automatically as low-level competition between the stimulus features (Akman et al., 2009; Wilson et al, 2000). Furthermore, it is well known that changes in stimulus features can bias perception in one or another direction, (Klink, et al., 2012). In order to explore this question, we used multi-stable motion stimuli and specifically moving plaids consisting of three superimposed gratings moving in equidistant directions (difference of 120 deg). These stimuli induce the perception of component and pattern motion simultaneously since any two component gratings bind together and are perceived to move in the opposite direction of the third grating component. We modulated properties of the stimuli such as grating speed and size and recorded the responses of human subjects reporting the direction of the single grating using one of three buttons for each direction. Preliminary results show that perceptual dominance is greatly affected by the selection of grating speeds. Grating size did not greatly change the predominance of the different gratings. We find that gratings with speed closer to physiological values have greater probability to be perceived and that gratings with similar speeds tend to group more often than gratings with different speeds. Further manipulations of other stimulus features like contrast and spatial frequency allow parametric variations of the relative probabilities of different interpretations. Our future goal is to use this information to built models of perceptual alternations using probabilistic inference.}, web_url = {http://www.frontiersin.org/10.3389/conf.fncom.2012.55.00058/event_abstract}, event_name = {Bernstein Conference 2012}, event_place = {München, Germany}, state = {published}, DOI = {10.3389/conf.fncom.2012.55.00058}, author = {Li Q{qinglinli}{Department Physiology of Cognitive Processes}; Fleming RW{roland}{Department Human Perception, Cognition and Action}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ BannertB2012_2, title = {The yellow of a gray banana: Decoding colors from fMRI signals in the absence of chromatic stimulation}, journal = {Frontiers in Computational Neuroscience}, year = {2012}, month = {9}, day = {14}, volume = {Conference Abstract: Bernstein Conference 2012}, pages = {173}, abstract = {Some objects that we deal with on a daily basis are associated with an object-specific color – such as yellow for bananas, red for strawberries, green for lettuce, etc. Such objects are referred to as color-diagnostic and their associated color as their memory color (Hering, 1920). Psychophysical evidence shows that achromatic , i.e. grayscale, images of color-diagnostic objects elicit percepts that are differentially biased towards their memory color (Hansen et al., 2006; Olkkonen et al., 2008). This phenomenon suggests some form of learned and automatic association between colors and particular objects. In the present study we tested whether neural responses to color-diagnostic objects convey color-specific information, even when the objects were presented achromatically to subjects who were naïve to the purpose of the study. We first collected fMRI data while participants viewed grayscale images of 8 different colordiagnostic objects (4 colors, 2 per color). We then recorded responses to chromatic stimulation with red, green, blue, and yellow abstract color stimuli that contained no object information. All object and color stimuli were set to equiluminance for each subject individually. To analyze the data, we applied a whole-brain searchlight procedure by training linear support vector machine classifiers to distinguish between local voxel patterns associated with the four colors. They were then tested on patterns elicited by color-diagnostic achromatic objects to predict their correct memory colors. At the group level, we found significant decoding accuracy in a large cluster covering foveal regions of early visual cortex. In some but not all individual subjects, smaller clusters were also evident in the fusiform gyrus. Our results suggest that memory color and color signals evoked by chromatic stimulation share a common neural mechanism in early visual cortex. Retinotopic mapping in combination with classification techniques will be used to clarify the contribution of individual visual areas to this mechanism.}, web_url = {http://www.frontiersin.org/10.3389/conf.fncom.2012.55.00049/event_abstract?sname=Bernstein_Conference_2012}, event_name = {Bernstein Conference 2012}, event_place = {München, Germany}, state = {published}, DOI = {10.3389/conf.fncom.2012.55.00049}, author = {Bannert MM{mbannert}{Department Physiology of Cognitive Processes}; Bartels A{abartels}{Department Physiology of Cognitive Processes}} } @Poster{ KayserBP2012, title = {Slow oscillations and the rhythmic input sampling of auditory cortex neurons}, year = {2012}, month = {9}, day = {2}, volume = {4}, pages = {95}, abstract = {Human electrical imaging studies have shown that slow oscillatory (theta-band) activity in auditory cortex entrains to the rhythmic structure of naturalistic sounds such as speech or animal vocalizations (Luo & Poeppel, Neuron 2007). Assuming that slow oscillations reflect changes in the excitation-inhibition balance of local networks this suggests that as a consequence of the entrainment and the locking of spikes to slow oscillations auditory cortical neurons should sample the environment in a rhythmic fashion (Giraud & Poeppel, Nat Neurosci 2012). We here confirm this hypothesis using auditory cortical responses recorded in the alert non-human primate. We recorded single neuron and local field potential responses to long sequences of naturalistic sounds in macaque auditory cortex (Kayser et al Neuron 2009). We then used methods of single-trial decoding and spectro-temporal receptive field (STRF) mapping to study how neural coding varies as a function of oscillatory phase (derived from theta-band 4-8Hz field potentials). Neurons fired more during one half of the oscillatory cycle than during the other, resulting in systematic variations of firing rate and stimulus information with oscillation cycle (both by about 20%). However, the coding capacity, defined as information per spike was roughly constant across the cycle. STRFs mapped separately for spikes in different phase quadrants differed both quantitatively and qualitatively. During the phase range of higher firing STRFs yielded better prediction quality (best vs. worst quadrant: 0.35 vs. 0.2 median cross-validation correlation) and exhibited stronger excitation-inhibition ratios (medians 1.3 vs. 1) and signal-to-noise ratios (medians 20 vs. 12) than during the remaining cycle (even when corrected for changes in overall spike count). This suggests that the degree to which linear models can account for neural response selectivity varies systematically during the oscillatory cycle. The time epoch of greatest selectivity (time lag of peak in STRF) also systematically varied along the cycle rather than being constant. Lags of STRFs derived using only spikes occurring during later phase quadrants became progressively longer, resulting in a clustering of the peak sensitivity of all STRFs in time. Spikes occurring e.g. during the fourth phase quadrant were evoked not much later as spikes occurring during the phase quadrant, resulting a clustered and periodic input sampling of auditory cortical neurons. Our findings demonstrate that the quality of linear STRFs of auditory cortical neurons depends on phase of slow and stimulus driven oscillatory network activity, with linear models performing much better during certain phases of the slow rhythm. These observations may have important implications for the interpretation of STRFs. In addition, our results directly confirm the hypothesis that auditory neurons do not unfold incoming stimuli linearly in time; rather they periodically sample the environment based on the auditory cortical theta rhythm. These findings have important implications for the understanding of auditory coding and perception that both seem to operate in a periodic fashion.}, web_url = {http://wp.unil.ch/auditorycortex2012/}, event_name = {4th International Conference on Auditory Cortex}, event_place = {Lausanne, Switzerland}, state = {published}, author = {Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Brasselet R{rbrasselet}{Department Physiology of Cognitive Processes}; Panzeri S{stefano}} } @Poster{ PerrodinKLP2012_3, title = {Visual influences on neurons in voice-preferring cortex}, year = {2012}, month = {9}, day = {2}, volume = {4}, pages = {153}, abstract = {Many animals use face and voice information during communication, but it remains unclear how the brain integrates such cross-sensory input. Functional imaging evidence suggests that the brains of human and nonhuman primates contain voice- and face-preferring regions, and some human studies have reported that multisensory interactions occur in these regions. Yet, to date neurons in monkey voice/face regions have been studied exclusively with unisensory stimuli, or electrophysiological studies of voice/face interactions have focused on other parts of the brain. We investigated whether and how neurons in a monkey voice-preferring cluster would be modulated by multisensory (face/voice) influences. Using fMRI-guided electrophysiology, we targeted neurons in a voice-preferring fMRI cluster in the right hemisphere on the supra-temporal plane of two rhesus macaques. We used dynamic vocalizing faces and voices for stimulation, presented in auditory, visual and audiovisual conditions, including congruent and incongruent audiovisual pairs. The multifactorial experimental design also included stimuli from different familiar and unfamiliar monkeys and humans, and allowed us to analyze the impact of the following factors on the audiovisual modulation of neuronal responses: 'caller's species', 'caller's familiarity to the subject', 'caller's identity', and 'call type'. We obtained recordings from 149 auditory responsive units, 45% of which demonstrated visual influences. The vast majority of the visual modulation was characterized by audiovisual responses that significantly deviated from the sum of the responses to both unimodal stimuli (i.e., non-additive multisensory influences). Next we used ANOVA within our multifactorial design to analyze the impact of the different stimulus features on the population of responsive units. First, we found that human vocalizations (where humans imitated monkey 'coo' vocalizations) elicited similar visual modulation as monkey 'coo' calls, but were more likely to elicit sub-additive interactions than the monkey calls. This result suggests qualitatively similar but quantitatively different audiovisual processing of conspecific relative to heterospecific voices and faces, at least for heterospecific stimuli that involved humans imitating monkey coos. Second, while auditory responses were comparable across different speakers (but different for coo vs grunt calls), both the call type and speaker identity factors turned out to be significant when visual influences were considered. Finally, despite familiar and unfamiliar callers eliciting similar auditory responses, the caller familiarity factor had a significant effect on the visual modulation, with familiar voices consistently eliciting stronger audiovisual interactions than unfamiliar voices. These results suggest that some stimulus features differentially modulate the direction and/or magnitude of visual influences on neuronal auditory responses. We also compared neural responses to congruent vs. incongruent audiovisual pairs. We found that under a number of conditions the congruency/incongruency of the stimuli generally did not affect neuronal responses, except for one stimulus pairing involving a monkey voice/face combination where the original voice was replaced with a human voice. In this case, the majority of units selectively integrated the congruent, but not the incongruent, stimulus, and the reliability of the neuronal response was significantly decreased (as measured by a drop in the Fano factor in audiovisual responses to the incongruent pair). In summary, our results identify a considerable level of visual (face) influences on the auditory processing by neurons in an fMRI identified voice-preferring region in the primate brain. The results also showed stimulus-related specificity of the visual influences that provide insights on the type of multisensory influences in this region, which we discuss in relation to those that have been reported for other parts of the brain. These results extend our understanding of the multisensory influences evident at the neuronal level in primate voice-sensitive clusters, link to the fMRI studies in humans and hypothesize that face-sensitive regions would also show strong cross-sensory influences.}, web_url = {http://wp.unil.ch/auditorycortex2012/}, event_name = {4th International Conference on Auditory Cortex}, event_place = {Lausanne, Switzerland}, state = {published}, author = {Perrodin C{cperrodin}{Department Physiology of Cognitive Processes}; Kayser C{kayser}{Department Physiology of Cognitive Processes}{Research Group Physiology of Sensory Integration}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Petkov CI{chrisp}{Department Physiology of Cognitive Processes}} } @Poster{ OrtizSALR2012, title = {Functional neuroimaging of sound motion in the macaque dorsal stream}, year = {2012}, month = {9}, day = {1}, volume = {4}, pages = {75}, abstract = {The macaque ventral intraparietal area (VIP), located in the fundus of the intraparietal sulcus (IPS), is considered a polymodal association area that responds to visual, tactile, vestibular and auditory stimuli (Schlack et al., 2005). In particular, VIP neurons are responsive to moving visual and auditory stimuli. VIP receives projections from multiple visual areas (especially from the middle temporal area [MT] and the medial superior temporal complex [MST]) and from auditory regions in the posterior superior temporal (pST) cortex (Lewis & Van Essen, 2000). Neurons in pST, in particular the caudolateral area (CL), show selective responses to particular sound locations regardless of sound type (Tian et al., 2001; Recanzone, 2001). In humans, several studies have reported activation of the pST and IPS to sound source motion (Warren et al., 2000; Krumbholz et al., 2005), confirming the existence of a dorsal processing stream for spatial aspects of sound in humans. In order to bridge the gap between single-unit recordings in monkeys and neuroimaging studies in humans, we used high-resolution fMRI in monkeys to further investigate these results. First, we created a virtual auditory space environment using binaural sound recording techniques with miniature microphones inserted into a macaque head cast. We validated the technique by measuring saccadic eye movements to sound sources in different locations during playback. We then performed fMRI to identify cortical areas sensitive to sound motion in azimuth of the left and right hemifields. All fMRI data were pre-processed and aligned with the 112RM-SL_T1 rhesus monkey template for identification of cortical fields (McLaren et al., 2009). Preliminary results showed that all moving sounds activated areas MT, MST and the IPS. Contrasting left and right sound-motion conditions against center (i.e. no motion) yielded greater activation in contralateral VIP. These results suggest that interaural information induced by lateralized sounds is processed along a dorsal cortical processing stream comprising VIP in the respective contralateral hemisphere.}, web_url = {http://wp.unil.ch/auditorycortex2012/}, event_name = {4th International Conference on Auditory Cortex}, event_place = {Lausanne, Switzerland}, state = {published}, author = {Ortiz M{mortiz}{Department Physiology of Cognitive Processes}; Steudel T{steudel}{Department Physiology of Cognitive Processes}; Augath M{mark}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauschecker JP} } @Poster{ SmirnakisKSPL2012, title = {Population receptive field measurements in macaque visual cortex}, journal = {Journal of Vision}, year = {2012}, month = {8}, volume = {12}, number = {9}, pages = {1397}, abstract = {Visual receptive fields have dynamic properties that may change with the conditions of visual stimulation or with the state of chronic visual deprivation. We used 4.7 Tesla functional magnetic resonance imaging (fMRI) to study the visual cortex of two normal adult macaque monkeys and one macaque with binocular central retinal lesions due to a form of juvenile macular degeneration (MD). FMRI experiments were performed under light remifentanyl induced anesthesia (Logothetis et al. Nat. Neurosci. 1999). Standard moving horizontal/vertical bar stimuli were presented to the subjects and the population receptive field (pRF) method (Dumoulin and Wandell, Neuroimage 2008) was used to measure retinotopic maps and pRF sizes in early visual areas. FMRI measurements of normal monkeys agree with published electrophysiological results, with pRF sizes and electrophysiology measurements showing similar trends. For the MD monkey, the size and location of the lesion projection zone (LPZ) was consistent with the retinotopic projection of the retinal lesion in early visual areas. No significant BOLD activity was seen within the V1 LPZ, and the retinotopic organization of the non-deafferented V1 periphery was regular without distortion. Interestingly, area V5/MT of the MD monkey showed more extensive activation than area V5/MT of control monkeys which had part of their visual field obscured (artificial scotoma) to match the scotoma of the MD monkey. V5/MT PRF sizes of the MD monkey were on average smaller than controls. PRF estimation methods allow us to measure and follow in vivo how the properties of visual areas change as a function of cortical reorganization. Finally, if there is time, we will discuss a different method of pRF estimation that yields additional information.}, web_url = {http://www.journalofvision.org/content/12/9/1397.abstract}, event_name = {12th Annual Meeting of the Vision Sciences Society (VSS 2012)}, event_place = {Naples, FL, USA}, state = {published}, DOI = {10.1167/12.9.1397}, author = {Smirnakis SM{ssmirnakis}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}; Shao Y{yshao}{Department Physiology of Cognitive Processes}; Papanikolaou A{amalia}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ BahmaniLK2012, title = {The role of parietal visual cortex in perceptual transitions during bistable perception}, journal = {Journal of Vision}, year = {2012}, month = {8}, volume = {12}, number = {9}, pages = {683}, abstract = {Several imaging studies in humans have shown the involvement of a frontoparietal network of cortical areas in perceptual transitions during bistable perception. To investigate further the possible role of parietal visual areas in perceptual alternations, we recorded extracellular neural activity in the lateral intraparietal area (LIP) of the rhesus macaque. The subject was initially presented with congruent patterns to the two eyes. Then the stimulus was switched for either one or both eyes (binocular flash suppression versus physical alternation), both resulting in perception of the newly presented stimulus. The recorded cells typically showed an initial burst of activity at stimulus onsets as well as stimulus switches. In contrast to previous reports by a number of fMRI studies, we found strong transient activity during physical alternations at the single cell level. This signal was also present during binocular flash suppression but to a lesser extent. Importantly, the amplitude of the signal dropped substantially in control conditions where physical changes were introduced in the stimuli but did not induce concomitant changes in perception. The transient response of the recorded neurons was followed by a tonic response which exhibited independent dynamics. Interestingly, this sustained activity was significantly lower during incongruent versus congruent stimulation. We conjecture that areas at the high end of the dorsal pathway might be involved in multistable perception in a different way in comparison with feature and object selective areas of the ventral pathway. The transient signal recorded in LIP neurons during perceptual transitions could potentially trigger reorganization of activity in constellations of feature selective neurons in the ventral pathway. In addition, the suppression of the sustained activity in LIP during incongruent stimulation may reflect inhibitory processes involved in the resolution of conflict between the two stimuli or indicate a failure to bind the sensory input into a coherent percept.}, web_url = {http://www.journalofvision.org/content/12/9/683.abstract}, event_name = {12th Annual Meeting of the Vision Sciences Society (VSS 2012)}, event_place = {Naples, FL, USA}, state = {published}, DOI = {10.1167/12.9.683}, author = {Bahmani H{hbahmani}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Keliris GA{george}{Department Physiology of Cognitive Processes}} } @Poster{ EvrardFL2012_3, title = {Areal Distribution Of The Von Economo In The Anterior Insular And Anterior Cingulate Cortices In The Macaque Monkey}, year = {2012}, month = {7}, volume = {8}, number = {p136.23}, abstract = {The anterior insular (AIC) and anterior cingulate (ACC) cortices and their unique spindle-shaped von Economo neurons (VENs) emerged within the last decade as having a potentially major role in interoceptive, emotional and social awareness and cognition in humans. A role of the VENs in these fundamental phenomena is supported by their selective depletion in highly detrimental neuropsychiatric diseases characterized by a loss of self-conscious emotion and empathy and by a lack of appropriate behavioral response in emotionally-salient situations. The much-needed invasive examination of the VENs in the laboratory has been limited so far by the assumption that this neuron occurs among primates exclusively in humans and great apes. In a recent contribution, we demonstrated the presence of VENs in the agranular anterior insula and ACC in two species of macaque monkeys (rhesus and cynomolgus) typically used in the laboratory. VENs were also found in the same regions in a broad range of monkeys and in lesser apes. In the present contribution, we demonstrate that VENs in the macaque occur in an architectonically distinct area of the agranular anterior insula, namely ´Ia5´, and in several distinct areas in ACC and in the medial wall of the prefrontal cortex. This specific areal distribution of the VENs suggests that their developmental fate is bound to the overall plan of development and parcellation of the cerebral cortex in primates. It also offers a unique opportunity to examine the primal function and connections of the VENs on the basis of what is already known about these areas in the macaque monkey. Such examination could provide significantly new and valuable information on the possible role of the VENs in human self-awareness, social cognition and related neuropsychiatric disorders.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_35097/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Evrard HC{evrard}{Department Physiology of Cognitive Processes}; Forro T{tforro}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ DianaMMAPMULFLCLI2012, title = {Brainstem Afferents To The Hippocampal Formation: Comparative Inmunohistochemical Study In The Macaca Fascicularis Monkey}, year = {2012}, month = {7}, volume = {8}, number = {p159.08}, abstract = {The neuroanatomical connections in the nonhuman primate of the brainstem structures to the Hippocampal Formation (HF, which includes the dentate gyrus -DG-, CA3, CA2, CA1, subiculum, pre-parasubiculum and the entorhinal cortex -EC-) are still unclear. Previous tracer studies in nonhuman primates show retrogradely labeled neurons in the brainstem including the Ventral Tegmental Area (VTA), Locus Coeruleus (LC) and Raphe Nuclei (RN), after deposits in the hippocampus (Amaral and Cowan, 1980), as well as in the EC (Insausti et al., 1987). In order to characterize the neurotransmitters associated to those projections (presumably dopaminergic -DA, VTA-, noradrenergic -NA, LC-, and serotoninergic -5-HT, RN-, respectively), and the topographic and laminar differences, we studied comparatively the innervation in the HF using immunohistochemical techniques. Inmunohistochemistry for DA (Tirosine Hidroxilase, TH), NA (Dopamine Beta Hidroxilase, DBH), and 5-HT showed: a) The DG molecular layer had TH-immunoreactive fibers, while the polymorphic layer contained positive 5-HT fiber labeling, b) CA3 pyramidal layer showed denser 5-HT labeling than TH, c) CA1 had scattered TH and 5-HT fibers, d) The superficial layer of the rostral EC (I and II) had TH- and 5-HT-labelled processes, e) TH and DBH positive cells were primarily found in the lateral subdivisions of the EC (ELR/ELc). The preferential location of these positive fibers in ELR/ELc, is significant, as this portion of the EC receives abundant unimodal and polymodal sensory input and innervates the body and tail of the hippocampus, and therefore it might be a crucial link in the consolidation of memory through the monoaminergic modulation of the HF.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_35737/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Diana H; Munoz M; Marcos P; Arroyo-Jimenez MDM; P{\'e}rula E; Mohedano-Moriano A; Ubero MDM{mubero}{Department Physiology of Cognitive Processes}; Legidos-Garcia ME; Fuentes J; Lagartos MJ; Cebada S; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Insausti R} } @Poster{ vanKeulenLE2012, title = {Differential Noradrenergic Modulation Of Sensory Processing In The Rat Somatosensory And Prefrontal Cortex}, year = {2012}, month = {7}, volume = {8}, number = {p131.15}, abstract = {Alerting sensory stimuli activate the nucleus Locus Coeruleus (LC) and the associated release of Noradrenaline (NE) improves sensory signaling. We compared the LC-mediated modulation of sensory responses in the primary sensory cortex (S1) and the medial prefrontal cortex (mPFC), a higher integrative cortical region. We performed recordings in S1, mPFC, and LC in response to mild electrical foot shocks (0.5ms, 5mA) and manipulated the activity level of LC-NE system by clonidine, an alpha2-receptor agonist, in the urethane-anesthetized rat. We used systemic and local (in LC) application of clonidine, both leading to decreased level of NE in the brain. Iontophoretic application of clonidine (50nA, 50µl/ml, 20min) into LC resulted in complete cessation of both spontaneous and evoked activity of LC-NE neurons. Systemic clonidine injection (50 µl/ml,i.p.) produced a decrease in LC spontaneous firing, however the LC sensory responses were preserved. The short-latency (~17ms) evoked responses in S1 were minimally affected by clonidine, while late response component (~336ms) was decreased. In contrast, bi-directional changes were observed in mPFC. The response amplitude of mPFC neurons was substantially decreased following both local and systemic clonidine administration. Conversely, proportion of initially non-responsive mPFC neurons became responsive following local (22% of neurons) or systemic (38%) clonidine application. The LFPs displayed regular slow (~1Hz) oscillations that are characteristic for synchronized cortical state induced by anesthesia. Sensory stimulation evoked transient (~1s) periods of desynchronized (activated) state in 58% of cases, which were abolished by local (60% of cases) and systemic (75%) injection of clonidine. The latter effect strongly correlated with a degree of LC inhibition by clonidine. Thus, LC-NE system is critically involved in shifting cortical activity to desynchronized state that is beneficial for sensory processing. Overall, while NE effects were observed in both cortical regions, our results indicate that mPFC receives a stronger NE neuromodulatory input.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_34966/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {van Keulen S{svankeulen}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ vonPfostlZLVZLR2012, title = {Electrophysiological Effects Of Lactate On Primary Visual Cortex Of Non-Human Primates}, year = {2012}, month = {7}, volume = {8}, number = {p140.27}, abstract = {Recent evidence suggests that increased metabolic demand of neurons can be met by lactate, a metabolite of glucose. In addition, during neuronal activation lactate production in the brain is increased. We already demonstrated that this physiological formation of lactate can contribute to the BOLD signal. Here we set out to determine the underlying mechanism that drives the observed increase in BOLD baseline. This effect could be explained by an increase in CBF or also increased neuronal activity. The influence of lactate on cerebral blood flow has been already established. To test if lactate has also an effect on neuronal activity we performed electrophysiological recordings in V1 of anesthetized non-human primates. Lactate was applied slow and continuously (0.04 mmol/kg/min). This infusion induced a significant increase in local field potential (LfpH, 24-90 Hz) power and visual stimulus induced modulation. An average increase of 23.0±1.2% and 76.0±20% was recorded for power and modulation of LfpH respectively; this effect reached significance 4.8±3.1 min after the start of the injection and lasted for 19.5±5.0 min. The timing of the effects is comparable to the timing of the BOLD signal increase evoked by the same infusion protocol of lactate. In the multiunit activity (MUA, 400-3000 Hz) no significant effect was observed. In summary, by applying lactate, a potential fuel for activated neurons, we increase LfpH power and modulation but not the spiking activity. Since LfpH is a reliable driver of the BOLD signal at least part of the lactate effect on the BOLD signal can be explained by an increase in neuronal activity.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_35355/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Li J{juan}{Department Physiology of Cognitive Processes}; Viswanath S{sviswanath}{Department Physiology of Cognitive Processes}; Zhang X{xiaozhe}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}} } @Poster{ UberoMartinezMAMMAHLLI2012, title = {Hippocampal Formation Projection To Ventral Tegmental Area: An Anatomical Study In The Non-Human Primate}, year = {2012}, month = {7}, volume = {8}, number = {p069.14}, abstract = {The Hippocampal Formation (HF) has a critical role in episodic memory. One of the major components in episodic memory is the encoding of novel stimuli, which is associated to dopaminergic system. Lisman and Grace (2005) proposed that novelty signals in the hippocampus modulate the activity of dopaminergic neurons in the ventral tegmental area (VTA) and that, via a feedback loop, the increase of dopamine in hippocampal neurons promotes the encoding for the novel event. Retrograde tracer studies have demonstrated that the VTA projects directly to the HF in primates (Amaral and Cowan, 1980; Insausti et al., 1987) as well as in rodents. However, whether these projections are reciprocal or not is unknown. Despite this lack of evidence of a direct projection, functional studies indicate that the dopaminergic neurons of the VTA are strongly influenced by the hippocampus indirectly through either lateral septum (Luo et al. 2011) or nucleus accumbens-ventral pallidum pathways (Lisman and Grace 2005). In order to determine the existence of direct inputs from the HF to the VTA and which are the specific fields within the HF responsible of the projection, the retrograde tracers were placed in the mesencephalic ventral and dorsal tegmentum of the Macaca fascicularis monkey, including the VTA. The retrograde cell labeling was analyzed with an epifluorescence microscope coupled to a computerized charting system. Our preliminary results showed scarce labeled cells in the HF, specifically in dorsal subiculum, and deep layers of the caudomedial portion of the entorhinal cortex (subfield EO and medialmost EI). These results clarify the functional HF-VTA loop playing a role in learning and memory, and different neuropsychiatric diseases (schizophrenia, Alzheimer´s and Parkinson's disease.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_33135/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Ubero Martinez MDM{mubero}{Department Physiology of Cognitive Processes}; Mohedano Moriano A; Arroyo Jimenez MDM; Munoz M; Marcos P; Artacho Perula E; Hernandez Mombiela D{dhernandez}{Department Physiology of Cognitive Processes}; Legidos Garcia ME; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Insausti R} } @Poster{ NovitskayaLE2012, title = {Noradrenergic Modulation Of Cortical And Hippocampal Activity During Natural Sleep In Rats}, year = {2012}, month = {7}, volume = {8}, number = {p052.2}, abstract = {The activity of noradrenergic (NA) neurons of the brain stem neuromodulatory nucleus Locus Coeruleus (LC) fluctuates across sleep/wake cycle; LC firing being highest during awake, substantially decreased during slow-wave sleep (SWS) and essentially absent during REM. Due to reduced level of NA during sleep, little attention has been given to the NA modulation of sleep-associated brain rhythms. We recently reported that LC firing is tightly related to the cortical slow oscillations in naturally sleeping rats. Psychiatric disorders, which are characterized by enhanced activity of NA system, are often accompanied by sleep disturbances. Neurophysiological mechanisms underlying this phenomenon remain unknown. The present study aimed to characterize changes in cortical and hippocampal activity produced by increased tonic firing of LC during sleep. Extracellular electrophysiological recordings in cortex and hippocampus were made using linear electrode arrays. The LC activity was modulated by electrical microstimulation via chronically implanted electrode in LC. Trains of pulses (100-500ms, 20-100Hz) were delivered to the LC unilaterally at the onset of SWS every 10s continuously for 10 min. None of the stimulation parameters resulted in behavioral waking up or any visible discomfort of the animal. The LC stimulation with relatively long (50Hz, 500ms) trains of pulses or high-frequency LC stimulation with relatively short trains (100Hz, 100ms) immediately reduced slow wave (1-4Hz) and sigma (12-15Hz) activity in cortex. It resulted in complete elimination of the sleep spindles, characteristic for normal SWS. The slow activity in hippocampus was also strongly affected by LC stimulation. The effect of a single train lasted for up to 6 sec until recovery of neural activity to the baseline level. Our results demonstrate that a mildly elevated LC activity affects a microstructure of the sleep pattern, as indicated by electrophysiological correlates of sleep, without influencing the sleep/awake cycle or inducing behavioral arousal.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_32696/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Novitskaya Y{ynovitskaya}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Eschenko O{oeschenko}{Department Physiology of Cognitive Processes}} } @Poster{ AzevedoALR2012, title = {Responses Of Neurons In The Nucleus Basalis To Visual Stimuli Differing In Their Familiarity, Category And Coherence}, year = {2012}, month = {7}, volume = {8}, number = {p039.28}, abstract = {The nucleus basalis of Meynert (NBM) provides all non-intrinsic cholinergic input to the neocortex. It has been implicated in signal detection and in cortical plasticity. Previous studies have proposed that NBM neurons respond differentially to certain characteristics of a stimulus, such as its familiarity. However, one possible explanation is that the expected reward or other arousal value of the visual stimulus and not familiarity would account for such response selectivity. To test this hypothesis, we tested two monkeys (Macaca mulatta) with visual stimuli presented at the centre of fixation while they performed a fixation task. Single electrodes and tetrodes were implanted in the NBM and the visual responses of single neurons and neuronal ensembles were recorded while three image parameters were changed: 1) familiarity/novelty, 2) image category (monkeys or flowers) and 3) coherence (salience). In all these cases all stimuli had an equal chance of receiving a reward. We selected neurons that had visual responses that exceeded two standard deviations from the spontaneous activity for at least some stimuli for a statistical analysis. Quantification of the response selectivity of these nucleus basalis neurons using a measure of sparseness indicated that they had little selectivity for any of the three factors employed: stimulus novelty, category or coherence. All responsive neurons responded to all types of stimuli employed, including to non-coherent stimuli consisting of white visual noise. This result favours the hypothesis that the determining factor in the responses of nucleus basalis neurons is the association of a stimulus with reward.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_32342/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Azevedo FAC{fazevedo}{Department Physiology of Cognitive Processes}; Aggelopoulos NC{aggelopoulos}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}; Rainer G{gregor}{Department Physiology of Cognitive Processes}} } @Poster{ ZaldivarLvWGRL2012, title = {The Modulatory Role Of Dopamine In The Early Visual System Of Macaques Investigated By Fmri, Neurochemistry And Neurophysiology}, year = {2012}, month = {7}, volume = {8}, number = {p063.19}, abstract = {The presence of dopamine-(DA)-receptors-(DARs) and innervations in early sensory pathways has previously been demonstrated in monkeys and humans. Nonetheless, their possible role in the sensory processing is still far from being understood. Anatomical evidence has shown that DARs are expressed in early-visual-system. These studies indicated that D1Rs are found in primary-visual-cortex, while D2Rs are predominantly expressed in the lateral-geniculate-nucleus-(LGN). D1Rs have a facilitating effect on neuronal processing whereas D2Rs show a dampening effect. Given their differences in anatomical distribution and functionality the two kinds of DARs may have a differential effect on thalamocortical information transfer. Here, we set out to investigate DAergic impact on V1 by using combined fMRI, neurophysiology and neurochemistry measurements in anesthetized non-human-primates, during systemic-application of L-DOPA-Carbidopa (2.1/0.5mg/kg, respectively). Our results show that the stimulus-induced modulation of the BOLD-signal decreases by 40±5% for 10±3min (n=8,p < 0.05). This decrease is concomitant with an improvement in the signal-to-noise-ratio-(SNR) in multi-unit-activity-(MUA: 900-3200Hz) as well as in the CV (p< 0.05) of the theta (4-8Hz), low-gamma (20-60Hz) and gamma (65-120Hz) bands of LFP. In contrast, local application of DA in V1 did not induce any changes in neuronal activity indicating that the observed effects are most probably mediated by D2Rs of LGN. DAergic neuromodulation decreased the SNR of the neuronal recordings in V1 which reflects a sparse and dampened firing pattern. Neurochemical sampling in V1 has shown an increased glutamate/GABA-ratio which might reflect a change in the excitation/inhibition balance induced by DA. The additional measured lactate/pyruvate-ratio has also shown a change indicating a decreased metabolic demand. These findings suggest that the visual inputs are attenuated by the local DAergic-circuitry of LGN (D2Rs) generating sparse and precise neuronal firing in V1. At the same time, however, the reduced mass-activity appears to reduce the energy demands, and the stimulus-induced-modulation of the BOLD-signal.}, web_url = {http://fens.ekonnect.co/FENS_331/poster_33040/program.aspx}, event_name = {8th Forum of European Neuroscience (FENS 2012)}, event_place = {Barcelona, Spain}, state = {published}, author = {Zaldivar D{dzaldivar}{Department Physiology of Cognitive Processes}; Li J{juan}{Department Physiology of Cognitive Processes}; von Pf\"ostl V{vpfoestl}{Department Physiology of Cognitive Processes}; Whittingstall K{kevin}{Department Physiology of Cognitive Processes}; Goense J{jozien}{Department Physiology of Cognitive Processes}; Rauch A{arauch}{Department Physiology of Cognitive Processes}; Logothetis NK{nikos}{Department Physiology of Cognitive Processes}} } @Poster{ PerrodinKLP2012_2, title = {Visual Influences On Neurons In Voice-Sensitive Cortex}, year = {2012}, month = {7}, volume = {8}, number = {p038.23}, abstract = {Many animals use cross-sensory information during communication, but it remains un