This file was created by the Typo3 extension sevenpack version 0.7.14 --- Timezone: CEST Creation date: 2013-05-21 Creation time: 21-08-32 --- Number of references 47 article LogothetisEMASEBO2012 Nature 2012 11 491 7425 547–553 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.nature.com/nature/journal/v491/n7425/full/nature11618.html 10.1038/nature11618 nikosNKLogothetis oeschenkoOEschenko yusukeYMurayama markMAugath steudelTSteudel evrardHCEvrard besserveMBesserve axelAOeltermann article BiessmannMLMM2012 NeuroImage 2012 7 61 4 1031–1042 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science/article/pii/S1053811912003965 10.1016/j.neuroimage.2012.04.015 fbiessmaFBiessmann yusukeYMurayama nikosNKLogothetis klausKRMüller FCMeinecke article EschenkoENBML2011 NeuroImage 2012 2 59 4 3252–3265 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science/article/pii/S1053811911013127 10.1016/j.neuroimage.2011.11.031 oeschenkoOEschenko evrardHCEvrard ricardoRMNeves bayoMBeyerlein yusukeYMurayama nikosNKLogothetis article MagriSMPL2011 Journal of Neuroscience 2012 1 32 4 1395-1407 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.jneurosci.org/content/32/4/1395.full.pdf+html 10.1523/​JNEUROSCI.3985-11.2012 cmagriCMagri schriddeUSchridde yusukeYMurayama stefanoSPanzeri nikosNKLogothetis article MurayamaAL2011 Magnetic Resonance Imaging 2011 12 29 10 1351-1357 We have recently used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in lateral geniculate nucleus (LGN) increases the fMRI signal in the regions of primary visual cortex receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. Intracortical injection experiments showed that such suppression is due to synaptic inhibition. During these experiments, we have consistently observed activation of superior colliculus (SC) following LGN stimulation. Since LGN does not directly project to SC, the current study investigated the origin of SC activation. By examining experimental manipulations inactivating the primary visual cortex, we present here evidence that the robust SC activation, which follows the stimulation of LGN, is due to the activation of corticocollicular pathway. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271222&_user=29041&_pii=S0730725X11002815&_check=y&_origin=&_coverDate=31-Dec-2011&view=c&wchp=dGLbVlk-zSkWb&md5=3345ba26e8571bce55f0cf39b413ca17/1-s2.0-S0730725X11002815-main.pdf 10.1016/j.mri.2011.08.002 yusukeYMurayama markMAugath nikosNKLogothetis article SultanAMTL2011 Magnetic Resonance Imaging 2011 12 29 10 1374-1381 Combining electrical stimulation with fMRI (esfMRI) has proven to be an important tool to study the global effects of electrical stimulation on neural networks in the brain. Here we extend our previous studies to stimulating the upper superior temporal sulcus (STS) in the anesthetized monkey. Our results show that stimulating area V5/MT and surrounding areas leads to positive BOLD responses in the majority of cortical areas known to receive direct/monosynaptic connections from the stimulation site. We confirm our previous results from stimulating primary visual cortex that the propagation of electrically induced activity is limited in its transsynaptic propagation to the first synapse also for extrastriate areas. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271222&_user=29041&_pii=S0730725X11001354&_check=y&_origin=&_coverDate=31-Dec-2011&view=c&wchp=dGLzVBA-zSkWz&md5=1ebff3056d9b781fb0d326346e0f58f1/1-s2.0-S0730725X11001354-main.pdf 10.1016/j.mri.2011.04.005 FSultan markMAugath yusukeYMurayama atoliasASTolias nikosNKLogothetis article WatanabeCMUATL2011 Science 2011 11 334 6057 829-831 Although recent psychophysical studies indicate that visual awareness and top-down attention are two distinct processes, it is not clear how they are neurally dissociated in the visual system. 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 nonsignificant blood oxygenation level–dependent (BOLD) effects in the human primary visual cortex (V1). Directing attention toward and away from the target had much larger and robust effects across all study participants. 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencemag.org/content/334/6057/829.full.pdf 10.1126/science.1203161 watanabeMWatanabe KCheng yusukeYMurayama KUeno TAsamizuya KTanaka nikosNKLogothetis article 6854 ACS Chemical Neuroscience 2010 12 1 12 819-828 Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd3+ complex linked to an aminobis(methylenephosphonate) group for chelating Ca2+ was synthesized and investigated. The longitudinal relaxivity (r1) of this complex decreases during the relaxometric titration with Ca2+ from 5.76 to 3.57 mM&amp;amp;amp;#8722;1 s&amp;amp;amp;#8722;1 upon saturation. The r1 is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu3+ complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium&amp;amp;amp;#8722;diethylenetriaminepentaacetic acid (Gd&amp;amp;amp;#8722;DTPA). http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://pubs.acs.org/doi/pdf/10.1021/cn100083a Biologische Kybernetik Max-Planck-Gesellschaft en 10.1021/cn100083a ilgarIMamedov canalsSCanals JHenig bayoMBeyerlein yusukeYMurayama HAMayer nikosNKLogothetis goranGAngelovski article SultanHMSL2010 Magnetic Resonance Imaging 2010 10 28 8 1159-1164 Flattened representations are a useful approach to represent the convoluted complex surface of the neocortex of primates and other large-brained mammals. In this study, we compared the flattened representation of neocortical areas obtained from the recently published MRI and histology atlas of the rhesus monkey brain (Saleem KS, Logothetis NK. A combined MRI and histology atlas of the rhesus monkey brain in stereotaxic coordinates. London: Academic; 2007) with other previously published maps. Our results confirm that flat map representations are advantageous due to their ease of use and that current flat maps are well comparable to each other. Some differences arise due to different distinguishing criteria and here too flat maps can help to reveal them. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MiamiImageURL&_cid=271222&_user=29041&_pii=S0730725X1000086X&_check=y&_origin=&_coverDate=31-Oct-2010&view=c&wchp=dGLzVlB-zSkzk&md5=dc56dbea6e82bd698ef5b3393ef1e1fe/1-s2.0-S0730725X1000086X-main.pdf 10.1016/j.mri.2010.03.023 FSultan SHamodeh yusukeYMurayama KSSaleem nikosNKLogothetis article 6272 Magnetic Resonance Imaging 2010 10 28 8 1095-1103 Functional magnetic resonance imaging (fMRI) based on the so-called blood oxygen level-dependent (BOLD) contrast is a powerful tool for studying brain function not only locally but also on the large scale. Most studies assume a simple relationship between neural and BOLD activity, in spite of the fact that it is important to elucidate how the “when” and “what” components of neural activity are correlated to the “where” of fMRI data. Here we conducted simultaneous recordings of neural and BOLD signal fluctuations in primary visual (V1) cortex of anesthetized monkeys. We explored the neurovascular relationship during periods of spontaneous activity by using temporal kernel canonical correlation analysis (tkCCA). tkCCA is a multivariate method that can take into account any features in the signals that univariate analysis cannot. The method detects filters in voxel space (for fMRI data) and in frequency–time space (for neural data) that maximize the neurovascular correlation without any assumption of a hemodynamic response function (HRF). Our results showed a positive neurovascular coupling with a lag of 4–5 s and a larger contribution from local field potentials (LFPs) in the γ range than from low-frequency LFPs or spiking activity. The method also detected a higher correlation around the recording site in the concurrent spatial map, even though the pattern covered most of the occipital part of V1. These results are consistent with those of previous studies and represent the first multivariate analysis of intracranial electrophysiology and high-resolution fMRI. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&amp;amp;_imagekey=B6T9D-4Y6T7WF-2-C&amp;amp;_cdi=5112&amp;amp;_user=29041&amp;amp;_pii=S0730725X09003087&amp;amp;_orig=search&amp;amp;_coverDate=01%2F21%2F2010&amp;amp;_sk=999999999&amp;amp;view=c&amp;amp;wchp Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2009.12.016 yusukeYMurayama fbiessmaFBiessmann FCMeinecke klausK-RMüller markMAugath axelAOeltermann nikosNKLogothetis article 6794 Nature Neuroscience 2010 10 13 10 1283-1291 Electrical stimulation has been used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increasing use in electrotherapy and neural prostheses. However, the manner in which electrical stimulation–elicited signals propagate in brain tissues remains unclear. We used combined electrostimulation, neurophysiology, microinjection and functional magnetic resonance imaging (fMRI) to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We found that stimulation of a site in the lateral geniculate nucleus (LGN) increased the fMRI signal in the regions of primary visual cortex (V1) that received input from that site, but suppressed it in the retinotopically matched regions of extrastriate cortex. Consistent with previous observations, intracranial recordings indicated that a short excitatory response occurring immediately after a stimulation pulse was followed by a long-lasting inhibition. Following microinjections of GABA antagonists in V1, LGN stimulation induced positive fMRI signals in all of the cortical areas. Taken together, our findings suggest that electrical stimulation disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.nature.com/neuro/journal/v13/n10/pdf/nn.2631.pdf Biologische Kybernetik Max-Planck-Gesellschaft en 10.1038/nn.2631 nikosNKLogothetis markMAugath yusukeYMurayama arauchARauch FSultan jozienJGoense axelAOeltermann hellmutHMerkle article 6148 Neuroimage 2010 2 49 3 2544-2555 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=PdfDownloadURL&amp;_uoikey=B6WNP-4XM6K9C-1&amp;_tockey=%23toc%236968%239999%23999999999%2399999%23FLA%23&amp;_orig=search&amp;_acct=C000003178&amp;_version=1&amp;_userid=29041&amp;md5=3bf6091d834384671282cddb6fdb75 Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.neuroimage.2009.10.079 oeschenkoOEschenko canalsSCanals ISimanova bayoMBeyerlein yusukeYMurayama nikosNKLogothetis article 5874 NeuroImage 2009 5 45 4 1080-1089 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&amp;_imagekey=B6WNP-4VF56VB-1-7&amp;_cdi=6968&amp;_user=29041&amp;_orig=search&amp;_coverDate=05%2F01%2F2009&amp;_sk=999549995&amp;view=c&amp;wchp=dGLbVlb-zSkWb&amp;md5=89b06d7d2a46322519b4d916c334b3ba&amp;ie= Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.neuroimage.2009.01.010 nikosNKLogothetis yusukeYMurayama markMAugath theodorTSteffen joachimJWerner axelAOeltermann article 4909 Magnetic Resonance Imaging 2008 9 26 7 978-986 The hippocampal formation is a brain system that is implicated in learning and memory. The major input to the hippocampus arrives from the entorhinal cortex (EC) to the dentate gyrus (DG) through the perforant path. In the present work, we have investigated the functional properties of this connection by concomitantly applying electrophysiological techniques, deep-brain electric microstimulation and functional magnetic resonance imaging in anesthetized rats. We systematically delivered different current intensities at diverse stimulation frequencies to the perforant path while recording electrophysiological and blood-oxygenation-level-dependent (BOLD) signals. We observed a linear relationship between the current intensity used to stimulate the hippocampal formation and the amplitude and extension of the induced BOLD response. In addition, we found a frequency-dependent spatial pattern of activation. With stimulation protocols and train frequencies used for kindling, the activity strongly spreads ipsilaterall y through the hippocampus, DG, subiculum and EC. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6T9D-4SH1HXR-B-5&_cdi=5112&_user=29041&_orig=search&_coverDate=09%2F30%2F2008&_sk=999739992&view=c&wchp=dGLzVtb-zSkWz&md5=e7e95446b785f4dd0f51d9b02acb372d&ie=/sdarticle.pdf Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2008.02.018 canalsSCanals bayoMBeyerlein yusukeYMurayama nikosNKLogothetis article 5249 Journal of Neuroscience 2008 5 28 22 5696-5709 Local field potentials (LFPs) reflect subthreshold integrative processes that complement spike train measures. However, little is yet known about the differences between how LFPs and spikes encode rich naturalistic sensory stimuli. We addressed this question by recording LFPs and spikes from the primary visual cortex of anesthetized macaques while presenting a color movie. We then determined how the power of LFPs and spikes at different frequencies represents the visual features in the movie. We found that the most informative LFP frequency ranges were 1&amp;amp;amp;amp;amp;#8211;8 and 60&amp;amp;amp;amp;amp;#8211;100 Hz. LFPs in the range of 12&amp;amp;amp;amp;amp;#8211;40 Hz carried little information about the stimulus, and may primarily reflect neuromodulatory inputs. Spike power was informative only at frequencies &amp;amp;amp;amp;lt;12 Hz. We further quantified "signal correlations" (correlations in the trial-averaged power response to differen t stimuli) and " noise correlatio ns" (trial-by-tr ial correlations in the fluctuations around the average) of LFPs and spikes recorded from the same electrode. We found positive signal correlation between high-gamma LFPs (60&amp;amp;amp;amp;amp;#8211;100 Hz) and spikes, as well as strong positive signal correlation within high-gamma LFPs, suggesting that high-gamma LFPs and spikes are generated within the same network. LFPs &amp;amp;amp;amp;lt;24 Hz shared strong positive noise correlations, indicating that they are influenced by a common source, such as a diffuse neuromodulatory input. LFPs &amp;amp;amp;amp;lt;40 Hz showed very little signal and noise correlations with LFPs &amp;amp;amp;amp;gt;40 Hz and with spikes, suggesting that low-frequency LFPs reflect neural processes that in natural conditions are fully decoupled from those giving rise to spikes and to high-gamma LFPs. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.jneurosci.org/cgi/reprint/28/22/5696 Biologische Kybernetik Max-Planck-Gesellschaft en 10.1523/JNEUROSCI.0009-08.2008 belitskiABelitski arthurAGretton cmagriCMagri yusukeYMurayama MAMontemurro nikosNKLogothetis stefanoSPanzeri article 4894 Neuroimage 2008 4 40 2 458-472 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WNP-4RC6R7X-4-S&_cdi=6968&_user=29041&_orig=search&_coverDate=04%2F01%2F2008&_sk=999599997&view=c&wchp=dGLbVtz-zSkzS&md5=dabfb44094d1137121dd895184e159cc&ie=/sdarticle.pdf Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.neuroimage.2007.12.007 canalsSCanals bayoMBeyerlein akellerALKeller yusukeYMurayama nikosNKLogothetis article 4946 Journal of Neurophysiology 2008 3 99 3 1461-1476 We investigated whether it is possible to infer spike trains solely on the basis of the underlying local field potentials (LFPs). Using support vector machines and linear regression models, we found that in the primary visual cortex (V1) of monkeys, spikes can indeed be inferred from LFPs, at least with moderate success. Although there is a considerable degree of variation across electrodes, the low-frequency structure in spike trains (in the 100-ms range) can be inferred with reasonable accuracy, whereas exact spike positions are not reliably predicted. Two kinds of features of the LFP are exploited for prediction: the frequency power of bands in the high gamma-range (40&amp;amp;amp;amp;amp;amp;#8211;90 Hz) and information contained in lowfrequency oscillations ( 10 Hz), where both phase and power modulations are informative. Information analysis revealed that both features code (mainly) independent aspects of the spike-to-LFP relationship, with the low-frequency LFP phase coding for temporally clustered spiking activity. Although both features and prediction quality are similar during seminatural movie stimuli and spontaneous activity, prediction performance during spontaneous activity degrades much more slowly with increasing electrode distance. The general trend of data obtained with anesthetized animals is qualitatively mirrored in that of a more limited data set recorded in V1 of non-anesthetized monkeys. In contrast to the cortical field potentials, thalamic LFPs (e.g., LFPs derived from recordings in the dorsal lateral geniculate nucleus) hold no useful information for predicting spiking activity. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://jn.physiology.org/cgi/reprint/99/3/1461 Biologische Kybernetik Max-Planck-Gesellschaft en doi:10.1152/jn.00919.2007 raschMJRasch arthurAGretton yusukeYMurayama WMaass nikosNKLogothetis article 5115 Current Biology 2008 3 18 5 375-380 We investigated the hypothesis that neurons encode rich naturalistic stimuli in terms of their spike times relative to the phase of ongoing network fluctuations rather than only in terms of their spike count. We recorded local field potentials (LFPs) and multiunit spikes from the primary visual cortex of anaesthetized macaques while binocularly presenting a color movie. We found that both the spike counts and the low-frequency LFP phase were reliably modulated by the movie and thus conveyed information about it. Moreover, movie periods eliciting higher firing rates also elicited a higher reliability of LFP phase across trials. To establish whether the LFP phase at which spikes were emitted conveyed visual information that could not be extracted by spike rates alone, we compared the Shannon information about the movie carried by spike counts to that carried by the phase of firing. We found that at low LFP frequencies, the phase of firing conveyed 54% additional information beyond that conveyed by spike counts. The extra information available in the phase of firing was crucial for the disambiguation between stimuli eliciting high spike rates of similar magnitude. Thus, phase coding may allow primary cortical neurons to represent several effective stimuli in an easily decodable format. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6VRT-4S0GXTD-7-B&_cdi=6243&_user=29041&_orig=search&_coverDate=03%2F11%2F2008&_sk=999819994&view=c&wchp=dGLzVlz-zSkzk&md5=cb1a6bb2099bc83600ddc8cc9656be3b&ie=/sdarticle.pdf Biologische Kybernetik Max-Planck-Gesellschaft en http://dx.doi.org/10.1016/j.cub.2008.02.023 MAMontemurro raschMJRasch yusukeYMurayama nikosNKLogothetis stefanoSPanzeri article 3989 Magnetic Resonance Imaging 2006 4 24 4 401-409 http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/artifactFmri_3989[0].pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&amp;amp;amp;amp;_imagekey=B6T9D-4JS20BB-1-S&amp;amp;amp;amp;_cdi=5112&amp;amp;amp;amp;_user=29041&amp;amp;amp;amp;_orig=browse&amp;amp;amp;amp;_coverDate=05%2F31%2F2006&amp;amp;amp;amp;_sk=999759995&amp;amp;am Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2005.12.036 arthurAGretton belitskiABelitski yusukeYMurayama bsBSchölkopf nikosNKLogothetis article 3986 Magnetic Resonance Imaging 2006 3 24 4 349-358 The application of MRI-visible paramagnetic tracers to reveal in vivo connectivity can provide important subject-specific information for multisite, multielectrode intracortical recordings in combined behavioral and physiology experiments. To establish the use of such tracers in the nonhuman primate, we recently compared the specificity of the anterograde tracer Mn2+ with that of wheat-germ-agglutinin conjugated to horseradish peroxidase (WGA-HRP) in experiments tracing the neuronal connections of the basal ganglia of the monkey. It was shown that Mn2+ and WGA-HRP yield the same projection patterns and that the former tracer crosses at least two synapses, for it could be found in thalamus following injections into the striatum. Here we provide evidence that Mn2+ reaches the cortex following striatum injections and, thus, is transferred even further than previously shown. In other words, used as a paramagnetic MRI tracer, Mn2+ can permit the visualization of neural networks covering at least four processing st ages. Moreover, unilateral intravitreal injections show that Mn2+ is sufficiently synapse specific to permit visualization of the lamina of the dorsal lateral geniculate nucleus (dLGN). Interestingly, the transfer rate of the substance reflected the well-known axonal size differences between the parvocellular and magnocellular layers of dLGN. After intravitreal injections, we were able to demonstrate transfer of Mn2+ into several subcortical and cortical areas, including the inferotemporal cortex. The specificity of the transsynaptic transfer of manganese that we report here indicates the value of this tracer for chronic studies of development and plasticity, as well as for studies of brain pathology. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science?_ob=MImg&amp;_imagekey=B6T9D-4JHMRYV-2-C&amp;_cdi=5112&amp;_user=29041&amp;_orig=browse&amp;_coverDate=05%2F31%2F2006&amp;_sk=999759995&amp;view=c&amp;wchp=dGLbVzb-zSkWW&amp;md5=90b5c081dc0a86b8f124af1027602bb5&amp;ie= Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2005.12.031 yusukeYMurayama weberBWeber SSKadharbatcha markMAugath nikosNKLogothetis article 2054 Cerebral Cortex 2003 4 13 4 422-433 We examined fluctuations in band-limited power (BLP) of local field potential (LFP) signals recorded from multiple electrodes in visual cortex of the monkey during different behavioral states. We asked whether such signals demonstrated coherent fluctuations over time-scales of seconds and minutes, and would thus serve as good candidates for direct comparison with data obtained from functional magnetic resonance imaging (fMRI). We obtained the following results. (i) The BLP of the local field displayed fluctuations at many time-scales, with particularly large amplitude at very low frequencies (<0.1 Hz). (ii) These fluctuations exhibited high coherence between electrode pairs, particularly for BLP signals derived from the gamma (g) frequency range. (iii) Coherence in the BLP, unlike that in the raw LFP, did not fall off sharply as a function of cortical distance. (iv) The structure and coherence of BLP changes were highly similar under distinctly different behavioral states. These results demonstrate the existence of widespread coherent activity fluctuations in the brain of the awake monkey over very long time-scales. We propose that such signals may make a significant contribution to the high variability observed in the time course of physiological signals, including those measured with functional imaging techniques. The results are discussed in the context of combined fMRI/electrophysiological recordings. http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/pdf2054.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://cercor.oxfordjournals.org/content/13/4/422.full.pdf+html Biologische Kybernetik Max-Planck-Gesellschaft 10.1093/cercor/13.4.422 davidlDALeopold yusukeYMurayama nikosNKLogothetis article 1319 Cerebral Cortex 2002 12 62-74 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Biologische Kybernetik Max-Planck-Gesellschaft YWang IFujita HTamura yusukeYMurayama article 1589 Nature Neuroscience 2000 3 8 807-813 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Biologische Kybernetik Max-Planck-Gesellschaft YWang IFujita yusukeYMurayama inproceedings 3174 AISTATS 2005 2005 1 112-119 We discuss reproducing kernel Hilbert space (RKHS)-based measures of statistical dependence, with emphasis on constrained covariance (COCO), a novel criterion to test dependence of random variables. We show that COCO is a test for independence if and only if the associated RKHSs are universal. That said, no independence test exists that can distinguish dependent and independent random variables in all circumstances. Dependent random variables can result in a COCO which is arbitrarily close to zero when the source densities are highly non-smooth. All current kernel-based independence tests share this behaviour. We demonstrate exponential convergence between the population and empirical COCO. Finally, we use COCO as a measure of joint neural activity between voxels in MRI recordings of the macaque monkey, and compare the results to the mutual information and the correlation. We also show the effect of removing breathing artefacts from the MRI recording. http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/pdf3174.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://www.gatsby.ucl.ac.uk/aistats/proceedings.htm Cowell, R. , Z. Ghahramani AISTATS 2005 Biologische Kybernetik Max-Planck-Gesellschaft MPI for Biological Cybernetics, Spemannstr 38 72076 Tuebingen Barbados Tenth International Workshop on Artificial Intelligence and Statistics (AI & Statistics 2005) en 0-9727358-1-X arthurAGretton smolaAJSmola bousquetOBousquet RHerbrich belitskiABelitski markMAugath yusukeYMurayama jpaulsJPauls bsBSchölkopf nikosNKLogothetis poster BesserveBML2012 2012 10 42 507.20 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. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Department Schölkopf http://www.sfn.org/am2012/ New Orleans, LA, USA 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012) besserveMBesserve abartelsABartels yusukeYMurayama nikosNKLogothetis poster PanzeriMKMQML2011 2011 11 41 483.10 Natural visual environments contain a variety of continuously changing visual features . In order to represent the richness of such environments, neurons in visual areas need to encode information both about “what” aspects of the visual world (for example, the level of contrast) and how these aspects change over time. So far, little is known about how the responses of visual cortical neurons can encode both types of information concurrently. Here we explored the hypothesis that aspects of visual features defined on different time scales are to some extent encoded by different aspects of the neural responses. We recorded single unit activity and LFPs in primary visual cortex of anaesthetized macaques during the binocular presentation of naturalistic color movies. By means of computational analysis, we extracted two visual features from the area of the movie inside the receptive fields (RFs) of each single neuron. The first was the Michelson contrast in the RF. The second was a form of temporal contrast, quantifying the average frame to frame variations of pixel luminance in the RF. We then used information theoretic analysis to investigate systematically which types of neural codes carried information either about the current value of these features in each frame or about the time course of these features on slower time scales. We found that spike rates encoded both the current value and the frame by frame change of the Michelson contrast, but did not encode information about the time course of these features on slower time scales. We then considered the information carried by the “phase of firing”, defined as the timing of spikes measured with respect to the phase of low frequency [1-4 H] Local Field Potential fluctuations. The phase of firing carried information about the temporal changes of contrast over a time scale of several hundred milliseconds (which are the scales carrying the most power in natural movies), but did not carry information about the current value of contrast in each frame or about its frame to frame variations. These results demonstrate that different aspects of visual features, such as their current value and their dynamics on slow time scales, are represented in complementary neural codes operating on different time scales. They hence suggest that the nervous system uses multiplexing to keep a simultaneous representation of several important aspects of the external world. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Research Group Kayser Department Logothetis http://www.sfn.org/am2011/ Washington, DC, USA 41st Annual Meeting of the Society for Neuroscience (Neuroscience 2011) stefanoSPanzeri AMazzoni kayserCKayser yusukeYMurayama RQuian Quiroga JMartinez nikosNKLogothetis poster MagriSPML2011 BMC Neuroscience 2011 7 12 Suppl 1 P204 Blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most widely used noninvasive imaging technique for investigating brain activity. However, the BOLD signal is only indirectly coupled to the underlying neural activity and the relationship between the two signals is not fully understood [1]. Recordings in anaesthetized and awake monkeys have shown that hemodynamic responses are strongly related to local field potentials (LFPs) [2,3]. LFPs are thought to represent the input and intracortical processing in a cortical area and are usually separated into different frequency bands that reflect different neural processes [4]. Previous studies have shown that different LFP bands correlate differently with the BOLD signal [3,5,6]. However little is known about which property of the BOLD signal is reflected by each band and whether different bands convey different information about the BOLD signal. To address this question we performed simultaneous recordings of neural activity and BOLD fMRI in early visual areas V1 and V2 in 4 anesthetized monkeys. All measurements were performed with the monkeys sitting in complete darkness while no stimulus was being presented. We computed mutual information between LFP power and BOLD fMRI to determine which frequencies in the LFPs were most informative about the BOLD signal. We found three highly informative bands, namely the alpha band [8-12Hz], the gamma band [40-100Hz] and the [18-35 Hz] “nMod” band that was previously found to be unrelated to visual stimuli and was thus suggested to primarily reflect neuromodulatory input [4]. We found that gamma power was the most informative about BOLD fMRI and reflected well changes in the amplitude of the BOLD signal. In particular, an increase in gamma power above its median value was followed, on average, by an increase in BOLD signal, and the BOLD signal decreased, instead, following a decrease in gamma power below its median. Moreover, we found that gamma and nMod power were complementary, i.e. that by combining nMod power together with gamma power we could extract 30% more information than could be extracted from gamma power alone. We investigated the origin of this complementarity and we found that the power in the nMod band reflected the timing with which changes in BOLD signal occurred following changes in gamma power. Finally, we found that, as suggested by previous theoretical work [7], an increase in alpha power without a change in total LFP power was followed by a decrease in BOLD signal and vice versa. These results indicate that distinct neural processes are reflected differently in the BOLD signal and that, consequently, it may be possible to retrieve information about the different contributions from the recorded BOLD time course. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.biomedcentral.com/content/pdf/1471-2202-12-S1-P204.pdf Stockholm, Sweden Twentieth Annual Computational Neuroscience Meeting (CNS*2011) 10.1186/1471-2202-12-S1-P204 cmagriCMagri schriddeUSchridde stefanoSPanzeri yusukeYMurayama nikosNKLogothetis poster MazzoniKMMQLP2011 BMC Neuroscience 2011 7 12 Suppl 1 P248 The natural visual environment is characterized by both “what/where” aspects (image features such as contrast or orientation which are defined by the relationship between visual signals simultaneously presented at different points in space) and “when” aspects, describing the temporal variations of the image features. Both “when” and “what/where” information is necessary to describe and understand the natural visual environment, and to take appropriate behavioral decisions. While “where” can be considered embedded as retinotopy, it is likely that localized neural populations in the visual cortex keep a simultaneous representation of both “what” and “when” aspects of the visual stimuli. However, little is yet known about how the spike trains of neurons in primary visual cortex encode both sources of information. The traditional hypothesis in systems neuroscience is that sensory variables are represented by a rate code, i.e. all sensory information is encoded by the number of spikes emitted over relatively long time windows. Although the relevance of rate in encoding static features is well established, this code can be inherently ambiguous in changing environments [1] and it is unlikely that this code is rich enough to represent simultaneously different types of information. Therefore here we explore the hypothesis that the timing of spikes is a crucial variable in representing both “what” and “when” aspects of the natural visual environment. To address these issues, we recorded single unit activity and LFPs in primary visual cortex of opiate anaesthetized macaques during the binocular presentation of naturalistic color movies. By means of computational analysis, we extracted several image features (color, orientation, luminance, space and time contrast, motion) from the receptive fields of each single neuron. We then considered two different spike timing codes previously studied in both the auditory [2] and the visual cortex [3]. In the first code, which we call spike patterns code, sequences of spike times from single neurons are measured (with a resolution of the order of 10 ms) with respect to the time course of the external stimulus. In the second code, which we call phase of firing code, spikes are measured with respect to the phase of the concurrent low frequency LFPs recorded from the same electrode as the spikes. We then used these data to investigate systematically which types of neural codes carry information about the static features of the image and which neural codes carry information about the time course of these features. We found that both “when” and “what” aspects are encoded simultaneously by spike times of visual cortical neurons. However, “what” and “when” are encoded by two different neural information streams; “what” aspects are encoded (on a fine scale of few ms) by spike patterns, and “when” stimulus aspects are encoded by the phase of firing (on a coarse scale of hundreds of ms). http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Research Group Kayser Department Logothetis http://www.biomedcentral.com/1471-2202/12/S1/P248 Stockholm, Sweden Twentieth Annual Computational Neuroscience Meeting (CNS*2011) 10.1186/1471-2202-12-S1-P248 AMazzoni kayserCKayser yusukeYMurayama JMartinez RQQuiroga nikosNKLogothetis stefanoSPanzeri poster 7067 2010 11 40 553.13 Recently, it was shown that the power of high frequency bands like gamma (>40 Hz) or spiking rate of cortical neurons is modulated by the phase of low frequency bands (especially delta 1-4Hz) - referred to as cross-frequency coupling (CFC). CFC has been shown in wakefulness and under anesthesia during either spontaneous activity or sensory stimulation; and might play an important role in sensory processing and influencing information flow in brain. Here we studied CFC within and between early visual areas V1 and V2 in three anesthetized monkeys (Macaca mulatta). We simultaneously recorded spontaneous activities from 2+2 electrodes localized in V1 and V2 respectively. The signals were filtered into delta (1-4 Hz), low-gamma (20-60 Hz), gamma (65-120 Hz), high-gamma (125-300 Hz) and multiple unit activity (MUA) (900-3200 Hz). The amplitude envelop for low-gamma, gamma, high-gamma and MUA, along with the instantaneous phase [-π, π] for the delta band were extracted using the Hilbert transform. CFC between delta-phase and the amplitude of low-gamma, gamma, high-gamma and MUA was first calculated separately for V1 and V2, and then between V1 and V2 (e.g. comparing the phase of V1 with the power of V2). We found significant CFC in V1 and V2, as well as between V1 and V2. While there were no differences in CFC within the same areas, we observed differences in CFC between the various frequency bands studied and between different areas. Generally the peak for the low-gamma amplitude fell onto the rising phase of the delta oscillation, while the amplitude of the gamma band peaked during the negative slope of the delta phase. The amplitude for high-gamma and MUA peaked when delta was in its negative trough (0 phase). Interestingly, while the preferred phase for intra-area CFC was always around zero, combining the delta phase from either V1 or V2 with the amplitude of the high frequency signals from either V2 or V1 revealed a different picture. When taking the delta phase from V1, the preferred phase of the amplitude of high frequency signals from V2 fell onto the rising phase of the delta oscillation; however, when the delta phase came from V2, the amplitudes of the high frequency bands in V1 peaked during the negative slope of the delta oscillation. Our data suggest that CFC is a general property of the early visual areas, and that different profiles of inter-area CFC might reflect feed forward and feedback processing between cortical areas. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/am2010/index.aspx?pagename=abstracts_main Biologische Kybernetik Max-Planck-Gesellschaft San Diego, CA, USA 40th Annual Meeting of the Society for Neuroscience (Neuroscience 2010) en schriddeUSchridde kevinKWhittingstall yusukeYMurayama nikosNKLogothetis poster 7046 2010 11 40 616.2 Functional correlates of Rhythms in the gamma band (30-100Hz) are observed in the mammalian brain with a large variety of functional correlates. Nevertheless, their functional role is still debated. One way to disentangle this issue is to go beyond usual correlation analysis and apply causality measures that quantify the directed interactions between the gamma rhythms and other aspects of neural activity. These measures can be further compared with other aspects of neurophysicological signals to find markers of neural interactions. In a recent study, we analyzed extracellular recordings in the primary visual cortex of 4 anesthetized macaques during the presentation of movie stimuli using a causality measure named Transfer Entropy. We found causal interactions between high frequency gamma rhythms (60-100Hz) recorded in different electrodes, involving in particular their phase, and between the gamma phase and spiking activity quantified by the instantaneous envelope of the MUA band (1-3kHz). Here, we further investigate in the same dataset the meaning of these phase-MUA and phase-phase causal interactions by studying the distribution of phases at multiple recording sites at lags around the occurrence of spiking events. First, we found a sharpening of the gamma phase distribution in one electrode when spikes are occurring in other recording site. This phenomena appeared as a form of phase-spike synchronization and was quantified by an information theoretic measure. We found this measure correlates significantly with phase-MUA causal interactions. Additionally, we quantified in a similar way the interplay between spiking and the phase difference between two recording sites (reflecting the well-know concept of phase synchronization). We found that, depending on the couple of recording site, spiking can correlate either with a phase synchronization or with a desynchronization with respect to the baseline. This effect correlates very well with the phase-phase causality measure. These results provide evidence for high frequency phase-spike synchronization to reflect communication between distant neural populations in V1. Conversely, both phase synchronization or desynchronization may favor neural communication between recording sites. This new result, which contrasts with current hypothesis on the role of phase synchronization, could be interpreted as the presence of inhibitory interactions that are suppressed by desynchronization. Finally, our findings give new insights into the role of gamma rhythms in regulating local computation in the visual cortex. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://www.sfn.org/am2010/index.aspx?pagename=abstracts_main Biologische Kybernetik Max-Planck-Gesellschaft San Diego, CA, USA 40th Annual Meeting of the Society for Neuroscience (Neuroscience 2010) en besserveMBesserve yusukeYMurayama bsBSchölkopf nikosNKLogothetis stefanoSPanzeri poster 6816 2010 6 2010 77 Natural stimuli modulate the activity of visual cortex on a variety of temporal scales, yet it is still unclear whether visual cortical neurons employ more than one response time scale to encode such stimuli. We investigated this issue by analyzing the activity of neurons recorded in primary visual cortex (V1) of anesthetized macaques during binocular presentation of naturalistic color movies, and we used information theory to quantify the amount of information carried by neural codes operating at different temporal scales. We divided the recording time into stimulus windows of 40–80 ms, and we computed the information carried by the neural response in each window about which stimulus window was being shown. First we measured the information carried by the spike count, simply quantified by the total number of spikes in the stimulus window. Then we measured the information carried by the temporal pattern of spikes, the latter being computed by subdividing each stimulus window into smaller time bins of size Δt and converting the spike train into a sequence of 0s and 1s denoting the absence/presence of spikes inside each bin [1]. When considering temporal patterns of spikes with a temporal resolution Δt of 8 or 16 ms, the information about which part of the movie was being shown conveyed by temporal spike patterns was up to 15% more than that conveyed by the spike count. This information gain did not increase further when considering resolutions finer than 8 ms, indicating that spike patterns carry information with a resolution of 8–16 ms or coarser. A previous study [2] showed that V1 neurons encode information also with respect to the phase of low frequency (1–4 Hz range) Local Field Potential (LFP) fluctuations. We investigated whether spike patterns carried information complementary to that carried by the phase of firing by quantifying if the joint knowledge of the precise spike pattern and the LFP phase of firing carried more information than either code considered alone. We found that this was the case: The information about the scene of the movie being shown gained by the simultaneous knowledge of the phase of low frequency LFPs and of the spike patterns occurred [3] was 50% higher than the information carried by spike patterns alone and 15 % higher than the information carried by the phase of firing alone. This suggests that the information carried by slow LFP fluctuations complements that carried by spike patterns. In summary, we found evidence for multiple and complementary response time scales for the encoding of naturalistic stimuli in visual cortex. Informative codes range from spike timing precision at 10ms resolution to the much coarser phase of firing with respect to low frequency (few Hz) fluctuations. These findings suggest that, as hypothesized e.g. in [3,4], sensory cortices may enhance their information capacity by multiplexing complementary information at different time scales. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Research Group Kayser http://www.areadne.org/2010/home.html Hatsopoulos, N. G., S. Pezaris Biologische Kybernetik Max-Planck-Gesellschaft Santorini, Greece AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles en AMazzoni kayserCKayser yusukeYMurayama JMartinez RQQuiroga nikosNKLogothetis stefanoSPanzeri poster 6813 2010 6 2010 51 Neural activity in the brain is correlated with the blood-oxygen level dependent (BOLD) contrast which can be measured non-invasively by functional magnetic resonance imaging (fMRI). Up to date, many fMRI analysis methods are based on simplifying assumptions about the BOLD signal. Two popular assumptions are spatial independence and homogeneity of the haemodynamic response function (HRF) across voxels. As single voxels usually are not independent and moreover also exhibit different haemodynamic response characteristics, these assumptions might lead astray interpretations of fMRI data. In this study we present an analysis framework that reveals the spatio-temporal correlation structure between simultaneously measured intracortical neurophysiological activity in primary visual cortex of the non-human primate and BOLD response. Given the spectrograms of neurophysiological activity and the simultaneously recorded BOLD data we compute a spatiotemporal convolution that links the activity measured at the electrode to the multivariate BOLD response. The convolution can be interpreted as the pattern in time-voxel space that reflects best the neural activity as it maximises the canonical correlation [1] between neural and haemodynamic activity. Inspection of the estimated time-voxel patterns yields new insights in the spatio-temporal dependency structure of neurovascular coupling mechanisms. This study thereby extends previous results reported in [2,3], where the convolution was a time-frequency convolution estimated for the neurophysiological activity. We show results from data collected during spontaneous activity and during visual stimulation. The analysis resulted in robust spatio-temporal coupling patterns across different experimental conditions. We compared the multivariate patterns with univariate coupling measures and spatial principal component analysis (SPCA), a popular method for connectivity analysis on fMRI data. Our findings suggest that neither univariate methods nor unimodal methods such as SPCA, which are based on autocorrelations of fMRI data only, can recover the multivariate spatio-temporal coupling structure in primary visual cortex. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.areadne.org/2010/home.html Hatsopoulos, N. G., S. Pezaris Biologische Kybernetik Max-Planck-Gesellschaft Santorini, Greece AREADNE 2010: Research in Encoding And Decoding of Neural Ensembles en fbiessmaFBiessmann yusukeYMurayama FCMeinecke nikosNKLogothetis klausK-RMüller poster 6285 2009 10 39 367.21 The CNS consists of a large number of neurons organized in different brain regions and connected into a complex network. Studies of the connectivity of the brain has emphasized the point to point direct connections between brain regions. However, it has often been argued that in principle only a few synaptic steps are required to propagate activity from any location in the brain to any other. Hence not surprisingly questions regarding the efficacy, gating properties and coincident activation have become important issues as to how activity is propagated polysynaptically. The advent of the method of esfMRI - combining electrical stimulation with fMRI - has provided us with a new method to study the connectivity in spatially distributed networks. Here we show that electrical stimulation of the deep cerebellar nuclei (DCN) reveals BOLD responses in different brain sites that are only indirectly connected to the stimulation site, in fact we observe BOLD responses in brain sites that are dislodged away by at least three synaptic steps from the DCN. Hence we show that some neuronal pathways can propagate synchronous stimuli effectively and can lead to the activity of widespread brain regions via polysynaptic pathways that have not been considered so far. These findings are in marked contrast to our previous observations of a lack of propagation of electrically induced activation when stimulating neocortical brain sites (Tolias et al. 2005). Hence, our findings point to surprisingly divergent behaviours in different networks in their ability to propagate synchronous activity. We speculate that under physiological conditions these excitable subcortical networks are controlled by the inhibition of the cerebellar cortex which in our experiments is short-circuited by electrical stimulating the DCN. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=aa77b529-16c6-4a04-9bcb-f2d0780872b0&cKey=21bfa24c-ac10-43f7-9822-9a476aaa6d19 Biologische Kybernetik Max-Planck-Gesellschaft Chicago, IL, USA 39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009) en FRSultan markMAugath SHamodeh yusukeYMurayama PThier nikosNKLogothetis poster 4996 2007 11 37 103.18 Local Field Potentials (LFP) and Multiple Unit Activity (MUA) are indicators of perisynaptic and spiking activity respectively. An analysis of changes in dependence between these two types of signals may help us understand computations at the level of small networks and characterize the type of processing carried out by a cortical area. The goal of our research is to develop a principled and theoretically sound approach to measuring the information content of electrical signals in the brain (LFPs and spikes), as it relates to stimulus. Traditionally, the LFP has been broken up into a series of well established bands from the EEG literature (delta, alpha, beta), however it is not clear that this decomposition is maximally informative in relating the stimulus and response. To better understand this issue we analyze multiple electrode recordings from the macaque primary visual cortex (V1), under stimulation by continuous natural movies. We first decompose the information about the stimulus, contained in the LFPs and spikes, into different frequency bands, so as to determine which parts of the signal carry the most stimulus content. We also determine the interaction between different LFP and spike frequencies, and test the extent to which these interactions are stimulus driven. In this way, we are able to determine whether bands are synergistic (contain more information jointly than if viewed separately), independent, or redundant. This analysis leads to a frequency decomposition methodology for the LFP that follows the signal structure, rather than prior beliefs; clarifies the dependence between different LFP frequencies and spikes; and gives insight into the neurophysiological mechanisms for stimulus encoding. We further measure the effect of temporal resolution on these information theoretic quantities, to determine the timescale over which information transfer occurs. It is also possible to extract component features from the input stimulus, using image processing methods: examples include flow fields, frame-to-frame per-pixel differences, contrast, luminance, and low and high frequency power in each frame. We investigate the extent to which neural activity is driven by particular stimulus features, and find the fraction of total information transmission associated with each of these. Finally, we investigate the information between neural signals as a function of separation between recording sites. In particular, it can be determined, as a function of signal frequency, the distance at which no significant dependence of any kind exists between signals; this may then be compared to known anatomical features (e.g column width) of the cortex. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://www.sfn.org/am2007/ Biologische Kybernetik Max-Planck-Gesellschaft San Diego, CA, USA 37th Annual Meeting of the Society for Neuroscience (Neuroscience 2007) en belitskiABelitski arthurAGretton cmagriCMagri yusukeYMurayama MMontemurro nikosNKLogothetis stefanoSPanzeri poster 4616 2007 5 2007 2464 481 One of the main problems in systems biology is to obtain information between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge the applicability of this technique. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. On the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps.Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/07/ Biologische Kybernetik Max-Planck-Gesellschaft International Society of Magnetic Resonance in Medicine Berlin, Germany 2007 Joint Annual Meeting ISMRM-ESMRMB en canalsSCanals bayoMBeyerlein akellerALKeller yusukeYMurayama nikosNKLogothetis poster 4302 Neuroforum 2007 4 13 Supplement 1221 One of the main problems in systems biology is to obtain information on signal processing between interconnected groups of neurons in highly distributed networks. The recently introduced technique of manganese (Mn2+) enhanced MRI (MEMRI) to study neuronal connectivity in vivo opens the possibility to these studies. However, several drawbacks exist that challenge its applicability. High Mn2+ concentrations produce cytotoxic effects that can perturb the circuits under study. In the other hand, the MR signal is proportional to the Mn2+ concentration in tissue and thus, significant amounts of Mn2+ are required to produce detectable contrast and reliable connectivity maps. Here we attempt to optimize the MEMRI technique by preventing toxicity and improving the quality and extension of the obtained connectivity maps. The somatosensory cortex of male SD rats was stereotaxically injected with different Mn2+-containing solutions. Total amount of injected Mn2+ ranged between 1 and 16 nmol and the injected volumes between 10 and 80 nL. Osmolarity and pH effects were investigated injecting pH buffered solutions of Mn2+ (pH 7.3 in Tris-HCl buffer vs. 5.5 in H2O) at different concentration (0.05, 0.1 and 0.8 M MnCl2). Same amounts of Mn2+ (8nmol) delivered to the tissue at different infusion rates were also compared. Following the injection, T1-weighted MR imaging (250 mm isotropic resolution) was performed in a 7T scanner at different time points. Fifteen days after the injection animals were sacrificed and brains processed for histology. Nissl staining as well as GFAP and NeuN immunohistochemistry (selective staining for astrocytes and neurons, respectively) were performed in the brain sections to examine cellular toxicity. All injections produced connectivity maps consistent with the known anterograde projections of SI cortex based on classical neuronal tract-tracing techniques. Our results show that pH buffered solution improve the effectiveness of MEMRI, increasing T1 contrast in the projection sites. In addition, injections of pH buffered and isotonic solutions of 50 and 100 mM MnCl2 yielded more extensive connectivity maps, in particular, ipsiand contra-lateral corticocortical connections were evident in all animal injected with those solutions but not with the more usual MEMRI protocol (0.8M MnCl2 in H2O). Hypertonic and non-buffered solutions containing 8nmol Mn2+ resulted in neuronal death and astrogliosis in extensive areas around the injection point. In sharp contrast, no neuronal toxicity was observed with injections containing up to 8nmol of Mn2+ in isotonic solutions of up to 100 mM MnCl2 and pH 7.3. Slow infusion rates demonstrated also to be advantageous and permitted application of larger amounts of Mn2+ without toxic effects, resulting in better T1 contrast in the low density projection fields. Any sign of toxicity was observed in any condition in the projection fields. We conclude that refined protocols for MEMRI improve the quality and extension of connectivity maps and preserves tissue viability, assuring the application of this technique in longitudinal experiments. http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/T38-4C_4302[0].pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.neuro.uni-goettingen.de/nbc.php?sel=archiv Biologische Kybernetik Max-Planck-Gesellschaft Göttingen, Germany 31st Göttingen Neurobiology Conference en canalsSCanals bayoMBeyerlein akellerALKeller yusukeYMurayama nikosNKLogothetis poster GrettonBMSL2005 2005 11 35 689.17 A fundamental problem in neuroscience is determining whether or not particular neural signals are dependent. The correlation is the most straightforward basis for such tests, but considerable work also focuses on the mutual information (MI), which is capable of revealing dependence of higher orders that the correlation cannot detect. That said, there are other measures of dependence that share with the MI an ability to detect dependence of any order, but which can be easier to compute in practice. We focus in particular on tests based on the functional covariance, which derive from work originally accomplished in 1959 by Renyi. Conceptually, our dependence tests work by computing the covariance between (infinite dimensional) vectors of nonlinear mappings of the observations being tested, and then determining whether this covariance is zero - we call this measure the constrained covariance (COCO). When these vectors are members of universal reproducing kernel Hilbert spaces, we can prove this covariance to be zero only when the variables being tested are independent. The greatest advantage of these tests, compared with the mutual information, is their simplicity – when comparing two signals, we need only take the largest eigenvalue (or the trace) of a product of two matrices of nonlinearities, where these matrices are generally much smaller than the number of observations (and are very simple to construct). We compare the mutual information, the COCO, and the correlation in the context of finding changes in dependence between the LFP and MUA signals in the primary visual cortex of the anaesthetized macaque, during the presentation of dynamic natural stimuli. We demonstrate that the MI and COCO reveal dependence which is not detected by the correlation alone (which we prove by artificially removing all correlation between the signals, and then testing their dependence with COCO and the MI); and that COCO and the MI give results consistent with each other on our data. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Schölkopf Department Logothetis http://www.sfn.org/absarchive/ Washington, DC, USA 35th Annual Meeting of the Society for Neuroscience (Neuroscience 2005) arthurAGretton belitskiABelitski yusukeYMurayama bsBSchölkopf nikosNKLogothetis poster FustPAOML2003 2003 11 33 69.14 The state of unconsciousness during anaesthesia is not characterized by a global disruption of CNS activity. Instead consciousness is mediated by a specific subset of brain states or processes selectively affected by anaesthetics. Our aim is to study the action sites of different types of anaesthetics in the monkey brain (M. mulatta). Here we report on the neural effects of Ketamine, a dissociative anaesthetic acting primarily on the NMDA receptor, and Midazolam, a benzodiazepine affecting GABA(A)-receptors. Ketamine exhibits both inhibitory and excitatory effects at different brain sites. Midazolam, however, is known to increase the GABA(A)-receptor function, and therefore to inhibit cortical activity. To study the primary sites-of-action of these agents in the monkey brain, high-resolution functional magnetic resonance imaging (fMRI) was used to measure stimulus induced activity changes in the alert and anaesthetized monkey. The activity of neurons in visual cortex was recorded during scanning, as well as in separate experiments outside the scanner. Following the acquisition of base-line data, a bolus of the test-substance was applied intravenously via a computerized infusion pump. Brain activity was monitored continuously before, during and after the infusion. The data presented here focus on the effects of anaesthetics on subthreshold and spiking activity and the BOLD-signal. A comparison of the influences on these different neural signals allows studying the site and type of action of anaesthetics in more detail. In addition it has the potential to afford further insights into the neural processes underlying the BOLD-signal. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/index.aspx?pagename=annualmeeting_futureandpast New Orleans, LA, USA 33rd Annual Meeting of the Society for Neuroscience (Neuroscience 2003) AFust jpaulsJPauls markMAugath axelAOeltermann yusukeYMurayama nikosNKLogothetis poster 2404 NeuroImage 2003 6 19 2:Supplement e567-e568 Negative BOLD responses (NBRs; i.e. below baseline) are pervasive in human fMRI experiments, but commonly ignored. A recent study characterized a robust sustained NBR in the human occipital cortex, triggered by stimulating part of the visual-field (Shmuel et al., 2002). The NBR depends on the pattern of neuronal activity and is coupled to the positive BOLD response (PBR). The NBR is correlated with reductions in cerebral blood flow (CBF) and with decreases in oxygen consumption. The findings from this human study corroborate contributions to the NBR by 1) a significant component of reduction in neuronal activity and possibly 2) a component of hemodynamic changes independent of the local changes in neuronal activity. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sciencedirect.com/science/article/pii/S1053811905700033 Biologische Kybernetik Max-Planck-Gesellschaft New Orleans, LA, USA Ninth Annual Meeting of the Organization for Human Brain Mapping (OHBM 2003) http://www.sciencedirect.com/science/article/pii/S1053811905700033 amirsAShmuel markMAAugath axelAOeltermann jpaulsJPauls yusukeYMurayama nikosNKLogothetis poster 956 2002 2 5 214 Sensory processing, as well as motor planning and execution, are well-studied aspects of primate brain function. However, it is well known that cortical and subcortical structures engage in significant activity unrelated to a sensory stimulus or motor response. Much of this activity is not random, but rather reflects the brain’s own homeostatic mechanisms, typically involving interactions between diverse cortical and subcortical structures. Such activity changes are particularly pronounced during transitions of consciousness, such as those occurring during natural sleep or anesthesia. In the present study, we examined the dynamics of changes in sensory processing accompanying the loss of consciousness in monkeys undergoing anesthetic induction. We measured the auditory evoked potential (AEP) to a series of short clicks (5 Hz, 0.1 msec.) in monkeys during anesthetic induction. In all cases, the animals were brought to the setup awake and maintained spontaneous respiration throughout the course of the experiment. On different days, the anesthetics ketamine (KET), propofol (PRO), isoflurane (ISO), and sevoflurane (SEVO) were administered while the animal was awake. KET and PRO were delivered intravenously using a remote controlled syringe pump. ISO and SEVO were provided via mask from an anesthesia machine. Prior to anesthesia, consistent peaks appeared at 30 ms (Pa) and 50 ms (Nb) in the AEP. The amplitude and latency of these peaks are known to be affected by anesthetic level. We found that during induction and emergence with ISO and PRO, the changes in both the latency and amplitude were more closely related to the animal’s visible state than to the measured anesthetic concentration. The results suggest that, at least for light anesthetic levels, conscious transitions draw upon endogenous mechanisms that are impacted by, but not unambiguously determined by, anesthetic concentration. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.twk.tuebingen.mpg.de/twk02/ Biologische Kybernetik Max-Planck-Gesellschaft Tübingen, Germany 5. Tübinger Wahrnehmungskonferenz (TWK 2002) FHaiss davidlDALeopold yusukeYMurayama nikosNKLogothetis poster 1068 2001 11 31 821.34 Neural firing in the visual cortex is highly irregular. Much work suggests that the spontaneous activity changes experienced by a cortical neuron are highly correlated with those experienced by its neighbors. We have previously shown that multiunit activity between distant sites in monkey visual cortex can display significant covariation during the performance of a visual task. In the present study, we recorded from electrodes separated by up to 10 mm in striate and extrastriate visual cortex under a variety of behavioral conditions including 1) actively performing a visual task, 2) relaxing between trials, 3) in light sleep, and 4) under general anesthesia. We recorded single and multiunit activity, as well as local field potentials. We were primarily interested to understand how identifiable events contribute to covariation observed in the various states. These included external events such as changes in the sensory stimulus, internal events such as spontaneous perceptual changes during binocular rivalry, behavioral events such as blinks and eye movements, and physiological events such as sleep spindles. We found that inter-site correlation was diminished during the visual task compared other states. It was particularly diminished during the perceptual instability accompanying binocular rivalry. Preliminary results also demonstrated significant anti-correlation between areas accompanying blinks and eye movements. A substantial portion of the common variability could not be accounted for by events we could identify. We will discuss these results in terms of the magnitude, frequency coherence, and spatial distribution of the covariation patterns. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/index.aspx?pagename=abstracts_ampublications Biologische Kybernetik Max-Planck-Gesellschaft San Diego, CA, USA 31st Annual Meeting of the Society for Neuroscience (Neuroscience 2001) davidlDALeopold yusukeYMurayama nikosNKLogothetis poster 1064 2001 11 31 722.16 The functional properties of neurons in the inferotemporal cortex (IT) have been studied extensively in both awake and anesthetized monkeys. While neurons in these areas show high selectivity for complex patterns, faces, and objects, their role in perception remains unclear. A previous electrophysiological study demonstrated that during binocular rivalry, when excitatory and non-excitatory stimuli were continually presented, most neurons in the inferotemporal cortex responded only when the excitatory stimulus was perceived (Sheinberg and Logothetis, 1997), suggesting that the activity of IT neurons is tightly linked with conscious perception. Recent evidence from our laboratory has suggested that active visual mechanisms of perceptual organization, including those related to binocular rivalry, can continue to operate under diminished states of consciousness that follow the administration of low doses of the dissociative anesthetic ketamine. In the present study, we examined the perception-related responses of IT neurons during rivalry in the monkey under a variety of conscious states, including wakefulness, ketamine dissociation, and general anesthesia. Single unit, multiunit, and local field activity was measured during extended periods of dichoptic stimulation, as well as during Flash suppression stimulus sequences that strongly bias subject's perception in the normal condition. Our analysis will focus on the extent of perception-related modulation of neural signals in the different conditions and characterize the functional significance of IT to perceptual organization. Supported by Max Planck Society. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/index.aspx?pagename=abstracts_ampublications Biologische Kybernetik Max-Planck-Gesellschaft San Diego, CA, USA 31st Annual Meeting of the Society for Neuroscience (Neuroscience 2001) yusukeYMurayama davidlDALeopold nikosNKLogothetis poster 1044 2000 11 30 498.10 Previous neurophysiological recordings in monkeys used the paradigm of binocular rivalry to investigate activity of single neurons in the visual cortex during multistable perception. These studies revealed that a subset of cells throughout visual cortex, including the striate and extrastriate areas, is directly involved in spontaneous perceptual reorganizations of an unchanging sensory stimulus. In the present study, the role of perception-related networks is further examined using simultaneous multiple electrode measurements in several visual cortical areas. As in previous studies, monkeys were trained to report their changing percept during rivalry by pressing levers, with optokinetic responses to moving stimuli serving as an additional behavioral control. Rivalry-inducing stimuli consisted of a variety of relatively large (>5 deg) patterns, including images, gratings and moving random dots. Multiple electrodes measured extracellular activity simultaneously in striate and extrastriate visual cortex. In addition to isolated neural responses, local field potential (LFP) as well as multiunit activity (MUA) was measured and analyzed. During rivalry, perceptual changes were reflected not only in the spiking of individual cells, but also in MUA as well as several frequency ranges of the LFP at individual sites. In an effort to better understand the overall flow and organization of perception-related activity in the visual cortex, the temporal covariation between the various neural signals was evaluated with respect to the animal’s changing percept, its state of arousal, as well as its pattern of spontaneous eye movements. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/absarchive/ Biologische Kybernetik Max-Planck-Gesellschaft New Orleans, LA, USA 30th Annual Meeting of the Society for Neuroscience (Neuroscience 2000) davidlDALeopold yusukeYMurayama nikosNKLogothetis poster 998 2000 11 30 448.11 When humans or monkeys are stereoscopically shown a pair of dissimilar images they experience a sequence of spontaneous perceptual fluctuations known as binocular rivalry. This phenomenon has been studied extensively, and has recently been used as a means to investigate neural mechanisms of perceptual organization. While it is now known that several areas in visual cortex participate in rivalry, the fundamental basis and origin of the spontaneous alternations remain poorly understood. Some evidence suggests that conscious perception is a critical component, since multistable perception is intimately related to attention and awareness. Yet, it is also possible that the brain, given a pair of discordant visual stimuli, automatically generates a sequence of state-changes, alternately processing each conflicting pattern in turn. Such automatic changes could be initiated by passive, free-running sensory networks, or alternatively by more complex mechanisms involving a variety of brain areas. In either case, the subjective perception experienced during waking would simply reflect these automatic processes. The present study addressed these issues by measuring neural activity (single unit responses, multiunit activity, and local field potentials) in the cortex of anesthetized monkeys under visual stimulus conditions that would normally give rise to binocular rivalry. Multiple electrodes afforded the simultaneous monitoring of sites in several striate and extrastriate visual areas. Analysis focused on the identification and characterization of spontaneous state-changes related to the conflicting stimuli that might serve as a basis for perceptual alternation. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/absarchive/ Biologische Kybernetik Max-Planck-Gesellschaft New Orleans, LA, USA 30th Annual Meeting of the Society for Neuroscience (Neuroscience 2000) yusukeYMurayama davidlDALeopold nikosNKLogothetis conference BiessmannMMLM2010 Frontiers in Computational Neuroscience 2010 10 Conference Abstract: Bernstein Conference on Computational Neuroscience In the past years multimodal brain imaging methods have yielded valuable insights into how functional magnetic resonance imaging (fMRI) signals are related to the underlying neural activity. However, the rapid advances in multimodal imaging technology were not accompanied by the development of appropriate analysis methods for multimodal data. We present a multimodal analysis framework, temporal kernel Canonical Correlation Analysis (tkCCA) [1,2], and show how it can be used to analyse the spatio-temporal and time-frequency correlation structure between simultaneously measured intracortical neurophysiological recordings and high dimensional fMRI signals. Given the spectrograms of neurophysiological activity and the simultaneously recorded fMRI data we estimate a convolution linking di_erent bands of neural bandpower to an activity pattern of fMRI signals. The convolution can be interpreted as the pattern in time-frequency and time-voxel space that maximises the canonical correlation [3] between neural and haemodynamic activity. We show results from data recorded in primary visual cortex during spontaneous activity and during visual stimulation. The analysis resulted in robust neurovascular coupling patterns across different experimental conditions. We compared the multivariate patterns with univariate coupling measures and spatial principal component analysis (SPCA) by measuring the accuracy when predicting neural activity from BOLD signals. Our _ndings suggest that the _lters estimated by tkCCA predict neural activity better than univariate methods and unimodal methods such as SPCA. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Department Schölkopf Abstract Talk http://www.frontiersin.org/10.3389/conf.fncom.2010.51.00075/event_abstract Berlin, Germany Bernstein Conference on Computational Neuroscience 2010 10.3389/conf.fncom.2010.51.00075 fbiessmaFBiessmann FCMeinecke yusukeYMurayama nikosNKLogothetis klausKRMüller conference MazzonikMMQLP2010 Frontiers in Computational Neuroscience 2010 10 Conference Abstract: Bernstein Conference on Computational Neuroscience Natural stimuli have a rich temporal structure, yet it is still unclear whether the encoding of such stimuli employs more than one response time scale. To investigate this issue, we analyzed the activity of neurons recorded in primary visual cortex of anesthetized macaques during presentation of naturalistic movies, and we quantified the amount of information carried by neural codes operating at different temporal scales. We divided the recording time into stimulus windows of tens of ms, and computed the information carried by the neural response about which stimulus window was being shown. Within each time window, responses were quantified using either the spike count, or using binary spike patterns, defined by the absence/presence of spikes within short time bins (t). We found that temporal spike patterns with precision t of 8 or 16 ms provided more stimulus information than spike counts, but this information gain did not increase further when reducing the bins size t. This suggests a response precision of single neurons on the scale of 8ms. In addition, we found that the joint knowledge of spike patterns and the phase of low frequency LFPs at which these patterns occurred - computed as in (Kayser et al. Neuron 2009) - carried more information than either code considered by itself. This suggests that the information carried by slow LFP fluctuations complements that carried by spike patterns. In summary, we found evidence for complementary response time scales for the encoding of naturalistic stimuli in visual cortex. Informative codes range from spike timing precision at about 10 ms resolution to the much coarser phase of firing with respect to low frequency fluctuations. These findings indicate that sensory cortices may enhance their information capacity by multiplexing complementary information at different time scales. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Research Group Kayser Abstract Talk http://www.frontiersin.org/10.3389/conf.fncom.2010.51.00101/event_abstract Berlin, Germany Bernstein Conference on Computational Neuroscience 2010 10.3389/conf.fncom.2010.51.00101 AMazzoni kayserCKayser yusukeYMurayama jmartinezJMartinez RQQuiroga nikosNKLogothetis stefanoSPanzeri conference LogothetisSMASO2006 2006 10 36 114.10 We have recently combined electrical stimulation and fMRI and demonstrated that the excitability properties of the directly stimulated elements in neocortex using this method are very similar to those obtained with either intracortical recordings or behavioral methods (Tolias et al., 2005). Microstimulation in cortical area V1 of the macaque activated mainly the pyramidal fibers, and the effective current spread, that was measured by means of the BOLD activation, was found to be greater than that obtained with the other two methods. Stimulation of V1 (and in later studies of MT), however, revealed mainly the monosynaptic targets of each stimulated region. Here we set out to elucidate the conditions for which transsynaptic effects can be obtained. Experiments were conducted in anesthetized and alert monkeys in a 4.7T/40cm and 7T/60 scanner, respectively. Electrical stimulation was delivered using a biphasic pulse generator attached to a constant-current stimulus isolation unit. Constant-current charge-balanced, band-limited pulses of different center frequency, pulse duration and current strength were delivered to the brain for periods of 4 sec preceded and followed by 4 sec and 12 sec blank periods, respectively. The compensation circuit, designed to minimize interference generated by the switching gradients during recording, was always active, alleviating all gradient-induced currents in the range of the stimulation current. Local microstimulation was applied in dLGN, pulvinar, striate and extrastriate cortex. The areas activated upon stimulation of each of these sites was found to depend primarily on the central frequency of the frequency band used. Transsynaptic activation also depended on stimulation condition. Differences between the anesthetized and alert monkey experiments will be discussed. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Abstract Talk http://www.sfn.org/index.aspx?pagename=abstracts_ampublications Atlanta, GA, USA 36th Annual Meeting of the Society for Neuroscience (Neuroscience 2006) nikosNKLogothetis FSultan yusukeYMurayama markMAugath steudelTSteudel axelAOeltermann