This file was created by the Typo3 extension sevenpack version 0.7.14 --- Timezone: CEST Creation date: 2013-05-26 Creation time: 09-04-44 --- Number of references 41 article GoenseML2012_2 Neuron 2012 11 76 3 629–639 The six cortical layers have distinct anatomical and physiological properties, like different energy use and different feedforward and feedback connectivity. It is not known if and how layer-specific neural processes are reflected in the fMRI signal. To address this question we used high-resolution fMRI to measure BOLD, CBV, and CBF responses to stimuli that elicit positive and negative BOLD signals in macaque primary visual cortex. We found that regions with positive BOLD responses had parallel increases in CBV and CBF, whereas areas with negative BOLD responses showed a decrease in CBF but an increase in CBV. For positive BOLD responses, CBF and CBV increased in the center of the cortex, but for negative BOLD responses, CBF decreased superficially while CBV increased in the center. Our findings suggest different mechanisms for neurovascular coupling for BOLD increases and decreases, as well as laminar differences in neurovascular coupling. 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/S0896627312008549 10.1016/j.neuron.2012.09.019 jozienJGoense hellmutHMerkle nikosNKLogothetis article vonPfostlLZGZSLR2012 NeuroImage 2012 5 61 1 98–105 In contrast to the limited use of functional magnetic resonance imaging (fMRI) in clinical diagnostics, it is currently a mainstay of neuroimaging in clinical and basic brain research. However, its non-invasive use in combination with its high temporal and spatial resolution would make fMRI a perfect diagnostic tool. We are interested in whether a pharmacological challenge imposed on the brain can be reliably traced by the blood oxygen level-dependent (BOLD) signal and possibly further exploited for diagnostics. We have chosen a systemic challenge with lactate and pyruvate to test whether the physiological formation of these monocarboxylic acids contributes to the BOLD signal and can be detected using fMRI. This information is also of interest because lactate levels in the cerebrospinal fluid rise concomitantly with reduced vascular responsiveness of the brain during the progression of Alzheimer disease (AD). We studied the BOLD response after a low-dose lactate challenge and monitored the induced plasma lactate levels in anesthetized non-human primates. We observed reliable lactate-induced BOLD responses, which could be confirmed at population and individual level by their strong correlation with systemic lactate concentrations. Comparable BOLD effects where observed after a slow infusion of pyruvate. We show here that physiological changes in lactate and pyruvate levels are indeed reflected in the BOLD signal, and describe the technical prerequisites to reliably trace a lactate challenge using BOLD-fMRI. 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/S1053811912002698 10.1016/j.neuroimage.2012.02.082 vpfoestlVvon Pföstl juanJLi dzaldivarDZaldivar jozienJGoense xiaozheXZhang nserrNSerr nikosNKLogothetis arauchARauch article StoewerGKBLDS2012 PLoS One 2012 1 7 1 1-13 fMRI experiments with awake non-human primates (NHP) have seen a surge of applications in recent years. However, the standard fMRI analysis tools designed for human experiments are not optimal for analysis of NHP fMRI data collected at high fields. There are several reasons for this, including the trial-based nature of NHP experiments, with inter-trial periods being of no interest, and segmentation artefacts and distortions that may result from field changes due to movement. We demonstrate an approach that allows us to address some of these issues consisting of the following steps: 1) Trial-based experimental design. 2) Careful control of subject movement. 3) Computer-assisted selection of trials devoid of artefacts and animal motion. 4) Nonrigid between-trial and rigid within-trial realignment of concatenated data from temporally separated trials and sessions. 5) Linear interpolation of inter-trial intervals and high-pass filtering of temporally continuous data 6) Removal of interpolated data and reconcatenation of datasets before statistical analysis with SPM. We have implemented a software toolbox, fMRI Sandbox (http://code.google.com/p/fmri-sandbox/), for semi-automated application of these processing steps that interfaces with SPM software. Here, we demonstrate that our methodology provides significant improvements for the analysis of awake monkey fMRI data acquired at high-field. The method may also be useful for clinical applications with subjects that are unwilling or unable to remain motionless for the whole duration of a functional scan. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0029697 10.1371/journal.pone.0029697 e29697 stoewerSStoewer jozienJGoense georgeGAKeliris abartelsABartels nikosNKLogothetis JDuncan natashaNSigala article GoenseWL2012 Wiley Interdisciplinary Reviews: Cognitive Science 2012 1 3 1 75–86 Functional Magnetic Resonance Imaging (fMRI) has quickly grown into one of the most important tools for studying brain function, especially in humans. Despite its prevalence, we still do not have a clear picture of what exactly the blood oxygenation level dependent (BOLD) signal represents or how it compares to the signals obtained with other methods (e.g., electrophysiology). We particularly refer to single neuron recordings and electroencephalography when we mention ‘electrophysiological methods’, given that these methods have been used for more than 50 years, and have formed the basis of much of our current understanding of brain function. Brain function involves the coordinated activity of many different areas and many different cell types that can participate in an enormous variety of processes (neural firing, inhibitory and excitatory synaptic activity, neuromodulation, oscillatory activity, etc.). Of these cells and processes, only a subset is sampled with electrophysiological techniques, and their contribution to the recorded signals is not exactly known. Functional imaging signals are driven by the metabolic needs of the active cells, and are most likely also biased toward certain cell types and certain neural processes, although we know even less about which processes actually drive the hemodynamic response. This article discusses the current status on the interpretation of the BOLD signal and how it relates to neural activity measured with electrophysiological techniques. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://onlinelibrary.wiley.com/doi/10.1002/wcs.153/pdf 10.1002/wcs.153 jozienJGoense kevinKWhittingstall nikosNKLogothetis article StoewerGKBLDS2011_2 Magnetic Resonance Imaging 2011 12 29 10 1390-1400 Functional magnetic resonance imaging (fMRI) experiments with awake nonhuman primates (NHPs) have recently seen a surge of applications. However, the standard fMRI analysis tools designed for human experiments are not optimal for NHP data collected at high fields. One major difference is the experimental setup. Although real head movement is impossible for NHPs, MRI image series often contain visible motion artifacts. Animal body movement results in image position changes and geometric distortions. Since conventional realignment methods are not appropriate to address such differences, algorithms tailored specifically for animal scanning become essential. We have implemented a series of high-field NHP specific methods in a software toolbox, fMRI Sandbox (http://kyb.tuebingen.mpg.de/~stoewer/), which allows us to use different realignment strategies. Here we demonstrate the effect of different realignment strategies on the analysis of awake-monkey fMRI data acquired at high field (7 T). We show that the advantage of using a nonstandard realignment algorithm depends on the amount of distortion in the dataset. While the benefits for less distorted datasets are minor, the improvement of statistical maps for heavily distorted datasets is significant. 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=S0730725X11001809&_check=y&_origin=&_coverDate=31-Dec-2011&view=c&wchp=dGLzVBA-zSkWb&md5=faaec51a67a063db4ac8f1979129b81b/1-s2.0-S0730725X11001809-main.pdf 10.1016/j.mri.2011.05.003 stoewerSStoewer jozienJGoense georgeGAKeliris abartelsABartels nikosNKLogothetis JDuncan natashaNSigala article KuTLG2011 Neuron 2011 4 70 2 352-362 The primate brain features specialized areas devoted to processing of faces, which human imaging studies localized in the superior temporal sulcus (STS) and ventral temporal cortex. Studies in macaque monkeys, in contrast, revealed face selectivity predominantly in the STS. While this discrepancy could result from a true species difference, it may simply be the consequence of technical difficulties in obtaining high-quality MR images from the ventral temporal lobe. By using an optimized fMRI protocol we here report face-selective areas in ventral TE, the parahippocampal cortex, the entorhinal cortex, and the hippocampus of awake macaques, in addition to those already known in the STS. Notably, the face-selective activation of these memory-related areas was observed although the animals were passively viewing and it was preserved even under anesthesia. These results point to similarly extensive cortical networks for face processing in humans and monkeys and highlight potential homologs of the human fusiform face area. 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=B6WSS-52R37RY-C-S&_cdi=7054&_user=29041&_pii=S0896627311002054&_origin=gateway&_coverDate=04%2F28%2F2011&_sk=999299997&view=c&wchp=dGLbVtz-zSkWb&md5=b6710cd9134892714e88e07b1c5ccd35&ie=/sdarticle.pdf 10.1016/j.neuron.2011.02.048 shihpiSPKu atoliasASTolias nikosNKLogothetis jozienJGoense article 6597 Magnetic Resonance Imaging 2010 10 28 8 1183-1191 High signal-to-noise ratios (SNR) are essential for high-resolution anatomical and functional MRI. Phased arrays are advantageous for this but have the drawback that they often have inflexible and bulky configurations. Particularly in experiments where functional MRI is combined with simultaneous electrophysiology, space constraints can be prohibitive. To this end we developed a highly flexible multiple receive element phased array for use on anesthetized monkeys. The elements are interchangeable and different sizes and combinations of coil elements can be used, for instance, combinations of single and overlapped elements. The preamplifiers including control electronics are detachable and can serve a variety of prefabricated and phase matched arrays of different configurations, allowing the elements to always be placed in close proximity to the area of interest. Optimizing performance of the individual elements ensured high SNR at the cortical surface as well as in deeper laying structures. Performance of a v ariety of arrangements of gapped linear arrays was evaluated at 4.7 and 7T in high-resolution anatomical and functional MRI. 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-4YXKFP6-3-K&_cdi=5112&_user=29041&_pii=S0730725X10000895&_orig=search&_coverDate=04%2F24%2F2010&_sk=999999999&view=c&wchp=dGLzVlb-zSkzV&md5=21e78b6f15291 Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2010.03.026 jozienJGoense nikosNKLogothetis hellmutHMerkle article 6179 Magnetic Resonance Imaging 2010 10 28 8 1120-1128 Previous imaging work has identified a frontoparietal network in the human brain involved in many cognitive functions, as well as in simple updates of attended information. We examined the activation of frontoparietal areas during visual stimulation in the awake, fixating monkey, in order to determine if a similar network is present in the monkey brain and direct future electrophysiological recordings. We measured activity with BOLD fMRI in three animals and analysed the data individually for each animal, and at group level. We found reliable activations in lateral prefrontal and parietal areas, even though task-related decision making was minimal, as a response to simple update of visual information. These activations were significant for each individual animal, as well as at group level. Similar to human imaging results the update of visual input was enough to activate the frontoparietal cortex in the macaque brain, a network which is normally associated with complex cognitive control processes. 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-4Y960VY-6-C&_cdi=5112&_user=29041&_pii=S0730725X09003166&_orig=search&_coverDate=02%2F01%2F2010&_sk=999999999&view=c&wchp Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2009.12.024 stoewerSStoewer shihpiS-PKu jozienJGoense steudelTSteudel nikosNKLogothetis JDuncan natashaNSigala 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 6055 Methods 2010 3 50 3 178-188 In recent years, more and more laboratories have begun to develop fMRI for awake non-human primates. This research is essential to provide a link between non-invasive hemodynamic signals in the human brain and the vast body of knowledge gained from invasive electrophysiological studies in monkeys. Given that their brain structure is so closely related to that of humans and that monkeys can be trained to perform complicated behavioral tasks, results obtained with macaque fMRI and electrophysiology can be compared to fMRI results obtained in humans, thus providing information which is crucial to better understand the mechanisms by which different cortical areas perform their functions in the human brain. However, although the first publications on fMRI in awake behaving macaques appeared ten years ago [1], [2] and [3], relatively few laboratories perform such experiments routinely, a sign of the significant technical difficulties that must be overcome. The higher spatial resolution required because of the anima l’s smaller brain results in poorer signal-to-noise ratios than in human fMRI, which is further compounded by problems due to animal motion. Here, we discuss the special challenges and benefits of fMRI in the awake monkey and review the methodologies and strategies for scanning behaving macaques. 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&_uoikey=B6WN5-4X0F3VN-1&_tockey=%23toc%236953%239999%23999999999%2399999%23FLA%23&_orig=search&_acct=C000003178&_version=1&_userid=29041&md5=587179a4ac4bfa5bd95297e06bac1d Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.ymeth.2009.08.003 jozienJBMGoense kevinKWhittingstall nikosNKLogothetis article 5483 Journal of Neuroscience 2008 11 28 46 11796-11801 The spatial organization of the brain‘s object and face representations in the temporal lobe is critical for understanding high-level vision and cognition but is poorly understood. Recently, exciting progress has been made using advanced imaging and physiology methods in humans and nonhuman primates, and the combination of such methods may be particularly powerful. Studies applying these methods help us to understand how neuronal activity, optical imaging, and functional magnetic resonance imaging signals are related within the temporal lobe, and to uncover the fine-grained and large-scale spatial organization of object and face representations in the primate brain. 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/28/46/11796 Biologische Kybernetik Max-Planck-Gesellschaft en 10.1523/JNEUROSCI.3799-08.2008 HPOp De Beeck JJDCarlo jozienJGoense KGrill-Spector APapanastassiou MTanifuji DYTsao article 5482 Current Biology 2008 5 18 9 631-640 Background Simultaneous intracortical recordings of neural activity and blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in primary visual cortex of anesthetized monkeys demonstrated varying degrees of correlation between fMRI signals and the different types of neural activity, such as local field potentials (LFPs), multiple-unit activity (MUA), and single-unit activity (SUA). One important question raised by the aforementioned investigation is whether the reported correlations also apply to alert subjects. Results Monkeys were trained to perform a fixation task while stimuli within the receptive field of each recording site were used to elicit neural responses followed by a BOLD response. We show – also in alert behaving monkeys – that although both LFP and MUA make significant contributions to the BOLD response, LFPs are better and more reliable predictors of the BOLD signal. Moreover, when MUA responses adapt but LFP remains unaffected, the BOLD signal remains unaltered. Conclusions The persistent coupling of the BOLD signal to the field potential when LFP and MUA have different time evolutions suggests that BOLD is primarily determined by the local processing of inputs in a given cortical area. In the alert animal the largest portion of the BOLD signal‘s variance is explained by an LFP range (20–60 Hz) that is most likely related to neuromodulation. Finally, the similarity of the results in alert and anesthetized subjects indicates that at least in V1 anesthesia is not a confounding factor. This enables the comparison of human fMRI results with a plethora of electrophysiological results obtained in alert or anesthetized animals. 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-4SBYX23-1-J&_cdi=6243&_user=29041&_orig=browse&_coverDate=05%2F06%2F2008&_sk=999819990&view=c&wchp=dGLzVlz-zSkWz&md5=cf054af241b9e9e767c907669da26ced&ie=/sdarticle.pdf Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.cub.2008.03.054 jozienJBMGoense nikosNKLogothetis article 4808 Journal of Cerebral Blood Flow and Metabolism 2008 3 28 3 640-652 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.nature.com/jcbfm/journal/v28/n3/pdf/9600564a.pdf Biologische Kybernetik Max-Planck-Gesellschaft en 10.1038/sj.jcbfm.9600564 aczappeA-CZappe josefJPfeuffer hellmutHMerkle nikosNKLogothetis jozienJBMGoense article 4824 NeuroImage 2008 2 39 3 1081-1093 Increasingly 7 T scanners are used for fMRI of humans and non-human primates, promising improvements in signal-to-noise, spatial resolution and specificity. A disadvantage of fMRI at 7 T, but already at 3 T, is that susceptibility artifacts from air-filled cavities like the ear canal and nasal cavity cause signal loss and distortion. This limits the applicability of fMRI in these areas, thereby limiting study of these areas, but it also limits study of processes that span large-scale cortical networks or the entire brain. Our goal is to study the inferior temporal (IT) lobe in awake monkeys because of its importance in object perception and recognition, but the functional signal is degraded by strong susceptibility gradients. To allow fMRI of this region, we used an optimized SE-EPI, which recovers signal lost with GE-EPI and we corrected for susceptibility-induced image distortion. SE-EPI has the added advantage that, in contrast to GE-EPI, where the functional signal derives to a large extent from veins, th e SE-EPI signal arises from the microvasculature, and hence it better represents the neural activation. We show fMRI at 7 T of the entire visual pathway in the awake primate with robust and widespread activation in all ventral areas of the brain, including areas adjacent to the ear canal. This allows fMRI of areas that normally suffer from artifact and thus more reliable whole-brain studies. 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-4PT2960-1-S&_cdi=6968&_user=29041&_orig=search&_coverDate=10%2F01%2F2007&_sk=999999999&view=c&wchp=dGLbVzb-zSkWA&md5=f951a759c6655f02492ab5f09f1a9e42&ie= Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.neuroimage.2007.09.038 jozienJBMGoense shihpiS-PKu hellmutHMerkle atoliasASTolias nikosNKLogothetis article 4630 Magnetic Resonance Imaging 2007 7 25 6 740-747 To understand the physiological mechanisms underlying the blood-oxygenation-level-dependent (BOLD) signal, the acquisition of data must be optimized to achieve the maximum possible spatial resolution and specificity. The term “specificity” implies the selective enhancement of signals originating in the parenchyma, and thus best reflecting actual neural activity. Such spatial specificity is a prerequisite for imaging aimed at the elucidation of interactions between cortical micromodules, such as columns and laminae. In addition to the optimal selection of functional magnetic resonance imaging pulse sequences, accurate superposition of activation patterns onto corresponding anatomical scans, preferably acquired during the same experimental session, is necessary. At high resolution, exact functional-to-structural registration is of critical importance, because even small differences in geometry, that arise when different sequences are used for functional and anatomical scans, can lead to misallocation of activ ation and erroneous interpretation of data. In the present study, we used spin-echo (SE) echo planar imaging (EPI) for functional scans, since the SE-BOLD signal is sensitive to the capillary response, together with SE-EPI anatomical reference scans. The combination of these acquisition methods revealed a clear spatial colocalization of the largest fractional changes with the Gennari line, suggesting peak activity in Layer IV. Notably, this very same layer coincided with the largest relaxivity changes as observed in steady-state cerebral blood volume measurements, using the intravascular agent monocrystalline iron oxide nanoparticles (MION). 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-4NPHMMS-1-1&_cdi=5112&_user=29041&_orig=browse&_coverDate=07%2F31%2F2007&_sk=999749993&view=c&wchp=dGLbVlb-zSkzV&md5=ae3e0e8d6da5dafbaa0557f0ec1c1eba&ie= Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2007.02.013 jozienJBMGoense aczappeA-CZappe nikosNKLogothetis article 3988 Magnetic Resonance Imaging 2006 3 24 4 381-392 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-4JG5FD7-3-9&_cdi=5112&_user=29041&_orig=browse&_coverDate=05%2F31%2F2006&_sk=999759995&view=c&wch Biologische Kybernetik Max-Planck-Gesellschaft en 10.1016/j.mri.2005.12.032 jozienJBMGoense nikosNKLogothetis inbook BartelsGL2011 2012 9 410-469 http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://audition.ens.fr/brette/HandbookMeasurement/index.htm Brette, R. , A. Destexhe Cambridge University Press

Cambridge, UK

Handbook for Neural Activity Measurement 978-0-521-51622-8 abartelsABartels jozienJGoense nikosNKLogothetis inbook GoenseL2010 2010 5 21-46 Functional magnetic resonance imaging (fMRI) and other non-invasive imaging methods have greatly expanded our knowledge of human brain function. Although MRI was invented in the early 1970s and has been used clinically since the mid-1980s, its use in cognitive neuroscience expanded greatly with the advent of blood oxygenation level dependent (BOLD) functional imaging, and by now, fMRI is a mainstay of neuroscience research. This chapter gives an overview of the relation between the BOLD signal and the underlying neural signals. It focuses on intracortically recorded neural signals, recorded with microelectrodes. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.oxfordscholarship.com/view/10.1093/acprof:oso/9780195372731.001.0001/acprof-9780195372731-chapter-2 Ullsperger, M. , S. Debener Oxford University Press

Oxford

Simultaneous EEG and fMRI: recording, analysis, and application 978-0-19-537273-1 10.1093/acprof:oso/9780195372731.003.0002 jozienJGoense nikosNKLogothetis poster KuGLB2012 2012 10 42 263.22 fMRI has revealed a face processing network in the macaque brain that encompasses regions in the superior temporal sulcus (STS), the lateral and ventral temporal cortex, the medial temporal lobe and in the prefrontal cortex (Tsao and Livingstone 2008; Ku, Tolias et al. 2011). However, the functionality of each individual face-responsive patch is largely unknown. In humans fMRI evidence suggests that the middle STS is important for facial expression encoding, while the ventral temporal cortex is primarily involved in identity encoding (Haxby, Hoffman et al. 2002). This is consistent with single unit studies showing facial expression selective cells in the STS and identity encoding neurons in LTG in monkeys. However, there is no equivalent evidence indicating such a functional segregation in terms of BOLD responses to face stimuli. In order to examine whether there is a similar response pattern in monkeys and to further identify more candidate brain regions which might be also important in encoding these two aspects of faces, we scanned two awake and five anesthetized monkeys at 7Tesla. Using an adaptation paradigm we found that STS was sensitive to changing facial expressions independent of changing of identities in all awake and anesthetized monkeys. In brain regions not covered in the awake monkeys, the same contrast revealed that the medial orbital frontal cortex (area 47/12 ) of four anesthetized monkeys was also sensitive to changing facial expressions. In addition, we found that the anterior hippocampus of the two awake and three anesthetized monkeys was sensitive to changing identities. The results suggest differential selectivities for the encoding of facial expressions and of identities across a network of regions in the monkey. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/am2012/ New Orleans, LA, USA 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012) shihpiS-PKu jozienJBGGoense nikosNKLogothetis abartelsABartels poster BohrausLG2012 2012 10 42 95.03 Commonly used fMRI signals measure local vascular and neural changes, with the former underlying a certain degree of spatiotemporal blurring. To minimize the latter, methods can be used that are less sensitive to partial volume effects. One such methodology capitalizes on high resolution, voxel-by-voxel CMRO2 measurements. Here we combined such measurements with so-called calibrated BOLD methodology to acquire CBF and BOLD maps during visual stimulation. Calibration was done by estimating a normalization factor (M) assessed in hypercapnia conditions, reflecting the upper limit of BOLD signal-changes. Quantitative description and interpretation of the data was done by using a model with parameters α, relating relative changes of CBV to CBF according to Grubb’s law (α=0.38), and β linking blood oxygenation to relaxivity (β=1.5). To improve the model, α was selected to account for changes in venous CBV only (α=0.23), i.e. to account for CBV-changes that are relevant to the BOLD signal, rather than to total CBV alterations. Alternatively, the model was compared to a more detailed model and showed highest accuracy with α=0.14 & β=0.91. We determined the CMRO2 in anesthetized macaques at 7T & high resolution to separate the visually induced percent changes in CMRO2 (%CMRO2) in gray matter from white matter and vessel signals. We subsequently repeated the calculations using the aforementioned α & β parameters in order to reassess the robustness of the results. CBF and BOLD signals were acquired simultaneously with a triple-echo sequence. The %CMRO2 changes, M and n (ratio of fractional CBF to CMRO2) were calculated in V1 and V2. At a resolution of 1x1x3 mm3, the average %CMRO2 was 12±5% (mean ± sem) with M=0.29 ± 0.05. The coupling constant n was 2.1 ± 0.4. Similar values were obtained for α=0.23. The calibration constant M slightly increased using α=0.14 & β=0.91 but remained consistent with the value of 0.3-0.4 in gray matter at 7T. %CMRO2 changes & n were not very sensitive to the choice of parameters. For resolution of 0.5x0.5x3mm3 the results suggested higher %CMRO2 changes in gray matter than in white matter with a possible peak in layer IV, being the main input layer in macaque monkey. CBF and BOLD percent changes during visual stimulation and hypercapnic challenge were increased at a resolution of 0.5x0.5x3mm3 compared to 1x1x3 mm3. In conclusion, using the calibrated BOLD method, we found high-resolution %CMRO2 changes of 12-14% and coupling ratios of 1.8-2.1, and demonstrated differences in %CMRO2 measured in gray and white matter. The reported results were found to be robust and insensitive to changes in the α & β parameters at high field. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.sfn.org/am2012/ New Orleans, LA, USA 42nd Annual Meeting of the Society for Neuroscience (Neuroscience 2012) ybohrausYBohraus nikosNKLogothetis jozienJGoense poster ZaldivarLvWGRL2012 2012 7 8 p063.19 The presence of dopamine-(DA)-receptors-(DARs) and innervations in early sensory pathways has previously been demonstrated in monkeys and humans. Nonetheless, their possible role in the sensory processing is still far from being understood. Anatomical evidence has shown that DARs are expressed in early-visual-system. These studies indicated that D1Rs are found in primary-visual-cortex, while D2Rs are predominantly expressed in the lateral-geniculate-nucleus-(LGN). D1Rs have a facilitating effect on neuronal processing whereas D2Rs show a dampening effect. Given their differences in anatomical distribution and functionality the two kinds of DARs may have a differential effect on thalamocortical information transfer. Here, we set out to investigate DAergic impact on V1 by using combined fMRI, neurophysiology and neurochemistry measurements in anesthetized non-human-primates, during systemic-application of L-DOPA-Carbidopa (2.1/0.5mg/kg, respectively). Our results show that the stimulus-induced modulation of the BOLD-signal decreases by 40±5% for 10±3min (n=8,p < 0.05). This decrease is concomitant with an improvement in the signal-to-noise-ratio-(SNR) in multi-unit-activity-(MUA: 900-3200Hz) as well as in the CV (p< 0.05) of the theta (4-8Hz), low-gamma (20-60Hz) and gamma (65-120Hz) bands of LFP. In contrast, local application of DA in V1 did not induce any changes in neuronal activity indicating that the observed effects are most probably mediated by D2Rs of LGN. DAergic neuromodulation decreased the SNR of the neuronal recordings in V1 which reflects a sparse and dampened firing pattern. Neurochemical sampling in V1 has shown an increased glutamate/GABA-ratio which might reflect a change in the excitation/inhibition balance induced by DA. The additional measured lactate/pyruvate-ratio has also shown a change indicating a decreased metabolic demand. These findings suggest that the visual inputs are attenuated by the local DAergic-circuitry of LGN (D2Rs) generating sparse and precise neuronal firing in V1. At the same time, however, the reduced mass-activity appears to reduce the energy demands, and the stimulus-induced-modulation of the BOLD-signal. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://fens.ekonnect.co/FENS_331/poster_33040/program.aspx Barcelona, Spain 8th Forum of European Neuroscience (FENS 2012) dzaldivarDZaldivar juanJLi vpfoestlVvon Pföstl kevinKWhittingstall jozienJGoense arauchARauch nikosNKLogothetis poster GoenseML2012 2012 5 20 0718 The relative contributions of excitation and inhibition to fMRI responses remain unknown. In principle, inhibition may increase or decrease fMRI signals depending on local circuitry. Negative BOLD signals and CBF decreases were shown for ring stimuli in primary visual cortex (V1). High-resolution fMRI can exploit the functional segregation in V1 to reveal differences between excitatory and inhibitory responses, including layer-specific differences. We measured high-resolution BOLD, CBV and CBF in macaque V1 and found laminar differences in the positive and negative fCBF responses, suggesting different neurovascular coupling mechanisms depending on the location within the cortical sheet. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/12/ Melbourne, Australia 20th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2012) jozienJGoense hellmutHMerkle nikosNKLogothetis poster GoenseL2011 2011 5 19 3600 http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/2011/ISMRM-2011-3600.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/11/index.htm Montréal, Canada 19th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2011) jozienJGoense nikosNKLogothetis poster BohrausLG2011 2011 5 19 3599 http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/2011/ISMRM-2011-3599.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/11/index.htm Montréal, Canada 19th Annual Meeting and Exhibition of the International Society for Magnetic Resonance in Medicine (ISMRM 2011) ybohrausYBohraus nikosNKLogothetis jozienJGoense poster 7072 2010 11 40 648.15 Lactate is a common metabolic product of anaerobic glucose metabolism. It can freely pass the blood brain barrier and it’s known to play also an important role in brain metabolism. We used pharmaco MRI and tested the effect of systemic lactate application on the BOLD signal in primary visual cortex (V1) of anesthetized non-human primates during visual stimulation. We also monitored the pharmacokinetics of the applied lactate in the blood using microdialysis and HPLC (high performance liquid chromatography) coupled to MS/MS (mass spectrometry). The lactate pharmacokinetics allows us to investigate the actual plasma concentrations of lactate, and thus, how this correlates to changes in the BOLD signal. After lactate infusion of 0.6 mmol/kg, we observed two consistent effects in the BOLD signal: An initial decrease in visually-induced modulation followed by a subsequent positive baseline shift (n = 10, p < 0.05). The plasma lactate levels significantly increased approximately 9 minutes after systemic application and were correlated with the positive baseline shift in the BOLD signal (p < 0.05). This is in line with a lactate-induced increase of CBF in sensory stimulated regions observed in earlier studies. However, the onsets of lactate increases were late - thereby indicating a lactate buffering mechanism. This could be due to an uptake of lactate by erythrocytes buffering lactate until this capacity is saturated, and plasma levels start to rise with some delay. We conclude that the positive baseline shift in the BOLD signal is triggered by a rise in CBF due to increased plasma lactate. Interestingly, during the observed decrease in visual modulation, (though lactate was already being applied), the lactate levels in the blood were still comparable to the pre-injection concentrations (p < 0.05). How this lactate uptake by erythrocytes influences the BOLD signal has to be further investigated. Nonetheless, our results reveal a complex interaction of lactate in the brain which was only detectable by using pharmaco MRI in combination with neurochemical monitoring of lactate. 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 vpfoestlVvon Pföstl juanJLi dzaldivarDZaldivar jozienJGoense xiaozheXZhang nikosNKLogothetis arauchARauch poster 7073 2010 11 40 834.2 Face perception is one of the most crucial abilities for social animals like humans and nonhuman primates. fMRI-, lesion- and electrophysiology studies in humans and monkeys have indicated the existence of a dedicated and wide-spread face-processing network. In humans the most robust face-selective brain areas are fusiform face area (FFA), occipital face area (OFA) and superior temporal sulcus (STS). However, in monkeys the strongest face selectivity is found predominantly in STS, and no reliable face selectivity has been reported in fusiform gyrus and occipital temporal region. These differences may be a species difference, or they may be due to technical difficulties, because in monkeys the fusiform gyrus and ventral occipital-temporal area are located in regions that are difficult to map with fMRI due to susceptibility artifacts from the ear canal. Here we used an optimized imaging protocol at 7T, which does not suffer from the usual signal loss in inferior temporal areas. We investigated the functional organization of face processing in 5 awake or anesthetized macaques while the subjects viewed faces, fruit, houses and fractal patterns. We found face-specific BOLD responses in STS, anterior medial temporal sulcus (AMTS), the regions anterior and lateral to AMTS and amygdala, consistent with previous fMRI and electrophysiology results. But in addition, entorhinal cortex (EC), ventral TE (posterior to AMTS), and hippocampus also contain face selective patches. These areas have not been reported to be face-selective in monkeys before, although they were shown to be responsive to faces with fMRI or intracortical recording in humans. The results indicate that there is much more extensive face selective brain activity than earlier studies have found in monkey ventral temporal lobe and suggests a large degree of similarity between the human and monkey face-processing network. 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 shihpiS-PKu atoliasASTolias nikosNKLogothetis jozienJGoense poster GoenseML2010 2010 5 2010 1189 The BOLD signal is a weak signal, and hence if no BOLD signal is found in an area this does not automatically mean there is no neural activity in that area. Signal dropout, artifacts, instability, physiological noise, RF-coil inhomogeneity etc. can all reduce the SNR locally leading to decreased detectability of the BOLD signal. Here we illustrate that calculation of the spatial distribution of the detection thresholds allows us to assign a degree of confidence to the activations as well as identify areas where detectability of functional activation is compromised. http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/ISMRM-2010-1189_6536.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/meetings-workshops/2010-annual-meeting-3/ Stockholm, Sweden ISMRM-ESMRMB Joint Annual Meeting 2010 jozienJGoense hellmutHMerkle nikosNKLogothetis poster 6178 2009 10 39 677.16 In the primate brain a frontoparietal network is involved in many aspects of cognitive control, e.g. during shifts of attention and switches of abstract rules. However, the frontoparietal network in the human brain is also active during simple update of attended information, when task-related decision making is minimal (1) or during the execution of voluntary eye movements (2). The goal of the present study was to identify the network of areas activated by a short series of visual stimuli (meaningless fractal images) while the animals were awake and maintained fixation, in order to compare with the activations elicited in the human brain and to inform and direct future single unit recordings. We obtained activation maps at 7T using BOLD fMRI in three alert macaque monkeys (Macaca mulatta). Functional images were realigned and co-registered with the high-resolution MRI images used in the Saleem and Logothetis atlas (3) to facilitate the identification of the anatomical structures. Areas that were reliably activated in all three animals included areas 8 and F5 around the arcuate sulcus (AS), and the lateral intraparietal area (LIP), along with early and higher areas of the visual system. As in the human, extensive frontoparietal activity was seen despite maintained fixation, and without active behavioural decisions. Additionally, we present preliminary psychophysical and BOLD fMRI results from a second study. In this experiment, we trained one animal to perform a colour discrimination task by making a saccade to the left (for green) or right (for red) of the screen, and then introduced conditions of increased task difficulty. 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=e599a515-6cac-432b-bd54-1c49698414ac&cKey=ab501a56-65bf-4152-a13d-9d50c2bd66d7 Biologische Kybernetik Max-Planck-Gesellschaft Chicago, IL, USA 39th Annual Meeting of the Society for Neuroscience (Neuroscience 2009) en stoewerSStoewer shihpiS-PPKu jozienJGoense nikosNKLogothetis JDuncan natashaNSigala poster UludagZGL2009 2009 4 17 3701 A BOLD signal model as a function oxygen extraction fraction and CBV was developed in order to determine change in oxidative metabolism from combined BOLD signal and CBF measurements. The new model is an alternative model to the widely used calibrated BOLD approach initally proposed by Davis and colleagues for GRE at 1.5T. The new model, however, takes also intra-vascular MRI signal into account and is developed for both GRE and SE from 1.5T up to 16.4T. In the current study, at 4.7T and 7T using SE and GRE, oxidative metabolism change during visual stimulation was determined in macaque monkeys. http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/ISMRM-2009-03701.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/09/ Honolulu, HI, USA 17th Annual Meeting of the International Society for Magnetic Resonance in Medicine (ISMRM 2009) kuludagKUludag aczappeA-CZappe jozienJGoense nikosNKLogothetis poster GoenseML2009 2009 4 17 1602 The fMRI response to a movie stimulus was compared in the ventral visual pathway of awake and anesthetized macaques. The ventral visual stream is essential for object recognition and memory, and in awake monkeys large swaths of the pathway are activated. In anesthetized monkeys the temporal lobe also shows large areas of activation, corresponding to the areas in awake monkeys. It is reported difficult to elicit activation beyond early sensory areas, but our results show robust activation high in the visual pathway in areas involved in object recognition. The robust activation seen here is possibly due to the higher CNR at 7T. http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/ISMRM-2009-01602.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/09/ Honolulu, HI, USA 17th Annual Meeting of the International Society for Magnetic Resonance in Medicine (ISMRM 2009) jozienJGoense hellmutHMerkle nikosNKLogothetis poster 5484 Magnetic Resonance Materials in Physics, Biology and Medicine 2008 10 21 Supplement 1 654-655 Introduction: Since high SNR is necessary for high-resolution FMRI it is advantageous to place the coils close against the monkey’s head whenever possible. To this end, we designed a flexible 4-channel receive-only phased array that can be used on monkeys of different sizes as well as for different cortical areas. In addition, the preamplifiers including control electronics are detachable and can serve a variety of prefabricated and phase-matched fourelement arrays of different configurations. Methods: A linear array of 4 circular coils of ~23 mm diameter with gaps of ~11 mm was sutured onto a soft plastic strip (Figure 1). The assembly having in-line connectors was attached to phase-matched coaxial cables to modified commercial high reflection coefficient preamplifiers (Stark Contrast Inc., Erlangen, Germany) via cable traps. Detuning of the individual coils during RF transmission was achieved using DC currents within the coaxial cables and pin diode controlled notch filters within the array elements. Experiments were done on anesthetized monkeys on a vertical 4.7T Bruker Biospec running ParaVision 5. The array was positioned over the occipital pole. RF transmission was done with a de-tunable ‘type D’ partial volume coil. We obtained high-resolution FLASH (Figure 2) and FMRI data using EPI with and without acceleration (GRAPPA). The stimulus was a full-field rotating checkerboard. FLASH: resolution 100x100x1000 μm, TE 23 ms, TR 2000 ms, 1 average; FMRI: GE-EPI, resolution 500x500x2000 μm, TE 21 ms, TR 750 ms, 8 segments with R = 1, or 4 segments with R = 2. Results: The high-resolution FLASH anatomical images show intracortical veins and the Gennari line in entire V1, including peripheral V1, which is located deep in the brain. Using a dual-coil setup, it is only possible to observe these features in parts of V1 that are close to the surface. The functional map proofs that the increased coverage allows us to obtain activation in V1-V5 in both hemispheres at high resolution (Figure 3). SNR was sufficient to also allow accelerated FMRI at the same resolution. Discussion: Compared to a dual-coil setup the phased array provides improved SNR and coverage, which allows for high resolution anatomical imaging and FMRI of the entire early visual cortex, including better performance in deep brain areas. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.esmrmb.org/index.php?id=/en/esmrmb_congress_2008.htm Biologische Kybernetik Max-Planck-Gesellschaft Valencia, Spain ESMRMB 2008 Congress: 25th Annual Meeting en 10.1007/s10334-008-0126-2 hellmutHMerkle nikosNKLogothetis jozienJBMGoense poster 5485 2008 5 16 153 27 High-resolution fMRI can aid in determining to what extent the BOLD signal arises from capillaries or larger vessels. In high-resolution functional activation maps both positive and negative BOLD signals associated with vessels were observed; this was seen for both GE- and SE-BOLD. Because of its higher specificity, the SE-BOLD signal was used to investigate the origin of these vessel signals. The location of the SE-BOLD signal from veins changed when the direction of the gradients was changed. This is in contrast to the peak SE-BOLD occurring in layer IV which arises from capillaries, and was insensitive to gradient reversal. http://www.kyb.tuebingen.mpg.defileadmin/user_upload/files/publications/ISMRM-2008-00153.pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/08/ Biologische Kybernetik Max-Planck-Gesellschaft International Society for Magnetic Resonance in Medicine Toronto, Canada 16th Scientific Meeting and Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM 2008) en jozienJBMGoense nikosNKLogothetis poster 4998 2007 11 37 396.3 In contrast to electrophysiological studies, the advantage of fMRI is that it allows simultaneous mapping of the functional organization of multiple cortical areas. FMRI of awake monkey has benefit of combining behavioral studies with BOLD-measurement to be used to precisely localize functional specific cortical areas for further invasive studies such as detailed electrophysiological single unit recordings. Although high magnetic field offers the benefit of increased signal-to-noise ratios and higher specificity, a drawback is the higher sensitivity to susceptibility gradients caused by the air-tissue interfaces. This can be particularly problematic in the lower floor of temporal lobe, because the large macroscopic susceptibility gradients near the ear canal result in distortion and loss of signal when the standard GE-EPI is used. For fMRI of such areas using spin-echo EPI (SE-EPI) is advantageous because it is less sensitive than GE-EPI to susceptibility artifacts, and does not suffer from signal dropout in these regions. Another advantage is that SE-EPI is less affected by frequency-changes in the main magnetic field, which are caused by movement of the animal. In this study, we compared SE-EPI and gradient-echo fMRI in the awake monkey (Macaca mulatta), using a vertical bore 7T MR system. A saddle coil optimized for temporal cortex was used to allow imaging of the major visual areas. The imaging parameters and slice orientation were optimized to minimize susceptibility effects. Resolution was typically 1.5x2x2mm, TE was 40 ms, TR was 1-2 s. In contrast to the GE-EPI images, which showed very large signal dropout in the temporal lobe, SE images showed minimal or no distortion or signal loss. Any remaining distortions were corrected using field-map correction to ensure matching of the functional map to the high-resolution T1-weighted anatomical images. Using movie- stimuli, we confirmed that reliable functional activation could be obtained with SE-EPI at high field, and we show robust activation in the temporal lobe and early visual areas. Using monkey faces, objects and fractal patterns we were also able to obtain functional activities in specific visual object sensitive areas in inferior temporal cortex. The reliability and specificity of the obtained activations with SE-EPI ensures the application of the method in our on-going visual perception studies. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de 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 shihpiS-PKu jozienJGoense atoliasASTolias nikosNKLogothetis poster 4694 2007 11 37 89.11 Using perfusion MRI with continuous arterial spin labeling (CASL) cerebral blood flow (CBF) can be measured directly at the capillary level [1]. The common belief is that perfusion MRI is more closely related to the neural activity than most functional MR imaging methods. It has successfully been used to reveal orientation columns in the cat, on the scale of ~1 mm [2]. It has been shown that the BOLD signal is higher in layer IV than in supra- and infragranular layers [3]. Since the BOLD contrast is a combination of several signals, we want to determine whether this reflects depth-dependent changes in CBF. Moreover, functional CBF (fCBF) can be interleaved with BOLD in the same scan to compute changes in oxygen consumption rate (CMRO2). We use striate cortex of the monkey which has a well-defined laminar structure, allowing determination of the precise location of functional CBF changes. MR imaging was performed on healthy adult monkeys (macaca mulatta) using a vertical 4.7T/40 cm primate scanner (Bruker Biospec) as described previously [4]. A saddle-shaped volume coil was used in combination with a 25 mm receive surface coil, and a cravat-shaped label coil for CASL, placed around the neck of the monkey. A labeling pulse of 2 s was followed by 200 or 800 ms postlabel delay (PLD), and images were acquired using a segmented, multi-slice GE-EPI with in-plane resolution of 375x333 μm and TE/TR of 11/3000 ms. The visual stimulus was a full field rotating checkerboard presented to both eyes. All data analysis was performed in MatLab (the Mathworks). We obtained robust high resolution fCBF maps in visual cortex with a signal-to-noise ratio of 25. The laminar profile of % fCBF obtained at 800 ms shows a clear peak at the level of the Gennari-line, i.e. in layer IV. At a short PLD a contribution from the larger pial vessels was seen in addition to a narrow peak in layer IV. The location of the cortical surface and the Gennari-line were identified based on anatomical scans. The PLD determines the relative contributions of the different vascular compartments. For scans with a sufficiently long PLD the functional signal represents the capillary fraction. For short PLDs our data show a contribution of arterioles to the fCBF map as hypothesized in [5]. Peak fCBF was observed in layer IV similar to the BOLD-results, possibly representing the higher metabolic activity of layer IV. In combination with calibrated BOLD this will allow determination of CMRO2 in vivo at high spatial resolution. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de 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 aczappeA-CZappe jozienJBMGoense nikosNKLogothetis poster 4428 2007 5 2007 616 136 High resolution fMRI allows us to determine more accurately the origins of the fMRI signal. This has shown that even at high field, the GE-BOLD signal has still a large vascular contribution [1]. Alternative methods like SE- and monocrystalline iron oxide nanocolloid (MION)-based methods have been shown to be spatially more specific than conventional BOLD, and are able to reveal functional subunits in the cortex [2-6]. Here we compare the specificity of BOLD and CBV fMRI methods in the macaque; its striate cortex shows very obvious laminar structure in anatomical images, allowing accurate determination of the precise location of the fMRI activation. http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/ISMRM2007-Zappe_4428[0].pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/07/ Biologische Kybernetik Max-Planck-Gesellschaft Berlin, Germany 2007 Joint Annual Meeting ISMRM-ESMRMB en aczappeA-CZappe nikosNKLogothetis jozienJBMGoense poster 5488 2007 5 2007 2015 399 Susceptibility gradients from the ear canal result in distortion and signal loss in GE-EPI, resulting in loss of functional activation in areas adjacent to the ear canal. Although susceptibility-related signal loss also occurs at low field, at 7T it is so severe that no functional activation is seen in these areas. We are interested in fMRI of the entire visual ventral stream in awake monkeys, because the ventral pathway is crucial for object recognition. To overcome the susceptibility problem in the temporal lobes, we used SE-EPI, which allowed us to recover functional activation in areas affected by susceptibility gradients. 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 Berlin, Germany 2007 Joint Annual Meeting ISMRM-ESMRMB en jozienJBMGoense shihpiS-PKu hellmutHMerkle atoliasASTolias nikosNKLogothetis poster KuGTL2007 Neuroforum 2007 4 13 Supplement 765 In contrast to electrophysiological studies, the advantage of fMRI is that it allows simultaneous mapping of the functional organization of multiple cortical areas. FMRI of awake monkey has benefit of combining behavioral studies with BOLD-measurement to be used to precisely localize functional specific cortical areas for further invasive studies such as detailed electrophysiological single unit recordings. Although high magnetic field offers the benefit of increased signal-to-noise ratios and higher specificity, a drawback is the higher sensitivity to susceptibility gradients caused by the air-tissue interfaces. This can be particularly problematic in the lower floor of temporal lobe because the large macroscopic susceptibility gradients near the ear canal result in distortion and loss of signal when the standard GE-EPI is used. For fMRI of such areas using spin-echo EPI (SE-EPI) is advantageous because it is less sensitive than GE-EPI to susceptibility artifacts, and does not suffer from signal dropout in these regions. Another advantage is that SE-EPI is less affected by frequency-changes in the main magnetic field, which are caused by movement of the animal. In this study, we compared SE-EPI and gradient-echo fMRI in the awake monkey (Macaca mulatta), using a vertical bore 7T MR system. A saddle coil optimized for temporal cortex was used to allow imaging of the major visual areas. The imaging parameters and slice orientation were optimized to minimize susceptibility effects. Resolution was typically 1.5x2x2mm, TE was 40 ms, TR was 1-2 s. In contrast to the GE-EPI images, which showed very large signal dropout in the temporal lobe, SE images showed minimal or no distortion or signal losses. Any remaining distortions were corrected using field-map correction to ensure perfect matching of the functional map to the high-resolution T1-weighted anatomical images. Using movie- stimuli, we confirmed that reliable functional activation could be obtained with SE-EPI at high field, and we show robust activation in the temporal lobe and early visual areas. Using random-dot kinematograms of various coherences we were also able to obtain functional activities in specific visual motion sensitive areas such as MT, MST and an area located within the lower bank of superior temporal sulcus by contract of high coherence (80%) and zero-coherence random dot stimuli. The reliability and specificity of the obtained activations with SE-EPI ensures the application of the method in our on-going visual perception studies. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.neuro.uni-goettingen.de/nbc.php?sel=archiv Göttingen, Germany 31st Göttingen Neurobiology Conference shipiS-PKu jozienJGoense atoliasATolias nikosNKLogothetis poster 4287 2006 6 50 For fMRI to be able to provide insight in the cortical circuitry, the spatial resolution and specificity of the fMRI signal need to be sufficient to visualize the microarchitecture of the cortex at the laminar and columnar level. The current spatial resolution of the fMRI signal however is too coarse to be able to reliably visualize the cortical microarchitecture. Cortical columns of ~1 mm have been observed with fMRI, but achieving higher (submillimeter) resolution is problematic, because the specificity of the activation is determined by the hemodynamic properties of the vascular bed. The conventional Gradient- Echo (GE) sequence used for BOLD-fMRI is sensitive to signal from veins and venules, and is strongest at the cortical surface, where draining vessels are located. This has limited the spatial specificity of the conventional fMRI signal to about 1 mm. By using the Spin-Echo (SE) fMRI signal instead, which is more sensitive to the capillary fraction, and less sensitive to veins, the specificity of the fMRI signal can be enhanced. Sequence optimization allowed us to further increase spatial specificity, and to achieve submillimeter spatial resolution. This resolution allows visualization of the cortical laminae, as shown in V1 in the anesthetized macaque (figure). The SE-BOLD signal was localized to layer IV/Duvernoy layer 3, with little activation in the upper cortical layers. The spatial resolution and specificity shown here allows determination of differences in laminar profiles depending on visual input. When motion and flicker stimuli were compared, the unequal laminar distribution of motion-direction selective laminae could be clearly discerned. Our results indicate that the point spread function for SE-fMRI is 0.5 mm or less, and is sufficient to observe differences in functional activation at laminar resolution. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.areadne.org/2006/ Biologische Kybernetik Max-Planck-Gesellschaft Santorini, Greece AREADNE 2006: Research in Encoding and Decoding of Neural Ensembles en jozienJBMGoense nikosNKLogothetis poster 4286 2006 5 14 3258 618 To relate fMRI signals to the underlying neural events, it is necessary to achieve a spatial resolution and specificity that permits visualization of the cortical functional units, e.g. cortical columns or laminae. Because the resolution of GE-fMRI is determined by intracortical veins and therefore limited, we used SEfMRI, which is weighted towards capillaries, to obtain specific BOLD responses. SE-EPI however is also sensitive to the venous fraction, potentially limiting spatial resolution. By decreasing the EPI acquisition window, we obtained highly specific functional activation. Activation was predominantly located in layer IV, while activation around surface vessels varied with acquisition window length. http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis http://www.ismrm.org/06/ Biologische Kybernetik Max-Planck-Gesellschaft International Society of Magnetic Resonance in Medicine Seattle, WA, USA 14th Scientific Meeting of the International Society of Magnetic Resonance in Medicine (ISMRM 2006) en jozienJBMGoense nikosNKLogothetis poster 3835 2005 11 35 620.5 The temporal lobe of the primate brain is thought to be important in high-level object recognition and learning. In contrast to electrophysiological studies, fMRI has the advantage that it allows simultaneous mapping of the functional organization of multiple cortical areas. However, there are few fMRI studies of the inferior temporal lobe in the non-human primate, because gradient-echo echo-planar-imaging (GE-EPI), which is commonly used, suffers from susceptibility related signal losses due to the ear canal and the cancellous nature of the temporal bone. The large macroscopic susceptibility gradients caused by air-tissue interfaces result in distortion and reduced signal-to-noise in affected areas. At high magnetic fields this is especially problematic, because in addition to increases in the BOLD signal, the susceptibility artifacts also increase. In areas of high susceptibility, using spin-echo EPI (SE-EPI) may be advantageous because it is less sensitive than GE-EPI to susceptibility artifacts, and does not suffer from signal dropout in these regions. In this study, we compare SE-EPI and gradient-echo fMRI in the awake monkey (Macaca mulatta), using a vertical bore 7T MR system. An 8 cm surface coil was positioned over the monkey’s ear, which covers one hemisphere, allowing imaging of the major visual areas. The imaging parameters and slice orientation were optimized to minimize susceptibility effects. Resolution was typically 1.5x2x2mm, TE was 40 ms, TR was 1-2 s. In contrast to the GE-EPI images, which showed very large signal dropout in the temporal lobe, SE images showed minimal or no distortion or signal losses. Using movies as a stimulus, reliable functional activation was obtained in the inferior temporal lobe (as well as in other visual areas). The reliability and specificity of the obtained activations with SE-EPI ensures the application of the method in our on-going visual perception and learning studies. 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 Washington, DC, USA 35th Annual Meeting of the Society for Neuroscience (Neuroscience 2005) en jozienJGoense shihpiS-PKu atoliasASTolias nikosNKLogothetis conference 4158 Magnetic Resonance Materials in Physics, Biology and Medicine 2006 9 21 19 Supplement 1 64 Activation maps acquired with perfusion-based FMRI are known to be more specific to the parenchyma and less sensitive to proximal draining veins compared to BOLD [1]. Here, the specificity of ASL activation maps in the nonhuman primate was investigated at high spatial resolution. Since the choice of labeling parameters can affect the specificity of the measured activation, the influence of the post-labeling-delay (PLD) and labeling-time (LT) on perfusion-based activation maps was evaluated. http://www.kyb.tuebingen.mpg.de/fileadmin/user_upload/files/publications/esmrmb2006_aczappe_4158[0].pdf http://www.kyb.tuebingen.mpg.de http://www.kyb.tuebingen.mpg.de Department Logothetis Abstract Talk http://www.springerlink.com/content/wvm3330668r40u55/fulltext.pdf Biologische Kybernetik Max-Planck-Gesellschaft Warsaw, Poland 23rd Annual Scientific Meeting of the ESMRMB 2006 en 10.1007/s10334-006-0040-4 aczappeA-CZappe jozienJBMGoense nikosNKLogothetis josefJPfeuffer