Center for Integrative Neuroscience

Stuttgart, Germany

Center for Integrative Neuroscience

Stuttgart, Germany
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Cavusoglu M.,Max Planck Institute for Biological Cybernetics | Cavusoglu M.,University of Tübingen | Bartels A.,Center for Integrative Neuroscience | Yesilyurt B.,Max Planck Institute for Biological Cybernetics | Uludag K.,Maastricht University
NeuroImage | Year: 2012

Cortical representations of the visual field are organized retinotopically, such that nearby neurons have receptive fields at nearby locations in the image. Many studies have used blood oxygenation level-dependent (BOLD) fMRI to non-invasively construct retinotopic maps in humans. The accuracy of the maps depends on the spatial extent of the metabolic and hemodynamic changes induced by the neural activity. Several studies using gradient-echo MRI at 1.5. T and 3. T showed that most of the BOLD signal originates from veins, which might lead to a spatial displacement from the actual site of neuronal activation, thus reducing the specificity of the functional localization. In contrast to BOLD signal, cerebral blood flow (CBF) as measured using arterial spin labeling (ASL) is less or not at all affected by remote draining veins, and therefore spatially and temporally more closely linked to the underlying neural activity. In the present study, we determined retinotopic maps in the human brain using CBF as well as using BOLD signal in order to compare their spatial relationship and the temporal delays of each imaging modality for visual areas V1, V2, V3, hV4 and V3AB. We tested the robustness and reproducibility of the maps across different sessions, calculated the overlap as well as signal delay times across visual areas. While area boundaries were relatively well preserved, we found systematic differences of response latencies between CBF and the BOLD signal between areas. In summary, CBF data obtained using ASL allows reliable retinotopic maps to be constructed; this approach is, therefore, suitable for studying visual areas especially in close proximity to large veins where the BOLD signal is spatially inaccurate. © 2011 Elsevier Inc.


Chiang L.-Y.,Max Delbrück Center for Molecular Medicine | Poole K.,Max Delbrück Center for Molecular Medicine | Oliveira B.E.,University of Cologne | Duarte N.,Max Delbrück Center for Molecular Medicine | And 6 more authors.
Nature Neuroscience | Year: 2011

Laminin-332 is a major component of the dermo-epidermal skin basement membrane and maintains skin integrity. The transduction of mechanical force into electrical signals by sensory endings in the skin requires mechanosensitive channels. We found that mouse epidermal keratinocytes produce a matrix that is inhibitory for sensory mechanotransduction and that the active molecular component is laminin-332. Substrate-bound laminin-332 specifically suppressed one type of mechanosensitive current (rapidly adapting) independently of integrin-receptor activation. This mechanotransduction suppression could be exerted locally and was mediated by preventing the formation of protein tethers necessary for current activation. We also found that laminin-332 could locally control sensory axon branching behavior. Loss of laminin-332 in humans led to increased sensory terminal branching and may lead to a de-repression of mechanosensitive currents. These previously unknown functions for this matrix molecule may explain some of the extreme pain experienced by individuals with epidermolysis bullosa who are deficient in laminin-332. © 2011 Nature America, Inc. All rights reserved.


Bouchard J.,University of California at San Francisco | Bouchard J.,Gladstone | Truong J.,Gladstone | Bouchard K.,University of California at San Francisco | And 10 more authors.
Journal of Neuroscience | Year: 2012

Peripheral immune cells and brain microglia exhibit an activated phenotype in premanifest Huntington's disease (HD) patients that persists chronically and correlates with clinical measures of neurodegeneration. However, whether activation of the immune system contributes to neurodegeneration in HD, or is a consequence thereof, remains unclear. Signaling through cannabinoid receptor 2 (CB2) dampens immune activation. Here, we show that the genetic deletion of CB2 receptors in a slowly progressing HD mouse model accelerates the onset of motor deficits and increases their severity. Treatment of mice with a CB2 receptor agonist extends life span and suppresses motor deficits, synapse loss, and CNS inflammation, while a peripherally restricted CB2 receptor antagonist blocks these effects. CB2 receptors regulate blood interleukin-6 (IL-6) levels, and IL-6 neutralizing antibodies partially rescue motor deficits and weight loss inHDmice. These findings support a causal link between CB2 receptor signaling in peripheral immune cells and the onset and severity of neurodegeneration in HD, and they provide a novel therapeutic approach to treat HD. © 2012 the authors.


Schindler A.,Center for Integrative Neuroscience | Schindler A.,University of Tübingen | Schindler A.,Max Planck Institute for Biological Cybernetics | Bartels A.,Center for Integrative Neuroscience | And 2 more authors.
Cerebral Cortex | Year: 2017

Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared withmatched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1?V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis,we showan optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding. © 2016 The Author. Published by Oxford University Press. All rights reserved.


Chaisanguanthum K.S.,Center for Integrative Neuroscience | Chaisanguanthum K.S.,University of California at San Francisco | Shen H.H.,Center for Integrative Neuroscience | Sabes P.N.,Center for Integrative Neuroscience | Sabes P.N.,University of California at San Francisco
Journal of Neuroscience | Year: 2014

Even well practiced movements cannot be repeated without variability. This variability is thought to reflect "noise" in movement preparation or execution. However, we show that, for both professional baseball pitchers and macaque monkeys making reaching movements, motor variability can be decomposed into two statistical components, a slowly drifting mean and fast trial-by-trial fluctuations about the mean. The preparatory activity of dorsal premotor cortex/primary motor cortex neurons in monkey exhibits similar statistics. Although the neural and behavioral drifts appear to be correlated, neural activity does not account for trial-by-trial fluctuations in movement, which must arise elsewhere, likely downstream. The statistics of this drift are well modeled by a double-exponential autocorrelation function, with time constants similar across the neural and behavioral drifts in two monkeys, as well as the drifts observed in baseball pitching. These time constants can be explained by an error-corrective learning processes and agree with learning rates measured directly in previous experiments. Together, these results suggest that the central contributions to movement variability are not simply trial-by-trial fluctuations but are rather the result of longer-timescale processes that may arise from motor learning. © 2014 the authors.


Guo D.,Center for Integrative Neuroscience | Hu J.,Center for Integrative Neuroscience
Neuroscience | Year: 2014

The gate control theory proposed that the nociceptive sensory information transmitted to the brain relies on an interplay between the inputs from nociceptive and non-nociceptive primary afferent fibers. Both inputs are normally under strong inhibitory control in the spinal cord. Under healthy conditions, presynaptic inhibition activated by non-nociceptive fibers modulates the afferent input from nociceptive fibers onto spinal cord neurons, while postsynaptic inhibition controls the excitability of dorsal horn neurons, and silences the non-nociceptive information flow to nociceptive-specific (NS) projection neurons. However, under pathological conditions, this spinal inhibition may be altered and lead to chronic pain. This review summarizes our knowledge of presynaptic inhibition in pain control, with particular focus on how its alteration after nerve or tissue injury contributes to neuropathic or inflammatory pain syndromes, respectively. © 2014 The Authors.


Seymour K.,University of Sydney | Seymour K.,Australian Center for Excellence in Vision Science | Clifford C.W.G.,University of Sydney | Clifford C.W.G.,Australian Center for Excellence in Vision Science | And 4 more authors.
Cerebral Cortex | Year: 2010

The processing of color and form is largely segregated within the visual brain. But there is also evidence to suggest that these features are coded in combination early in visual processing. Here, we combined high-resolution functional magnetic resonance imaging (fMRI) together with multivariate pattern classification to examine where in the visual cortex specific color form "conjunctions" are represented. Human subjects viewed visual displays containing colored spiral patterns. The spiral patterns could be red or green, and oriented either clockwise or counterclockwise, leading to 4 possible stimulus configurations. Two additional displays combined 2 of the above single color-form pairings, leading to double conjunctions. We applied linear classifiers to voxel activation patterns obtained while subjects viewed such displays. Our findings not only show that color and form information is coded across retinotopically defined visual areas, but also that the 2 double-conjunction stimuli can be distinguished. The voxels most informative about conjunctions were distinct from those most informative about color or form alone. Our results indicate that conjunctions of form and color may be coded by separate functional units as early as primary visual cortex. The results of this study have implications for theories concerning the segregation and binding of color and form information. The Author © 2009. Published by Oxford University Press. All rights reserved.


News Article | November 6, 2016
Site: www.sciencedaily.com

Philosophers have long struggled to define human consciousness. Now, a team of researchers led by neurologists at Beth Israel Deaconess Medical Center (BIDMC) has pinpointed the regions of the brain that may play a role maintaining it. Their finding were published today in journal Neurology. "For the first time, we have found a connection between the brainstem region involved in arousal and regions involved in awareness, two prerequisites for consciousness," said Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation and the Associate Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC. "A lot of pieces of evidence all came together to point to this network playing a role in human consciousness." Classical neurology holds that arousal and awareness are two critical components of consciousness. Arousal is likely regulated by the brainstem -- the portion of the brain, contiguous with the spinal cord, that is responsible for the sleep/wake cycle and cardiac and respiratory rates. Awareness, another critical component of consciousness, has long been thought to reside somewhere in the cortex, the outer layer of the brain responsible for many of its higher functions. The researchers analyzed 36 patients with brainstem lesions, of which 12 led to coma and 24 did not. Mapping the injuries revealed that a small "coma-specific" area of the brainstem -- the rostral dorsolateral pontine tegmentum -- was significantly associated with coma. Ten out of the 12 coma-inducing brainstem lesions involved this area, while just one of the 24 control lesions did. Armed with that information, Fox and colleagues, including lead author David Fischer, MD, then a medical student at Harvard Medical School, used a wiring diagram of the healthy human brain -- based on a large, shared data set called the Human Connectome -- to identify which other parts of the brain were connected to these coma-causing lesions. Their analysis revealed two areas in the cortex of the brain that were significantly connected to the coma-specific region of the brainstem. One sat in the left, ventral, anterior insula (AI), the other in the pregenual anterior cingulate cortex (pACC). Both regions have been implicated previously in arousal and awareness. "We now have a great map of how the brain is wired up in the Human Connectome," said Fox, who is also an Assistant Professor of Neurology at Harvard Medical School. "We can look at not just the location of lesions, but also their connectivity. Over the past year, researchers in my lab have used this approach to understand visual and auditory hallucinations, impaired speech, and movement disorders. A collaborative team of neuroscientists and physicians had the insight and unique expertise needed to apply this approach to consciousness." The team included co-lead author, Aaron Boes, MD, PhD, and co-senior author, Joel Geerling, MD, PhD, both formerly of BIDMC and now of University of Iowa Carver College of Medicine. Finally, the team investigated whether this brainstem-cortex network was functioning in another subset of patients with disorders of consciousness, including coma. Using a special type of MRI scan, the scientists found that their newly identified "consciousness network" was disrupted in patients with impaired consciousness. The findings -- bolstered by data from rodent studies -- suggest the network between the brainstem and these two cortical regions plays a role maintaining human consciousness. "The added value of thinking about coma as a network disorder is it presents possible targets for therapy, such as using brain stimulation to augment recovery," Boes said. A next step, Fox notes, may be to investigate other data sets in which patients lost consciousness to find out if the same, different or overlapping neural networks are involved. "This is most relevant if we can use these networks as a target for brain stimulation for people with disorders of consciousness," said Fox. "If we zero in on the regions and network involved, can we someday wake someone up who is in a persistent vegetative state? That's the ultimate question." Study coauthors include David B. Fischer, MD, Aaron D. Boes, MD, PhD, Joel C. Geerling, MD, PhD, Clifford B. Saper, MD, PhD, and Alvaro Pascual-Leone, MD, PhD, of BIDMC; Athena Demertzi, PhD, of the Brain and Spine Institute (Institut du Cerveau et de la Moelle épinière-ICM), Hôpital Pitié-Salpêtrière, Paris, France and the Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and University Hospital of Liège, Belgium; Steven Laureys, PhD, also of the Coma Science Group; Henry C. Evrard, PhD, of the Functional and Comparative Neuroanatomy Lab and the Centre for Integrative Neuroscience, Tübingen and the Max Planck Institute for Biological Cybernetics, Tübingen, Germany; Brian L. Edlow, MD, and Hesheng Liu, PhD. of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Charlestown, MA. This work was supported by the Howard Hughes Medical Institute, the Parkinson's Disease Foundation, the NIH (Shared Instrument Grant S10RR023043, K23NS083741, R01HD069776, R01NS073601, R01NS085477, R21MH099196, R21NS082870, R21NS085491, R21HD07616, R25NS065743, R25NS070682, T32 HL007901, P01HL095491), American Academy of Neurology/American Brain Foundation, Sidney R. Baer, Jr. Foundation, Harvard Catalyst, the Belgian National Funds for Scientific Research, the European Commission, the James McDonnell Foundation, the European Space Agency, Mind Science Foundation, the French Speaking Community Concerted Research Action (ARC-06/11-340), the Public Utility Foundation "Université Européenne du Travail," "Fondazione Europea di Ricerca Biomedica," the University and University Hospital of Liège, the Center for Integrative Neuroscience, and the Max Planck Society.


News Article | November 4, 2016
Site: www.eurekalert.org

BOSTON - Philosophers have long struggled to define human consciousness. Now, a team of researchers led by neurologists at Beth Israel Deaconess Medical Center (BIDMC) has pinpointed the regions of the brain that may play a role maintaining it. Their findings, which have already garnered multiple awards from the American Academy of Neurology, were published today in that society's journal, Neurology. "For the first time, we have found a connection between the brainstem region involved in arousal and regions involved in awareness, two prerequisites for consciousness," said Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation and the Associate Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC. "A lot of pieces of evidence all came together to point to this network playing a role in human consciousness." Classical neurology holds that arousal and awareness are two critical components of consciousness. Arousal is likely regulated by the brainstem - the portion of the brain, contiguous with the spinal cord, that is responsible for the sleep/wake cycle and cardiac and respiratory rates. Awareness, another critical component of consciousness, has long been thought to reside somewhere in the cortex, the outer layer of the brain responsible for many of its higher functions. The researchers analyzed 36 patients with brainstem lesions, of which 12 led to coma and 24 did not. Mapping the injuries revealed that a small "coma-specific" area of the brainstem - the rostral dorsolateral pontine tegmentum - was significantly associated with coma. Ten out of the 12 coma-inducing brainstem lesions involved this area, while just one of the 24 control lesions did. Armed with that information, Fox and colleagues, including lead author David Fischer, MD, then a medical student at Harvard Medical School, used a wiring diagram of the healthy human brain - based on a large, shared data set called the Human Connectome - to identify which other parts of the brain were connected to these coma-causing lesions. Their analysis revealed two areas in the cortex of the brain that were significantly connected to the coma-specific region of the brainstem. One sat in the left, ventral, anterior insula (AI), the other in the pregenual anterior cingulate cortex (pACC). Both regions have been implicated previously in arousal and awareness. "We now have a great map of how the brain is wired up in the Human Connectome," said Fox, who is also an Assistant Professor of Neurology at Harvard Medical School. "We can look at not just the location of lesions, but also their connectivity. Over the past year, researchers in my lab have used this approach to understand visual and auditory hallucinations, impaired speech, and movement disorders. A collaborative team of neuroscientists and physicians had the insight and unique expertise needed to apply this approach to consciousness." The team included co-lead author, Aaron Boes, MD, PhD, and co-senior author, Joel Geerling, MD, PhD, both formerly of BIDMC and now of University of Iowa Carver College of Medicine. Finally, the team investigated whether this brainstem-cortex network was functioning in another subset of patients with disorders of consciousness, including coma. Using a special type of MRI scan, the scientists found that their newly identified "consciousness network" was disrupted in patients with impaired consciousness. The findings - bolstered by data from rodent studies - suggest the network between the brainstem and these two cortical regions plays a role maintaining human consciousness. "The added value of thinking about coma as a network disorder is it presents possible targets for therapy, such as using brain stimulation to augment recovery," Boes said. A next step, Fox notes, may be to investigate other data sets in which patients lost consciousness to find out if the same, different or overlapping neural networks are involved. "This is most relevant if we can use these networks as a target for brain stimulation for people with disorders of consciousness," said Fox. "If we zero in on the regions and network involved, can we someday wake someone up who is in a persistent vegetative state? That's the ultimate question." Study coauthors include David B. Fischer, MD, Aaron D. Boes, MD, PhD, Joel C. Geerling, MD, PhD, Clifford B. Saper, MD, PhD, and Alvaro Pascual-Leone, MD, PhD, of BIDMC; Athena Demertzi, PhD, of the Brain and Spine Institute (Institut du Cerveau et de la Moelle épinière-ICM), Hôpital Pitié-Salpêtrière, Paris, France and the Coma Science Group, GIGA-Research & Cyclotron Research Centre, University and University Hospital of Liège, Belgium; Steven Laureys, PhD, also of the Coma Science Group; Henry C. Evrard, PhD, of the Functional and Comparative Neuroanatomy Lab and the Centre for Integrative Neuroscience, Tübingen and the Max Planck Institute for Biological Cybernetics, Tübingen, Germany; Brian L. Edlow, MD, and Hesheng Liu, PhD. of the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital, Charlestown, MA. This work was supported by the Howard Hughes Medical Institute, the Parkinson's Disease Foundation, the NIH (Shared Instrument Grant S10RR023043, K23NS083741, R01HD069776, R01NS073601, R01NS085477, R21MH099196, R21NS082870, R21NS085491, R21HD07616, R25NS065743, R25NS070682, T32 HL007901, P01HL095491), American Academy of Neurology/American Brain Foundation, Sidney R. Baer, Jr. Foundation, Harvard Catalyst, the Belgian National Funds for Scientific Research, the European Commission, the James McDonnell Foundation, the European Space Agency, Mind Science Foundation, the French Speaking Community Concerted Research Action (ARC-06/11-340), the Public Utility Foundation "Université Européenne du Travail," "Fondazione Europea di Ricerca Biomedica," the University and University Hospital of Liège, the Center for Integrative Neuroscience, and the Max Planck Society. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


Hu J.,Molecular Physiology of Somatic Sensation | Hu J.,Center for Integrative Neuroscience | Chiang L.-Y.,Molecular Physiology of Somatic Sensation | Koch M.,University of Cologne | Lewin G.R.,Molecular Physiology of Somatic Sensation
EMBO Journal | Year: 2010

The gating of ion channels by mechanical force underlies the sense of touch and pain. The mode of gating of mechanosensitive ion channels in vertebrate touch receptors is unknown. Here we show that the presence of a protein link is necessary for the gating of mechanosensitive currents in all low-threshold mechanoreceptors and some nociceptors of the dorsal root ganglia (DRG). Using TEM, we demonstrate that a protein filament with of length 100 nm is synthesized by sensory neurons and may link mechanosensitive ion channels in sensory neurons to the extracellular matrix. Brief treatment of sensory neurons with non-specific and site-specific endopeptidases destroys the protein tether and abolishes mechanosensitive currents in sensory neurons without affecting electrical excitability. Protease-sensitive tethers are also required for touch-receptor function in vivo. Thus, unlike the majority of nociceptors, cutaneous mechanoreceptors require a distinct protein tether to transduce mechanical stimuli. © 2010 European Molecular Biology Organization.

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