309 research outputs found

    30th European Congress on Obesity (ECO 2023)

    Get PDF
    This is the abstract book of 30th European Congress on Obesity (ECO 2023

    Brain Computations and Connectivity [2nd edition]

    Get PDF
    This is an open access title available under the terms of a CC BY-NC-ND 4.0 International licence. It is free to read on the Oxford Academic platform and offered as a free PDF download from OUP and selected open access locations. Brain Computations and Connectivity is about how the brain works. In order to understand this, it is essential to know what is computed by different brain systems; and how the computations are performed. The aim of this book is to elucidate what is computed in different brain systems; and to describe current biologically plausible computational approaches and models of how each of these brain systems computes. Understanding the brain in this way has enormous potential for understanding ourselves better in health and in disease. Potential applications of this understanding are to the treatment of the brain in disease; and to artificial intelligence which will benefit from knowledge of how the brain performs many of its extraordinarily impressive functions. This book is pioneering in taking this approach to brain function: to consider what is computed by many of our brain systems; and how it is computed, and updates by much new evidence including the connectivity of the human brain the earlier book: Rolls (2021) Brain Computations: What and How, Oxford University Press. Brain Computations and Connectivity will be of interest to all scientists interested in brain function and how the brain works, whether they are from neuroscience, or from medical sciences including neurology and psychiatry, or from the area of computational science including machine learning and artificial intelligence, or from areas such as theoretical physics

    Contribution du cortex prémoteur à la locomotion entravée chez le chat

    Full text link
    La locomotion est une composante fondamentale de la vie animale : elle permet l’accĂšs continu aux ressources nĂ©cessaires Ă  la survie ainsi que l’évitement de pĂ©rils variĂ©s. Les milieux naturels comme anthropiques regorgent toutefois d’obstacles s’élevant contre notre progression. Pour l’humain et les autres mammifĂšres terrestres naviguant principalement par la vision, le franchissement efficace de ces obstacles repose critiquement sur la capacitĂ© de modifier proactivement le positionnement et la trajectoire des pas en fonction des informations visuelles extraites durant leur approche. Au niveau du systĂšme nerveux, cette capacitĂ© implique un processus complexe oĂč le traitement des signaux visuels reflĂ©tant les paramĂštres de l’obstacle spĂ©cifie un cours d’action sĂ©curisant son franchissement, lequel est ultimement exĂ©cutĂ© par des altĂ©rations prĂ©cises Ă  l’activitĂ© musculaire. Des Ă©tudes approfondies chez le chat, l’un des modĂšles animaux les plus dĂ©veloppĂ©s et investiguĂ©s vis-Ă -vis du contrĂŽle locomoteur, ont prĂ©sentement impliquĂ© deux structures corticales dans ce processus. Le cortex pariĂ©tal postĂ©rieur contribuerait ainsi Ă  dĂ©terminer la position relative de l’obstacle et le cortex moteur primaire serait central Ă  l’exĂ©cution des modifications de la dĂ©marche. Cependant, notre comprĂ©hension du substrat neural impliquĂ© dans la transformation sensorimotrice joignant ces deux Ă©tapes est extrĂȘmement limitĂ©e. Plusieurs lignes d’évidences, particuliĂšrement dĂ©rivĂ©es de travaux chez le primate investiguant le contrĂŽle des mouvements volontaires du bras, pointent cependant vers une contribution potentiellement majeure du cortex prĂ©moteur Ă  cette fonction. Cette thĂšse entreprend de dĂ©terminer directement la contribution prĂ©motrice aux modifications de la dĂ©marche. Deux Ă©tudes rapportent ainsi l’activitĂ© de neurones individuels enregistrĂ©s dans deux larges subdivisions du cortex prĂ©moteur, les aires 6iffu et 4delta, chez le chat Ă©veillĂ© accomplissant librement une tĂąche de nĂ©gociation d’obstacles sur tapis roulant. Ces Ă©tudes font Ă©tat de changements d’activitĂ© distincts d’une subdivision Ă  l’autre et corrĂ©lĂ©s Ă  des aspects spĂ©cifiques de la tĂąche, incluant des changements prĂ©paratoires liĂ©s Ă  l’approche finale de l’obstacle et d’autres liĂ©s Ă  une ou plusieurs Ă©tapes des ajustements locomoteurs sĂ©quentiels entourant sa nĂ©gociation. Une troisiĂšme Ă©tude investigue par microstimulation intracorticale la capacitĂ© des diffĂ©rentes subdivisions prĂ©motrices du chat Ă  modifier la dĂ©marche. Cette Ă©tude expose une variĂ©tĂ© de rĂ©ponses Ă©lectromyographiques complexes s’intĂ©grant en phase avec la marche, oĂč plusieurs subdivisions prĂ©sentent des signatures distinctes d’effets multi-membres contrastant avec l’influence focale du cortex moteur primaire. Chacune de ces trois Ă©tudes est finalement complĂ©mentĂ©e d’investigations par traçage rĂ©trograde de connexions anatomiques dĂ©cisives Ă  l’interprĂ©tation fonctionnelle des subdivisions investiguĂ©es. Ensemble, ces travaux soutiennent et prĂ©cisent une contribution centrale du cortex prĂ©moteur aux modifications de la dĂ©marche sous guidage visuel. D’une part, ils rapportent pour la premiĂšre fois que l’activitĂ© neuronale de multiples subdivisions du cortex prĂ©moteur reflĂšte diffĂ©rentes Ă©tapes de la planification locomotrice stipulant les altĂ©rations Ă  entreprendre Ă  l’approche d’un obstacle et durant son franchissement. D’autre part, ils rĂ©vĂšlent complĂ©mentairement que l’activation de ces subdivisions a le pouvoir d’influencer profondĂ©ment la marche. Les donnĂ©es collectĂ©es soulignent finalement plusieurs points de comparaison entre les aires prĂ©motrices du chat et du primate, suggĂ©rant un degrĂ© d’analogie fonctionnelle extensible Ă  la locomotion humaine.Locomotion is a fundamental component of animal life: it provides continuous access to the resources necessary for survival as well as the means to elude potential perils. However, both natural and built environments teem with obstacles impeding one’s progress. For humans and other terrestrial mammals navigating primarily through vision, efficiently negotiating these obstacles critically requires the capacity to proactively adapt the positioning and trajectory of each step on the basis of visual information extracted during their approach. In the nervous system, this capacity involves a complex process through which the integration of visual signals reflecting the parameters and location of an obstacle specifies a course of action to ensure its negotiation, Extensive studies in the cat, one of the most common models used to study the neural mechanisms involved in the control of locomotion, have currently implicated two cortical structures to this process. The posterior parietal cortex is suggested to contribute to the determination of the obstacle’s relative position (with respect to the body) while the primary motor cortex is central to the execution of the gait modifications. However, our comprehension of the neural substrate implicated in the sensorimotor transformation linking these defined stages is extremely limited. Several lines of evidence, predominantly derived from work in the primate investigating the voluntary control of arm movements, nonetheless point towards a potentially major contribution of the premotor cortex to this function. This thesis sets out to directly determine the premotor contribution to the control of gait modifications. Two studies report the activity of individual neurons recorded in two large subdivisions of premotor cortex, areas 6iffu and 4delta, in awake cats freely performing an obstacle negotiation task on treadmill. These studies describe distinct changes in activity across subdivisions that correlate with specific aspects of the task, including preparatory changes related to the final approach of the obstacle and others related to one or more stages of the sequential locomotor adjustments surrounding its negotiation. A third study used intracortical microstimulation to investigate the capacity of different premotor subdivisions of the cat to modify gait. This study reveals a variety of complex electromyographic responses that are integrated into the gait cycle. Moreover, several subdivisions show distinct signatures of multi-limb effects that contrast with the focal influence of the primary motor cortex. Each of these three studies is finally complemented by retrograde tracing investigations of anatomical connections critical to the functional interpretation of the subdivisions examined. Together, these studies support and clarify a central contribution of the premotor cortex to the modification of gait under visual guidance. We report for the first time that the neural activity of multiple subdivisions of the premotor cortex reflects different stages of the locomotor plan specifying the gait alterations to perform during the approach and crossing of an obstacle. In addition, we reveal that activation of these subdivisions has the power to profoundly influence walking. The data collected finally highlight several points of comparison between the premotor areas of the cat and the primate, suggesting a degree of functional analogy extensible to human locomotion

    Cortico-spinal modularity in the parieto-frontal system: a new perspective on action control

    Get PDF
    : Classical neurophysiology suggests that the motor cortex (MI) has a unique role in action control. In contrast, this review presents evidence for multiple parieto-frontal spinal command modules that can bypass MI. Five observations support this modular perspective: (i) the statistics of cortical connectivity demonstrate functionally-related clusters of cortical areas, defining functional modules in the premotor, cingulate, and parietal cortices; (ii) different corticospinal pathways originate from the above areas, each with a distinct range of conduction velocities; (iii) the activation time of each module varies depending on task, and different modules can be activated simultaneously; (iv) a modular architecture with direct motor output is faster and less metabolically expensive than an architecture that relies on MI, given the slow connections between MI and other cortical areas; (v) lesions of the areas composing parieto-frontal modules have different effects from lesions of MI. Here we provide examples of six cortico-spinal modules and functions they subserve: module 1) arm reaching, tool use and object construction; module 2) spatial navigation and locomotion; module 3) grasping and observation of hand and mouth actions; module 4) action initiation, motor sequences, time encoding; module 5) conditional motor association and learning, action plan switching and action inhibition; module 6) planning defensive actions. These modules can serve as a library of tools to be recombined when faced with novel tasks, and MI might serve as a recombinatory hub. In conclusion, the availability of locally-stored information and multiple outflow paths supports the physiological plausibility of the proposed modular perspective

    Neural Signals of Video Advertisement Liking:Insights into Psychological Processes and their Temporal Dynamics

    Get PDF
    What drives the liking of video advertisements? The authors analyzed neural signals during ad exposure from three functional magnetic resonance imaging (fMRI) data sets (113 participants from two countries watching 85 video ads) with automated meta-analytic decoding (Neurosynth). These brain-based measures of psychological processes—including perception and language (information processing), executive function and memory (cognitive functions), and social cognition and emotion (social-affective response)—predicted subsequent self-report ad liking, with emotion and memory being the earliest predictorsafter the first three seconds. Over the span of ad exposure, while the predictiveness of emotion peaked early and fell, that of social cognition had a peak-and-stable pattern, followed by a late peak of predictiveness in perception and executive function.At the aggregate level, neural signals—especially those associated with social-affective response—improved the prediction of out-of-sample ad liking compared with traditional anatomically based neuroimaging analysis and self-report liking. Finally, earlyonset social-affective response predicted population ad liking in a behavioral replication. Overall, this study helps delineate the psychological mechanisms underlying ad processing and ad liking and proposes a novel neuroscience-based approach for generating psychological insights and improving out-of-sample predictions

    The Role Of The Nmda Receptor In Shaping Cortical Activity During Development

    Get PDF
    Currently, it is estimated that neuropsychiatric disorders will affect 20-25% of humans in their lifetime. These disorders are a major cause of mortality, suffering, and economic cost to society. Within this broad class, neurodevelopmental disorders (NDDs), including intellectual disability, autism spectrum disorder, and schizophrenia, are estimated to affect 2-5% percent of the world population. Devastatingly, we lack fundamental treatments for NDDs, which have proved some of the most imposing disorders to understand scientifically. The challenge is twofold: first, NDDs affect the most complex aspects of human cognition; second, pathogenesis begins early in neural circuit development, but we lack predictive biomarkers before overt behavioral deficits are apparent. Although we have identified many genes associated with these disorders, how underlying genetic disruptions lead to pathological neural network development and function remains unclear. The overarching framework of this dissertation is that all NPDs are disorders of distributed neural networks, and pathophysiology must be understood at this level to effectively intervene clinically. The cerebral cortex is necessary for complex human capacities, and cortical dysfunction is hypothesized to be central to the pathophysiology of NDDs. NMDA glutamate receptors (NMDARs) are important for the development of local circuit features in the cortex, for normal neurocognitive function, and are strongly implicated in NDDs. However, the role of NMDARs in the development of the large-scale cortical network dynamics that underly higher cognition has not been well examined. Understanding the role of NMDARs at this network level is critical because large-scale “functional connectivity” patterns are thought to be hallmarks of normal cortical function, are hypothesized to be disrupted in NDDs, and may be detectable in humans using non-invasive neuroimaging or electrophysiology. In the studies presented in this dissertation, I (in collaboration and with the support of my colleagues) tested the role of the NMDAR in shaping large-scale cortical network organization using in vivo widefield imaging of whole cortex spontaneous activity in developing mice. I found that NMDAR function in the lineage that includes cortical excitatory neurons and glia, specifically, was critical for the elaboration of normal cortical activity patterns and dynamic network organization. In the first set of experiments, NMDARs were deleted in glutamatergic excitatory neurons (Emx1-cre+/WT/Grin1f/f ; referred to as EX-NMDAR KO mice) or GABAergic inhibitory neurons (Nkx2.1+/WT/Grin1f/f; referred to as IN-NMDAR KO mice). The developing cortex normally exhibits a diverse range of spatio-temporal patterns, reflecting the emergence of functionally associated sub-networks. In EX-NMDAR KO mice, normal patterns of spontaneous activity were severely disrupted and reduced to a nearly one-dimensional dynamic space dominated by large, cortex-wide events. Interestingly, in IN-NMDAR KO mice, the structure and complexity of spontaneous activity was largely normal. In the next set of experiments, I tested the role of extrinsic thalamic neurotransmission on cortical activity during development. Deleting the vesicular glutamate transporter from thalamic neurons while leaving cortical NMDARs intact (Sert-Cre+/−,vglut1−/−,vglut2fl/fl; referred to as TH-VG KO mice) led to a shift in cortical activity patterns towards large domains of activity, reminiscent of patterns observed in EX-NMDAR KO mice. This manipulation also reduced the dimensionality of cortical activity, though not as severally as in EX-NMDAR KO mice. In a final set of experiments, I tested cortical activity in three established mouse models of mono-genetic causes of NDDs in humans: the FMR1-KO mouse based on Fragile X Syndrome, the CNTNAP2-KO mouse, and the TS2-neo mouse based on Timothy Syndrome. In all three of these mouse models, I found that large-scale cortical activity patterns were largely normal, but there was a statistically significant shift towards reduced cortex-wide synchrony and increased dimensionality of spontaneous activity, which may be consistent with the disconnectivity hypothesis of autism. In a final set of experiments, we tested our hypothesis, based on past literature and our results in EX-NMDAR KO and TH-VG KO mice, that the disruptions in cortical activity was predominantly due to the developmental loss of activity-dependent wiring of circuits. To test the developmental versus acute role of NMDAR function in shaping cortical activity, I blocked NMDAR pharmacologically in wild-type mice. I found that acute NMDAR blockade shifted cortical activity to a restricted dynamic space similar to that observed in EX-NMDAR KO mice and more extreme than that observed in TH-VG KO mice. These results strongly reinforce the critical role of NMDAR in shaping cortical activity during development, and suggest that a substantial component of that may be through NMDAR’s role in synaptic transmission and moment to moment cortex-wide circuit function. Overall, these results provide critical insight into the role of NMDARs and the glutamatergic system in cortical network functional organization during development. Specifically, they highlight the essential role of NMDARs in excitatory neurons on the functional connectivity and dynamic repertoire of the cortical network during development. These results make novel contribution to our understanding of how NMDARs may contribute to the pathophysiology of NDDs. Specifically, they contribute powerful new insight into to a critical mechanistic question about the cell-specific role of NMDARs in the pathophysiology of schizophrenia and the mechanisms of NMDAR antagonists, which have transformed psychiatry recently due to their rapid-acting anti-depressant and anti-suicidal properties. Furthermore, they identify a patterns of large-scale network dysfunction that might be detectable in humans using noninvasive functional imaging or electrophysiology

    Distinct VIP interneurons in the cingulate cortex encode anxiogenic and social stimuli

    Get PDF
    A hallmark of higher-order cortical regions is their functional heterogeneity, but it is not well understood how these areas are able to encode diverse behavioral information. The anterior cingulate cortex (ACC), for example, is known to be important in a large range of behaviors, including, decision making, emotional regulation and social cognition. In support of this, previous work shows activation of the ACC to anxiety-related and social stimuli but does not use cellular resolution or cell-type specific techniques to elucidate the possible heterogeneity of its subcircuits. In this work, I investigate how subpopulations of neurons or microcircuits within the ACC encode these different kinds of stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to alter the activity of clusters of pyramidal excitatory neurons, often by inhibiting other types of inhibitory cells. Prior to this research, it was unknown whether the activity of VIP cells in the ACC (VIPACC) encodes anxiety-related or social information and whether all VIPACC activate similarly to the same behavioral stimuli. Using in vivo Ca2+ imaging and 3D-printed miniscopes in freely behaving mice to monitor VIPACC activity, I have identified distinct subpopulations of VIPACC that preferentially activate to either anxiogenic, anxiolytic, social, or non-social stimuli. I also demonstrate that these stimulus-selective subpopulations are largely non-overlapping and that clusters of cells may co-activate, improving their encoding. Finally, I used trans-synaptic tracing to map monosynaptic inputs to VIP and other interneuron subtypes in the ACC. I found that VIPACC receive widespread inputs from regions implicated in emotional regulation and social cognition and that some inputs differ between types of ACC interneurons. Overall, these data demonstrate that the ACC is not homogeneous – there is marked functional heterogeneity within one interneuron population in the ACC and connective heterogeneity across ACC cell types. This work contributes to our broader understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior

    Xenopus

    Get PDF
    This book focuses on the amphibian, Xenopus, one of the most commonly used model animals in the biological sciences. Over the past 50 years, the use of Xenopus has made possible many fundamental contributions to our knowledge in cell biology, developmental biology, molecular biology, and neurobiology. In recent years, with the completion of the genome sequence of the main two species and the application of genome editing techniques, Xenopus has emerged as a powerful system to study fundamental disease mechanisms and test treatment possibilities. Xenopus has proven an essential vertebrate model system for understanding fundamental cell and developmental biological mechanisms, for applying fundamental knowledge to pathological processes, for deciphering the function of human disease genes, and for understanding genome evolution. Key Features Provides historical context of the contributions of the model system Includes contributions from an international team of leading scholars Presents topics spanning cell biology, developmental biology, genomics, and disease model Describes recent experimental advances Incorporates richly illustrated diagrams and color images Related Titles Green, S. L. The Laboratory Xenopus sp. (ISBN 978-1-4200-9109-0) Faber, J. & P. D. Nieuwkoop. Normal Table of Xenopus laevis (Daudin): A Systematical & Chronological Survey of the Development from the Fertilized Egg till the End of Metamorphosis (ISBN 978-0-8153-1896-5) Jarret, R. L. & K. McCluskey. The Biological Resources of Model Organisms (ISBN 978-1-0320-9095-5
    • 

    corecore