The Experts below are selected from a list of 4662 Experts worldwide ranked by ideXlab platform
Amy J Bastian - One of the best experts on this subject based on the ideXlab platform.
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The cerebellum as a movement sensor
Neuroscience Letters, 2018Co-Authors: Amanda S. Therrien, Amy J BastianAbstract:Abstract In this article, we review a broad range of studies of Cerebellar Function and dysFunction and interpret them within the framework that the cerebellum acts as part of a mechanism of predictive control. We describe studies that span human behaviour and consider the motor and sensory impairments that result from Cerebellar damage. We conclude that a parsimonious explanation of Cerebellar Function is as a predictor of the sensory outcomes of movement. However, future studies are needed to more rigorously test this hypothesis and determine how the Cerebellar circuit might perform this type of computation.
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Cerebellar transcranial direct current stimulation ctdcs a novel approach to understanding Cerebellar Function in health and disease
The Neuroscientist, 2016Co-Authors: Giuliana Grimaldi, Georgios P D Argyropoulos, Amy J Bastian, Mar Cortes, Nick J Davis, Dylan J Edwards, Roberta Ferrucci, Felipe Fregni, Joseph M Galea, Masahi HamadaAbstract:The cerebellum is critical for both motor and cognitive control. DysFunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and Function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of Cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human Cerebellar Function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from Cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of Cerebellar-motor cortex connectivity, likely via Cerebellar-thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions.
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predicting and correcting ataxia using a model of Cerebellar Function
Brain, 2014Co-Authors: Nasir H Bhanpuri, Amy J Bastian, Allison M OkamuraAbstract:Cerebellar damage results in uncoordinated, variable and dysmetric movements known as ataxia. Here we show that we can reliably model single-joint reaching trajectories of patients ( n = 10), reproduce patient-like deficits in the behaviour of controls ( n = 11), and apply patient-specific compensations that improve reaching accuracy ( P < 0.02). Our approach was motivated by the theory that the cerebellum is essential for updating and/or storing an internal dynamic model that relates motor commands to changes in body state (e.g. arm position and velocity). We hypothesized that Cerebellar damage causes a mismatch between the brain’s modelled dynamics and the actual body dynamics, resulting in ataxia. We used both behavioural and computational approaches to demonstrate that specific Cerebellar patient deficits result from biased internal models. Our results strongly support the idea that an intact cerebellum is critical for maintaining accurate internal models of dynamics. Importantly, we demonstrate how subject-specific compensation can improve movement in Cerebellar patients, who are notoriously unresponsive to treatment.
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active force perception depends on Cerebellar Function
Journal of Neurophysiology, 2012Co-Authors: Amy J Bastian, Nasir H Bhanpuri, Allison M OkamuraAbstract:Damage to the cerebellum causes characteristic movement abnormalities but is thought to have minimal impact on somatosensory perception. Traditional clinical assessments of patients with Cerebellar lesions reveal no perceptual deficits despite the fact that the cerebellum receives substantial somatosensory information. Given that abnormalities have been reported in predicting the visual consequences of movement, we suspect that the cerebellum broadly participates in perception when motor output is required (i.e., active perception). Thus we hypothesize that Cerebellar integrity is essential for somatosensory perception that requires motor activity, but not passive somatosensory perception. We compared the perceptual acuity of human Cerebellar patients to that of healthy control subjects in several different somatosensory perception tasks with minimal visual information. We found that patients were worse at active force and stiffness discrimination but similar to control subjects with regard to passive cutaneous force detection, passive proprioceptive detection, and passive proprioceptive discrimination. Furthermore, the severity of movement symptoms as assessed by a clinical exam was positively correlated with impairment of active force perception. Notably, within the context of these perceptual tasks, control subjects and Cerebellar patients displayed similar movement characteristics, and hence differing movement strategies are unlikely to underlie the differences in perception. Our results are consistent with the hypothesis that the cerebellum is vital to sensory prediction of self-generated movement and suggest a general role for the cerebellum in multiple forms of active perception.
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learning to predict the future the cerebellum adapts feedforward movement control
Current Opinion in Neurobiology, 2006Co-Authors: Amy J BastianAbstract:The role of the cerebellum in motor control and learning has been largely inferred from the effects of Cerebellar damage. Recent work shows that Cerebellar damage produces greater impairment of movements that require predictive as opposed to reactive control. This dissociation is consistent across many different types of movement. Predictive control is crucial for fast and ballistic movements, but impaired prediction can also affect slow movements, because of increased reliance on time-delayed feedback signals. The new findings are compatible with theories of Cerebellar Function, but still do not resolve whether the cerebellum operates by predicting the optimal motor commands or future sensory states. Prediction mechanisms must be learned and maintained through comparisons between predicted and observed outcomes. New results show that not all such error information is equivalent in driving Cerebellar learning.
Peter L Strick - One of the best experts on this subject based on the ideXlab platform.
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consensus paper towards a systems level view of Cerebellar Function the interplay between cerebellum basal ganglia and cortex
The Cerebellum, 2017Co-Authors: Daniele Caligiore, Kenji Doya, Giovanni Pezzulo, Gianluca Baldassarre, Andreea C Bostan, Peter L Strick, Rick C Helmich, Michiel F Dirkx, James C Houk, Henrik JörntellAbstract:Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive Functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the Function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the Function of Cerebellar-basal ganglia circuitry in both motor and non-motor Functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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the basal ganglia communicate with the cerebellum
Proceedings of the National Academy of Sciences of the United States of America, 2010Co-Authors: Andreea C Bostan, Peter L StrickAbstract:The basal ganglia and cerebellum are major subcortical structures that influence not only movement, but putatively also cognition and affect. Both structures receive input from and send output to the cerebral cortex. Thus, the basal ganglia and cerebellum form multisynaptic loops with the cerebral cortex. Basal ganglia and Cerebellar loops have been assumed to be anatomically separate and to perform distinct Functional operations. We investigated whether there is any direct route for basal ganglia output to influence Cerebellar Function that is independent of the cerebral cortex. We injected rabies virus (RV) into selected regions of the Cerebellar cortex in cebus monkeys and used retrograde transneuronal transport of the virus to determine the origin of multisynaptic inputs to the injection sites. We found that the subthalamic nucleus of the basal ganglia has a substantial disynaptic projection to the Cerebellar cortex. This pathway provides a means for both normal and abnormal signals from the basal ganglia to influence Cerebellar Function. We previously showed that the dentate nucleus of the cerebellum has a disynaptic projection to an input stage of basal ganglia processing, the striatum. Taken together these results provide the anatomical substrate for substantial two-way communication between the basal ganglia and cerebellum. Thus, the two subcortical structures may be linked together to form an integrated Functional network.
Detlef H Heck - One of the best experts on this subject based on the ideXlab platform.
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loss of Cerebellar Function selectively affects intrinsic rhythmicity of eupneic breathing
Biology Open, 2020Co-Authors: Shuhua Qi, Fridtjof Thomas, Brittany L Correia, Angela P Taylor, Roy V Sillitoe, Detlef H HeckAbstract:ABSTRACT Respiration is controlled by central pattern generating circuits in the brain stem, whose activity can be modulated by inputs from other brain areas to adapt respiration to autonomic and behavioral demands. The cerebellum is known to be part of the neuronal circuitry activated during respiratory challenges, such as hunger for air, but has not been found to be involved in the control of spontaneous, unobstructed breathing (eupnea). Here we applied a measure of intrinsic rhythmicity, the CV2, which evaluates the similarity of subsequent intervals and is thus sensitive to changes in rhythmicity at the temporal resolution of individual respiratory intervals. The variability of intrinsic respiratory rhythmicity was reduced in a mouse model of Cerebellar ataxia compared to their healthy littermates. Irrespective of that difference, the average respiratory rate and the average coefficient of variation (CV) were comparable between healthy and ataxic mice. We argue that these findings are consistent with a proposed role of the cerebellum in modulating the duration of individual respiratory intervals, which could serve the purpose of coordinating respiration with other rhythmic orofacial movements, such as fluid licking and swallowing.
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loss of Cerebellar Function selectively affects intrinsic rhythmicity of eupneic breathing
bioRxiv, 2019Co-Authors: Shuhua Qi, Fridtjof Thomas, Brittany L Correia, Angela P Taylor, Roy V Sillitoe, Detlef H HeckAbstract:ABSTRACT Respiration is controlled by central pattern generating circuits in the brain stem, whose activity can be modulated by inputs from other brain areas to adapt respiration to autonomic and behavioral demands. The cerebellum is known to be part of the neuronal circuitry activated during respiratory challenges, such as hunger for air, but has not been found to be involved in the control of unobstructed breathing at rest (eupnea). Here we applied a measure of intrinsic rhythmicity, the CV2, which evaluates the similarity of subsequent intervals and is thus sensitive to changes in rhythmicity at the temporal resolution of individual respiratory intervals. The variability of intrinsic respiratory rhythmicity was reduced in a mouse model of Cerebellar ataxia compared to their healthy littermates. Irrespective of that difference, the average respiratory rate and the average coefficient of variation (CV) were comparable between healthy and ataxic mice. We argue that these findings are consistent with a proposed role of the cerebellum in the coordination of respiration with other rhythmic orofacial movements, such as fluid licking and swallowing.
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analysis of Cerebellar Function in ube3a deficient mice reveals novel genotype specific behaviors
Human Molecular Genetics, 2008Co-Authors: Detlef H Heck, Yu Zhao, Mark S Ledoux, Lawrence T ReiterAbstract:Angelman syndrome (AS) is a childhood-onset neurogenetic disorder characterized by Functionally severe developmental delay with mental retardation, deficits in expressive language, ataxia, appendicular action tremors and unique behaviors such as inappropriate laughter and stimulus-sensitive hyperexcitibility. Most cases of AS are caused by mutations which disrupt expression of maternal UBE3A. Although some progress has been made in understanding hippocampal-related memory and learning aspects of the disorder using Ube3a deficient mice, the numerous motoric abnormalities associated with AS (ataxia, action tremor, dysarthria, dysphagia, sialorrhea and excessive chewing/mouthing behaviors) have not been fully explored with mouse models. Here we use a novel quantifiable analysis of fluid consumption and licking behavior along with a battery of motor tests to examine Cerebellar and other motor system defects in Ube3a deficient mice. Mice with a maternally inherited Ube3a deficiency (Ube3am−/p+) show defects in fluid consumption behavior which are different from Ube3am−/p− mice. The rhythm of fluid licking and number of licks per visit were significantly different among the three groups (m−/p−, m−/p+, m+/p+) and indicate that not only was fluid consumption dependent on Ube3a expression in the cerebellum, but may also depend on low levels of Ube3a expression in other brain regions. Additional neurological testing revealed defects in both Ube3am−/p+ and Ube3am−/p− mice in rope climbing, grip strength, gait and a raised-beam task. Long-term observation of fluid consumption behavior is the first phenotype reported that differentiates between mice with a maternal loss of Function versus complete loss of Ube3a in the brain. The neuronal and molecular mechanisms underlying mouse fluid consumption defects specifically associated with maternally inherited Ube3a deficiency may reveal important new insights into the pathobiology of AS in humans.
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the detection and generation of sequences as a key to Cerebellar Function experiments and theory
Behavioral and Brain Sciences, 1997Co-Authors: Detlef H Heck, F SultanAbstract:Starting from macroscopic and microscopic facts of Cerebellar histology, we propose a new Functional interpretation that may elucidate the role of the cerebellum in movement control. The idea is that the cerebellum is a large collection of individual lines (Eccles's “beams”: Eccles et al. 1967a) that respond specifically to certain sequences of events in the input and in turn produce sequences of signals in the output. We believe that the sequence-in/sequence-out mode of operation is as typical for the Cerebellar cortex as the transformation of sets into sets of active neurons is typical for the cerebral cortex, and that both the histological differences between the two and their reciprocal Functional interactions become understandable in the light of this dichotomy. The response of Purkinje cells to sequences of stimuli in the mossy fiber system was shown experimentally by Heck on surviving slices of rat and guinea pig cerebellum. Sequential activation of a row of eleven stimulating electrodes in the granular layer, imitating a “movement” of the stimuli along the folium, produces a powerful volley in the parallel fibers that strongly excites Purkinje cells, as evidenced by intracellular recording. The volley, or “tidal wave,” has maximal amplitude when the stimulus moves toward the recording site at the speed of conduction in parallel fibers, and much smaller amplitudes for lower or higher “velocities.” The succession of stimuli has no effect when they “move” in the opposite direction. Synchronous activation of the stimulus electrodes also had hardly any effect. We believe that the sequences of mossy fiber activation that normally produce this effect in the intact cerebellum are a combination of motor planning relayed to the cerebellum by the cerebral cortex, and information about ongoing movement, reaching the cerebellum from the spinal cord. The output elicited by the specific sequence to which a “beam” is tuned may well be a succession of well timed inhibitory volleys “sculpting” the motor sequences so as to adapt them to the complicated requirements of the physics of a multijointed system.
Mario Manto - One of the best experts on this subject based on the ideXlab platform.
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consensus paper roles of the cerebellum in motor control the diversity of ideas on Cerebellar involvement in movement
The Cerebellum, 2012Co-Authors: Mario Manto, Richard B Ivry, James M. Bower, Adriana Bastos Conforto, Jose M Delgadogarcia, Suzete Nascimento Farias Da Guarda, Marcus Gerwig, Christophe Habas, Nobuhiro Hagura, Peter MarienAbstract:Considerable progress has been made in developing models of Cerebellar Function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this consensus paper, we discuss the literature on the role of the Cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), Cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-Cerebellar interaction in visuokinesthetic perception of hand movement, Functional neuroimaging studies, and magnetoencephalographic mapping of cortico-Cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address Cerebellar Function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.
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The Cerebellum, Cerebellar Disorders, and Cerebellar Research—Two Centuries of Discoveries
The Cerebellum, 2008Co-Authors: Mario MantoAbstract:Research on the cerebellum is evolving rapidly. The exquisiteness of the Cerebellar circuitry with a unique geometric arrangement has fascinated researchers from numerous disciplines. The painstaking works of pioneers of these last two centuries, such as Rolando, Flourens, Luciani, Babinski, Holmes, Cajal, Larsell, or Eccles, still exert a strong influence in the way we approach Cerebellar Functions. Advances in genetic studies, detailed molecular and cellular analyses, profusion of brain imaging techniques, emergence of behavioral assessments, and reshaping of models of Cerebellar Function are generating an immense amount of knowledge. Simultaneously, a better definition of Cerebellar disorders encountered in the clinic is emerging. The essentials of a trans-disciplinary blending are expanding. The analysis of the literature published these last two decades indicates that the gaps between domains of research are vanishing. The launch of the society for research on the cerebellum (SRC) illustrates how Cerebellar research is burgeoning. This special issue gathers the contributions of the inaugural conference of the SRC dedicated to the mechanisms of Cerebellar Function. Contributions were brought together around five themes: (1) Cerebellar development, death, and regeneration; (2) Cerebellar circuitry: processing and Function; (3) mechanisms of Cerebellar plasticity and learning; (4) Cerebellar Function: timing, prediction, and/or coordination?; (5) anatomical and disease perspectives on Cerebellar Function.
Chris I De Zeeuw - One of the best experts on this subject based on the ideXlab platform.
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Questioning the Cerebellar Doctrine
Progress in Brain Research, 2020Co-Authors: Elisa Galliano, Chris I De ZeeuwAbstract:The basic principles of Cerebellar Function were originally described by Flourens, Cajal, and Marr/Albus/Ito, and they constitute the pillars of what can be considered to be the classic Cerebellar doctrine. In their concepts, the main Cerebellar Function is to control motor behavior, Purkinje cells are the only cortical neuron receiving and integrating inputs from climbing fiber and mossy-parallel fiber pathways, and plastic modification at the parallel fiber synapses onto Purkinje cells constitutes the substrate of motor learning. Yet, because of recent technical advances and new angles of investigation, all pillars of the Cerebellar doctrine now face regular re-examination. In this review, after summarizing the classic concepts and recent disputes, we attempt to synthesize an integrated view and propose a revisited version of the Cerebellar doctrine.
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Time window control: a model for Cerebellar Function based on synchronization, reverberation, and time slicing.
Progress in Brain Research, 2020Co-Authors: Werner M Kistler, J.l. Van Hemmen, Chris I De ZeeuwAbstract:We present a new hypothesis of Cerebellar Function that is based on synchronization, delayed reverberation, and time windows for triggering spikes. Our model suggests that granule cells admit mossy fiber activity to the parallel fibers only in the Golgi cells are firing synchronously and if the mossy-fiber spikes arrive within short and well-defined time windows. The concept of time window control organizes neuronal activity in discrete ‘time slices’ that can be used to discern meaningful information from background noise. In particular, Purkinje cell activity can trigger rebound spikes in deep Cerebellar nuclei cells, which project via brain stem nuclei and mossy fibers back to the Cerebellar cortex. Using a detailed model of deep Cerebellar nuclei cells, we demonstrate that the delayed firing of rebound spikes is a robust mechanism so as to ensure that the reverberated activity re-arrives in the mossy fibers just during the granule-cell time window. Large network simulations reveal that synaptic plasticity (LTD and LTP) at the parallel fiber/Purkinje cell synapses that relies on the timing of the parallel fiber and climbing fiber activities allows the system to learn, store, and recall spatiotemporal patterns of spike activity. Climbing fiber spikes Function both as teacher and as synchronization signals. The temporal characteristics of the climbing fiber activity are due to intrinsic oscillatory properties of inferior olivary neurons and to reverberating projections between deep Cerebellar nuclei, the mesodiencephalic junction, and the inferior olive. Thus, the reverberating loops of the mossy fiber system and climbing fiber system may interact directly with the time windows provided by the circuitry of the Cerebellar cortex so as to generate the appropriate spatio-temporal firing patterns in the deep Cerebellar nuclei neurons that control premotor systems. In future studies the model will be extended in that high frequency simple strike activities will be included and that their relevance for motor control will be addressed.
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time windows and reverberating loops a reverse engineering approach to Cerebellar Function
The Cerebellum, 2003Co-Authors: Werner M Kistler, Chris I De ZeeuwAbstract:We review a reverse-engineering approach to Cerebellar Function that pays particular attention to temporal aspects of neuronal interactions. This approach offers new vistas on the role of GABAergic synapses and reverberating projections within the olivoCerebellar system. More specifically, our simulations show that Golgi cells can control the ring time of granule cells rather than their ring rate and that Purkinje cells can trigger precisely timed rebound spikes in neurons of the deep Cerebellar nuclei. This rebound activity can reverberate back to the Cerebellar cortex giving rise to a complex oscillatory dynamics that may have interesting Functional implications for working memory and timed-response tasks.