Distributed sensory coding by cerebellar complex spikes in units of cortical segments.

Sensory processing is essential for motor control. Climbing fibers from the inferior olive transmit sensory signals to Purkinje cells, but how the signals are represented in the cerebellar cortex remains elusive. To examine the olivocerebellar organization of the mouse brain, we perform quantitative Ca imaging to measure complex spikes (CSs) evoked by climbing fiber inputs over the entire dorsal surface of the cerebellum simultaneously.

Pathophysiology of Cerebellar Tremor: The Forward Model-Related Tremor and the Inferior Olive Oscillation-Related Tremor.

Lesions in the Guillain-Mollaret (G-M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO).

Physiology of Cerebellar Reserve: Redundancy and Plasticity of a Modular Machine.

The cerebellum is endowed with the capacity for compensation and restoration after pathological injury, a property known as cerebellar reserve. Such capacity is attributed to two unique morphological and physiological features of the cerebellum. First, mossy fibers that convey peripheral and central information run mediolaterally over a wide area of the cerebellum, resulting in the innervation of multiple microzones, commonly known as cerebellar functional units.

Dynamic Modulation of a Learned Motor Skill for Its Recruitment.

Humans learn motor skills (MSs) through practice and experience and may then retain them for recruitment, which is effective as a rapid response for novel contexts. For an MS to be recruited for novel contexts, its recruitment range must be extended. In addressing this issue, we hypothesized that an MS is dynamically modulated according to the feedback context to expand its recruitment range into novel contexts, which do not involve the learning of an MS.

The critical need to develop tools assessing cerebellar reserve for the delivery and assessment of non-invasive cerebellar stimulation.

Non-invasive cerebellar stimulation (NICS) aims to modulate cerebello-cerebral loops and cerebro-spinal loops, both for research and clinical applications. It is of paramount importance to establish and validate morphological and functional tools to quantify cerebellar reserve, defined as the capacity for restoration and compensation to pathology of the cerebellum. Using NICS without efforts to estimate cerebellar reserve will end up in conflicting results due to the very high heterogeneity of cerebellar disorders encountered in daily practice.

Dysmetria and Errors in Predictions: The Role of Internal Forward Model.

The terminology of cerebellar dysmetria embraces a ubiquitous symptom in motor deficits, oculomotor symptoms, and cognitive/emotional symptoms occurring in cerebellar ataxias. Patients with episodic ataxia exhibit recurrent episodes of ataxia, including motor dysmetria. Despite the consensus that cerebellar dysmetria is a cardinal symptom, there is still no agreement on its pathophysiological mechanisms to date since its first clinical description by Babinski.

The Cerebro-Cerebellum as a Locus of Forward Model: A Review.

This review surveys physiological, behavioral, and morphological evidence converging to the view of the cerebro-cerebellum as loci of internal forward models. The cerebro-cerebellum, the phylogenetically newest expansion in the cerebellum, receives convergent inputs from cortical, subcortical, and spinal sources, and is thought to perform the predictive computation for both motor control, motor learning, and cognitive functions. This predictive computation is known as an internal forward model.

Contribution of the Cerebellum to Predictive Motor Control and Its Evaluation in Ataxic Patients.

Goal-directed movements are predictive and multimodal in nature, especially for moving targets. For instance, during a reaching movement for a moving target, humans need to predict both motion of the target and movement of the limb. Recent computational studies show that the cerebellum predicts current and future states of the body and its environment using internal forward models.

Neural Evidence of the Cerebellum as a State Predictor.

We here provide neural evidence that the cerebellar circuit can predict future inputs from present outputs, a hallmark of an internal forward model. Recent computational studies hypothesize that the cerebellum performs state prediction known as a forward model. To test the forward-model hypothesis, we analyzed activities of 94 mossy fibers (inputs to the cerebellar cortex), 83 Purkinje cells (output from the cerebellar cortex to dentate nucleus), and 73 dentate nucleus cells (cerebellar output) in the cerebro-cerebellum, all recorded from a monkey performing step-tracking movements of the right wrist.

Electromyogram refinement using muscle synergy based regulation of uncertain information.

Electromyogram signal (EMG) measurement frequently experiences uncertainty attributed to issues caused by technical constraints such as cross talk and maximum voluntary contraction. Due to these problems, individual EMGs exhibit uncertainty in representing their corresponding muscle activations. To regulate this uncertainty, we proposed an EMG refinement, which refines EMGs with regulating the contribution redundancy of the signals from EMGs to approximating torques through EMG-driven torque estimation (EDTE) using the muscular skeletal forward dynamic model.

Physiological and Morphological Principles Underpinning Recruitment of the Cerebellar Reserve.

Background: In order to optimize outcomes of novel therapies for cerebellar ataxias (CAs), it is desirable to start these therapies while declined functions are restorable: i.e. while the so-called cerebellar reserve remains.

Muscle Synergy-Driven Robust Motion Control.

Humans are able to robustly maintain desired motion and posture under dynamically changing circumstances, including novel conditions. To accomplish this, the brain needs to optimize the synergistic control between muscles against external dynamic factors. However, previous related studies have usually simplified the control of multiple muscles using two opposing muscles, which are minimum actuators to simulate linear feedback control.

Quantitative evaluation of age-related decline in control of preprogramed movement.

In this paper, we examined the age-related changes in control of preprogramed movement, with emphasis on its accuracy. Forty-nine healthy subjects participated in this study, and were divided into three groups depending on their ages: the young group (20-39 years) (n = 16), the middle-age group (40-59 years) (n = 16), and the elderly group (60-79 years) (n = 17). We asked the subjects to perform step-tracking movements of the wrist joint with a manipulandum, and recorded the movements.

Diverse coordinate frames on sensorimotor areas in visuomotor transformation.

The visuomotor transformation during a goal-directed movement may involve a coordinate transformation from visual 'extrinsic' to muscle-like 'intrinsic' coordinate frames, which might be processed via a multilayer network architecture composed of neural basis functions. This theory suggests that the postural change during a goal-directed movement task alters activity patterns of the neurons in the intermediate layer of the visuomotor transformation that recieves both visual and proprioceptive inputs, and thus influence the multi-voxel pattern of the blood oxygenation level dependent signal. Using a recently developed multi-voxel pattern decoding method, we found extrinsic, intrinsic and intermediate coordinate frames along the visuomotor cortical pathways during a visuomotor control task.

The cerebro-cerebellum: Could it be loci of forward models?

It is widely accepted that the cerebellum acquires and maintain internal models for motor control. An internal model simulates mapping between a set of causes and effects. There are two candidates of cerebellar internal models, forward models and inverse models.

Overlooked Holmes' clinical signs: reevaluation by recent physiological findings.

Holmes proposed not only the term ataxia, but also opposite clinical signs related to muscle recruitment, which have escaped clinical attention; (1) asthenia, representing delay in initiating muscle contraction and slowness in attaining exertion of full power, and (2) adventitiousness, representing adventitious movements. Recent physiological studies have shown that cerebellar outputs are modified by release or facilitation of Purkinje cell-mediated inhibition on dentate neurons. We believe that asthenia and adventitiousness, which correlate with deficits in the control of disinhibition and inhibition, respectively, deserve more attention in clinical examination.

Information processing in the hemisphere of the cerebellar cortex for control of wrist movement.

A region of cerebellar lobules V and VI makes strong loop connections with the primary motor (M1) and premotor (PM) cortical areas and is assumed to play essential roles in limb motor control. To examine its functional role, we compared the activities of its input, intermediate, and output elements, i.e.

A New Method for Functional Evaluation of Motor Commands in Patients with Cerebellar Ataxia.

Quantitative evaluation of motor functions of patients with cerebellar ataxia is vital for evidence-based treatments and has been a focus in previous investigations of movement kinematics. Due to redundancy of the musculoskeletal system, muscle activities contain more information than the movement kinematics. Therefore, it is preferable to analyze causal anomalies of muscle activities to evaluate motor functions in patients.

Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias.

In the last few years, a lot of publications suggested that disabling cerebellar ataxias may develop through immune-mediated mechanisms. In this consensus paper, we discuss the clinical features of the main described immune-mediated cerebellar ataxias and address their presumed pathogenesis. Immune-mediated cerebellar ataxias include cerebellar ataxia associated with anti-GAD antibodies, the cerebellar type of Hashimoto's encephalopathy, primary autoimmune cerebellar ataxia, gluten ataxia, Miller Fisher syndrome, ataxia associated with systemic lupus erythematosus, and paraneoplastic cerebellar degeneration.

Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum.

The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN) that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs).