Does cerebellar cortex function as a forward internal model for motor control?

描述(申请人提供)：运动控制理论家假设，产生快速、协调的运动需要控制电路，通过提供对运动命令造成的后果的估计，可以绕过感觉反馈延迟。这个被称为前向内部模型的控制元件接收运动命令的传出副本和关于当前状态的信息，以便预测肢体的未来状态(即，位置和速度等运动学变量)。先前的心理物理、影像和患者案例研究表明，小脑是实施内部模型的可能位置。然而，很少有电生理学研究调查小脑神经元的放电是否与前向内部模型的性质一致。这个项目的最终目标是评估小脑中间区/外侧区小叶IV-VI小叶中的浦肯野细胞(PC)的简单棘波放电是否与正向内部模型的输出一致。虽然没有一个单一的结果可以最终证明这一假设，但我们提出了两个检测猕猴手运动的电生理学实验，以测试正向内部模型的几个方面。目标1将检查PC触发是否以独立于任务的方式预测未来的手部运动学。目标2将进一步评估模型的适应性，以及改变模型输入是否会改变预测的运动学。结果要么表明PC激发与正向模型的预期输出不相容，要么为未来的实验提供坚实的支持。 公共卫生相关性：增加对健康小脑功能的了解对于了解小脑损伤或疾病可能如何在临床上表现并导致运动协调、学习和运动时间选择方面的缺陷至关重要。在运动学习任务中，记录小脑皮质中一种特定类型的神经元-浦肯野细胞的活动，可能会增加对这些细胞如何作为一个网络来编码运动变量和学习新的运动任务的理解。也许最重要的是，对协调运动所需控制参数的洞察可能会导致对运动障碍患者进行更具体的康复治疗，并改进控制智能假肢的算法。

DESCRIPTION (provided by applicant): Motor control theorists have postulated that production of rapid, coordinated movements requires control circuitry that can bypass sensory feedback delays by providing an estimate of the consequences resulting from a motor command. This control element, termed a forward internal model, receives an efferent copy of the motor command and information about the current state in order to predict the future state of the limb (i.e., kinematic variables like position and velocity). Previous psychophysical, imaging, and patient case studies suggest that the cerebellum is a possible location for implementation of an internal model. However, few electrophysiological studies have investigated whether the firing discharge from cerebellar neurons is consistent with the properties of a forward internal model. The ultimate goal of this project is to evaluate whether the simple spike firing from Purkinje cells (PCs) in lobules IV-VI of the intermediate/lateral cerebellar zones is consistent with output from a forward internal model. Although no single result will conclusively prove this hypothesis, two electrophysiology experiments examining hand movements in rhesus macaques are proposed to test several aspects of a forward internal model. Aim 1 will examine whether PC firing predicts future hand kinematics in a task-independent manner. Aim 2 will further evaluate model adaptability and whether changing model inputs alters predicted kinematics. The results will either show that PC firing is incompatible with the output expected from a forward model or provide solid support for future experiments. PUBLIC HEALTH RELEVANCE: An increased knowledge of healthy cerebellar function is essential for understanding how cerebellar brain injury or disease might manifest clinically and lead to deficits in motor coordination, learning, and movement timing. Recording activity from Purkinje cells, a specific type of neuron in the cerebellar cortex, during movement learning tasks may lead to increased understanding of how these cells act as a network to encode movement variables and learn new motor tasks. Perhaps most importantly, insights regarding the control parameters required for coordinated movements may lead to more specific rehabilitation therapies for patients with movement disorders and improved algorithms for controlling smart prosthetics.