Cerebellum and Visually Guided Arm Movements

描述（由申请人提供）：这项拨款提案测试了小脑是手臂正向和反向内部模型所在地的整体假设。内部模型提供了电机设备或其逆的输入输出特性的表示。前向模型预测系统的状态，要么是运动变量，要么是感官输出，作为手臂当前状态和运动命令的结果。逆动力学模型将期望的轨迹转换为控制手臂所需的扭矩和力。许多心理物理学研究的结果支持中枢神经系统利用内部模型来控制运动的假设。尽管人们普遍假设小脑获得并储存了手臂的内部模型，但基于单细胞记录的这一假设的明确测试很少。我们最近的研究结果表明，前叶中间和外侧区域的浦肯野细胞不能发出运动动力学或肌肉活动的信号，因此不能为手臂的逆动力学模型提供神经基质。相反，这些浦肯野细胞的简单尖峰放电编码了手臂的运动学，可能与预测手臂状态的正演模型的输出一致。前两个特定目标扩展了我们对小脑是手臂逆动力学模型的假设的测试。Specific Aim 1研究了小脑核神经元的放电是否与手臂逆动力学模型的输出一致，该模型在施加粘性和弹性力场的同时记录核神经元。具体目标2解决浦肯野细胞放电是否与反向动力学模型的输出一致，如果力控制或力反馈对任务性能至关重要。通过运动学、等长和触觉跟踪，这些实验将测试浦肯野细胞简单脉冲放电信号的运动参数是否基于控制策略的类型或用于执行任务的反馈。具体目标3-5验证了浦肯野细胞是手臂向前内部模型的输出的假设。特异性目标3测试浦肯野细胞简单尖峰放电是否编码手臂运动而不是目标/光标运动。Specific Aim 4使用随机跟踪任务来检查浦肯野细胞的放电是否可以预测肢体的即将到来的状态，以及这种预测是否可以推广到肢体的动作。在具体目标5中，随机和提示扰动被用来操纵手臂和运动命令的状态，以进一步测试前向内部模型假设。小脑对于产生平稳、协调的运动至关重要。这些研究的结果可能有助于更好地理解小脑疾病的正常功能和异常处理。

DESCRIPTION (provided by applicant): This grant proposal tests the global hypothesis that the cerebellum is the site of both forward and inverse internal models of the arm. Internal models provide for representations of the input-output properties of the motor apparatus or their inverses. A forward model predicts the state of system, either the motor variables or the sensory output, as a consequence of the current state of the arm and the motor commands. An inverse dynamics model transforms the desired trajectory into the torques and forces needed to control the arm. The results of numerous psychophysical studies support the hypothesis that the central nervous system utilizes internal models to control movements. Although widely hypothesized that the cerebellum acquires and stores internal models of the arm, there are few explicit tests of this hypothesis based on single cell recordings. Our recent findings demonstrate that Purkinje cells in the intermediate and lateral zones of the anterior lobe do not signal movement dynamics or muscle activity and therefore, cannot provide the neural substrate for an inverse dynamics model of the arm. Instead, the simple spike discharge of these Purkinje cells encodes arm kinematics, potentially consistent with the output of a forward model that predicts the state of the arm. The first two Specific Aims expand our testing of the hypothesis that the cerebellum is the site of an inverse dynamics model of the arm. Specific Aim 1 examines whether the discharge of cerebellar nuclear neurons is consistent with the output of an inverse dynamics model of the arm, recording nuclear neurons while imposing viscous and elastic force fields. Specific Aim 2 addresses whether Purkinje cell discharge is consistent with the output of an inverse dynamics model, if force control or force feedback is critical to task performance. Using kinematic, isometric and haptic tracking, these experiments will test whether the movement parameters signaled by Purkinje cell simple spike discharge is conditional based on the type of control strategy or feedback used to perform the task. Specific Aims 3-5 test the hypothesis that Purkinje cells are the output of a forward internal model of the arm. Specific Aim 3 tests whether Purkinje cell simple spike discharge encodes arm kinematics as opposed to target/cursor motion. Specific Aim 4 uses a random tracking task to examine whether the discharge of Purkinje cells predicts the upcoming state of the limb and whether the prediction generalizes to reaching movements. In Specific Aim 5 both random and cued perturbations are used to manipulate both the state of the arm and the motor command to further test the forward internal model hypothesis. PUBLIC HEALTH RELEVANCE The cerebellum is essential for the production of smooth, coordinated movements. The results from these studies may lead to a better understanding of both normal function and the abnormal processing that occurs in cerebellar disease.