Neural Computations Underlying Cancellation of the Vestibular Consequences of Voluntary Movement

消除随意运动前庭后果的神经计算

• 批准号: 10434677
• 负责人: Kathleen E Cullen
• 金额: $ 53.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10434677
• 关键词: Address; Aging; American; Behavior; Brain; Brain Stem; Calibration; Cerebellar Cortex; Cerebellar Nuclei; Cerebellar vermis structure; Cerebellum; Code; Computer Models; Development; Diagnosis; Disease; Dizziness; Ensure; Equilibrium; Esthesia; Functional disorder; Generations; Goals; Head; Head Movements; Impairment; Knowledge; Labyrinth; Learning; Maintenance; Mediating; Modeling; Monkeys; Motion; Motivation; Motor; Movement; Neurons; Pathway interactions; Patients; Pattern; Perception; Performance; Play; Population; Postural response; Posture; Purkinje Cells; Quality of life; Reflex action; Research; Research Project Grants; Research Project Summaries; Rewards; Role; Sensory; Signal Transduction; Source; Stimulus; Symptoms; System; Testing; Update; Vestibular loss; Vestibular nucleus structure; base; behavioral study; density; design; experimental study; fall risk; gaze; improved; insight; motor control; neuromechanism; novel; programs; relating to nervous system; response; sensory feedback; sensory input; sensory stimulus; spinal reflex; vestibular pathway

Project Summary: This research program is motivated by three goals. First, we will establish the neural mechanisms that underlie the brain's ability to estimate and cancel self-generated vestibular (inner ear balance) input during active movement. Second, we will determine how the vestibular cerebellum learns to adapt to changes in the relationship between expected and actual sensory input to maintain stabile perception and accurate behavior. Third, we will assess how reward-motivation signals influence circuit performance. The brain's ability to distinguish sensory stimuli that are the result of self-generated (i.e., active) versus unexpected or externally generated (i.e., passive) stimulation is vital to ensuring perceptual stability and accurate motor control. Notably, in the vestibular system, the same central neurons that receive afferent input also send direct projections to motor centers to control balance and posture via the vestibular-spinal reflex. This reflex is essential for providing robust postural responses to unexpected vestibular stimuli, yet is counter- productive when the goal is to make active head movements. Accordingly, it is advantageous to suppress this pathway during active self-motion. Over the past two decades, we have made excellent progress toward identifying where brain makes the distinction between reafferent (i.e., active) and exafferent (i.e., passive) vestibular signals. Specifically, while the responses of vestibular afferents remain robust (and equivalent) regardless of whether stimulation is active or passive, neurons at the next stage of processing in the vestibular nuclei are significantly less responsive to active self-motion. In addition, we have shown that this suppression only occurs when sensory feedback matches that expected based on the motor command (e.g., during normal active movements). In the proposed research, we will address several fundamental questions that remain open regarding the computations that the brain performs to ensure stable perception and accurate motor control during self-motion. First, experiments in Aim 1 will investigate how the brain computes the vestibular cancellation signal that eliminates actively generated signals from early sensory processing. We predict that the cerebellar cortex plays an essential role in computing the mismatch between expected and actual vestibular input to compute a cancellation signal. Aim 2 will determine how the cerebellum learns to interpret active motion as self-generated when the relationship between the actual and expected sensory feedback is altered. These experiments will provide insight into the error-based mechanisms that ensure calibration of the vestibular reafference suppression mechanism is maintained. Finally, in Aim 3 we will determine whether and how motivation modulates cerebellum-mediated vestibular reafference suppression. Combined, these studies will (1) determine the source of the vestibular reafference cancellation signal, (2) advance our understanding of the cerebellum adapts to changes in vestibular input, and (3) clarify how neuronal mechanisms underlying reafference suppression can be leveraged by motivational influences to optimize performance.

项目摘要：该研究计划是由三个目标激励的。首先，我们将建立神经 大脑估计和取消自我生成前庭的能力的机制（内耳） 平衡）在主动运动过程中输入。其次，我们将确定前庭小脑如何学习 适应预期和实际感觉输入之间关系的变化以保持稳定感知 和准确的行为。第三，我们将评估奖励动机信号如何影响电路性能。 大脑区分感觉刺激的能力，这是自我生成（即活跃）与 出乎意料的或外部产生的（即被动）刺激对于确保感知稳定性和 准确的电机控制。值得注意的是，在前庭系统中，接收传入输入的同一中心神经元 还将直接投影发送到运动中心，以通过前庭脊柱反射控制平衡和姿势。 这种反射对于提供对意外的前庭刺激的稳健姿势反应至关重要，但是反对的 当目标是进行主动运动时，富有成效。因此，抑制这一点是有利的 主动自我运动期间的途径。在过去的二十年中，我们在 确定大脑在何处区分重申（即主动）和远期（即被动）的区别 前庭信号。具体而言，虽然前庭传入的响应仍然坚固（等效） 无论刺激是活跃还是被动的，在前庭处理的下一阶段神经元 核对主动自我运动的反应明显较小。此外，我们已经表明了这种抑制 仅在基于电机命令的预期的感觉反馈匹配时才发生（例如，在正常情况下 主动运动）。在拟议的研究中，我们将解决几个基本问​​题，这些问题保持开放 关于大脑执行的计算，以确保稳定的感知和准确的运动控制 在自我运动中。首先，AIM 1中的实验将研究大脑如何计算前庭 消除从早期感觉处理中消除主动产生的信号的取消信号。我们预测 小脑皮质在计算预期与实际的不匹配中起着至关重要的作用 前庭输入以计算取消信号。 AIM 2将决定小脑学会如何解释 当实际和预期的感觉反馈之间的关系是自我生成的主动运动是 改变。这些实验将为确保校准的基于错误的机制提供深入的了解 前庭重申抑制机制。最后，在AIM 3中，我们将确定是否以及是否 动机如何调节小脑介导的前庭抑制。结合了这些研究 （1）确定前庭重申取消信号的来源，（2）提高我们对 小脑适应前庭输入的变化，（3）阐明神经元机制的基础 可以通过动机的影响来利用抑制作用来优化性能。