Computational roles of inhibition in human action control

摘要 皮质-基底神经节回路的经典神经认知模型暗示兴奋性信号驱动， 信号抑制行为输出然而，抑制可以支持其他计算。重要研究 动物的运动系统和人类的感觉系统已经显示出抑制形状的增益和调谐特性 的神经种群。令人信服的证据表明，这两个计算支持行动准备 在人体运动系统中。本应用程序的总体目标是建立增益调制的作用 以及在动作准备过程中调整人体运动系统，并评估这些 计算与神经化学抑制能力有关。这项工作的长期目标是 表征生理和神经化学对人类行为背后的神经计算的贡献 控制和了解疾病相关的这些机制的破坏如何有助于行为 损伤因此，所提出的实验将测试中心假设，即增益和调谐内 人皮质脊髓通路在动作准备过程中发生动态变化，并与抑制 运动皮层的神经递质可用性。本申请的第一个具体目的是检验假设， 在动作准备期间，人类运动系统内的增益增加，以促进所选择的动作的执行。 行动上第二个具体的目的是测试的假设，空间调谐的运动表征锐化 在行动准备期间。运动表征的更精确调整预计将促进更细粒度的 通过促进参与准备动作的肌肉的选择性募集来进行控制。目标1 目标2考察了一种便于执行选定动作的计算机制， 用于从相邻和重叠表示的池中选择动作的计算机制。我们 将使用非侵入性脑刺激来检查给定肌肉内的兴奋性模式（目标1）， 在一组肌肉（目标2），以检测增益和调谐的变化，分别在行为任务 性能本应用程序的第三个具体目标是探索增益、调谐和局部 皮质中抑制性神经递质γ-氨基丁酸（GABA）的可用性。个人 将检查差异以测试局部GABA的可用性是否与增益的幅度相关 和调谐变化。我们假设运动皮层中GABA含量越高的个体， 在行动准备期间的增益和更尖锐的调谐。所提出的工作是创新的，因为增益的作用 和人类运动系统内的调谐是至关重要的研究不足， 完全没有被探索过这项研究意义重大，因为研究结果可能会改变我们对 抑制在行为控制中的作用抑制机制的缺失与症状有关 帕金森病，中风和肌张力障碍，以及从拟议的实验中获得的知识可以帮助 确定治疗干预的新目标。

ABSTRACT Classic neurocognitive models of cortico-basal ganglia circuits imply excitatory signals drive, and inhibitory signals suppress, behavioral output. However, inhibition can support other computations. Important research on animal motor systems and human sensory systems has shown inhibition shapes the gain and tuning properties of neural populations. Compelling evidence suggests these same two computations support action preparation in the human motor system. The overall objectives of this application are to establish roles for gain modulation and tuning within the human motor system during action preparation and to evaluate to what extent these computations relate to the neurochemical capacity for inhibition. The long-term goals of this work are to characterize physiological and neurochemical contributions to the neural computations underlying human action control and to understand how disease-related disruption of these mechanisms contributes to behavioral impairments. Accordingly, the proposed experiments will test the central hypothesis that gain and tuning within the human corticospinal pathway change dynamically during the preparation of actions and relate to inhibitory neurotransmitter availability in motor cortex. The first specific aim of this application is to test the hypothesis that gain within the human motor system increases during action preparation to facilitate the execution of a selected action. The second specific aim is to test the hypothesis that spatial tuning of motor representations sharpens during action preparation. Sharper tuning of motor representations is expected to promote more fine-grained control by facilitating the selective recruitment of muscles involved in a prepared action. Whereas Aim 1 examines a computational mechanism for facilitating the execution of a selected action, Aim 2 examines a computational mechanism for selecting actions from a pool of neighboring and overlapping representations. We will use non-invasive brain stimulation to examine the patterns of excitability within a given muscle (Aim 1) and across a group of muscles (Aim 2) to detect changes in gain and tuning, respectively, during behavioral task performance. The third specific aim of this application is to explore relationships between gain, tuning, and local availability of the inhibitory neurotransmitter gamma-amino butyric acid (GABA) in the cortex. Individual differences will be examined to test whether the availability of local GABA correlates with the magnitude of gain and tuning changes. We hypothesize individuals with more GABA in motor cortex will exhibit greater increases in gain and sharper tuning during action preparation. The proposed work is innovative because the roles of gain and tuning within the human motor system are crucially understudied and their links to neurochemical content are completely unexplored. This research is significant because the results could change our interpretation of the roles of inhibition in behavioral control. Abnormalities in inhibitory mechanisms are associated with symptoms of Parkinson’s disease, stroke, and dystonia, and knowledge gained from the proposed experiments can help identify new targets for therapeutic interventions.