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。动物研究 运动系统和人类感觉系统已经显示出抑制形状的增益和调谐特性的神经 人口。本应用程序的总体目标是建立增益调制和调谐的作用， 动作准备过程中的人体运动系统，并评估这些计算在多大程度上与 神经化学抑制能力。因此，所提出的实验将检验中心假设 人类皮质脊髓通路内的增益和调谐在准备过程中动态变化， 作用并与运动皮层中的抑制性神经递质可用性有关。第一个具体目标是 应用是测试在动作准备期间人类运动系统内的假设增益增加， 帮助执行选定的操作。第二个具体目标是测试的假设空间调谐 在动作准备期间，运动表征会变得尖锐。而目标1考察了一个计算的 机制，以促进选定的行动的执行，目标2检查了计算机制， 从相邻和重叠表示的池中选择动作。我们将使用非侵入性大脑 刺激，以检查给定肌肉（目标1）和一组肌肉内的兴奋性模式 (Aim 2）在行为任务执行期间分别检测增益和调谐的变化。第三特定 这个应用程序的目的是探索增益，调谐和抑制的局部可用性之间的关系， 神经递质γ-氨基丁酸（GABA）在皮层。将检查个体差异以检验 局部GABA的可用性是否与增益和调谐变化的幅度相关。我们假设 运动皮层中GABA含量较高的个体在动作过程中表现出更大的增益增加和更敏锐的调谐 准备.拟议的工作是创新的，因为在人类运动中的增益和调谐的作用 神经系统研究严重不足，它们与神经化学成分的联系也完全未被探索。这 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中作用的解释。 控制抑制机制的缺失与帕金森病、中风、 和肌张力障碍，从拟议的实验中获得的知识可以帮助确定新的治疗目标， 干预措施。 在这个多元化的补充，我们要求为速水女士西尾，在行动控制研究生的资金 实验室（PI Greenhouse），对非侵入性脑刺激产生的电场进行建模 在目标2中提出的技术。这一新的增加将把解剖学特性与神经化学特性分开， 可以影响电机系统调谐测量的特性。西尾女士将接受运动训练 生理学、导航脑刺激、计算方法和职业发展。

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. Research on animal motor systems and human sensory systems has shown inhibition shapes the gain and tuning properties of neural populations. 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. 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 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 spatial tuning of motor representations sharpens during action preparation. 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. In this diversity supplement, we request funding for Ms. Hayami Nishio, a graduate student in the Action Control Laboratory (PI Greenhouse), to model the electric fields produced by the non-invasive brain stimulation technique proposed in Aim 2. This novel addition will separate anatomical properties from neurochemical properties that can influence motor system tuning measurements. Ms. Nishio will receive training in motor physiology, navigated brain stimulation, computational methods, and career development.