Computational roles of inhibition in human action control

抑制在人类行为控制中的计算作用

• 批准号: 10741389
• 负责人: Ian Greenhouse
• 金额: $ 3.11万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10741389
• 关键词: Anatomy; Animals; Behavior Control; Behavioral; Brain; Butyric Acids; Cognitive; Computing Methodologies; Disease; Dystonia; Exhibits; Funding; Ganglia; Human; Individual; Individual Differences; Knowledge; Laboratories; Link; Measurement; Modeling; Motor; Motor Cortex; Muscle; Neurocognitive; Neurotransmitters; Output; Parkinson Disease; Pathway interactions; Pattern; Physiology; Population; Preparation; Property; Research; Role; Shapes; Signal Transduction; Stroke; Symptoms; System; Task Performances; Techniques; Testing; Therapeutic Intervention; Training; Work; career development; electric field; experimental study; graduate student; improved; innovation; method development; motor disorder; neural; neurochemistry; new therapeutic target; noninvasive brain stimulation; novel; sensory system

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.

抽象的 Cortico-Basal神经节电路的经典神经认知模型意味着兴奋性信号和抑制性 信号抑制行为输出。但是，抑制可以支持其他计算。动物研究 电机系统和人类感觉系统显示抑制作用形成了中性的增益和调谐特性 人群。本应用程序的总体目标是建立在内部增益调制和调整的角色 动作准备过程中的人类运动系统，并评估这些计算在何种程度上 抑制神经化学能力。彼此之间，提出的实验将检验中心假设 在制备过程中，人类皮质脊髓途径中的增益和调谐动态变化 动作和与运动皮层中抑制性神经递质的可用性有关。第一个具体目的 应用是测试人类运动系统中的假设增长在动作准备期间增加 促进执行选定的操作。第二个具体目的是测试假设的空间调整 在动作准备过程中，电机表示会逐渐变化。而目标1考试计算 支持执行选定动作的机制，AIM 2考试一种计算机制 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内的兴奋性模式（AIM 1）以及一组肌肉 （目标2）在行为任务绩效期间分别检测增益和调整的变化。第三个特定 该应用的目的是探索抑制性的增益，调整和局部可用性之间的关系 神经递质γ-氨基丁酸（GABA）在皮质中。将检查个体差异以测试 局部GABA的可用性是否与增益和调整变化的幅度相关。我们假设 运动皮层中有更多GABA的个体将在动作过程中表现出更大的增益和更大的调整 准备。拟议的工作是创新的，因为人类电动机中获得和调谐的作用 完全理解了系统，它们与神经化学内容的联系是完全出乎意料的。这 研究很重要，因为结果可以改变我们对抑制在行为中的作用的解释 控制。抑制机制的异常与帕金森氏病，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的新目标 干预措施。 在这种多样性补充中，我们要求为动作控制的研究生Hayami Nishio女士提供资金 实验室（PI Greenhouse），以对非侵入性脑刺激产生的电场进行建模 AIM 2中提出的技术。这种新颖的添加将使解剖学特性与神经化学分开 可能影响运动系统调整测量值的属性。 Nishio女士将接受电动机的培训 生理学，导航大脑刺激，计算方法和职业发展。