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: 10804179
• 负责人: Ian Greenhouse
• 金额: $ 7.97万
• 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/10804179
• 关键词: Address; Agonist; Anatomy; Animals; Behavior Control; Behavioral; Brain; Butyric Acids; Chemicals; Clinical Research; Cognitive; Data; Dimensions; Disease; Dystonia; Electromyography; Etiology; Evoked Potentials; Exhibits; Future; Ganglia; Goals; Grain; Human; Impairment; Individual; Individual Differences; Influentials; Knowledge; Laboratories; Link; Magnetic Resonance Spectroscopy; Maps; Measurement; Measures; Modeling; Motor; Motor Cortex; Muscle; Neurocognitive; Neurons; Neurotransmitters; Noise; Output; Parkinson Disease; Pathway interactions; Pattern; Physiological; Population; Preparation; Property; Publishing; Research; Rest; Role; Shapes; Signal Transduction; Stroke; Symptoms; System; Task Performances; Techniques; Testing; Therapeutic Intervention; Transcranial magnetic stimulation; Work; behavioral impairment; cognitive process; experimental study; gamma-Aminobutyric Acid; goal oriented behavior; improved; innovation; motor disorder; motor symptom; neural; neurochemistry; new therapeutic target; noninvasive brain stimulation; novel; novel marker; operation; recruit; response; sensory cortex; 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. 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.

摘要 皮质-基底节回路的经典神经认知模型暗示兴奋性信号驱动和抑制 信号抑制，行为输出。然而，抑制可以支持其他计算。的重要研究成果 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 神经种群的数量。令人信服的证据表明，同样的两个计算支持行动准备 在人类的运动系统中。本申请的总体目标是建立用于增益调制的角色 并在动作准备期间在人体运动系统内进行调整，并评估这些 计算与抑制的神经化学能力有关。这项工作的长期目标是 表征生理和神经化学对潜在人类行为的神经计算的贡献 控制和了解与疾病相关的这些机制的破坏如何有助于行为 减损。因此，拟议的实验将检验中心假设，即增益和调谐 人皮质脊髓通路在动作准备过程中的动态变化并与抑制有关 运动皮质中神经递质的可用性。这个应用程序的第一个具体目标是测试假设 人体运动系统内的增益在动作准备期间增加，以便于执行选定的 行动。第二个特定的目标是检验运动表征的空间调谐使其锐化这一假设。 在行动准备过程中。运动表示的更敏锐的调整预计将促进更细粒度的 通过促进有选择地招募参与有准备的动作的肌肉来控制。鉴于目标1 检查用于促进所选操作的执行的计算机制，目标2检查 用于从相邻和重叠表示池中选择操作的计算机制。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)和 跨一组肌肉(目标2)，分别检测行为任务中增益和调谐的变化 性能。此应用程序的第三个特定目标是探索增益、调整和本地之间的关系 抑制性神经递质γ-氨基丁酸(GABA)在大脑皮层的可用性。个体 将检查差异，以测试局部GABA的可用性是否与增益的大小相关 和调谐变化。我们假设，运动皮质中GABA含量较高的个体将表现出更大的增长 在动作准备过程中的增益和更锐利的调谐。拟议的工作具有创新性，因为Gain的作用 和人体运动系统内的调节被严重地忽视，以及它们与神经化学成分的联系 是完全未被开发的。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。抑制机制的异常与症状有关 帕金森氏症、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 确定新的治疗干预目标。