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.

抽象的 皮质基底节回路的经典神经认知模型意味着兴奋性信号驱动和抑制性信号驱动 信号抑制，行为输出。然而，抑制可以支持其他计算。 动物运动系统和人类感觉系统已显示出抑制形状的增益和调谐特性 令人信服的证据表明这两个计算支持行动准备。 该应用的总体目标是确定增益调制的作用。 并在动作准备期间调整人体运动系统，并评估这些效果的程度 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人类行为神经计算的贡献 控制并了解这些机制与疾病相关的破坏如何影响行为 因此，所提出的实验将测试增益和调谐的中心假设。 人类皮质脊髓通路在行动准备过程中动态变化并与抑制相关 该应用程序的第一个具体目的是测试以下假设： 在动作准备期间，人体运动系统内的增益会增加，以促进所选动作的执行 第二个具体目标是检验运动表征的空间调谐变得锐利的假设。 在动作准备过程中，对运动表征的更清晰的调整有望促进更细粒度的工作。 通过促进选择性募集参与准备好的动作（特别是目标 1）的肌肉来进行控制。 检查促进执行选定动作的计算机制，目标 2 检查 用于从相邻和重叠表示池中选择动作的计算机制。 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）以及 在行为任务期间，通过一组肌肉（目标 2）分别检测增益和调谐的变化 该应用程序的第三个具体目标是探索增益、调谐和局部性能。 大脑皮层中抑制性神经递质 γ-氨基丁酸 (GABA) 的可用性。 将检查差异以测试本地 GABA 的可用性是否与增益幅度相关 我们追求运动皮层中 GABA 含量更高的个体将表现出更大的增长。 所提出的工作是创新的，因为增益的作用。 人类运动系统内的调节和调节尚未得到充分研究，它们与神经化学成分的联系 这项研究意义重大，因为其结果可能会改变我们的解释。 抑制在行为控制中的作用 抑制机制的异常与症状相关。 帕金森病、中风和肌张力障碍的研究，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。