Organization and Dynamics of Premotor and Prefrontal Cortical Circuits Mediating Goal-Directed Behavior

调节目标导向行为的前运动和前额皮质回路的组织和动态

• 批准号: 9788105
• 负责人: Chandramouli Chandrasekaran
• 金额: $ 24.9万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788105
• 关键词: Aging; Anatomy; Area; Automobile Driving; Behavior; Behavioral; Brain; Calcium; Cognitive; Complement; Cues; Data; Development; Discrimination; Disease; Dorsal; Electrodes; Electrophysiology (science); Environment; Funding; Generations; Goals; Image; Impaired cognition; Lead; Left; Lesion; Light; Maps; Measurement; Measures; Mediating; Mental disorders; Mentors; Monkeys; Motor; Movement; Neurons; Paralysed; Patients; Pattern; Phase; Physiological; Population; Prefrontal Cortex; Primates; Process; Reaction Time; Reporting; Research; Resolution; Role; Schizophrenia; Sensory; Sensory Process; Stimulus; Stroke; Structure; Surface; Techniques; Testing; Therapeutic; Time; Visual; autism spectrum disorder; base; brain machine interface; calcium indicator; career; design; dynamic system; experience; experimental study; foot; innovation; nervous system disorder; neural patterning; neuromechanism; next generation; optical imaging; patient population; public health relevance; relating to nervous system; response; sensory stimulus; skills; statistics; tool; two-photon; visual stimulus

 DESCRIPTION (provided by applicant): Cognitive impairments related to stroke, schizophrenia, aging, and autism are characterized by the inability to select appropriate actions based on environment or circumstances. This process, termed goal-directed behavior, involves applying a learned rule to a sensory stimulus to decide on an abstract behavioral goal and to select the appropriate motor action to achieve the goal. To illustrate, encountering a red light when driving, results in a sequence of neural responses across several areas of your brain, which make you press the brakes (an action) with your foot to stop the car (a goal). Lesion and physiological studies implicate several cortical and subcortical circuits in this process. However, we currently have a quite limited understanding of the relative contributions of these circuits, circuit organization and the dynamical mechanism(s) that results in goal- directed behavior. My long-term goal is a research career focused on answering these questions with special emphasis on cortical circuits. This specific proposal focuses on understanding circuit organization and temporal dynamics in the dorsal premotor cortex (PMd) and the dorsolateral prefrontal cortex (DLPFC), two areas implicated in goal-directed behavior. During the K99 phase, I will focus on examining the functional circuit organization of PMd perpendicular (e.g. across the different layers of cortex) and parallel to the cortical surface. I will also examine th relationship between PMd activity and behavior on single trials. In the R00 phase, I will first tes the hypothesis that PMd and DLPFC are involved in different aspects of goal-directed behavior. Specifically, we postulate that PMd mediates the selection of action (e.g. pressing brakes) whereas PFC networks are involved in using the behavioral rule to process the sensory stimulus and decide on the behavioral goal (e.g. stop vs. go). I will then examine circuit organization in DLPFC during goal-directed behavior. In order to be able to answer these questions, the proposal introduces several innovative experimental approaches and techniques: 1) a reaction time discrimination task with a rich parametric red- green checkerboard stimulus, reaching as the behavioral report, and a task design separating out behavioral goals from performed actions, 2) laminar electrodes that allow simultaneous measurement of activity across several depths, 3) two-photon calcium imaging which allows recording with single neuron resolution from populations of neurons, 4) single trial analysis of relationship between population neural data and behavior. The significance of this research is that it will provide an understanding of the circuit organization and dynamics of premotor and prefrontal circuits mediating goal-directed behavior in a primate. This understanding in a primate when combined with tools for precise circuit manipulation might lead to circuit level therapeutics for patients suffering from psychiatrc and neurological disorders. It is also expected to guide the design and ideal placement of electrode arrays to decode cognitive and motoric components of goal-directed behavior thus enabling robust brain-machine interfaces for patients suffering from paralysis.

 描述（由申请人提供）：与中风、精神分裂症、衰老和自闭症相关的认知障碍的特点是无法根据环境或情况选择适当的行动。这个过程被称为目标导向行为，涉及将学到的规则应用于感官刺激，以决定抽象的行为目标并选择适当的运动动作来实现目标。举例来说，开车时遇到红灯，会导致大脑多个区域产生一系列神经反应，使您用脚踩刹车（一个动作）来停车（一个目标）。病变和生理学研究表明该过程涉及多个皮质和皮质下回路。然而， 目前，我们对这些回路、回路组织和导致目标导向行为的动力机制的相对贡献的了解相当有限。我的长期目标是致力于回答这些问题，特别是皮质回路的研究生涯。该具体提案的重点是了解背侧前运动皮层 (PMd) 和背外侧前额叶皮层 (DLPFC) 的回路组织和时间动态，这两个区域与目标导向行为有关。在 K99 阶段，我将重点检查 PMd 垂直（例如跨越皮层不同层）和平行于皮层表面的功能电路组织。我还将在单次试验中研究 PMd 活动和行为之间的关系。在 R00 阶段，我将首先测试 PMd 和 DLPFC 参与目标导向行为的不同方面的假设。具体来说，我们假设 PMd 介导行动的选择（例如踩刹车），而 PFC 网络参与使用行为规则来处理感官刺激并决定行为目标（例如停止还是继续）。然后我将检查目标导向行为期间 DLPFC 中的电路组织。为了能够回答这些问题，该提案引入了几种创新的实验方法和技术：1）具有丰富参数红绿棋盘刺激的反应时间辨别任务，达到行为报告，以及将行为目标与执行的动作分开的任务设计，2）允许同时测量多个深度的活动的层状电极，3）允许记录的双光子钙成像 使用神经元群体的单个神经元分辨率，4）群体神经数据和行为之间关系的单次试验分析。这项研究的意义在于，它将提供对调节灵长类动物目标导向行为的前运动和前额叶回路的回路组织和动力学的理解。当灵长类动物的这种理解与精确的回路操作工具相结合时，可能会为患有精神疾病和神经系统疾病的患者带来回路水平的治疗。它还有望指导电极阵列的设计和理想放置，以解码目标导向行为的认知和运动成分，从而为瘫痪患者提供强大的脑机接口。