Causal Roles of Dorsolateral Prefrontal and Dorsal Premotor Cortex in Perceptual Decision-Making

背外侧前额叶和背侧前运动皮层在知觉决策中的因果作用

• 批准号: 10790672
• 负责人: Chandramouli Chandrasekaran
• 金额: $ 43.69万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10790672
• 关键词: Address; Age; Animals; Area; Behavior; Behavior assessment; Behavioral; Bilateral; Brain; Brain region; Cerebral cortex; Choice Behavior; Cognition; Color; Craniotomy; Cues; Custom; Data; Decision Making; Devices; Disease; Dorsal; Electrodes; Electrophysiology (science); Exhibits; Experimental Designs; Eye Movements; Female; Goals; Grant; Ice Cream; Implant; Knowledge; Left; Life; Macaca; Measures; Mental disorders; Monkeys; Motor Cortex; Muscimol; Neurologic; Physiological; Population Dynamics; Prefrontal Cortex; Psychometrics; Randomized; Reaction Time; Reporting; Research; Role; Sensory; Signal Transduction; Task Performances; Techniques; Temperature; Testing; Time; Training; arm movement; clinically relevant; design; experimental study; frontal lobe; insight; kinematics; male; mental function; microstimulation; motor behavior; nervous system disorder; neural; normal aging; novel; novel therapeutics; optogenetics; sensory system

In this R21 grant, entitled “Causal Roles of Dorsolateral Prefrontal and Dorsal Premotor Cortex in Perceptual Decision Making,” we will test the causal roles of the dorsolateral prefrontal cortex (DLPFC) and dorsal premotor cortex (PMd) in the macaque monkey during perceptual decision making. Perceptual decision making is the ability to discriminate and integrate cues from different sensory systems to produce an action that supports behavioral goals. Our current studies demonstrate distinct neural dynamics in DLPFC and PMd during our novel red-green perceptual decision- making task. In this task, monkeys discriminate the dominant color of a central static checkerboard cue composed of red and green squares and report their decision with an arm movement to a left or right target. By randomizing the color identity of the target across trials, we can differentiate action choices (left vs. right) from color choice (red vs. green). We find that neural population dynamics in DLPFC encode the color choice, action choice, and target configuration, whereas neural population dynamics in PMd are only associated with the action choice. In addition, PMd firing rates closely covary with the reaction time (RT) of the animal before and after cue onset, suggesting a role for PMd in planning and executing an action choice. However, such correlative experiments are unable to fully answer whether these brain areas are differentially and causally involved in these aspects of decision-making. The goal of this research is to causally establish the roles of DLPFC or PMd during perceptual decision-making. Our central hypothesis based on our physiological recordings is that inactivation of DLPFC should bias color and action choice, whereas inactivation of PMd should only bias action choice and alter RT. To test this hypothesis, we will use custom-made cortical cooling deactivation to focally and temporarily silence PMd (Aim 1) or DLPFC (Aim 2) in monkeys trained to perform our behavioral task. Our overall approach is as follows: we will implant bilateral recording chambers over the DLPFC and PMd into which we will introduce a linear multicontact electrode and cooling devices. While monkeys perform our behavioral task, we will perform simultaneous electrophysiological recording before, during and after cooling of DLPFC or PMd. We will use various measures of task performance (psychometric curve, RT curve, kinematics of eye and arm movements etc.) to evaluate the impact of cooling on decision making behavior. Sessions will use unilateral or bilateral cooling and either complete cooling or mild cooling. Based on our physiological experiments, we predict three effects. First, we anticipate that cooling PMd will lead to slower RTs and biases in action choice but no biases in color choice. Second, we anticipate DLPFC deactivation will produce biases in both color choice and action choice behavior and lead to profound deficits in task performance. Finally, we anticipate bilateral deactivation to produce deficits of larger magnitude than unilateral deactivation. These data are first of its kind causal tests of the specific roles of DLPFC and PMd in perceptual decision-making behavior. Impact: our results could help better understand behavioral deficits that occur in these clinically relevant brain areas because of psychiatric and neurological disorders as well as in normal aging.

在这项 R21 拨款中，题为“背外侧前额叶和背侧前运动皮层在知觉决策中的因果作用” 制作”，我们将测试背外侧前额叶皮层 (DLPFC) 和背侧前运动皮层 (PMd) 的因果作用 猕猴在知觉决策过程中的表现。感性决策是辨别能力 并整合来自不同感官系统的线索以产生支持行为目标的行动。我们目前的 研究表明，在我们新的红绿知觉决策过程中，DLPFC 和 PMd 具有不同的神经动力学 - 制作任务。在这项任务中，猴子辨别由中央静态棋盘提示组成的主色 红色和绿色方块，并通过向左或右目标移动手臂来报告他们的决定。通过随机化 通过试验中目标的颜色标识，我们可以区分动作选择（左与右）和颜色选择（红色） 与绿色）。我们发现 DLPFC 中的神经群体动态编码颜色选择、动作选择和目标 配置，而 PMd 中的神经群体动态仅与动作选择相关。此外， PMd 放电率与提示出现前后动物的反应时间 (RT) 密切相关，表明 PMd 在规划和执行行动选择中的作用。但此类相关实验并不能完全 回答这些大脑区域是否差异性地、因果性地参与决策的这些方面。这 本研究的目标是因果关系地确定 DLPFC 或 PMd 在知觉决策过程中的作用。我们的 基于我们的生理记录的中心假设是 DLPFC 失活应该会偏向颜色和动作 选择，而 PMd 失活只会影响行动选择并改变 RT。为了检验这个假设，我们将使用 定制的皮质冷却失活，以局部和暂时沉默 PMd（目标 1）或 DLPFC（目标 2） 猴子经过训练来执行我们的行为任务。我们总体的做法是这样的：我们会植入双边录音 我们将在 DLPFC 和 PMd 上方的室中引入线性多接触电极和冷却装置。 当猴子执行我们的行为任务时，我们将同时进行电生理记录， DLPFC 或 PMd 冷却期间和之后。我们将使用各种任务绩效衡量标准（心理曲线、 RT曲线、眼睛和手臂运动的运动学等）来评估冷却对决策行为的影响。 会议将使用单侧或双边冷却以及完全冷却或轻度冷却。根据我们的生理 实验中，我们预测了三种效应。首先，我们预计 PMd 的冷却将导致 RT 变慢和偏差 动作选择但颜色选择没有偏见。其次，我们预计 DLPFC 失活将会在以下两个方面产生偏差： 颜色选择和动作选择行为并导致任务表现的严重缺陷。最后，我们预计 双边失活比单边失活产生更大程度的赤字。这些数据是其第一 DLPFC 和 PMd 在知觉决策行为中的具体作用的因果检验。影响：我们的结果 可以帮助更好地理解这些临床相关大脑区域发生的行为缺陷，因为 精神和神经系统疾病以及正常衰老。