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

在这项R21拨款中，题为“背外侧前额叶和背前额叶皮质在知觉决策中的因果作用” 我们将测试背侧前额叶皮质(DLPFC)和背侧运动前皮质(PMD)的因果作用。 在猕猴的感知决策过程中。感性决策是指辨别事物的能力 并整合来自不同感觉系统的线索，以产生支持行为目标的行动。我们目前的情况 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- 制造任务。在这项任务中，猴子辨别中央静态棋盘球杆的主色 红色和绿色方块，并报告他们的决定与手臂运动向左或右目标。通过随机化 在试验中目标的颜色识别，我们可以区分动作选择(左和右)和颜色选择(红色 VS绿色)。我们发现DLPFC中的神经种群动态编码了颜色选择、动作选择和目标 配置，而PMD的神经群动态只与动作选择有关。此外, PMD的放电率与动物在线索开始前后的反应时间(RT)密切相关，这表明 PMD在计划和执行行动选择中的角色。然而，这样的相关实验无法完全 回答这些大脑区域是否不同地和因果地参与决策的这些方面。这个 本研究的目的是从因果关系上确定DLPFC或PMD在知觉决策中的作用。我们的 基于我们的生理记录的中心假设是，DLPFC的失活应该会影响颜色和动作 而PMD的失活只会影响动作选择和改变RT。为了检验这一假设，我们将使用 定制的皮质冷却停用可使PMD(目标1)或DLPFC(目标2)局部暂时静音 被训练来执行我们的行为任务的猴子。我们的总体做法如下：我们将植入双边录音 我们将在DLPFC和PMD上安装一个线性多触点电极和冷却装置。 当猴子执行我们的行为任务时，我们将执行之前的同步电生理记录， 在DLPFC或PMD冷却期间和之后。我们将使用任务绩效的各种测量方法(心理测量曲线、 RT曲线、眼睛和手臂运动的运动学等)评估降温对决策行为的影响。 会议将使用单侧或双侧冷却，以及完全冷却或轻度冷却。基于我们生理上的 实验中，我们预测了三种影响。首先，我们预计冷却PMD将导致较慢的RTS和偏置 行动选择，但在颜色选择上没有偏见。其次，我们预计DLPFC停用将在两者中产生偏见 颜色选择和动作选择行为会导致任务绩效的严重缺陷。最后，我们预计 双侧停用产生比单侧停用更大幅度的缺陷。这些数据是其第一个 DLPFC和PMD在知觉决策行为中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在这些临床相关的大脑区域发生的行为缺陷，因为 精神和神经障碍以及正常衰老。

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.