Prefrontal network dynamics and top-down control of spatial representation

描述（由申请人提供）：人脑灵活地处理感官输入，以提取最有用的信息，并在给定当前行为策略和目标的情况下产生最有利的响应。这种类型的计算灵活性通常被称为执行控制，特别是当它涉及大脑选择实施一个认知过程而不是另一个认知过程，以便在给定的背景下确定最佳行动方案时。我们对执行控制是如何由皮层神经元的生理事件介导的了解有限。为了增加我们对执行控制的细胞基础的了解，我建议同时记录20-30个单独分离的神经元在前额叶皮层（46区）和后顶叶皮层（7a区）的猴子的合奏的电活动，因为他们执行一项任务，要求他们对空间认知施加执行控制。具体来说，猴子会根据我们指导的可变分组标准（规则）将视觉刺激分配给替代空间类别，并在逐个试验的基础上进行更改。在这个任务中，我们提出了一条作为类别边界的线，并将空间类别定义为与线具有相同空间关系的空间位置组-例如，线左边的所有点都包含一个类别，而右边的所有点都包含另一个类别。通过移动和旋转边界，我们需要大脑以规则依赖的方式灵活地将一组固定的空间位置重新分配给替代的空间类别，这需要大脑对空间分类作为认知和生理过程施加执行控制。我们的目标是发现如何执行控制空间分类是在细胞水平上实现的，通过测量规则依赖的变化，在分布式神经表征的空间类别，大脑分配了一个刺激下，一个给定的规则。我们将测试的假设，规则依赖的类别表征的变化将首先出现，并在前额叶皮层最强。这将支持我们的假设，即前额叶皮层位于顶叶皮层之上，在分布式皮层系统中，在一个层次结构中，前额叶皮层介导了对认知处理的执行控制，并提供了有关这种控制在细胞水平上实施的神经机制的一些第一批细节。公共卫生相关性：本研究的目的是探讨非人类灵长类动物大脑前额叶皮层网络中执行控制的神经机制。执行控制是指大脑根据行为规则、目标或策略选择性地执行替代认知过程的能力。为了了解执行控制是如何由皮层神经元实现的，我们将记录猴子在执行一项规则支配空间认知处理的任务时，前额叶和后顶叶皮层中神经元组的电活动。前额叶和顶叶皮层在解剖学上是相连的，共同支持空间认知功能。通过发现规则如何调节与皮层网络中的认知处理相关的电活动模式，我们将能够发现执行控制如何在细胞水平上实现，并进一步确定前额叶皮层是否在调解执行控制中起主导作用。这反过来将有助于我们理解在人类疾病（如前额中风或精神分裂症）中，可能会被破坏以产生执行功能缺陷的神经过程。

DESCRIPTION (provided by applicant): The human brain processes sensory input flexibly to extract the most useful information and generate the most advantageous response given current behavioral strategies and goals. Computational flexibility of this type is often referred to as executive control, particularly when it involves the brain selecting to implement one cognitive process over another in order to determine the best course of action within a given context. We have a limited understanding of how executive control, as such, is mediated by physiological events in cortical neurons. To increase our knowledge of the cellular basis of executive control, I propose to simultaneously record the electrical activity of ensembles of 20-30 individually isolated neurons in prefrontal cortex (area 46) and in posterior parietal cortex (area 7a) of monkeys as they perform a task requiring them to exert executive control over spatial cognition. Specifically, monkeys will assign visual stimuli to alternative spatial categories according to a variable grouping criterion (rule) that we instruct and change on a trial-by-trial basis. In this task, we present a line that serves as a category boundary, and define spatial categories as groups of spatial positions that bear the same spatial relationship to the line - such that, for example, all points to the left of the line comprise one category, and all points to the right another. By shifting and rotating the boundary, we require the brain to flexibly reassign a fixed set of spatial positions to alternative spatial categories in a rule- dependent manner, and this requires the brain to exert executive control over spatial categorization as a cognitive and physiological process. Our objective is to discover how executive control over spatial categorization is implemented at a cellular level, by measuring rule-dependent changes in distributed neural representations of the spatial category to which the brain has assigned a stimulus under a given rule. We will test the hypothesis that rule-dependent changes in category representation will emerge first and be strongest in prefrontal cortex. This will support our hypothesis that prefrontal cortex sits above parietal cortex in a hierarchy of areas mediating executive control over cognitive processing in distributed cortical systems, and provide some of the first detail about the neural mechanisms by which this control is implemented at a cellular level. PUBLIC HEALTH RELEVANCE: The research described in this proposal investigates the neural mechanisms of executive control in prefrontal cortical networks of the nonhuman primate brain. Executive control refers to the capacity of the brain to selectively implement alternative cognitive processes on the basis of behavioral rules, goals or strategies. To understand how executive control is implemented by cortical neurons, we will record the electrical activity of groups of neurons in the prefrontal and posterior parietal cortex of monkeys as they perform a task in which rules govern spatial cognitive processing. Prefrontal and parietal cortexes are anatomically connected and jointly support spatial cognitive function. By discovering how rules modulate patterns of electrical activity associated with cognitive processing in this cortical network, we will be able to discover how executive control is implemented at a cellular level, and further determine whether prefrontal cortex plays a predominant role in mediating executive control. This in turn will help us understand the neural processes that may be disrupted to produce deficits in executive function in human diseases, such as prefrontal stroke, or schizophrenia.