Frontal Cortex and Executive Function

描述(由申请人提供)： 目标导向行为要求有能力监控和执行内部目标和意图，维护和处理工作记忆中的信息，选择与任务相关的信息，并组织行动计划来实现这些目标。拟议的研究计划将采用多学科方法，旨在调查这种“执行控制”过程背后的神经机制。神经认知方法--特别是神经成像和神经心理学技术--加深了我们对这种过程的理解。事实上，众所周知，前额叶皮质(PFC)在各种目标导向行为的执行控制中起着关键作用。然而，我们对PFC本身是如何组织的，以及它是如何动态控制其他皮质和皮质下区域的理解还不太清楚。我们将开发和利用广泛的补充方法来探索执行控制过程。这些方法包括生理学技术(例如猴子的单单位记录、健康受试者的功能磁共振成像、癫痫患者的皮质脑电图术)、神经心理学方法(例如中风局灶性病变患者的行为研究、健康受试者的经颅磁刺激)、药理学技术(例如多巴胺能药物在健康受试者中的作用、帕金森氏病患者服药前后的行为研究)和发育方法(例如健康儿童的研究)。该计划的核心项目将提供对神经科患者的详细神经心理学和神经解剖学评估，最先进的神经成像和电生理设施，以及将促进研究人员之间思想和方法相互交融的综合智力环境。三个拟议的项目将解决与目标导向行为相关的执行控制过程问题。项目1将讨论方案支助委员会内各区域的职能组织及其对行政控制的贡献。项目2将侧重于PFC启动自上而下信号到后脑皮质区域以执行对自下而上激活的控制的机制。项目3将重点研究额纹状体回路以及它们如何对决策和反应计划做出贡献。从这项工作中获得的知识有可能具有核心临床意义，因为许多神经系统疾病包括执行控制过程中的障碍。此外，这些知识可能为开发认知和药物疗法提供基础，以治疗以执行控制缺陷为特征的广泛疾病。

DESCRIPTION (provided by applicant): Goal-directed behavior requires the ability to monitor and execute internal goals and intentions, maintain and manipulate information in working memory, select task-relevant information, and organize action plans to accomplish these goals. The proposed research program will employ a multidisciplinary approach directed toward investigations of the neural mechanisms underlying such "executive control" processes. Neurocognitive methods-particularly neuroimaging and neuropsychological techniques- have sharpened our understanding of such processes. Indeed, it is well established that the prefrontal cortex (PFC) is critically involved in the executive control of a variety of goal-directed behaviors. Yet, our understanding of how the PFC is itself organized and how it dynamically controls other cortical and subcortical regions is less well understood. We will develop and utilize a wide range of complementary methodologies to explore executive control processes. These methods include physiological techniques (e.g. single unit recording in monkeys, functional MRI in healthy subjects, electocorticography in epilepsy patients), neuropsychological methods (e.g. behavioral studies of patients with focal lesions due to stroke, transcranial magnetic stimulation of healthy subjects), pharmacological techniques (e.g. effects of dopaminergic agents in healthy subjects, behavioral studies of Parkinson's disease patients on and off their medication) and developmental methods (e.g., studies of healthy children). The Core of the Program Project will provide detailed neuropsychological and neuroanatomical assessment of neurological patients, state-of-the-art neuroimaging and electrophysiological facilities, and an integrative intellectual environment that will facilitate cross-fertilization of ideas and methods among investigators. Three proposed projects will address issues of executive control processes associated with goal-directed behavior. Project 1 will address the functional organization of regions within PFC and how they contribute to executive control. Project 2 will focus on mechanisms by which the PFC initiates top-down signals to posterior cortical regions in order execute control over bottom-up activations. Project 3 will focus 'on fronto-striatal circuits and how they contribute to decision-making and response plans. The knowledge gained from this work has the potential to be of central clinical significance, as many neurological disorders include impairment in executive control processes. Moreover, such knowledge may provide a foundation for developing cognitive and pharmacological therapies for treating the wide range of disorders characterized as deficits in executive control.