Functional Imaging of the Human FEF

描述（由申请人提供）：前额叶皮层（PFC）对于适应性高阶认知行为至关重要，这些认知行为受到各种精神健康障碍的损害，包括精神分裂症（ADHD）、物质滥用障碍、阿尔茨海默病和帕金森病以及艾滋病相关痴呆。更好地了解基本的神经机制将导致改进的诊断，预后和治疗程序。尽管前额叶皮层对于计划、维持、选择和执行意志行为至关重要，但我们对它实现这些目标的机制知之甚少。我们在这方面取得进展的障碍包括：1）对PFC功能的关键动物工作如何转化为我们试图了解的人类物种的理解不足，以及2）缺乏对PFC如何通过与其他大脑区域的功能相互作用影响持续行为的理解。在这里，我们提出了一个分而治之的策略，以更好地了解PFC的功能。在AIM 1中，我们将本地化的PFC，人类同系物的猴子额眼场（FEF）的一个关键部分，并把它作为一个模型系统的PFC功能的详细研究。我们战略性地选择FEF作为我们的模型，因为1）与其他PFC区域不同，我们有方法将其定位于人类，2）与其他PFC区域相比，来自猴子FEF的数据提供了关于物种之间功能同源性的可测试预测，最重要的是3）FEF涉及许多与PFC一般所涉及的相同的高水平认知行为。我们将研究人类FEF用于计划，注意力，记忆和选择的机制。在一个更好定义和约束的系统中工作，如眼神经系统，可能很快导致对这些功能的机械解释，而在一个更复杂和更少理解的系统中，如PFC作为一个整体，可能不太站得住脚。虽然PFC被认为是通过与其他大脑区域的功能相互作用来影响正在进行的行为，但缺乏证据支持这一理论。在AIM 2中，我们将使用功能磁共振成像来测量PFC和其他大脑区域之间的功能相互作用，这些区域可能共同形成支持关键行为的网络。这两个AIMS共同包含了本地层面的功能专业化和网络层面的分布式处理，并将使我们能够测试有关PFC如何支持意图，注意力和工作记忆的关键假设。

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) is critical for adaptive higher-order cognitive behaviors that are compromised by a wide variety of mental health disorders including schizophrenia, (ADHD), substance abuse disorders, Alzheimer's and Parkinson's Disease, and AIDS-related dementia. A better understanding of basic neural mechanisms will lead to improved diagnostic, prognostic, and therapeutic procedures. Although the PFC is critical for the planning, maintenance, selection, and execution of willed behavior, we know very little about the mechanisms by which it accomplishes these goals. Barriers to our progress in this regard include 1) a poor understanding of how the crucial animal work on PFC functions translates to the human species we are trying to understand, and 2) a lack of understanding of how the PFC influences ongoing behavior through its functional interactions with other brain areas. Here we propose a divide-and-conquer strategy for better understanding the functions of the PFC. In AIM 1, we will localize a key portion of the PFC, the human homolog of the monkey frontal eye field (FEF) and treat it as a model system for detailed study of PFC functions. We strategically chose the FEF as our model because 1) unlike other PFC areas, we have methods for localizing it in humans, 2) data from monkey FEF, as compared to other PFC areas, offer testable predictions about the functional homologies between the species, and most importantly 3) the FEF is implicated in many of the same high-level cognitive behaviors that the PFC in general is implicated. We will study the mechanisms that the human FEF uses for planning, attention, memory, and selection. Working within a better-defined and constrained system like the oculomotor system may quickly lead to mechanistic accounts of these functions that may be less tenable in a more complicated and less understood system like the PFC as a whole. Although the PFC is thought to influence ongoing behavior through its functional interactions with other brain areas, there is a dearth of evidence to support this theory. In AIM 2, we will use fMRI to measure functional interactions between the PFC and other brain areas that together may form networks supporting the critical behaviors. Together, the two AIMS embrace both functional specialization at the local level and distributed processing at the network level and will allow us to test critical hypotheses about how the PFC supports intention, attention, and working memory.