PFC-MTL Interactions During Controlled Episodic Retrieval

描述（由申请人提供）：记忆的策略性使用是目标导向行为执行的基础，并被假设由前额皮质（PFC）和内侧颞叶（MTL）共同支持；然而，PFC对MTL的调节影响的证据仍然主要是间接的，正如这些相互作用在人类中的解剖学基础一样。本研究的目的是通过应用功能磁共振成像（fMRI）数据的有效连通性分析，在DTI束状图的指导下，更好地表征PFC和MTL在受控记忆处理过程中相互作用的途径。所提出的研究提供的核心数据可以作为解决有关记忆的认知控制的基本机制问题的基础。在两个功能磁共振实验中，我们将系统地表征在不同条件下PFC和MTL之间的相关通路和动态。当自动记忆检索机制无法恢复任务相关信息时，采用控制检索处理。因此，它们对于灵活的、目标导向的行为的执行和计划至关重要。所获得的认知控制和记忆的基本知识可用于许多临床应用。痴呆症是神经系统疾病的普遍症状，也是许多流行的神经心理疾病的特征，如缺血性血管性痴呆、阿尔茨海默病和帕金森病，以及伴随健康衰老和发育的记忆缺陷。因此，拟议的研究可以为患有记忆和执行功能障碍的患者提供诊断指南和临床治疗的发展。目前的建议是朝着这个更广泛的研究计划迈出的必要的第一步。在三个目标中，我们将：1)使用fMRI识别在受控检索过程中激活的PFC和MTL区域，2)评估与受控检索相关的病灶是否具有物质特异性（优先处理概念或视觉空间记忆），以及3)使用扩散张量成像（DTI）束状图和有效的连接措施表征PFC和MTL相互作用的功能解剖途径。

DESCRIPTION (provided by applicant): The strategic use of memory is fundamental to the execution of goal-directed behavior and is hypothesized to be jointly supported by the prefrontal cortex (PFC) and medial temporal lobes (MTL); however evidence for a modulatory influence of PFC on MTL is still primarily indirect, as is the anatomical basis for these interactions in humans. The objective of the research in this proposal is to better characterize the pathways by which PFC and MTL interact during controlled memory processing through the application of effective connectivity analysis of functional magnetic resonance imaging (fMRI) data, guided by DTI tractography. Core data provided by the proposed research can serve as the basis for addressing fundamental mechanistic questions about the cognitive control of memory. In two fMRI experiments, we will systematically characterize the relevant pathways and dynamics between PFC and MTL under varying conditions of controlled retrieval - retrieval facilitated by top-down modulation of ongoing cue-driven memory retrieval. Controlled retrieval processing is recruited when automatic memory retrieval mechanisms fail to recover task- relevant information. As such, they are critical for the execution and planning of flexible, goal-directed behavior. Basic knowledge gained about cognitive control and memory is applicable to a number of clinical applications. Dementia is a pervasive symptom of neurological disease and a feature of many prevalent neuropsychological disorders such as ischemic vascular dementia and Alzheimer's and Parkinson's Diseases and the memory deficits that accompany healthy aging and development. As such, the proposed research could inform both diagnostic guidelines and the development of clinical treatments for patients afflicted with memory and executive dysfunction. The present proposal presents a necessary first step toward this broader research program. In three aims, we will: 1) identify regions within PFC and MTL activated during controlled retrieval using fMRI, 2) assess whether foci associated with controlled retrieval are material specific (preferentially process conceptual or visuospatial memoranda), and 3) characterize the functional-anatomic pathways by which PFC and MTL interact using diffusion tensor imaging (DTI) tractography and effective connectivity measures. PUBLIC HEALTH RELEVANCE: The proposed project seeks to characterize the functional pathways by which the prefrontal cortex and the medial temporal lobes interact during the cognitive control of memory. Basic knowledge gained about cognitive control and memory is applicable to a number of clinical applications as memory impairments are a pervasive symptom of neurological disease and a feature of prevalent neuropsychological disorders such as ischemic vascular dementia, Alzheimer's and Parkinson's Diseases, and are also associated with healthy aging and development. As such, the proposed research could inform both diagnostic guidelines and the development of clinical treatments for patients afflicted with impairments of memory and cognitive function.