PFC-MTL Interactions During Controlled Episodic Retrieval

描述（由申请人提供）：记忆的策略性使用是执行目标导向行为的基础，并假设由前额叶皮层（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，这是人类这些相互作用的解剖学基础。本研究的目的是更好地表征PFC和MTL在受控记忆处理过程中相互作用的途径，通过应用有效的连接分析功能性磁共振成像（fMRI）数据，DTI纤维束成像的指导下。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。在两个功能磁共振成像实验中，我们将系统地表征PFC和MTL之间的相关通路和动力学在不同条件下的控制检索-检索促进自上而下的调制正在进行的线索驱动的记忆检索。当自动记忆提取机制不能恢复与任务相关的信息时，控制性提取过程被激活.因此，它们对于灵活的、目标导向的行为的执行和规划至关重要。获得的关于认知控制和记忆的基本知识适用于许多临床应用。痴呆是神经系统疾病的普遍症状，并且是许多流行的神经心理障碍的特征，例如缺血性血管性痴呆和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一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识别在控制性提取期间激活的PFC和MTL内的区域，2）评估与控制性提取相关的病灶是否是材料特异性的（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）纤维束成像和有效的连接测量来表征PFC和MTL相互作用的功能解剖通路。 公共卫生相关性：该项目旨在描述前额叶皮层和内侧颞叶在记忆的认知控制过程中相互作用的功能途径。获得的关于认知控制和记忆的基本知识适用于许多临床应用，因为记忆障碍是神经系统疾病的普遍症状和流行的神经心理障碍（例如缺血性血管性痴呆、阿尔茨海默病和帕金森病）的特征，并且还与健康的衰老和发育相关。因此，拟议的研究可以为患有记忆和认知功能障碍的患者提供诊断指南和临床治疗的发展。

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.