High-Resolution fMRI of Medial Temporal Lobe Mechanisms in Declarative Memory

描述(由申请人提供)：陈述性记忆允许有机体在过去和现在之间架起桥梁，提供关于先前事件的信息，从而为现在的决定和行动提供信息。陈述性记忆在很大程度上依赖于内侧颞叶(MIL)，内侧颞叶由海马结构(齿状回、腺角区和下丘脑)以及周围的内嗅觉、外嗅觉和海马旁皮质组成。尽管几十年来的研究一直致力于描述MIL在陈述性记忆中的作用，但关于特定MTL亚结构的功能贡献仍然存在一些基本问题。功能成像的最新进展现在已经使在人类身上开始解决这些问题成为可能。这项拟议的研究将使用高分辨率功能磁共振和基于解剖学的分析方法来描述特定的MTL皮层和海马区在陈述性记忆中的作用。拟议的实验将测试解剖学信息理论驱动的关于陈述性记忆的性质及其对MTL功能的依赖的假说。例1-3将研究在MTL的前轴/后轴和冠轴的新颖性编码过程，重点是内容敏感的编码效应是否存在于不同的MTL皮质和海马亚区。Expt4-9将探索MTL子结构的功能及其在声明性记忆编码和提取过程中的相互作用，重点是支持合取记忆和项目记忆的机制的分解。摘录10-12将测试关于MTL提取机制的性质的假设，包括它们对研究-测试知觉相似性的依赖。例文13-14将研究目标定向注意如何影响海马区和MTL皮层编码机制，编码项目和连接记忆，包括注意力依赖的MTL反应的增强和抑制。从测试陈述记忆和MTL子结构功能的理论驱动的假设的程序性努力中获得的基本知识有望对临床人群中学习和记忆障碍的性质产生新的见解。陈述性记忆缺陷伴随着许多临床疾病，包括精神分裂症、轻度认知障碍和阿尔茨海默病。我们将直接将获得的结果转化为我们关于精神分裂症MTL功能障碍的合作研究。

DESCRIPTION (provided by applicant): Declarative memory permits an organism to bridge the past with the present, providing information about prior events that serves to inform present decisions and action. Declarative memory critically depends on the medial temporal lobe (MIL), which is composed of the hippocampal formation (dentate gyrus, fields of cornu Ammonis, and subiculum) and the surrounding entorhinal, perirhinal, and parahippocampal cortices. Though decades of research have aimed to characterize the role of MIL in declarative memory, fundamental questions remain regarding the functional contributions of specific MTL substructures. Recent advances in functional imaging have now made it possible to begin to address these questions in humans. The proposed research will use high-resolution functional MRI and anatomically-based analysis methods to delineate the role of specific MTL cortical and hippocampal subfields in declarative memory. The proposed experiments will test anatomically-informed theory-driven hypotheses regarding the nature of declarative memory and its dependence on MTL function. Expts 1-3 will examine novelty-encoding processes in the anterior/posterior and coronal axes of MTL, focusing on whether content-sensitive encoding effects are present within distinct MTL cortices and hippocampal subfields. Expts 4-9 will explore the function of MTL substructures and their interactions during declarative memory encoding and retrieval, focusing on decomposition of mechanisms that support conjunctive and item memory. Expts 10-12 will test hypotheses about the nature of MTL retrieval mechanisms signaling item familiarity and temporal recency, including their dependence on study- test perceptual similarity. Expts 13-14 will examine how hippocampal and MTL cortical encoding mechanisms that encode item and conjunctive memories are impacted by goal-directed attention, including attention-dependent enhancement and suppression of MTL responses. The basic knowledge to be gained from this programmatic effort to test theory-driven hypotheses of declarative memory and MTL substructure function promises to yield new insights into the nature of learning and memory impairments in clinical populations. Declarative memory deficits accompany a number of clinical conditions, including schizophrenia, mild cognitive impairment, and Alzheimer's disease. We will directly translate the obtained outcomes to inform our collaborative studies of MTL dysfunction in schizophrenia.