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连接过去和现在，提供有关先前事件的信息，用于通知当前的决定和行动。陈述性记忆主要依赖于内侧颞叶（MIL），它由海马结构（齿状回、脑角区和下带）和周围的嗅内皮层、嗅周皮层和海马旁皮层组成。尽管几十年的研究旨在描述MIL在陈述性记忆中的作用，但关于特定MTL子结构的功能贡献的基本问题仍然存在。最近在功能成像方面的进展使得在人类身上解决这些问题成为可能。该研究将使用高分辨率功能性MRI和基于解剖学的分析方法来描述特定MTL皮层和海马亚区在陈述性记忆中的作用。提出的实验将测试解剖学信息理论驱动的假设，关于陈述性记忆的性质及其对MTL功能的依赖。专家1-3将研究颞叶前/后和冠状轴的新颖性编码过程，重点研究内容敏感编码效应是否存在于不同的颞叶皮层和海马亚区。专家4-9将探讨MTL子结构的功能及其在陈述性记忆编码和检索中的相互作用，重点是支持连接记忆和项目记忆的分解机制。专家10-12将测试关于MTL检索机制的性质的假设，包括它们对研究测试感知相似性的依赖。专家13-14将研究海马和MTL皮层编码机制编码项目记忆和联合记忆如何受到目标定向注意的影响，包括注意依赖性增强和MTL反应的抑制。从测试陈述性记忆和MTL子结构功能的理论驱动假设的程序性努力中获得的基本知识有望对临床人群的学习和记忆障碍的本质产生新的见解。陈述性记忆缺陷伴随着许多临床病症，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.