Medial temporal lobe contributions to episodic memory

描述（由申请人提供）：尽管人们普遍认为内侧颞叶（MTL）对于情景联想记忆的形成和提取是必要的，但在理解记忆巩固或稳定的编码后过程方面存在根本性的差距。这种知识上的差距是一个关键问题，因为许多精神和神经疾病都源于MTL的原发性功能障碍以及它如何有助于联想记忆。长期目标是了解支持记忆巩固的机制，以及这些变化对我们的新记忆与过去经验的整合有什么影响。目前的建议的目的是测试一个模型，如何编码后激活MTL子结构内已知参与编码的不同方面的经验与巩固这些经验。该项目的中心目标是建立作为人类情景记忆巩固机制的再激活，并揭示与不同类型记忆相关的不同再激活模式。这项研究的基本原理是，更好地理解记忆如何随着时间的推移而变得稳定，将导致一个强大的理论框架，在这个框架内，将制定理解精神疾病破坏记忆的策略。目的是识别、调节和寻找再激活的长期后果，这将通过追求三个具体目标来实现：1）识别编码后的再激活模式，其表征最近的先前经历并与不同内容的记忆的后期联想记忆相关; 2）通过将再激活与先前学习和海马活动的量相联系来调节编码后的再激活;以及3）将编码后的再激活与记忆表征中的长期变化联系起来。强有力的初步数据证明了申请人手中的项目目标的可行性。在目标1下，在人类海马内已经确定了特定编码经验的重新激活的证据，并且在编码任务呈现不同的记忆之后，已经确定了不同MTL相互作用的证据。根据目标2，初步数据提供的证据表明，编码过程中海马激活的幅度与编码后的海马-皮质相互作用相关。在目标3下，初步数据确定了在再激活过程中关联记忆网络表示的预期变化模式，这些模式与关联记忆强度的行为测量有关，从而在大脑中的记忆巩固变化和记忆行为的加强之间提供了急需的联系。该方法是创新的和重要的，因为我们知道很少关于MTL区域之间的相互作用如何有助于记忆巩固;它是高度程序化的，因为它是直接从我们以前的工作动机的MTL子区域的作用，记忆编码，并使用新的方法来研究巩固通过寻找模式的再激活后编码休息。

DESCRIPTION (provided by applicant): Despite the widespread appreciation that the medial temporal lobe (MTL) is necessary for episodic associative memory formation and retrieval, there is a fundamental gap in understanding the post-encoding processes by which memories are consolidate, or stabilized. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of the MTL and how it contributes to associative memory. The long-term goal is to understand the mechanisms that support memory consolidation and what consequences these changes have on the integration of our new memories with past experience. The objective of the current proposal is to test a model of how post-encoding reactivation within MTL substructures known to be involved in encoding different aspects of an experience relate to the consolidation of those experiences. The central aim of the project is to establish reactivation as a mechanism for human episodic memory consolidation and to reveal distinct patterns of reactivation related to distinct kinds of memories. The rationale for the proposed research is that a better understanding of how the memories become stabilized over time will lead to a strong theoretical framework within which strategies for the understanding of mental disease disrupting memory will develop. The objective will be to identify, modulate and look for long-term consequences of reactivation which will be accomplished by pursuing three specific aims: 1) identify post-encoding patterns of reactivation that characterize recent prior experiences and relate to later associative memory for memories of different content; 2) modulate post-encoding reactivation by linking reactivation with the amount of prior learning and hippocampal activity; and 3) linking post-encoding reactivation with longer-term changes in the memory representations. Strong preliminary data demonstrate the feasibility of project aims in the applicant's hands. Under aim 1, evidence for reactivation of specific encoding experiences has been identified within the human hippocampus and evidence for distinct MTL interactions following encoding tasks presenting different memoranda. Under aim 2, preliminary data provide evidence that the magnitude of hippocampal activation during encoding correlates with post-encoding hippocampal-cortical interactions. Under aim 3, preliminary data identify expected patterns of change in the network representation of associative memories during reactivation that relate to behavioral measures of associative memory strength thus providing a much needed link between memory consolidation changes in the brain and strengthening of memories behaviorally. The approach is innovative and significant because we know very little about how interactions between MTL regions contribute to memory consolidation; it is highly programmatic because it is directly-motivated from our prior work on the role of MTL subregions to memory encoding and uses novel approaches to studying consolidation by looking for patterns of reactivation during post-encoding rest.