Medial temporal lobe contributions to episodic memory

内侧颞叶对情景记忆的贡献

• 批准号: 8992914
• 负责人: LILA DAVACHI
• 金额: $ 37.99万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2017-06-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992914
• 关键词: Address; Affect; Alzheimer' s Disease; Animal Model; Animals; Behavioral Paradigm; Binding; Brain; Brain region; Clinical; Data; Data Reporting; Diagnosis; Disease; Emotional; Epilepsy; Episodic memory; Functional disorder; Funding; Goals; Hand; Hippocampus (Brain); Human; Hypoxia; Knowledge; Lead; Learning; Life; Link; Measures; Medial; Memory; Mental disorders; Mission; Modeling; Pattern; Performance; Physiological; Process; Progress Reports; Psyche structure; Public Health; Research; Research Personnel; Rest; Retrieval; Rodent; Role; Sleep; Specificity; Staging; Stimulus; Stroke; Structure; Task Performances; Temporal Lobe; Testing; Time; Work; awake; behavior measurement; experience; innovation; memory consolidation; memory encoding; nervous system disorder; neuronal patterning; normal aging; novel; novel strategies; paired stimuli; research study; stem; success; theories

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.

描述（由申请人提供）：尽管人们普遍认识到内侧颞叶（MTL）对于情景联想记忆的形成和检索是必要的，但在理解记忆巩固或稳定的后编码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源于MTL的主要功能障碍，以及它如何促进联想记忆。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。当前提案的目的是测试MTL子结构编码后再激活的模型，已知MTL子结构参与编码经验的不同方面，与这些经验的巩固有关。该项目的中心目标是建立再激活作为人类情景记忆巩固的机制，并揭示与不同类型的记忆相关的不同的再激活模式。这项研究的基本原理是，更好地理解记忆是如何随着时间的推移而稳定下来的，这将导致一个强有力的理论框架，在这个框架内，理解破坏记忆的精神疾病的策略将得到发展。目标将是识别、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)识别表征最近先前经验的再激活后编码模式，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量和海马活动联系起来，调节编码后的再激活；3)将编码后再激活与记忆表征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项目目标的可行性。在目标1中，已经在人类海马体中确定了特定编码经验再激活的证据，以及在呈现不同记忆的编码任务后不同MTL相互作用的证据。在目的2下，初步数据提供了证据，证明编码过程中海马的激活程度与编码后海马-皮层的相互作用有关。在目标3下，初步数据确定了联想记忆在再激活过程中网络表征的预期变化模式，这些变化与联想记忆强度的行为测量有关，从而提供了大脑中记忆巩固变化与行为强化之间急需的联系。这种方法具有创新性和重要意义，因为我们对MTL区域之间的相互作用如何促进记忆巩固知之甚少；它是高度程序化的，因为它直接来自于我们之前关于MTL子区域在记忆编码中的作用的工作，并使用新颖的方法通过寻找编码后休息期间的再激活模式来研究巩固。