Medial temporal lobe contributions to episodic memory

内侧颞叶对情景记忆的贡献

• 批准号: 8206105
• 负责人: LILA DAVACHI
• 金额: $ 37.41万
• 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 2016-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8206105
• 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 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. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which memories consolidate in the normal brain is necessary to illuminate the mechanisms that could go awry in diseases that compromise the medial temporal lobes such as Alzheimer's disease. Specifically, the proposed research is relevant to NIH's mission because is expected to advance translational knowledge by providing empirical support in humans for processes identified in animals models and, thus, to strengthen theories of memory consolidation within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.

描述(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着根本的差距。这一知识差距是一个关键问题，因为许多精神和神经疾病源于MTL的原发功能障碍，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产生了什么后果。目前提议的目标是测试一个模型，即编码后在MTL子结构内的重新激活如何与这些经验的巩固有关，这些子结构已知涉及编码经验的不同方面。该项目的中心目标是建立重新激活作为人类情景记忆巩固的一种机制，并揭示与不同类型的记忆相关的不同的重新激活模式。这项拟议研究的基本原理是，更好地理解记忆是如何随着时间的推移变得稳定的，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扰乱记忆的策略。我们的目标将是识别、调节和寻找重新激活的长期后果，这将通过追求三个具体目标来实现：1)识别编码后重新激活的模式，这些模式表征了最近的先前经验，并与不同内容的记忆的后来联想记忆有关；2)通过将重新激活与先前学习和海马体活动的量联系起来来调节编码后重新激活；以及3)将编码后重新激活与记忆表征的较长期变化联系起来。强劲的初步数据证明了项目目标在申请者手中的可行性。在目标1下，在人类海马体中发现了重新激活特定编码经验的证据，并在呈现不同记忆的编码任务后发现了不同的MTL相互作用的证据。在目标2下，初步数据提供了证据，表明编码过程中海马体激活的大小与编码后的海马体-皮质相互作用相关。在目标3下，初步数据确定了在重新激活期间联想记忆网络表征的预期变化模式，这些模式与联想记忆强度的行为测量有关，从而在大脑中记忆巩固的变化和记忆行为的加强之间提供了亟需的联系。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；它具有高度的程序性，因为它直接源于我们之前关于MTL亚区对记忆编码的作用的工作，并使用新的方法通过寻找编码后休息期间的重新激活模式来研究巩固。 与公共健康相关：这项拟议的研究与公共健康相关，因为我们有必要进一步了解记忆在正常大脑中巩固的机制，以阐明在阿尔茨海默病等损害内侧颞叶的疾病中可能出现问题的机制。具体地说，这项拟议的研究与NIH的任务相关，因为预计将通过在人类中为动物模型中确定的过程提供经验支持来促进翻译知识，从而加强记忆巩固理论，在此理论中，临床研究人员可以制定诊断和治疗精神和神经疾病的策略。