Medial temporal lobe contributions to flexible use of memory

内侧颞叶对灵活运用记忆的贡献

• 批准号: 8256289
• 负责人: Dagmar Zeithamova
• 金额: $ 5.37万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2014-09-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8256289
• 关键词: Address; Affect; Alzheimer' s Disease; Behavior; Behavioral; Binding; Brain; Cues; Detection; Elements; Environment; Episodic memory; Event; Functional Magnetic Resonance Imaging; Generations; Goals; Hippocampus (Brain); Imaging Techniques; Individual; Judgment; Knowledge; Lead; Learning; Link; Measures; Medial; Mediating; Memory; Mental Depression; Methods; Pattern; Performance; Play; Population; Procedures; Process; Research; Resolution; Role; Schizophrenia; Signal Transduction; Structure; Temporal Lobe; Testing; base; experience; flexibility; memory recall; mild neurocognitive impairment; novel; research study; response; shared memory; theories; tool development

DESCRIPTION (provided by applicant): A powerful aspect of episodic memory-memory for individual events-is the ability to flexibly apply and combine information from past experiences to guide new behavior. Such flexibility to combine experiences in novel ways to infer new relationships is essential to behavior in ever-changing environment. The structures of the medial temporal lobe (MTL) are critical for the formation of new episodic memories that bind information within single episodes. However, how MTL supports the flexible combination of information gained across distinct episodes is not well understood. The research presented in this proposal will use functional magnetic resonance imaging (fMRI) to investigate the mechanisms that enable binding of information across distinct episodes, or cross-episode binding. We will further investigate how individual regions of the MTL support these mechanisms. Experiment 1 will test the hypothesis that cross-episode binding relies on reactivation of prior memories that share elements with the current experiences. A novel method will be used that allows inference about brain states, such as inferring a general content of a recalled memory, without an external behavioral response. We will examine whether encoding of new events that overlap with prior experience triggers reactivation of the prior experience, leading to a flexible use of memory. Experiments 2 and 3 will use high- resolution fMRI to investigate how individual MTL subregions support the processes critical for cross-episodic binding. Experiment 2 will test whether the CA3 field of the hippocampus supports reactivation within MTL cortex, as predicted by the role of CA3 in pattern completion-recollection of stored memories from a partial cue. The overlap between current and prior experience may serve as such a partial cue. The proposed research will provide the first direct evidence that MTL mediates reactivation of past events during overlapping experiences and that such reactivation supports cross-episode binding to promote the flexible use of memory. Experiment 3 will test how spatial contexts that are either the same or different across two experiences affect the likelihood of combining information across the two episodes and investigate how comparison between current and prior experience promotes cross-episode binding. A comparison between recalled memories and current events may serve to detect a change from a stored memory and trigger new encoding, leading to an integration of the new information into existing memories. This comparator function is thought to rely on the CA1 field of the hippocampus. This research will elucidate how MTL subregions support the abstraction of new knowledge from the relationship between distinct episodes and provide new evidence for the role of context in eliciting cross-episode binding. Knowing how MTL subregions combine information across events will provide a means to both predict and promote the occurrence of flexible learning and potentially enable the development of tools to enhance these processes in specific populations characterized by deficits in flexibility, such as individuals with schizophrenia, mild cognitive impairment, Alzheimer's disease and depression. PUBLIC HEALTH RELEVANCE: The proposed research investigates how the structures of the medial temporal lobe support memory formation and flexible use of memory. Understanding the mechanisms that allow the flexible use of experience will provide a means to both predict and promote the occurrence of flexible learning and potentially enable the development of tools to enhance these processes in specific populations characterized by deficits in flexibility, such as individuals with schizophrenia, mild cognitive impairment, Alzheimer's disease and depression. !

描述（由申请人提供）：情景记忆的一个强大方面--对单个事件的记忆--是灵活应用和联合收割机从过去的经验中获得的信息来指导新行为的能力。这种以新颖的方式将联合收割机经验结合起来以推断新关系的灵活性，对于在不断变化的环境中的行为至关重要。内侧颞叶（MTL）的结构对于新的情景记忆的形成至关重要，这些记忆将信息绑定在单个情景中。然而，MTL如何支持跨不同事件获得的信息的灵活组合还没有得到很好的理解。本提案中提出的研究将使用功能性磁共振成像（fMRI）来研究使信息在不同事件或跨事件绑定之间绑定的机制。我们将进一步研究MTL的各个区域如何支持这些机制。实验1将检验跨情节绑定依赖于与当前经历共享元素的先前记忆的重新激活的假设。将使用一种新的方法，允许推断大脑状态，例如推断回忆记忆的一般内容，而无需外部行为反应。我们将研究是否编码新的事件，与先前的经验重叠触发重新激活先前的经验，导致灵活使用的记忆。实验2和3将使用高分辨率功能磁共振成像来研究单个MTL亚区如何支持跨情节结合的关键过程。实验2将测试海马CA 3区是否支持MTL皮层内的再激活，正如CA 3在模式完成-从部分线索回忆存储的记忆中的作用所预测的那样。当前经验和先前经验之间的重叠可以作为这样的部分线索。拟议的研究将提供第一个直接的证据，MTL介导的重叠的经验，过去的事件的再激活，这种再激活支持跨情节绑定，以促进灵活使用的记忆。实验3将测试两个经验中相同或不同的空间背景如何影响两个事件中组合信息的可能性，并研究当前和先前经验之间的比较如何促进跨事件绑定。回忆的记忆和当前事件之间的比较可以用来检测存储的记忆的变化并触发新的编码，从而导致新信息整合到现有的记忆中。这种比较器功能被认为依赖于海马体的CA 1场。这项研究将阐明MTL亚区如何支持从不同事件之间的关系中提取新的知识，并为上下文在引发跨事件绑定中的作用提供新的证据。了解MTL子区域如何跨事件联合收割机组合信息将提供一种手段来预测和促进灵活学习的发生，并可能使工具的开发能够在以灵活性缺陷为特征的特定人群中增强这些过程，例如患有精神分裂症、轻度认知障碍、阿尔茨海默病和抑郁症的个体。 公共卫生关系：本研究旨在探讨内侧颞叶的结构如何支持记忆的形成和记忆的灵活运用。了解允许灵活使用经验的机制将提供一种手段来预测和促进灵活学习的发生，并可能使工具的开发能够在以灵活性缺陷为特征的特定人群中增强这些过程，例如精神分裂症，轻度认知障碍，阿尔茨海默病和抑郁症患者。!