Medial temporal lobe contributions to flexible use of memory

描述(由申请人提供)：情节记忆的一个强大方面--对个别事件的记忆--是灵活地应用和组合过去经验的信息来指导新行为的能力。这种以新颖的方式结合经验来推断新关系的灵活性，对于在不断变化的环境中的行为是必不可少的。内侧颞叶(MTL)的结构对于形成新的情节记忆是至关重要的，这些记忆将信息绑定在单个情节中。然而，MTL如何支持跨不同情节获得的信息的灵活组合还没有被很好地理解。这项提案中提出的研究将使用功能磁共振成像(FMRI)来研究跨不同情节的信息绑定或跨情节绑定的机制。我们将进一步调查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验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，允许对大脑状态进行推断，例如推断回忆记忆的一般内容，而不需要外部行为反应。我们将研究对与先前经验重叠的新事件的编码是否会触发先前经验的重新激活，从而导致对记忆的灵活使用。实验2和实验3将使用高分辨率的fMRI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将测试海马区的CA3区是否支持MTL皮质内的重新激活，正如CA3在模式完成-从部分线索回忆存储的记忆中所起的作用所预测的那样。当前和以前的经验之间的重叠可以作为这样的部分线索。这项拟议的研究将提供第一个直接证据，证明MTL在重叠经历中调节过去事件的重新激活，并且这种重新激活支持跨情节绑定以促进记忆的灵活使用。实验3将测试两个经历相同或不同的空间背景如何影响两个情节合并信息的可能性，并调查当前和先前经验之间的比较如何促进跨情节绑定。召回的记忆和当前事件之间的比较可以用于检测来自存储的记忆的改变并触发新的编码，从而将新的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区的CA1区。本研究将阐明MTL亚区如何支持从不同情节之间的关系中提取新知识，并为语境在引发跨情节绑定中的作用提供新的证据。了解MTL亚区如何将不同事件的信息结合在一起，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不足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的个人。 与公共健康相关：这项拟议的研究调查了内侧颞叶的结构如何支持记忆的形成和记忆的灵活使用。了解允许灵活使用经验的机制将提供一种方法来预测和促进灵活学习的发生，并潜在地使工具的开发能够在以灵活性不足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的个人。好了！

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. !