The role of context in sleep-related memory reactivation in humans

项目摘要/摘要 睡眠对巩固记忆至关重要，其益处通常被认为是通过重新激活而发生的 记忆，从而加强支持它们的神经基础设施。对睡眠的理论描述- 相关巩固侧重于独立但自然地增强记忆的过程 背景个人记忆永远不会存在于真空中。重要的是，记忆嵌入的背景 在编码过程中，控制检索和决策行为。然而，环境在整合中的作用有 没有被直接勘探过。拟议项目的目标是提高我们对 通过开发一个基于经验的框架来统一语境对记忆的影响模型来实现记忆过程 以及与睡眠相关的巩固模型(目标1；实验1-3)。此外，该框架可以支持 翻译干预以改变睡眠中的记忆。目标2(实验4-5)将尝试恢复 睡眠时的抑制背景有效地削弱了记忆。这一努力将为今后的缓解工作提供参考 患有创伤后应激障碍的临床人群的记忆相关症状。鉴于 这两个目标的概念验证将在本奖项的K99阶段进行演示，R00阶段将用于 增强理论框架，建立外部效度。翻译部门和基础科学部门 这项工作将在我的独立职业生涯中并行进行，在我的职业生涯中，我将使用我完全组装的 探索睡眠对记忆的贡献以及支持睡眠的神经基础设施的神经认知工具包。 这一提议中使用的主要行为操作是定向记忆重新激活，即不引人注目的 在睡眠中呈现与学习相关的刺激，从而增强记忆力。实验1(K99阶段)测试 是否可以直接重新激活上下文，并考虑与重新激活相关的好处之间的相互作用 个人的记忆和背景。实验2(K99阶段)调查个体的线索是否 睡眠期间呈现的记忆以传播到其他记忆的方式重新激活学习环境 上下文链接在一起。实验3(R00阶段)使用功能磁共振图像分析技术揭示 无论是背景、个人记忆，还是两者都在自然、不受干扰的睡眠中被重新激活。实验4 (K99阶段)在睡眠期间，试图将个体记忆嵌入先前无关的背景中：重新激活 将用链接到个体记忆的听觉提示来呈现(由气味提示的)“抑制”上下文， 假想会在睡眠中削弱它们。实验5(R00阶段)将使用类似的技术尝试 减轻健康参与者在创伤手法后的痛苦侵入性记忆。 对于这个项目，我已经为K99阶段组建了一个专家指导团队，其中包括职能部门的领导者 MRI模式分析，上下文和记忆的计算模型，以及嗅觉刺激，覆盖整个 所需专业知识的范围。西北大学拥有一个充满活力的认知神经科学社区， 所需的方法以及所有所需的设备和设施都有很强的代表性。

PROJECT SUMMARY/ABSTRACT Sleep is crucial for memory consolidation and its benefit is most commonly thought to occur via the reactivation of memories, thereby strengthening the neural infrastructure supporting them. Theoretical accounts of sleep- related consolidation focus on the process by which memories are independently strengthened, but in natural settings individual memories never exist in a vacuum. Importantly, the context in which memories are embedded during encoding governs retrieval and decision making behavior. However, context’s role in consolidation has not been directly explored. The goal of the proposed project is to improve our fundamental understanding of memory processes by developing an empirically-based framework unifying models of context’s effect on memory and models of sleep-related consolidation (Aim 1; Experiments 1–3). Additionally, the framework may support translational interventions to alter memories during sleep. Aim 2 (Experiments 4–5) will attempt to reinstate a suppression context during sleep to effectively weaken memories. This effort will inform future work on alleviating memory-related symptoms in clinical populations suffering from post-traumatic stress disorder. Whereas the proof-of-concept for both aims will be demonstrated in the K99 phase of this award, the R00 phase will serve to enhance the theoretical framework and establish external validity. Both the translational and basic-science arms of this work will continue in parallel throughout my independent career, in which I will use my fully assembled neurocognitive toolkit to explore sleep’s contribution to memory and the neural infrastructure supporting it. The main behavioral manipulation used in this proposal is targeted memory reactivation, the unobtrusive presentation of learning-related stimuli during sleep, thereby enhancing memory. Experiment 1 (K99 phase) tests whether contexts may be reactivated directly and considers the interactions between reactivation-related benefits of individual memories and contexts. Experiment 2 (K99 phase) investigates whether cues for individual memories presented during sleep reactivate the learning context in a manner that propagates to other memories contextually linked together. Experiment 3 (R00 phase) uses functional MRI pattern analysis techniques to reveal whether contexts, individual memories or both are reactivated during natural, undisturbed sleep. Experiment 4 (K99 phase) attempts to embed individual memories in a previously unrelated context during sleep: a reactivated “suppression” context (cued by an odor) will be presented with auditory cues linked to individual memories, hypothetically weakening them during sleep. Experiment 5 (R00 phase) will use a similar technique to try and alleviate distressful intrusive memories following a trauma manipulation in healthy participants. For this project, I have assembled an expert mentorship team for the K99 phase, including leaders in functional MRI pattern analysis, computational models of context and memory, and olfactory stimulation, covering the entire scope of required expertise. Northwestern University has a vibrant cognitive neuroscience community, with the required methodologies strongly represented, as well as all the needed equipment and facilities.