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

项目摘要 该项目的R00阶段将在加州大学欧文分校生物科学学院神经生物学和行为系进行。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记忆来实现的，从而加强了支持记忆的神经基础设施。睡眠相关巩固的理论描述侧重于记忆被独立强化的过程，但在自然环境中，个人记忆从来不存在于真空中。重要的是，记忆在编码过程中嵌入的环境控制着提取和决策行为。然而，背景在合并中的作用还没有得到直接的探讨。该项目的目标是通过开发一个基于经验的框架来提高我们对记忆过程的基本理解，该框架统一了环境对记忆的影响模型和与睡眠相关的巩固模型(目标1)。此外，该框架将用于支持翻译干预，以改变睡眠期间的记忆。目标2将尝试在睡眠期间恢复抑制环境，以有效地削弱记忆。这一努力将为未来缓解创伤后应激障碍临床人群记忆相关症状的工作提供指导。 该项目将结合选择性地偏向记忆重新激活的新技术；从神经数据中破译与记忆相关内容的机器学习算法；以及监测不同区域和时间尺度上的大脑连接和节律的神经科学方法。对于目标1，将使用功能磁共振模式分析技术来揭示在自然、未受干扰的睡眠期间，环境、个人记忆或两者是否重新激活。对于目标2，使用的主要行为操作将是目标记忆重新激活，即在睡眠期间不引人注目地呈现与学习相关的刺激，从而增强记忆。在目标2中包含的一项实验中，个体记忆将在睡眠期间嵌入到先前无关的背景中：重新激活的“抑制”背景(由气味提示)将呈现与个体记忆相关联的听觉线索，假设在睡眠期间削弱个体记忆。另一项实验将使用类似的技术来尝试和缓解健康参与者在创伤操作后的痛苦侵入性记忆。综上所述，这些实验应该会为更丰富地了解睡眠期间记忆重新激活的程度铺平道路，并为有选择地操纵睡眠的特定内容干预铺平道路，从而改善心理健康和福祉。

Project Summary The R00 phase of this project will be conducted at the University of California, Irvine in the Department of Neurobiology and Behavior, School of Biological Sciences. 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). Additionally, the framework will be used to support translational interventions to alter memories during sleep. Aim 2 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. This project will combine novel techniques to selectively bias memory reactivation; machine-learning algorithms to decipher memory-related content from neural data; and neuroscientific methods for monitoring brain connectivity and rhythms in different regions and timescales. For Aim 1, functional MRI pattern analysis techniques will be used to reveal whether contexts, individual memories or both are reactivated during natural, undisturbed sleep. For Aim 2, the main behavioral manipulation used will be targeted memory reactivation, the unobtrusive presentation of learning-related stimuli during sleep, thereby enhancing memory. In one experiment included in Aim 2, individual memories will be embedded 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. An additional experiment will use a similar technique to try and alleviate distressful intrusive memories following a trauma manipulation in healthy participants. Taken together, these experiments should pave the way towards a richer understanding of the extent of memory reactivation during sleep, and toward content-specific interventions to selectively manipulate sleep, thereby improving mental health and wellbeing.