An assembly-line model of sleep, dreaming and memory enhancement: investigating the coordinated roles of REM and nonREM sleep in human memory consolidation

快速眼动（REM）和非快速眼动（NREM）睡眠都积极地有助于记忆改善，某些振荡事件，如睡眠纺锤波（11-16 Hz EEG活动的爆发），是这种活动的可靠生物标志物。关于梦是否在记忆中起作用，特别是梦对新记忆的重放是否也构成这样一种生物标志物，证据更加复杂。我们最近重复了NREM和REM睡眠以互补的方式影响记忆的发现，更重要的是，首次表明NREM睡眠纺锤波，REM睡眠量以及做梦的长度和内容都是相互关联的措施。这些相关性在第三个睡眠周期中优先表现得很强，这表明这是一个特别有利于记忆可塑性的时间，这种现象以前只在啮齿动物中表现出来。作为新的发现，这些NREM-REM-做梦的相关性需要被复制，扩展到其他记忆改善的睡眠措施，并使用允许得出因果结论的工具进行评估。拟议的研究旨在通过仔细复制和使用经过验证的目标记忆再激活（TMR）方法在睡眠期间增强记忆来实现这些目标。在TMR中，音调在任务期间出现，然后在NREM睡眠期间再次出现;这些声音可能会重新激活在任务学习期间形成的神经回路。我们将通过在NREM睡眠中呈现与任务相关的音调，并测量NREM，REM和做梦措施如何改变来增强学习。在一个典型的实验中，我们的任务将在虚拟现实（VR）环境中完成，并将涉及导航迷宫。我们将评估，在NREM睡眠中，纺锤波活动是否增加;在REM睡眠中，眼球运动是否改变;以及在梦境报告中，VR任务回放是否出现。如果睡眠周期3是记忆处理的特权窗口，那么对于在周期3期间（与周期2或4期间相比）播放TMR声音的受试者，任务改善和睡眠/梦变化应该最大。这项研究将对研究睡眠和记忆，做梦或TMR的人感兴趣，并应提供有关睡眠如何控制记忆储存的见解。它将具有特殊的相关性，以显示定时和刺激睡眠事件如何优化记忆，从而更精确地增强学习。研究结果还可能有助于解释梦是否以及如何与记忆有关，即，通过阐明它与睡眠纺锤波的关系，以及它是否会重放新学习的元素。因此，这项工作可能会导致对记忆和睡眠的更深刻的理解，并支持越来越多的加拿大人通过获得更多的睡眠来改善他们的认知功能。这种类型的研究可能会导致开发基于睡眠的方法来增强，优化和恢复记忆，并在面临与年龄相关或与疾病相关的衰退时保护它。

Both rapid eye movement (REM) and nonREM (NREM) sleep actively contribute to memory improvement and certain oscillatory events, such as sleep spindles (bursts of 11-16 Hz EEG activity), are reliable biomarkers of this activity. Evidence is more mixed as to whether dreaming plays a role in memory and, especially, whether dream replays' of new memories also constitute such a biomarker. We recently replicated findings that NREM and REM sleep influence memory in a complementary fashion and, more importantly, showed for the first time that NREM sleep spindles, amount of REM sleep and dreaming length and content are all inter-correlated measures. These correlations were preferentially strong for the third sleep cycle, suggesting that it is a time particularly conducive to memory plasticity, a phenomenon previously shown only for rodents. As new discoveries, these NREM-REM-dreaming correlations need to be replicated, extended to other sleep measures of memory improvement, and evaluated with tools that permit drawing conclusions about cause and effect. The proposed research aims to achieve these objectives by careful replication and by enhancing memory during sleep using a validated, targeted memory reactivation (TMR), method. With TMR, tones are presented during a task and then again during NREM sleep; the sounds presumably reactivate neural circuits that were formed during task learning. We will enhance learning by presenting task-associated tones in NREM sleep and measuring how NREM, REM and dreaming measures are altered. In a typical experiment, our task will be completed in a virtual reality (VR) setting and will involve navigating a maze. We will assess, in NREM sleep, if spindle activity increases; in REM sleep, if eye movements change; and, in dream reports, if VR task replays appear. If sleep cycle 3 is a privileged window for memory processing, then task improvement and sleep/dream changes should be greatest for subjects to whom TMR sounds are played during cycle 3 (vs. during cycles 2 or 4).***The research will be of interest to persons studying sleep and memory, dreaming or TMR and should provide insights into how sleep controls memory storage. It will have a particular relevance for showing how timing and stimulating sleep episodes can optimize memory and thus enhance learning with greater precision. Findings may also help explain if and how dreaming is implicated in memory, i.e., by clarifying its relationship to sleep spindles and whether it replays elements of new learning. Thus, the work may lead to a more profound understanding of both memory and sleep and support a growing outreach to Canadians to improve their cognitive functioning by getting more sleep. This type of research may lead to the development of sleep-based methods for enhancing, optimizing and rehabilitating memory and in protecting it in the face of age-related or illness-related decline.