The evolution of memories across wake and sleep

描述(由申请者提供)：我们几乎不记得我们所承诺的记忆。是什么决定了哪些记忆最终将被保留，以及睡眠依赖的记忆巩固在确保它们保留方面的作用尚不清楚。长期目标是了解清醒和睡眠中的离线记忆处理如何相互作用，以控制我们记住什么和忘记什么。这项研究的目的是确定编码后唤醒过程中的记忆处理对睡眠依赖记忆巩固的影响。中心假设是，最近形成的记忆的强度和突出性导致它们以某种方式进行修改，从而增强了它们随后依赖于睡眠的巩固的可能性。(术语“觉醒过程中的记忆修改”(MMW)用于表示训练后清醒过程中的过程，该过程调节这些记忆随后依赖于睡眠的巩固。)进一步假设，MMW通过在睡眠期间触发存储器的重新激活以及通过调节睡眠的结构以增强修改后的存储器的巩固来促进依赖于睡眠的巩固。这项研究的基本原理是，了解清醒过程中离线记忆处理与睡眠依赖记忆巩固的相互作用，以确定我们最终记住的内容，将增加我们对记忆随时间正常演变的理解，并提供线索，说明这些过程和相互作用的崩溃如何导致与一系列精神和神经疾病相关的记忆缺陷。测试这一假说的三个具体目标是：(I)测量新形成的记忆的强度和突出性对其在清醒和睡眠中的保持的影响，期望在睡眠中产生更大的影响；(Ii)使用编码后休息中与记忆相关的大脑活动的功能连接(FC)MRI和高密度(HD)EEG测量来量化MMW，并将这些测量与随后的记忆保持相关联；以及(Iii)确定在特定睡眠阶段的记忆重新激活在调节MMW对记忆保持的影响中所起的作用。目标1和目标3将使用被展示的控制记忆强度和突显性的方法，以及睡眠阶段和记忆重新激活。在训练后的安静休息期间，将使用目标1和目标3的hdEEG和目标2的fcMRI记录与学习相关的大脑活动，并用来确定训练后大脑活动的模式，以预测随后的睡眠依赖记忆保持。这种方法是创新的，因为它代表了第一次尝试对清醒和睡眠过程中睡眠依赖记忆过程的调节进行综合描述。这项研究很有意义，因为它可以增加我们在编码后唤醒和随后的睡眠过程中的记忆处理知识。获得这些知识是确定这些过程中的障碍如何导致精神和神经疾病中的记忆障碍，并开发逆转这些障碍的治疗方法的第一步。

DESCRIPTION (provided by applicant): We remember little of what we commit to memory. What determine which memories will ultimately be retained, and the role of sleep-dependent memory consolidation in ensuring their retention, are unknown. The long-term goal is to understand how offline memory processing in wake and sleep interact to control what we remember and what we forget. The objective of the proposed research is to determine the impact of memory processing during post-encoding wake on sleep-dependent memory consolidation. The central hypothesis is that the strength and salience of recently formed memories lead to their modification in a manner that enhances the likelihood of their subsequent sleep-dependent consolidation. (The term "memory modification during wake" (MMW) is used to denote processes during post-training wake that modulate the subsequent sleep-dependent consolidation of those memories.) It is further hypothesized that MMW facilitates sleep-dependent consolidation by triggering the reactivation of memories during sleep and by modulating the structure of sleep to enhance consolidation of the modified memories. The rationale for this research is that understanding how offline memory processing during wake interacts with sleep-dependent memory consolidation to determine what we ultimately remember will increase our understanding of the normal evolution of memories over time, and provide clues into how breakdowns in these processes and interactions contribute to the memory deficits associated with a range of psychiatric and neurologic disorders. Three Specific Aims test this hypothesis: (i) Measure the impact of the strength and salience of newly formed memories on their retention across wake and sleep, expecting larger effects across sleep; (ii) Use functional connectivity (fc) MRI and high density (hd) EEG measures of memory related brain activity in post- encoding rest to quantify MMW, and correlate these measures with subsequent memory retention; and (iii) Determine the role of memory reactivation during specific sleep stages in mediating the effects of MMW on memory retention. Methods shown to manipulate memory strength and salience, as well as sleep stages and memory reactivation, will be used for Aims 1 and 3. Learning-related brain activity will be recorded during post-training quiet rest with hdEEG in Aims 1 and 3 and with fcMRI for Aim 2, and used to identify patterns of post-training brain activity that predict subsequent sleep-dependent memory retention. This approach is innovative because it represents the first attempt to produce an integrated description of the regulation of sleep-dependent memory processing across wake and sleep. This research is significant because it is can increase our knowledge of memory processing during both post-encoding wake and subsequent sleep. Gaining this knowledge is the first step toward identifying how breakdowns in these processes contribute to the memory dysfunction seen in psychiatric and neurologic disorders, and in developing treatments to reverse these breakdowns.