The evolution of memories across wake and sleep

描述（由申请人提供）：我们记得很少我们承诺的记忆。是什么决定了哪些记忆最终会被保留，以及睡眠依赖的记忆巩固在确保记忆保留中的作用，都是未知的。长期目标是了解清醒和睡眠时的离线记忆处理如何相互作用，以控制我们记住和忘记的内容。本研究的目的是确定编码后唤醒过程中记忆处理对睡眠依赖性记忆巩固的影响。核心假设是，最近形成的记忆的强度和显著性导致它们以一种方式进行修改，这种方式增加了它们随后依赖睡眠的巩固的可能性。(The术语“觉醒期间的记忆修改”（MMW）用于表示训练后觉醒期间的过程，这些过程调节了这些记忆随后的睡眠依赖性巩固。）进一步假设MMW通过在睡眠期间触发记忆的重新激活和通过调节睡眠结构以增强修改的记忆的巩固来促进睡眠依赖性巩固。这项研究的基本原理是，了解清醒时离线记忆处理如何与睡眠依赖性记忆巩固相互作用，以确定我们最终记住的内容，将增加我们对记忆随时间推移的正常演变的理解，并提供线索，了解这些过程和相互作用的破坏如何导致与一系列精神和神经系统疾病相关的记忆缺陷。 三个特定目的测试该假设：（i）测量新形成的记忆的强度和显著性对它们在清醒和睡眠期间的保持的影响，预期在睡眠期间的影响更大;（ii）使用编码后休息中的记忆相关脑活动的功能连接性（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）确定特定睡眠阶段记忆再激活在介导MMW对记忆保持的影响中的作用。已证明可操纵记忆强度和显著性以及睡眠阶段和记忆再激活的方法将用于目标1和3。在目标1和3中，将在训练后安静休息期间使用hdEEG记录学习相关脑活动，在目标2中使用fcMRI记录学习相关脑活动，并用于识别预测后续睡眠依赖性记忆保留的训练后脑活动模式。 这种方法是创新的，因为它代表了第一次尝试产生一个完整的描述睡眠依赖的记忆处理的监管跨越清醒和睡眠。这项研究意义重大，因为它可以增加我们对编码后唤醒和随后睡眠期间记忆处理的了解。获得这些知识是确定这些过程中的故障如何导致精神和神经系统疾病中的记忆功能障碍以及开发逆转这些故障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.