Brain rhythms-assisted memory enhancement

 描述（由申请人提供）：学习是一个漫长的过程，它允许在巩固期间修改记忆痕迹。三个突出的振荡脑模式与巩固有关：海马尖波波纹（SPW-R），新皮层的缓慢振荡和丘脑皮层睡眠纺锤波。其中，SPW-R在记忆中的因果作用是最好理解的，因为选择性消除SPW-R严重损害啮齿动物的记忆表现。然而，虽然纺锤波和慢振荡在时间上与海马SPW-Rs相关，但尚不清楚这些新皮层模式是否会影响SPW-Rs或独立发挥其有益作用。不管它们之间的关系如何，我们假设选择性地增强（或消除）这些模式可以改善（或恶化）啮齿动物和人类的记忆表现。因此，我们建议在啮齿动物和人类受试者中实验性地操纵这些不同的脑节律，并研究这些干预措施如何影响记忆表现。在啮齿动物中，将进行海马和选定的新皮层区域的一系列大规模记录，结合光遗传学和经颅电刺激（TES）实验。这些电路扰动的行为影响将在记忆任务中进行评估，已知依赖于SPW-R。具体来说，SPW-R和纺锤体将通过光遗传学实验人工产生，或者这些自发发生的振荡将在闭环TES实验中增强或中断。在另一组实验中，海马SPW-R和丘脑皮质纺锤体之间的耦合将通过光遗传学或TES加强（或减弱），并与记忆表现相关。人体研究包括非侵入性和侵入性干预策略。非侵入性实验将涉及开环和闭环TES（结合头皮EEG记录）的应用，以确定慢振荡阶段的时间如何影响健康受试者的睡眠生理学和记忆巩固。侵入性实验将涉及接受颅内EEG监测的癫痫手术患者在慢波睡眠期间内嗅皮层的开环和闭环直接皮层刺激（DCS）。DCS后新皮层慢/纺锤波振荡和大脑皮层-新皮层网络连接的变化将与记忆表现相关。总之，这些发现将使我们更清楚地了解这些振荡脑模式在记忆巩固中的因果作用，并为记忆障碍提供潜在的治疗方法。

 DESCRIPTION (provided by applicant): Learning is a protracted process, which allows for modification of the memory trace during the consolidation period. Three prominent oscillatory brain patterns have been linked to consolidation: hippocampal sharp wave ripples (SPW-Rs), slow oscillations of the neocortex, and thalamocortical sleep spindles. Of these, the causal role of SPW-Rs in memory is best understood, as selective elimination of SPW-Rs severely impairs memory performance in rodents. However, while both spindles and slow oscillations are temporally correlated with hippocampal SPW-Rs, it is unclear whether these neocortical patterns entrain SPW-Rs or exert their beneficial effects independently. Irrespective of their relationships, we hypothesize that selective enhancement (or elimination) of these patterns can improve (or deteriorate) memory performance in rodents and humans. Accordingly, we propose to experimentally manipulate these distinct brain rhythms in both rodents and human subjects and examine how such interventions affect memory performance. In rodents, a series of large-scale recordings in both hippocampus and selected neocortical areas, combined with optogenetics and transcranial electrical stimulation (TES) experiments, will be performed. The behavioral impact of these circuit perturbations will be assessed in a memory task, known to be dependent on SPW-Rs. Specifically, SPW-Rs and spindles will be artificially generated through optogenetic experiments, or these spontaneously occurring oscillations will be enhanced or interrupted in closed-loop TES experiments. In another set of experiments, coupling between hippocampal SPW-Rs and thalamocortical spindles will be strengthened (or weakened) by optogenetics or TES and correlated with memory performance. The human studies include both non-invasive and invasive intervention strategies. Non-invasive experiments will involve the application of open- and closed-loop TES (combined with scalp EEG recordings) to determine how the timing to the phase of slow oscillations affects sleep physiology and memory consolidation in healthy subjects. The invasive experiments will involve both open- and closed-loop direct cortical stimulation (DCS) of the entorhinal cortex during slow wave sleep in patients undergoing intracranial EEG monitoring for epilepsy surgery. Changes in neocortical slow/spindle oscillations and hippocampal-neocortical network connectivity after DCS will be correlated with memory performance. Taken together, the findings will provide a clearer understanding of the causal role of these oscillatory brain patterns in memory consolidation and offer potential treatments for memory disorders.