Brain rhythms-assisted memory enhancement

 描述(申请人提供)：学习是一个漫长的过程，允许在巩固期间修改记忆痕迹。有三种显著的脑振荡模式与固缩有关：海马区尖锐的波纹(SPW-Rs)，新皮质的缓慢振荡，以及丘脑皮质睡眠纺锤体。其中，SPW-R在记忆中的因果作用被最好地理解，因为选择性地消除SPW-R严重损害啮齿动物的记忆性能。然而，尽管纺锤波和慢振荡都与海马SPW-R在时间上相关，但这些新皮质模式是否携带SPW-R或独立发挥其有益作用尚不清楚。不管它们之间的关系如何，我们假设这些模式的选择性增强(或消除)可以改善(或恶化)啮齿动物和人类的记忆表现。因此，我们建议在实验中操纵啮齿动物和人类受试者的这些不同的大脑节奏，并检查这些干预措施如何影响记忆表现。在啮齿类动物中，将进行一系列大规模的海马区和选定的新皮质区域的记录，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，已知该任务依赖于SPW-R。具体地说，SPW-R和纺锤体将通过光遗传实验人工产生，或者这些自发发生的振荡将在闭环TES实验中被增强或中断。在另一组实验中，光遗传学或TES将增强(或减弱)海马SPW-Rs和丘脑皮质纺锤体之间的耦合，并与记忆能力相关。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(结合头皮脑电记录)的应用，以确定慢振荡阶段的时机如何影响健康受试者的睡眠生理和记忆巩固。侵入性实验将包括在接受脑电监测的癫痫手术患者的慢波睡眠期间，对内嗅皮层进行开环和闭环式直接皮质刺激(DC)。分散控制后新皮质慢/纺锤波和海马-新皮质网络连通性的变化将与记忆表现相关。综上所述，这些发现将使人们更清楚地了解这些振荡的大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.