Mediotemporal cross-frequency coupling during sleep and its relevance for memory consolidation

以往的研究表明，脑电交叉频率耦合是支持工作记忆和长时记忆中信息表征的重要机制。根据一个有影响力的模型，工作记忆中的多个项目由叠加在theta振荡上的伽马周期来表示，这种振荡表示被转移到长期记忆中。这种神经编码将通过theta相位对伽马幅度的调制以及伽马和theta振荡之间的相位耦合来反映。另一方面，记忆形成的两个阶段模型假设，长期记忆在睡眠期间重新激活和巩固，涉及从海马体到新皮质部位的信息传输。根据这两个模型的含义，跨频耦合模式的重新激活，特别是在中颞脑区，应该发生在睡眠期间，这类似于编码相关的模式，并支持记忆巩固。然而，目前还缺乏支持这一预测的直接证据。因此，植入深度电极的癫痫患者将获得术前评估的颅内夜间睡眠和午睡记录。不同的联想长时记忆任务将在夜间睡眠前、小睡前和小睡后的短暂编码阶段、夜间睡眠后的提取阶段以及小睡后的编码阶段进行。将针对不同的睡眠阶段和记录位置(例如，海马体、鼻腔、颞侧等)来评估相位幅度和相位耦合。并探讨与记忆巩固有关的睡眠成分，如慢波、睡眠纺锤波、波纹等的相互关系。此外，个体行为巩固测量和神经心理评分将与交叉耦合测量和睡眠图形元素的出现相关。将通过多元回归分析来评估和比较不同的颅内脑电指标预测记忆表现的能力，特别是交叉耦合指标与图形元素的能力。这些数据将阐明，在睡眠期间发生了哪些中时跨频耦合模式，以及这些耦合模式是否与记忆巩固有关。

Previous research suggests that EEG cross-frequency coupling is an important mechanism supporting the representation of information in working and long-term memory. According to an influential model multiple items are represented in working memory by gamma cycles superposed on theta oscillations and this oscillatory representation is transferred to long-term memory. This neural code would be reflected by a modulation of gamma amplitudes by theta phases and by phase-phase coupling between gamma and theta oscillations. On the other hand, two stage models of memory formation postulate that long-term memories are reactivated and consolidated during sleep involving an information transfer from the hippocampus to neocortical sites. Based on the implications of both models, a reactivation of cross-frequency coupling patterns, particularly in mediotemporal brain regions, should occur during sleep, which resemble encoding-related patterns and support memory consolidation. However, direct evidence for this prediction is yet lacking. Therefore, intracranial night sleep and nap recordings will be obtained from epilepsy patients undergoing presurgical evaluation with implanted depth electrodes. Different associative long-term memory tasks will be conducted with encoding phases before night sleep, as well as before and briefly after the naps, and retrieval phases after night sleep, as well as after the naps. Phase amplitude and phase-phase coupling will be evaluated with regard to different sleep stages and recording sites (e.g. hippocampal, rhinal, temporo-lateral etc.) and the interrelation with sleep graphoelements related to memory consolidation, such as slow waves, sleep spindles and ripples will be investigated. Furthermore, individual behavioral consolidation measures and neuropsychological scores will be correlated to the crosscoupling measures and the occurrence of sleep graphoelements. The capability of the different intracranial EEG measures to predict memory performance, in particular crosscoupling measures versus graphoelements, will be evaluated and compared by multiple regression analyses. These data will elucidate, which patterns of mediotemporal crossfrequency coupling occur during sleep and whether these coupling patterns are relevant for memory consolidation.