Mechanisms of action of oscillatory transcranial direct current stimulation during sleep on electrophysiological correlates and memory consolidation – assessed via presurgically implanted electrodes in patients with epilepsy

本研究的主要目的是阐明睡眠依赖性记忆巩固的机制。我们将评估术前植入颅电极治疗药物难治性癫痫的患者。在平衡交叉设计中，我们将在90分钟的小睡期间使用慢振荡经颅阳极直流刺激（sotDCS）或假刺激。在睡眠过程中，我们将使用表面脑电图和有创脑电图记录慢皮层振荡（SO）、纺锤波和波纹。此外，一些记忆任务将在睡眠前学习，睡眠依赖性记忆巩固将在睡眠后作为刺激条件的函数进行评估。下面的问题将被解决：a)在海马体中，梭状到纺锤体和纺锤体到波纹之间的层次耦合是否与巩固新记忆的能力有关？b) so-tDCS对海马-丘脑-皮质网络，特别是海马波纹活动的影响是什么？c) so -to-spindle和spindle -to-ripple的耦合调制是否与巩固新记忆的能力有关？d)刺激结束后，SO - tdcs对SO、梭形波和波纹的影响是否持续存在，其后续影响是否取决于夹带？结合微扰法与so-tDCS和癫痫患者的颅内记录，为评估皮层下振荡（包括海马波纹活动）与成功记忆巩固的因果关系提供了独特的可能性。除了进一步提高基本的神经科学知识，这项研究将使我们能够评估和提高sot-DCS在改善衰老和早期神经退行性疾病中睡眠依赖性记忆巩固方面的治疗潜力。So-tDCS作为一种针对睡眠及其神经生理相关的无创、低风险治疗方法，可能会给患者带来症状性（记忆巩固）甚至可能是因果性（淀粉样蛋白清除）的益处，这是一个具有重要临床意义的问题。然而，在对相关患者队列进行更大规模的临床研究之前，最重要的是在对本研究的潜在机制有更深入的了解的基础上，优化干预措施。

The main aim of this study is to elucidate the mechanisms underlying sleep-dependent memory consolidation. We will evaluate patients implanted presurgically with intracranial electrodes for treatment of pharmacorefractory epilepsy. In a balanced cross-over design, we will apply either slow oscillatory transcranial anodal direct current stimulation (sotDCS) or sham stimulation during a 90 min nap. During sleep, we will record slow cortical oscillations (SO), spindles, and ripples, using surface EEG and invasive EEG. Moreover, several memory tasks will be learned before sleep, and sleep-dependent memory consolidation will be evaluated after sleep as a function of the stimulation condition. The following questions will be addressed: a) Is the hierarchical coupling between SO-to- spindles, and spindles-to-ripples in the hippocampus, associated with the ability to consolidate novel memories? b) What is the impact of so-tDCS on hippocampal-thalamo-cortical networks, and particularly hippocampal ripple-activity? c) Is the modulation of coupling of SO-to-spindles, and spindles-to-ripples, associated with the ability to consolidate novel memories? d) Does the so-tDCS-Effects on SO, spindles, and ripples persist after end of stimulation, and do the after-effects depend on entrainment? Combination of a perturbation approach with so-tDCS, and intracranial recordings in epilepsy patients offers the unique possibility to assess subcortical oscillations including hippocampal ripple-activity with regard to their causal relevance for successful memory consolidation. In addition to furthering basic neuroscientific knowledge, the study will allow us to evaluate and to improve the therapeutic potential of sot-DCS with regard to improving sleep-dependent memory consolidation in aging and in incipient neurodegenerative disease. So-tDCS, as a non-invasive and low-risk treatment approach that targets sleep and its neurophysiological correlates, may convey symptomatic (memory consolidation) and possibly even causal (amyloid-clearance) benefit to patients, an issue of great clinical relevance. However, before testing this approach in larger clinical studies in relevant patient cohorts, it is paramount to optimize the intervention, on the basis of a more thorough understanding of the underlying mechanisms that will result from the present study.