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。我们将对术前植入颅内电极治疗药物难治性癫痫的患者进行评价。在平衡交叉设计中，我们将在90分钟的午睡期间应用缓慢振荡经颅阳极直流电刺激（sotDCS）或假刺激。在睡眠期间，我们将使用表面EEG和侵入性EEG记录缓慢的皮层振荡（SO）、纺锤波和波纹。此外，将在睡眠前学习几个记忆任务，并在睡眠后评估睡眠依赖性记忆巩固作为刺激条件的函数。以下问题将得到解决：（1）海马体中SO到纺锤体以及纺锤体到波纹之间的层级耦合是否与巩固新记忆的能力有关？B）so-tDCS对海马-丘脑-皮层网络，特别是海马波纹活动的影响是什么？c）SO-纺锤波和纺锤波-波纹耦合的调制是否与巩固新记忆的能力有关？d）在刺激结束后，SO、纺锤波和波纹上的so-tDCS效应是否持续存在，并且后效是否取决于夹带？结合干扰方法与so-tDCS，颅内记录癫痫患者提供了独特的可能性，以评估皮质下振荡，包括海马波纹活动方面的因果关系，成功的记忆巩固。除了促进基本的神经科学知识，这项研究将使我们能够评估和改善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学相关性的非侵入性和低风险治疗方法，可能会向患者传达症状性（记忆巩固）甚至可能是因果性（淀粉样蛋白清除）的益处，这是一个具有重大临床意义的问题。 然而，在相关患者队列的大型临床研究中测试这种方法之前，最重要的是在对本研究产生的潜在机制进行更透彻理解的基础上优化干预。

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.