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记忆巩固的机制。我们将评估术前植入颅内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分钟的午睡中应用慢振荡经颅阳极直流电刺激(SotDC)或假刺激。在睡眠期间，我们将使用体表脑电和侵袭性脑电记录缓慢的皮质振荡(SO)、纺锤波和波纹。此外，睡眠前会学习几个记忆任务，睡眠后依赖睡眠的记忆巩固将作为刺激条件的函数进行评估。以下问题将被解决：a)在海马体中的梭形和纺锤形波纹之间的等级耦合是否与巩固新记忆的能力有关？B)SO-tDCs对海马-丘脑-皮质网络，特别是对海马波活动的影响是什么？C)主轴与主轴、主轴与波纹之间的耦合是否与巩固新奇记忆的能力有关？D)刺激结束后，SO-tDCS对SO、纺锤波和波纹的影响是否持续，以及后遗症是否依赖于夹带？微扰法与SO-TDC和癫痫患者的颅内记录相结合，为评估包括海马波活动在内的皮质下振荡与成功记忆巩固的因果相关性提供了独特的可能性。除了进一步加深基本的神经科学知识，这项研究还将使我们能够评估和改进SOT-DC在改善老年和早期神经退行性疾病中睡眠依赖记忆巩固方面的治疗潜力。因此，作为一种针对睡眠及其神经生理学相关的非侵入性和低风险的治疗方法，可能会向患者传达症状(记忆巩固)甚至因果(淀粉样蛋白清除)的好处，这是一个具有重要临床意义的问题。然而，在相关患者队列的更大临床研究中测试这种方法之前，在更彻底地了解本研究将产生的潜在机制的基础上，优化干预是至关重要的。

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.