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

睡眠期间振荡经颅直流电刺激对电生理相关性和记忆巩固的作用机制 â 通过术前植入的电极对癫痫患者进行评估

• 批准号: 413459402
• 负责人: Professorin Dr. Agnes Flöel
• 金额: --
• 依托单位: Klinik und Poliklinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/413459402?language=en
• 关键词: Mechanisms; action; oscillatory; transcranial; direct

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.

这项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 分钟小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，我们将使用表面脑电图和侵入性脑电图记录缓慢的皮质振荡 (SO)、纺锤波和波纹。此外，一些记忆任务将在睡眠前学习，并且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。将解决以下问题：a）海马体中 SO 与纺锤体以及纺锤体与波纹之间的分层耦合是否与巩固新记忆的能力相关？ b) so-tDCS 对海马-丘脑-皮质网络，特别是海马波纹活动有什么影响？ c) SO 与纺锤体以及纺锤体与波纹的耦合调节是否与巩固新记忆的能力相关？ d) 刺激结束后，SO、纺锤体和波纹上的 so-tDCS 效应是否持续存在，后效是否取决于夹带？扰动方法与 so-tDCS 和癫痫患者的颅内记录相结合，为评估皮质下振荡（包括海马波纹活动）及其与成功记忆巩固的因果关系提供了独特的可能性。除了进一步加深基本的神经科学知识外，这项研究还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学相关因素的非侵入性、低风险治疗方法，可能会给患者带来症状（记忆巩固）甚至因果（淀粉样蛋白清除）益处，这是一个具有重大临床意义的问题。 然而，在对相关患者群体进行更大规模的临床研究测试这种方法之前，最重要的是在更彻底地了解本研究的潜在机制的基础上优化干预措施。