Ladenbauer Julia, Ladenbauer Josef, Külzow Nadine, de Boor Rebecca, Avramova Elena, Grittner Ulrike, Flöel Agnes
Department of Neurology and
NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany.
J Neurosci. 2017 Jul 26;37(30):7111-7124. doi: 10.1523/JNEUROSCI.0260-17.2017. Epub 2017 Jun 21.
Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO; 0.5-1 Hz) and thalamocortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep-state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in nine male and seven female human patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in EEG recordings. Moreover, visual declarative memory was improved by so-tDCS compared with sham stimulation and was associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and memory deficits in MCI patients and advance our understanding of offline memory consolidation. In the light of increasing evidence that sleep disruption is crucially involved in the progression of Alzheimer's disease (AD), sleep appears as a promising treatment target in this pathology, particularly to counteract memory decline. This study demonstrates the potential of a noninvasive brain stimulation method during sleep in patients with mild cognitive impairment (MCI), a precursor of AD, and advances our understanding of its mechanism. We provide first time evidence that slow oscillatory transcranial stimulation amplifies the functional cross-frequency coupling between memory-relevant brain oscillations and improves visual memory consolidation in patients with MCI.
阿尔茨海默病（AD）不仅涉及记忆功能丧失，还伴有睡眠生理的显著恶化，这在轻度认知障碍（MCI）阶段就已很明显。睡眠期间的皮层慢振荡（SO；0.5 - 1赫兹）和丘脑皮层纺锤波活动（12 - 15赫兹）及其时间协调性，被认为对记忆形成至关重要。我们研究了在白天小睡期间以睡眠状态依赖方式应用的慢振荡经颅直流电刺激（so - tDCS）调节这两种活动模式以及与睡眠相关的记忆巩固的潜力，研究对象为9名男性和7名女性MCI患者。刺激显著增加了整体SO和纺锤波功率，在SO上升期放大了纺锤波功率，并导致脑电图记录中SO与纺锤波功率波动之间更强的同步性。此外，与假刺激相比，so - tDCS改善了视觉陈述性记忆，且与更强的同步性相关。这些发现表明了一种耐受性良好的治疗方法，可用于治疗MCI患者的睡眠生理紊乱和记忆缺陷，并增进了我们对离线记忆巩固的理解。鉴于越来越多的证据表明睡眠中断在阿尔茨海默病（AD）进展中起关键作用，睡眠似乎是这种病理状态下一个有前景的治疗靶点，尤其是用于对抗记忆衰退。本研究证明了在轻度认知障碍（MCI）患者睡眠期间一种非侵入性脑刺激方法的潜力，MCI是AD的前驱阶段，并增进了我们对其机制的理解。我们首次提供证据表明，慢振荡经颅刺激增强了与记忆相关的脑振荡之间的功能性跨频耦合，并改善了MCI患者的视觉记忆巩固。
