Mirjalili Mina, Palamarchuk Iryna S, Brooks Heather, Zomorrodi Reza, Melichercik Ashley, Wang Wei, Nestor Sean M, Blumberger Daniel M, Datta Abhishek, Bowie Christopher, Mdawar Bernadette, Hynynen Kullervo, Kumar Sanjeev, Rajji Tarek K
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Adult Neurodevelopment and Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Front Psychiatry. 2025 Jun 2;16:1565881. doi: 10.3389/fpsyt.2025.1565881. eCollection 2025.
Mild Cognitive Impairment (MCI) is a clinical prodromal stage of Alzheimer's disease. Enhancing executive functions in patients with MCI could optimize cognitive compensatory mechanisms and slow cognitive decline. The prefrontal cortex (PFC) and its connections to the hippocampus support executive functions, including working memory. Transcranial alternating current stimulation (tACS) can modulate these connections by engaging theta-gamma coupling (TGC) and may thereby strengthen working memory. This study, "tACS to engage theta-gamma coupling and enhance working memory in MCI" (tACS-MCI), will assess the feasibility and cognitive effects of EEG and MRI-guided individualized tACS. The stimulation will target the prefrontal and temporal cortices in 20 MCI participants. Participants will be randomized to receive either individualized tACS or sham tACS for 10 days. tACS individualization will involve adjusting the theta frequency, tACS electrode locations, and current intensity for each participant. Cognitive and functional assessments will occur at baseline and post-intervention. We aim to determine: 1) the feasibility of individualized tACS in MCI, including recruitment and retention; 2) whether tACS engages TGC by assessing its increase in response to tACS; and 3) changes in N-back working memory performance following tACS, as well as whether changes in TGC mediate the changes in performance. The tACS-MCI study will employ an EEG and MRI-guided individualized approach to promote synchronization between frontal and temporal cortices, using participant's unique brain structure and neurophysiology. We aim to assess the feasibility of this novel intervention as a potential approach to more effectively prevent cognitive decline.
轻度认知障碍（MCI）是阿尔茨海默病的临床前驱阶段。增强MCI患者的执行功能可以优化认知补偿机制并减缓认知衰退。前额叶皮质（PFC）及其与海马体的连接支持包括工作记忆在内的执行功能。经颅交流电刺激（tACS）可以通过参与theta-γ耦合（TGC）来调节这些连接，从而可能增强工作记忆。这项名为“tACS参与theta-γ耦合并增强MCI患者的工作记忆”（tACS-MCI）的研究将评估脑电图（EEG）和磁共振成像（MRI）引导下的个体化tACS的可行性和认知效果。刺激将针对20名MCI参与者的前额叶和颞叶皮质。参与者将被随机分为接受个体化tACS或假tACS，为期10天。tACS个体化将包括为每个参与者调整theta频率、tACS电极位置和电流强度。认知和功能评估将在基线和干预后进行。我们的目标是确定：1）个体化tACS在MCI中的可行性，包括招募和保留情况；2）tACS是否通过评估其对tACS的反应增加来参与TGC；3）tACS后N-back工作记忆表现的变化，以及TGC的变化是否介导了表现的变化。tACS-MCI研究将采用EEG和MRI引导的个体化方法，利用参与者独特的脑结构和神经生理学来促进额叶和颞叶皮质之间的同步。我们旨在评估这种新型干预作为一种更有效预防认知衰退的潜在方法的可行性。
