STUDY PROTOCOL article
Front. Psychiatry
Sec. Neurostimulation
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1565881
Individualized Frequency and Montage tACS to Engage Theta-Gamma Coupling and Enhance Working Memory in Mild Cognitive Impairment
Provisionally accepted
Mina Mirjalili1
Iryna S. Palamarchuk1
Heather Brooks1
Reza Zomorrodi1
Ashley Melichercik1
Wei Wang1Sean M Nestor2Daniel M Blumberger1
Abhishek Datta3
Christopher Bowie1
Bernadette Mdawar1
Kullervo Hynynen2
Sanjeev Kumar1
Tarek K Rajji4*- 1The Centre for Addiction and Mental Health, Toronto, Canada
- 2Sunnybrook Health Science Centre, University of Toronto, Toronto, Ontario, Canada
- 3Soterix Medical Inc., New York, New York, United States
- 4University of Texas Southwestern Medical Center, Dallas, Texas, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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.
Keywords: Mild Cognitive Impairment, theta-gamma coupling, individualization, TACs, working memory
Received: 23 Jan 2025; Accepted: 12 May 2025.
Copyright: © 2025 Mirjalili, Palamarchuk, Brooks, Zomorrodi, Melichercik, Wang, Nestor, Blumberger, Datta, Bowie, Mdawar, Hynynen, Kumar and Rajji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Tarek K Rajji, University of Texas Southwestern Medical Center, Dallas, 75390, Texas, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.