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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1541126
This article is part of the Research TopicArtificial Intelligence-based Diagnosis and Neuromodulation in Neurological and Psychiatric DiseasesView all 8 articles
Cross-Frequency Neuromodulation: Leveraging Theta-Gamma Coupling for Cognitive Rehabilitation in MCI Patients
Provisionally accepted
Xiao Yuan1,2
Zhilan Tu2
Renren Li1,2
Chenxi Pan1,2
Jing Ma1,2
Meng Liu3
Dan Yang2
Hualan Yang2Fangyun Li2Zhi Bie2
Yixuan Ku4*
Yunxia Li1,2*- 1Tongji Hospital Affiliated to Tongji University, Shanghai, Shanghai, China
- 2Shanghai Pudong Hospital, Shanghai, Shanghai Municipality, China
- 3Department of Neurology, Changhai Hospital, Shanghai, Shanghai Municipality, China
- 4Department of Psychology, Sun Yat-sen University, Guang Dong, China
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Background: Theta-gamma coupling (TGC) plays a critical role in working memory (WM) processing, yet it is often dysregulated in mild cognitive impairment (MCI). While gamma activity is known to support cognitive functions, excessive gamma activity in MCI may impair WM. This study investigates how repetitive transcranial magnetic stimulation (rTMS) modulates gamma activity by regulating TGC to enhance WM in MCI patients.Objectives: This study aims to explore the effects of rTMS on WM by targeting TGC and reducing occipital gamma activity under varying WM loads.Methods: We recruited 34 participants, including 20 MCI patients and 14 healthy elderly controls (HC), from Shanghai Tongji Hospital. All participants received a one-week intervention of 10Hz rTMS targeting the left dorsolateral prefrontal cortex (DLPFC). Gamma power and TGC were measured using electroencephalography (EEG), and WM performance (accuracy, capacity, reaction time) was assessed through a visual WM paradigm.Results: The rTMS intervention significantly reduced gamma power in left occipital region, correlating with improved WM performance (enhanced accuracy, capacity, and faster reaction time). Changes in TGC between left frontal theta and occipital gamma oscillations were significantly associated with WM performance, indicating a neurocognitive link.Conclusion: This study highlights rTMS as a non-invasive tool for enhancing WM by modulating TGC and reducing gamma power. These findings suggest a promising strategy for improving cognitive function in MCI, with significant clinical implications for cognitive optimization and therapeutic interventions.
Keywords: Transcranial Magnetic Stimulation, theta-gamma coupling, working memory, Mild Cognitive Impairment, cognitive enhancement
Received: 10 Dec 2024; Accepted: 17 Apr 2025.
Copyright: © 2025 Yuan, Tu, Li, Pan, Ma, Liu, Yang, Yang, Li, Bie, Ku and Li. 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:
Yixuan Ku, Department of Psychology, Sun Yat-sen University, Guang Dong, 510006, China
Yunxia Li, Shanghai Pudong Hospital, Shanghai, 200032, Shanghai Municipality, China
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.