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Updated: Apr 28, 2026
Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method
Published on: August 2, 2021
High-intensity transcranial alternating current stimulation enhances functional connectivity of subcortical regions
1Beijing Key Laboratory of Intelligent Drug Research and Development for Mental Disorders, National Clinical Research Center for Mental Disorders, National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China; Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China; Beijing Key Laboratory of Clinical Engineering Solutions for Mental Health, Beijing, China.
Background:
Major depressive disorder (MDD) is associated with dysregulation of large-scale brain networks, particularly those supporting emotional regulation and cognitive control. Transcranial alternating current stimulation (tACS) has shown antidepressant potential, but its neurophysiological effects remain incompletely understood. This study investigates the effects of 77.5 Hz high-intensity tACS on functional connectivity (FC) within subcortical-limbic circuits in MDD.
Methods:
In a double-blind, randomized, sham-controlled study, 66 MDD patients were randomized to receive either active or sham tACS, with 31 patients completing the 4-week treatment and underwent functional magnetic resonance imaging scans. Seed-based FC analysis was performed to explore the impact of tACS on the subcortical regions.
Results:
Flexible factorial analysis revealed significant Group × Time interaction effects in the FC between dorsal anterior cingulate cortex and right middle frontal gyrus (pFWE = 0.022), and between pregenual anterior cingulate cortex and right superior parietal lobule (pFWE = 0.008). Post-hoc analyses indicated that, over the 4-week treatment period, the active group showed increased FC whereas the sham group showed decreased FC (all p < 0.05). However, no significant Group × Time interaction was observed for depressive symptoms, and no significant correlations were found between FC changes and symptom improvement.
Conclusion:
High-intensity 77.5 Hz tACS was associated with changes in FC within emotion-regulation networks in MDD. However, these neural effects were not accompanied by differential clinical improvements or correlations with symptoms change.
Limitations:
The relatively small sample size, high attrition rate, concurrent SSRI treatment, and absence of long-term follow-up limit the generalizability of these findings.
