Modulating positive self-referential processing by 40 Hz tACS in individuals with subthreshold depression: A double-blind, sham-controlled study

• Published in: Journal of psychiatric research Vol. 186; pp. 108 - 115
• Main Authors: Yao, Ziqing, Tu, Pui Yi, Zuo, Xibo, Wei, Jinwen, Hu, Xiaoqing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2025
• Subjects: Adult; Depression - physiopathology; Depression - therapy; Double-Blind Method; Female; Humans; Male; Prefrontal Cortex - physiology; Self Concept; Transcranial Direct Current Stimulation - methods; Young Adult
• ISSN: 0022-3956; 1879-1379; 1879-1379
• DOI: 10.1016/j.jpsychires.2025.04.004

A positive self-evaluation is essential to mental well-being. Despite of its importance, little is known how to modulate or enhance positive self-evaluation. Gamma-frequency (40 Hz) transcranial alternating current stimulation (tACS) has been shown to promote emotion regulation and memory, which may foster positive self-evaluations. Here, we investigated whether 40 Hz tACS over the medial prefrontal cortex (mPFC), a key brain region implicating self-referential processing, could enhance positive self-evaluation among individuals exhibiting subthreshold depression. We hypothesized that the 40 Hz stimulation would enhance self-evaluation. Participants with subthreshold depression were screened using the Center for Epidemiological Studies Depression Scale Revised-10 item (CES-D-10). In a double-blind, randomized, sham-controlled, between-subjects experiment, sixty participants were randomly assigned to two groups: in the active stimulation group, 31 participants received 20-min session of 40 Hz tACS over the mPFC via high-density tACS. In the sham group, 29 participants received the sham stimulation over the same region. Before and after the tACS, participants completed the Self-Referential Encoding Task (SRET), which they endorsed and recalled positive and negative personality traits. We found a significant interaction among stimulation group, depressive symptoms, trait valence (positive or negative). Among participants who received the 40 Hz stimulation, higher levels of baseline depressive symptoms were associated with increased endorsement/recall of positive personality traits compared to the sham group (p < 0.05). 40 Hz gamma tACS over the mPFC enhanced positive self-referential processing among individuals with subthreshold depression, an effect particularly evident among those with higher depressive symptoms. This effect highlights the potential therapeutic benefits of gamma-frequency stimulation in promoting positive self-evaluation among individuals with depression.