Neural Mechanisms of Temporal Interference Stimulation on Improving Social Reward Function in Depression

Major depressive disorder (MDD) is a mood disorder characterized primarily by low mood, diminished interest, and reduced energy. Traditional views considered depression a non-degenerative condition; however, recent epidemiological studies have revealed its significant association with impaired social functioning. Data indicate that 59.3% of patients with depression experience social dysfunction of varying severity \[1\], particularly manifesting as difficulties in social interaction and relationship maintenance \[2\]. Therefore, investigating the mechanisms underlying social dysfunction is of great importance for promoting functional recovery in MDD, and dysfunction within the social reward system may represent a core factor, though the specific neural mechanisms remain unclear. The ultimate goal of understanding the neural mechanisms underlying social reward impairment in depressed patients is to improve therapeutic outcomes. Temporal Interference (TI) stimulation, as a non-invasive deep brain stimulation technique, utilizes high-frequency current differentials to generate low-frequency amplitude-modulated electric fields, enabling precise targeting of deep brain regions. This study employs multimodal assessment methods-such as functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and specific cognitive-behavioral tasks-combined with TI stimulation to observe immediate changes in functional connectivity, neural activity, and related cognitive functions (e.g., decision-making, memory) across participant groups. The research aims to elucidate the roles of the parahippocampal gyrus, orbitofrontal cortex, and striatum in social reward impairment in depression, and to explore circuit-based intervention targets, thereby providing novel strategies for the recovery of social functioning in MDD.

NCT Number	NCT07287878
Lead Sponsor	Shanghai Mental Health Center
Conditions	Depression
Enrollment	120 participants
Start Date	2025-11-15
Primary Completion	2026-05-10 (estimated)
Study Completion	2026-07-10 (estimated)
Updated on ClinicalTrials.gov	2025-12-24