Intermittent theta-burst stimulation (iTBS) Modulates Abnormal Brain Activity During Emotional Arousal in Adolescent Depression

Background The rising incidence of adolescent depression in China causes significant impairments, necessitating rapid treatments such as accelerated Intermittent theta-burst stimulation(iTBS). However, responses to treatment vary. We used naturalistic functional magnetic resonance imaging(N-fMRI) to investigate the impact of depression on the neural processing of emotional arousal. The objectives of this study were: 1) to identify brain regions associated with treatment response, and 2) to correlate these neural signatures with clinical outcomes following accelerated iTBS. Methods Fifty-eight adolescents with depression and twenty-nine healthy controls underwent fMRI while viewing emotion-evoking videos. Forty-three patients completed accelerated iTBS treatment, with pre- and post-treatment fMRI scans. Statistical analysis of the MRI data was performed in SPM12, employing cluster-based family-wise error correction at a significance threshold of p < 0.05. Results Whole-brain analysis revealed that adolescents with depression exhibited significantly reduced emotion-arousal activation in the left superior frontal gyrus (L-SFG) and left middle frontal gyrus (L-MFG) compared to healthy controls during high-to-medium emotional arousal. Hamilton Depression Scale scores significantly decreased after iTBS treatment. L-MFG showed a marginally significant increase in emotion-arousal activation after iTBS. Correlation analysis between the Euclidean distance of treatment targets to the L-SFG and psychological scale scores revealed a significant negative association between the Euclidean distance and Generalized Anxiety Disorder-7 reduction rate. Conclusion This exploratory study suggests that abnormal activity in the L-SFG and L-MFG underlies the variable efficacy of accelerated iTBS in adolescent depression. Our findings indicate that proximity to the L-SFG is correlated with treatment response, and L-MFG beta values showed slightly increased post-treatment. These regions represent potential neuroanatomical targets for future investigation as biomarkers for iTBS mechanisms.