Frontostriatal Connectivity Changes in Major Depressive Disorder After Repetitive Transcranial Magnetic Stimulation: A Randomized Sham-Controlled Study

Objective: The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. Methods: Twenty-four patients with major depressive disorder diagnosed with DSM-IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. Results: Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P <.001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P <.05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P =.001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P =.023). Conclusions: High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network.