Structural-functional connectomics in major depressive disorder following aiTBS treatment

Major depressive disorder (MDD) has been associated with changes in the structural (SC) and functional connectivity (FC) of the brain. This study investigated the effects of accelerated intermittent theta burst stimulation (aiTBS) on SC-FC coupling and graph theory measures, focusing on the association between baseline SC-FC coupling of the dorsolateral prefrontal cortex (dlPFC) and clinical improvement. In a randomized, sham-controlled, quadruple-blind, crossover study, aiTBS was delivered to the left dlPFC of depressed patients with MDD, and diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were acquired. In 77 MDD patients, significantly increased whole-brain SC-FC coupling was observed, primarily driven by default mode network (DMN) SC-FC coupling, along with increased somatomotor network FC, and decreased FC between the DMN hubs and limbic regions after active aiTBS. Furthermore, significant increases were observed in structural global and local efficiency measures that were not specific to the stimulation condition (active/sham aiTBS). However, these changes did not significantly correlate with clinical improvement. Notably, baseline SC-FC coupling of the left dlPFC was a significant predictor of clinical improvement. Our findings highlight the potential of left dlPFC SC-FC coupling as a predictor of aiTBS treatment outcomes, as well as the effect of aiTBS in enhancing SC-FC coupling.