Accelerated iTBS treatment in depressed patients differentially modulates reward system activity based on anhedonia

Objectives: Accelerated intermittent theta-burst stimulation (aiTBS) anti-depressive working mechanisms are still unclear. Because aiTBS may work through modulating the reward system and the level of anhedonia may influence this modulation, we investigated the effect of aiTBS on reward responsiveness in high and low anhedonic MDD patients.Methods: In this registered RCT (NCT01832805), 50 MDD patients were randomised to a sham-controlled cross-over aiTBS treatment protocol over the left dorsolateral prefrontal cortex (DLPFC). Patients performed a probabilistic learning task in fMRI before and after each week of stimulation.Results: Task performance analyses did not show any significant effects of aiTBS on reward responsiveness, nor differences between both groups of MDD patients. However, at baseline, low anhedonic patients displayed higher neural activity in the caudate and putamen. After the first week of aiTBS treatment, in low anhedonic patients we found a decreased neural activity within the reward system, in contrast to an increased activity observed in high anhedonic patients. No changes were observed in reward related neural regions after the first week of sham stimulation.Conclusions: Although both MDD groups showed no differences in task performance, our brain imaging findings suggest that left DLPFC aiTBS treatment modulates the reward system differently according to anhedonia severity.