Therapeutic efficacy of connectivity‐directed transcranial magnetic stimulation on anticipatory anhedonia

Background There are currently no effective treatments specifically targeting anticipatory anhedonia, a major symptom of severe depression which is associated with poor outcomes. The present study investigated the efficacy of individualized repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (lDLPFC)–nucleus accumbens (NAcc) network on anticipatory anhedonia in depression. Methods This randomized, double-blind, sham-controlled clinical trial (NCT03991572) enrolled 56 depression patients with anhedonia symptoms. Each participant received 15 once-daily sessions of rTMS at 10 Hz and 100% motor threshold. Stimulation was localized to the site of strongest IDLPFC–NAcc connectivity by functional magnetic resonance imaging. The Hamilton depression rating scale (HAMD) was used to measure depression severity, the temporal experience pleasure scale (TEPS) to measure anticipatory and consummatory anhedonia to specifically measure anticipatory/motivational anhedonia. Event-related potentials during the monetary incentive delay (MID) task were recorded to evaluate the electrophysiological correlates of reward anticipation and response. Results Patients in the Real group showed significant improvements in anticipatory anhedonia and general depression symptoms posttreatment compared to the Sham group. The Real group also demonstrated more positive going cue-N2 and cue-P3 amplitude during MID reward trials after treatment. The change in cue-P3 posttreatment was positive correlated with improved TEPS-anti score. Conclusion Individualized rTMS of the lDLPFC–NAcc network can effectively alleviate anticipatory anhedonia and improved the reward seeking as evidenced by enhanced MID behavioral performance and more positive going cue-N2 and cue-P3. The lDLPFC-NAcc network plays a critical role in anticipatory reward and motivation processing.