Modulation of Emotion Regulation Deficits in Patients with Heroin Use Disorder by Intermittent Theta-Burst Transcranial Magnetic Stimulation

Background Dysfunctional Emotion regulation (ER) strategies may represent a promising treatment target for heroin use disorder (HUD). The therapeutic potential of transcranial magnetic stimulation to improve ER in HUD remains to be evaluated. Methods The present randomized sham-controlled pre-registered clinical trial determined the therapeutic efficacy of intermittent theta-burst transcranial magnetic stimulation (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) for 10 days in 39 HUD patients (21 real iTBS; 18 sham). The ER performance-associated electroencephalographic indices obtained by event-related potential, time-frequency, source localization, and connectivity analysis techniques served as outcomes and were assessed pre- and post-intervention, and one month later follow-up for real iTBS group. Results Compared to the sham iTBS group, the intervention group exhibited significantly more positive difference waves (DW) at 400–600ms, which was significantly related to reduced craving. The real iTBS group specifically showed changes over the intervention, with enhanced event-related synchronization in the delta/theta band during viewing neutral pictures and expressing suppression of unpleasant pictures (US); lower activation in the left supramarginal gyrus and right posterior cingulate cortex (PCC) in the above conditions, separately; and lower connectivity between left DLPFC and right PCC under US condition. During 1000–1200ms, their DW amplitudes at the follow-up period were significantly more negative than baseline. Conclusions The iTBS can improve the ER ability of HUD patients to use ER strategies, particularly expressive suppression, which are maintained following the intervention. Improved ER capability is associated with reduced craving, possibly due to enhanced frontal regulatory control.