Transcranial direct current stimulation to modulate fMRI drug cue reactivity in methamphetamine users: A randomized clinical trial.

Transcranial direct current stimulation (tDCS) has been studied as a therapeutic option to alter maladaptive brain functions associated with chronic substance use. We present a randomized, triple-blind, sham-controlled, clinical trial to determine the neural substrates of tDCS effects on drug craving. Sixty participants with methamphetamine use disorder were assigned to two groups: active tDCS (5 x 7 cm , 2 mA, 20 min, anode/cathode over the F4/Fp1) and sham stimulation. Neuroimaging data of a methamphetamine cue reactivity task were collected immediately before and after stimulation. There was a significant reduction in self-reported craving after stimulation without any significant effect of time-by-group interaction. Our whole-brain analysis demonstrated that there was a global decrease in brain reactivity to cues following sham but not active tDCS. There were significant time-by-group interactions in five main clusters in middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and precuneus with higher activations after active stimulation. There was a significant effect of stimulation type in the relationship between electrical current at the individual level and changes in task-modulated activation. Brain regions with the highest electric current in the prefrontal cortex showed a significant time-by-group interaction in task-modulated connectivity in the frontoparietal network. In this trial, there was no significant effect of the one session of active-F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, activation and connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues.