Discussion
depression, depressed, seizures
In this study, we investigated whether serial tDCS treatment administered using conventional or high-definition (HD) setups can induce structural plasticity in depressed participants. Structural MRI data was taken from a recently completed randomized, double-blind and sham-controlled clinical trial in depression that sought to confirm tDCS targeting and functional modulation of depression-relevant brain regions using novel imaging methods that did not include changes in brain structure as a primary hypothesis or criterion for target engagement (NCT03556124Approximately half of the patients in each treatment group were receiving stable standard antidepressant medications. The number of such patients did not differ significantly between the groups (Supplementary material S1) and the medication status of these patients was unchanged 6 weeks prior to and during their participation in this trial. Additionally, a post hoc region-of-interest analysis that excluded structural data from participants taking antidepressants showed that the patterns of structural changes across treatment groups remained similar for each significant region identified by the study analyses (see Supplementary material S3). Note that tDCS treatment was administered by study staff without any concurrent adjunctive experimental intervention. Blinding integrity was verified, and no significant differences in stimulation-related discomfort were observed between the treatment groups. Therefore, our results demonstrating significant HD tDCS induced gray matter changes cannot be attributed to these potential confounds, nor to the additive effects of an adjunct treatment, and are unlikely to be due to tDCS augmentation of ongoing antidepressant therapy. Overall, our findings indicate that 2 mA × 20 min state-of-the-art HD tDCS treatment protocols can induce long-term neurostructural changes in human subjects, despite potentially only a fraction of the applied tDCS current reaching the cortexTreatment-induced structural changes have been reported with other electromagnetic neuromodulation modalities. For example, repetitive transcranial magnetic stimulation (rTMS) studies targeting the same left DLPFC stimulation target in depressed participants have reported treatment-induced structural changes in cortical and subcortical brain regions including the cingulate gyrus and hippocampusThe cellular basis of these electromagnetic treatment-induced morphological changes is not well understood. In ECT, the administered large strength, short duration electric currents are designed to induce seizures