Asymmetric Modulation of Brain Connectivity by Anodal Transcranial Direct Current Stimulation in Healthy Individuals: A Single‐Blind, Randomized Sham‐Controlled Trial

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) has shown asymmetric behavioral effects, though the underlying neurophysiological mechanisms remain unclear. In this preliminary study with 34 healthy individuals, tDCS was applied to either the left or right DLPFC or a sham group. Behavioral and neurophysiological changes were examined by the Stroop test and resting-state fMRI, respectively, which were measured before and after a 15-min tDCS session. Seed-to-voxel connectivity analysis with seeds placed under the tDCS target regions (F3 and F4) showed no significant changes, but voxel-to-voxel whole-brain intrinsic connectivity (IC) analysis revealed significant 3 × 2 interaction effects (stimulation site × time) in the right DLPFC (18 mm off from the F4). Post hoc analysis showed that only the right DLPFC stimulation led to an increase in IC from pre- to post-stimulation. Consistent with this finding, right DLPFC stimulation improved Stroop task performance measured by increased interference score, which represents better inhibition of irrelevant information. These findings provide further insights into the hemispheric difference of tDCS effects and its underlying neurophysiological mechanisms. However, the small sample size limits the generalizability of the results and necessitates further research with a larger cohort for confirmation.