Genetic profile for dopamine signaling predicts brain functional reactivity to repetitive transcranial magnetic stimulation

Research integrating molecular and imaging data provides important insights into how the genetic profile associated with dopamine signaling influences inter-individual differences in brain functions. However, the effects of genetic variations in dopamine signaling on the heterogeneity of brain changes induced by repetitive transcranial magnetic stimulation (rTMS) still remain unclear. The current study examined the composite effects of genetic variations in dopamine-related genes on rTMS-induced brain responses in terms of the functional network connectivity and working memory performance. Healthy individuals (n = 30) participated in a randomized, double-blind, sham-controlled study with a crossover design of five consecutive days where active rTMS or sham stimulation sessions were administered over the left dorsolateral prefrontal cortex (DLPFC) of the brain. Participants were mostly women (n = 29) and genotyped for polymorphisms in the catechol-O-methyltransferase and D2 dopamine receptor genes and categorized according to their genetic composite scores: high vs. low dopamine signaling groups. Pre- and post-intervention data of resting-state functional magnetic resonance imaging and working memory performance were obtained from 27 individuals with active rTMS and 30 with sham stimulation sessions. The mean functional connectivity within the resting-state networks centered on the DLPFC increased in the high dopamine signaling group. Working memory performance also improved with rTMS in the high dopamine signaling group compared to that in the low dopamine signaling group. The present results suggest that genetic predisposition to higher dopamine signaling may be a promising neurobiological predictor for rTMS effects on cognitive enhancement. Trial registration: ClinicalTrials.gov (NCT02932085).