Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial

Background/objectives Obesity is associated with reduced neurocognitive performance. Individuals with obesity show decreased activation in the left dorsolateral prefrontal cortex (DLPFC), a key brain region relevant to the regulation of eating behavior. Transcranial direct current stimulation (tDCS) has emerged as a potential technique to correct these abnormalities. However, there is limited information to date, particularly in clinical settings and regarding long-term effects of tDCS. This study aimed to investigate the effects of DLPFC-targeted tDCS in young women with obesity. Subject/methods Randomized, double-blind, sham-controlled parallel-design clinical trial conducted in 38 women, aged 20-40 years, with BMI 30-35 kg/m(2). Study design: Phase I: target engagement (immediate effects of tDCS on working memory performance), Phase II: tDCS only (ten sessions, 2 weeks), Phase III: tDCS + hypocaloric diet (six sessions, 30% energy intake reduction, 2 weeks, inpatient), Phase IV: follow-up at 1, 3, and 6 months. Primary outcome: change in body weight. Secondary outcomes: change in eating behavior and appetite. Additional analyses: effect of Catechol-O-methyl transferase (COMT) gene variability. Data were analyzed as linear mixed models. Results There was no group difference in change in body weight during the tDCS intervention. At follow-up, the active group lost less weight than the sham group. In addition, the active group regained weight at 6-month follow-up, compared with sham. Genetic analysis indicated that COMT Met noncarriers were the subgroup that accounted for this paradoxical response in the active group. Conclusion Our results suggest that in young women with class I obesity, tDCS targeted to the DLPFC does not facilitate weight loss. Indeed, we found indications that tDCS could have a paradoxical effect in this population, possibly connected with individual differences in dopamine availability. Future studies are needed to confirm these findings.