Neuromodulation of the prefrontal cortex facilitates diet-induced weight loss in midlife women: a randomized, proof-of-concept clinical trial.

Background: High body mass index (BMI) is associated with neurocognitive impairments that contribute to overeating and interfere with weight loss efforts. Overweight and obesity at midlife can accelerate neurodegenerative changes and increase the risk of late-life dementia. Noninvasive neuromodulation represents a novel, affordable and scalable approach to improve neurocognitive function in this context. The purpose of this proof-of-concept study was to examine whether transcranial direct current stimulation (tDCS) aimed at enhancing prefrontal cortex activity could enhance weight loss, in combination with a hypocaloric diet, and study underlying mechanisms.

Methods: Overall, 38 women with BMI 25-35 kg/m underwent a 4 week randomized, double-blinded, sham-controlled, and parallel-design intervention, during which they received eight sessions of tDCS (n = 18 sham, n = 20 active) in combination with a diet (caloric goal of 20 kcal/kg/day). We evaluated longitudinal changes in body weight, appetite and food craving. In addition, we examined the contribution of cognitive-executive processes via food-modified computerized tasks.

Results: We found that the active group had more reduction in body weight than the sham group throughout the study (p = 0.020) and significant weekly weight loss. At 4 weeks, the active group lost 2.32% of initial body weight (sham: 1.29%). Components of subjective appetite and food craving showed a trend toward more reduction in the active group. These changes were paralleled by significant improvements in task performance in the active group, particularly in a dual task that required inhibitory control and working memory (p = 0.007-0.031). Improvement in inhibitory control performance predicted reduction in lack of control overeating, explaining 43.5% of its variance at the end of the study (p = 0.003). No significant adverse effects were observed.

Conclusions: Our results provide proof-of-concept validation of prefrontal-targeted tDCS, combined with a diet, in midlife women with excess body weight, paving the way for larger studies evaluating clinical efficacy and long-term effects of this intervention.