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

Authors: FASSINI, PRISCILLA - HARVARD MEDICAL SCHOOL; DAS, SAI KRUPA - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; MAGEROWSKI, GRETA - HARVARD MEDICAL SCHOOL; MARCHINI, JULIO - UNIVERSIDAD DE SAO PAULO; ARAUJO DA SILVA JR, WILSON - UNIVERSIDAD DE SAO PAULO; ROZATTE DA SILVA, ISABELA - UNIVERSIDAD DE SAO PAULO; DESOUZARIBIERO SALG, RAFAELLA - FEDERAL UNIVERSITY OF SAO PAULO; DIAS MACHADO, CASSIA - UNIVERSIDAD DE SAO PAULO; MARQUES MIGUEL SUEN, VIVIAN - UNIVERSIDAD DE SAO PAULO; ALONSO-ALONSO, MIGUEL - HARVARD MEDICAL SCHOOL

Submitted to: International Journal of Obesity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2020
Publication Date: 2/19/2020
Citation: Fassini, P., Das, S., Magerowski, G., Marchini, J.S., Araujo da Silva Jr, W., Rozatte da Silva, I., de Souza Ribiero Salguiero, R., Dias Machado, C., Marques Miguel Suen, V., Alonso-Alonso, M. 2020. Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial. International Journal of Obesity. 44:1279-1290. https://doi.org/10.1038/s41366-020-0545-3.
DOI: https://doi.org/10.1038/s41366-020-0545-3

Interpretive Summary: Obesity is linked with reduced brain and cognitive function. In particular, people with obesity show decreased activity in specific brain regions related to eating behavior. A novel treatment approach that targets brain area(s) by sending a constant, low-intensity current may help reduce appetite and improve weight loss if aimed at the reward centers of the brain. Adult women with obesity were enrolled in a weight loss program and randomly assigned to receive either the novel treatment or a placebo treatment and were followed up at 1, 3 and 6 months after treatment. There was no difference in change in weight between treatment and placebo groups. At 1- and 3-month follow-up time points, the treatment group lost less weight than the placebo group. The treatment group also regained weight at 6 months. Genetic analysis suggested that the gene that plays a role in regulating eating behavior contributed to the contradictory results in the treatment group.

Technical Abstract: 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/m2. 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.