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Clinical Research

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

International Journal of Obesity volume 44, pages 1279–1290 (2020)Cite this article

Subjects

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.

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Fig. 1: Experimental design: randomized, double-blind, sham-controlled clinical trial comparing active versus sham tDCS, with four stages.
Fig. 2: Primary outcome.
Fig. 3: Secondary outcome.
Fig. 4: Cognitive performance.
Fig. 5: Effect of COMT polymorphism.

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Acknowledgements

This study was funded by a research grant from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo); São Paulo Research Foundation (Funding reference 2016/04766-6, 2016/10785-3, 2016/14592-5); and FAEPA (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto—USP, Funding reference 27/2018). Additional support came from Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR002541), and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health.

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Author notes

  1. These authors contributed equally: Vivian Marques Miguel Suen, Miguel Alonso-Alonso

Authors and Affiliations

  1. Laboratory of Bariatric and Nutritional Neuroscience, Center for the Study of Nutrition Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA

    Priscila Giacomo Fassini, Greta Magerowski & Miguel Alonso-Alonso

  2. Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Avenida Bandeirantes 3900, Bairro Monte Alegre, CEP, Ribeirão Preto, São Paulo, 14049-900, Brazil

    Priscila Giacomo Fassini, Júlio Sérgio Marchini, Wilson Araújo da Silva Junior, Isabela Rozatte da Silva, Rafaella de Souza Ribeiro Salgueiro, Cássia Dias Machado & Vivian Marques Miguel Suen

  3. Energy Metabolism Laboratory, Jean Mayer USDA Human Nutrition Center on Aging, Tufts University, 711 Washington Street, Boston, MA, 02111-1524, USA

    Sai Krupa Das

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Contributions

PGF and MAA had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: MAA, PGF, SKD, VMMS, and GM. Acquisition, analysis, or interpretation of data: PGF and MAA. Drafting of the paper: PGF and MAA. Critical revision of the paper for important intellectual content: PGF, MAA, SKD, VMMS and GM. Statistical analysis: PGF and MAA. Obtained funding: VMMS and PGF. Administrative, technical, or material support: PGF, MAA, SKD, VMMS, GM, JSM, WAS, IRS, RSRS, and CDM. Study supervision: MAA and VMMS.

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Correspondence to Miguel Alonso-Alonso.

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Fassini, P.G., Das, S.K., Magerowski, G. et al. Noninvasive neuromodulation of the prefrontal cortex in young women with obesity: a randomized clinical trial. Int J Obes 44, 1279–1290 (2020). https://doi.org/10.1038/s41366-020-0545-3

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