Abstract

Background Reduced inhibitory control is associated with obesity and neuroimaging studies indicate that diminished prefrontal cortex activity influence eating behavior and metabolism. The hypothalamus regulates energy homeostasis and is functionally connected to cortical and subcortical regions especially the frontal areas.

Objectives We tested network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in appetite control.

Methods In a randomized, double-blind parallel group design, 44 adults with overweight or obesity (BMI 30.6 kg/m2, 52.3 % female) received active (anodal or cathodal) or sham 12-channel net-tDCS on the hypothalamus appetite-control network for 25 minutes on three consecutive days while performing a Stop-Signal-Task to measure response inhibition. Before and after stimulation, state questionnaires assessed changes in desire to eat and food craving. Directly after stimulation, participants received a breakfast buffet to evaluate ad-libitum food intake. An oral glucose tolerance test was conducted at follow-up. Resting-state functional MRI was obtained at baseline and follow-up.

Results The Stop-Signal Reaction Time (SSRT) was shorter in both active groups versus sham, indicating improved response inhibition. Additionally, a stronger increase in hypothalamic functional connectivity was associated with shorter SSRT. Caloric intake of sweet food was lower in the anodal group versus sham, but no main effects between groups were observed on total and macronutrient intake, food craving ratings and desire to eat. At follow-up, no differences were observed between groups on peripheral metabolism.

Conclusion Our study suggests that modulating hypothalamic functional network connectivity patterns via net-tDCS may improve food choice and inhibitory control.

Highlights

Active net-tDCS groups showed better inhibitory control compared to the sham group.

Stronger increase in hypothalamic functional connectivity associated with better inhibitory control after active net-tDCS.

No differences were found between the active net-tDCS and sham groups for total kilocaloric intake.

Anodal net-tDCS showed lower sweet food intake compared to the sham group.

Competing Interest Statement

Declaration of competing interest GR is a co-founder and shareholder and works for Neuroelectrics, a company developing medical devices for NIBS. RS works for Neuroelectrics. Outside of the current work, MH reports participation in advisory board for Boehringer Ingelheim, Sanofi and Amryt, and lecture fees from Amryt, AstraZeneca, Bayer, Sanofi, Eli Lilly, Novartis, Novo Nordisk and Boehringer Ingelheim. TEN, RV, MB, LT, MG, JT, DL, ALB, CP, HP and SK report no conflict of interest.

Clinical Trial

NCT04420650

Funding Statement

The study was supported in parts by a grant (01GI0925) from the Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.).

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Ethics Committee of the Medical Faculty of the Eberhard Karls University and the University Hospital Tuebingen, located at Gartenstrasse 47, 72074 Tuebingen, gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

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AbbreviationsAICAkaike Information CriterionBMIBody Mass IndexCANTABCambridge Neuropsychological Test Automated BatterydlPFCDorsolateral Prefrontal CortexFCFunctional ConnectivityFCQ-SFood Craving Questionnaire StatefMRIFunctional Magnetic Resonance ImagingGIPGlucose-Dependent Insulinotropic PolypeptideGIRsGlucose Infusion RatesGLMGeneral Linear ModelGLP1Glucagon-like Peptide 1HbA1cGlycohemoglobin A1cHD-tDCSHigh-definition Transcranial Direct Current StimulationIFGInterior Frontal GyrusISIInsulin Sensitivity IndexKcalKilocaloriesLMERLinear Mixed Effects ModelmAMilliampereMRIMagnetic Resonance ImagingNet-tDCSNetwork Transcranial Direct Current StimulationNIBSNon-Invasive Brain StimulationoGTTOral Glucose Tolerance TestμAMicroamperePANASPositive and Negative Affect ScalePFCPrefrontal CortexSBCSeed-Based Connectivity MapsSDStandard DeviationSSRTStop-Signal Reaction TimeSSTStop-Signal TaskT2DMType 2 Diabetes MellitustDCSTranscranial Direct Current StimulationVASVisual Analogue ScaleWHRWaist-to-Hip Ratio