Improving Insulin Sensitivity by Non-invasive Brain Stimulation

Efforts in curing and preventing obesity and type 2 diabetes (T2D) have been elusive thus far. One reason for that is the lack of understanding of the role of the brain in the development and treatment of the disease. In recent studies, the hypothalamus was identified as part of a brain network including higher cognitive regions that is particularly vulnerable to insulin resistance. Furthermore, the central insulin response in this network predicted food craving and hunger. In this project, transcranial direct current stimulation (tDCS) is implemented as a tool to stimulate brain networks. The investigators hypothesize that stimulating the hypothalamus-cognitive network will enhance insulin sensitivity and reduce food intake, food craving and hunger. Furthermore, the project will provide the unique opportunity to investigate novel mechanisms of insulin resistance in participants who have been extensively metabolically characterized.

Objectives The overarching aim of the study is to stimulate the hypothalamus-cognitive brain network to improve insulin sensitivity and eating behavior. Specific Objectives Implement tDCS stimulation compared to sham stimulation in overweight and obese adults to assess the impact on eating behavior, cognition and metabolism. Evaluate whether 3-day non-invasive brain stimulation of the hypothalamus-cognitive network has a causal effect on metabolism. Evaluate whether 3-day non-invasive brain stimulation has a significant effect on brain functional connectivity and diffusion parameters.

Insulin Resistance, Transcranial Direct Current Stimulation, Obesity, Diabetes, Magnetic Resonance Imaging

Single blind sham stimulation (ramp-up ramp-down stimulation will be applied for 30 seconds in order to simulate the active condition without any further continuous administration of current)

Free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented.

On a visual analogue scale, subjective feeling of hunger and food craving will be assessed using a questionnaire.

Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT).

Using a computer based task, participants rate food pictures of low caloric and high caloric foods and snacks on a 5-point scale based on subjective tastiness and healthiness.

Using a computer based task, participants have to choose food items they preferred to eat compared to a reference food on a 5-point choice scale. The reference (or "neutral") food item is individually determined based the health and taste rating [Scale: 1= not tasty/ not healthy up to 5= very tasty/ very heahlty].

Resting-state functional connectivity of the hypothalamus-cognitive network is assessed by functional magnetic resonance imaging (fMRI)

Inclusion Criteria: Body mass index (BMI) between 25.5 and 39.5 kg/m2 Age between 20 to 66 years of age Waist circumference > 80 cm for women, > 94 cm for men Exclusion Criteria: Insufficient knowledge of the German language Persons who cannot legally give consent Pregnancy or lactation History of severe mental or somatic disorders including neurological diseases (incl. epileptic seizures) Taking psychotropic drugs Previous bariatric surgery Acute infection within the last 4 weeks Hemoglobin values less than 12g/dl for women, less than 14 g/dl for men Current participation in a lifestyle intervention study or a pharmaceutical study Contradictions to a MRI measurement (e.g. metal implants)