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Disturbances in the hypothalamus communication pathways with other regions in the brain and the periphery may represent a potential link between metabolic and cognitive health. The current project evaluates whether enhancing synaptic plasticity of this pathway can improve weight management, insulin sensitivity, and cognitive functions. In recent studies, we were able to show that the human brain is sensitive to insulin with favorable effects on peripheral metabolism and cognition. These brain regions encompass the hypothalamus and its connections to the striatum and prefrontal cortex. We want to investigate whether it is possible to enhance neuroplasticity of insulin-responsive brain regions to suppress the weight gain trajectory and improve dopamine-dependent cognitive functions in people with a high risk to develop type 2 diabetes. For this purpose, neuroimaging tools using high-definition transcranial direct current stimulation (HD-tDCS) and magnetic resonance imaging (MRI) will be implemented to assess synaptic plasticity of a neural network essential for metabolic and cognitive health.
The overarching aim of the study is to investigate the possibility to enhance neuroplasticity of the hypothalamus network to improve metabolism and dopamine-dependent cognitive functions.
Specific objectives
Participants will receive a thorough screening to obtain body composition by MRI, anthropometric measures, fasting glucose and insulin, indirect calorimetry, and general cognitive functions. Thereafter, participants will participate in three measurement days (separated by approx. one week) to receive a 25 min tDCS stimulation targeting the hypothalamus network in a double-blind cluster-randomized. Participant are randomized on three conditions: sham stimulation, anodal and cathodal stimulation. During the non-invasive brain stimulation, participants will perform a stop-signal task. On each measurement day, structural and functional MRI measurements are performed before and after stimulation. Dopamine-dependent behavior (i.e. reward task) will be assessed during fMRI measurement. Subsequently, participants will receive a breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented. Subjective feeling of hunger and food craving will be assessed using a visual analogue scale before stimulation, directly after stimulation and after breakfast. Food pictures will be rated on a laptop for taste and healthiness.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anodal stimulation | Active Comparator | Anodal tDCS of the hypothalamus network |
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| Cathodal stimulation | Active Comparator | Cathodal tDCS of the hypothalamus network |
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| Sham stimulation | Sham Comparator | Sham tDCS of the hypothalamus network |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anodal transcranial direct current stimulation | Device | anodal tDCS of the hypothalamus resting-state functional connectivity network using 12 Electrodes of the Starstim device by Neuroelectrics. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in neuroplasticity | Fractional anisotropy (FA) of the target network | 20 minutes directly before and after tDCS stimulation |
| Change in functional connectivity | Resting state functional connectivity of the target network | 20 minutes directly before and after tDCS stimulation |
| Change in eating behavior | Caloric intake (kcal), Free-choice, ad libitum food intake from a standardized breakfast buffet. The caloric intake from fat, carbohydrates and protein will be documented | 1 hour after tDCS stimulation |
| Change in dopamine-dependent cognitive function | Changes in dopamine-dependent cognitive function and reward sensitivity measured by a reward-based decision-making task | 20 minutes after tDCS stimulation |
| Measure | Description | Time Frame |
|---|---|---|
| Change in subjective ratings | Change in subjective ratings will be assessed using a visual analogue scale for hunger and subjective feeling of craving using a questionnaire (Food craving questionnaire). Visual analogue scale using a range from 0 to 10 cm, higher values indicating more hunger. Food craving questionnaire based on ordinal scale from 1 to 5, higher values indicating more food craving |
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Inclusion Criteria:
Overweight and obese participants:
Sex and age matched normal weight individuals:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Clinic Tübingen | Tübingen | 72076 | Germany |
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All participants receive sham stimulation, anodal stimulation and cathodal stimulation in a pseudo-randomized order on three separate measurement days.
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Stimulation protocol is applied in a double blind fashion.
|
|
| cathodal transcranial direct current stimulation | Device | anodal tDCS of the hypothalamus resting-state functional connectivity network using 12 Electrodes of the Starstim device by Neuroelectrics. The total injected current will never go beyond 4 milliamp, which will be split among the different stimulation electrodes. |
|
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| sham transcranial direct current stimulation | Device | Double blind sham stimulation of the hypothalamus resting-state functional connectivity network (ramp-up ramp-down stimulation will be applied for 30 seconds) |
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| 5 minutes before tDCS stimulation, 5 minutes after tDCS stimulation and 5 minutes after buffet |
| Performance during stop-signal task | Outcome measures cover direction errors, proportion of successful stops, reaction time on Go trials, and stop signal reaction time (SSRT) | task is performed during 25-minutes tDCS stimulation |
| Tastiness and healthiness rating of food stimuli | 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 | task is performed immediately after buffet |
| Food choice | 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 healthy] | task is performed immediately after buffet |
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| D009765 | Obesity |
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D065908 | Transcranial Direct Current Stimulation |
| ID | Term |
|---|---|
| D004599 | Electric Stimulation Therapy |
| D013812 | Therapeutics |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |
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