Validation of a Novel Cerebellar-striatal Satiety Circuit in Humans

Study Overview
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Brief Summary
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This study uses a noninvasive technique called transcranial magnetic stimulation (TMS) to study satiety in healthy individuals. TMS is a noninvasive way of stimulating the brain, using a magnetic field to change activity in the brain. The magnetic field is produced by a coil that is held next to the scalp. In this study, the investigators will be stimulating the brain to learn more about the role of the cerebellum in satiety.

Detailed Description
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The purpose of this study is to conduct a circuit manipulation experiment to test the hypothesis that targeting the cerebellum can alter activity in response to food cues to advance the understanding of the involvement of the cerebellar-striatal circuit in feeding behavior. Participants will undergo an initial screening session to complete informed consent and undergo baseline assessments including physical activity and food craving. Participants will additionally undergo an MRI scan that includes structural and resting-state functional magnetic resonance imaging (rsfMRI). These rsfMRI imagines will be used to isolate individual resting state networks for targeting of rTMS modulation. Participants will then complete two separate testing sessions involving MRI imaging and food intake assessments before and after rTMS. One visit will involve consumption of a filling meal; the other visit will be completed following an overnight fast.

Official Title
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Validation of a Novel Cerebellar-striatal Satiety Circuit in Humans

Conditions
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Appetitive Behavior, Obesity

Intervention / Treatment
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* Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
* Device: Sham repetitive Transcranial Magnetic Stimulation (rTMS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy individuals aged 18 to 65 BMI of 20-35.0 kg/m2 Normal or corrected-to-normal vision Good general health Ability to understand and willingness to sign written informed consent document Exclusion Criteria: Current and/or past medical conditions Current and/or past eating disorder On a restricted diet and/or taking weight loss medication(s) History of bariatric surgery Weight fluctuation >3% in past 3 months Recent history of illicit recreational drug abuse Current nicotine use Intellectual disability Conditions that might result in increased risks of side effects or complications from TMS or MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active cerebellar rTMS<br>Cerebellar targeted iTBS | Device: Repetitive Transcranial Magnetic Stimulation (rTMS)<br>* rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. Intermittent theta burst stimulation (iTBS) consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses (82), will be applied to the target. Cerebellar stimulation will be applied to the targets at 100% of aMT or 35% maximal stimulator output, whichever is higher.<br>* Other names: iTBS;|
| Sham Comparator: Sham cerebellar rTMS<br>Cerebellar targeted sham iTBS | Device: Sham repetitive Transcranial Magnetic Stimulation (rTMS)<br>* rTMS is a technique of TMS that allows for selective external manipulation of neural activity in a non-invasive manner. During rTMS a rapidly changing current is passed through an insulated coil placed against the scalp. This generates a temporary magnetic field, which in turn induces electrical current in neurons and allows for modulation of neural circuitry. Intermittent theta burst stimulation (iTBS) consisting of 2 s trains of 3 pulses at 50 Hz, repeated at 5 Hz, every 10s for a total of 600 pulses (82), will be applied to the target. Cerebellar stimulation will be applied to the targets at 100% of aMT or 35% maximal stimulator output, whichever is higher. Sham is achieved by using a coil with a magnetic shield preventing magnetic field from reaching the head.<br>* Other names: iTBS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BOLD response in the cerebellum | Change in functional activation of the cerebellum will be assessed before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit. | 30 minutes pre-TMS and 30 minutes post-TMS, at each of two main study visits (fed, fasted) | 
| Change in BOLD response in the ventral striatum | Change in functional activation of the ventral striatum will be assessed before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit. | 30 minutes pre-TMS and 30 minutes post-TMS, at each of two main study visits (fed, fasted) | 
| Change in food reward valuation | Change in food reward valuation of high-calorie foods will be assessed using the Willingness to Pay task, measured before (pre-TMS) and after (post-rTMS) rTMS stimulation, measured separately at the fed visit and at the fasted visit. | up to 60 minutes pre-TMS and up to 60 minutes post-TMS, at each of two main study visits (fed, fasted) | 
| Ad libitum snack food intake | Change in total caloric intake during the ad libitum snack food session will be assessed at the baseline visit and after (post-rTMS) rTMS stimulation, the latter measured separately at the fed visit and at the fasted visit. | baseline, up to 60 minutes post-TMS at each of two main study visits (fed, fasted) |