Stress and Brain Response Using MEG in PWS

Study Overview
=================
Brief Summary
-----------------
Individuals with Prader-Willi Syndrome (PWS) have increased hunger and food seeking behaviour, as well as learning (cognitive) challenges. In addition, some patients with PW been shown to have low cortisol production, particularly in stressful situations. However, research examining how hormonal, cognitive, and psychological factors are interrelated PWS is limited. To address this gap in knowledge, the goal of this project is to understand how changes in brain regions involved in controlling food intake and cognitive processes are related to changes in hormones regulating appetite, the stress hormone cortisol, and performance on neuropsychological tests.

Detailed Description
-----------------
Prader-Willi Syndrome (PWS) is characterized by hyperphagia, although the degree of food seeking can vary between individuals. This behaviour may be moderated by hormonal, neurocognitive, and psychological factors; however, data assessing these factors in an integrated fashion is scarce. The proposed research will address and identify relationships between three major challenges in PWS: 1) dysregulated feeding behaviour, 2) cognitive performance, and 3) chronic stress. The investigators will measure brain response to food cues, during a cognitive task, and at rest using magnetoencephalography (MEG) in adolescents with PWS and BMI-matched controls. This is an innovative design as previous studies in this population used only functional magnetic resonance imaging (fMRI) to examine food cue reactivity, which does not directly measure neuronal activity and lacks temporal-sensitivity. In contrast, MEG directly records neural firing and combines high spatial resolution with exquisite temporal resolution, allowing us to measure functional connectivity between brain regions. Importantly, MEG is also patient-friendly with fewer contraindications than MRI. To assess cognitive function, the investigators will utilize gold-standard neuropsychological measures, as well as emotional and social behavioural functioning. Lastly, the investigators will assess hair cortisol, which is a reflection of long term, month-by-month cortical exposure. This new area of research will explore neurobiological and cognitive mechanisms controlling feeding behaviour in PWS.

Official Title
-----------------
Chronic Stress, Cognition, and Food Cue Reactivity in Prader-Willi Syndrome: A Magnetoencephalography Study

Conditions
-----------------
Prader-Willi Syndrome

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Genetically diagnosed PWS (study population) Adolescents matched for age, sex, and BMI-percentile (controls) Exclusion Criteria: Past or current history of alcoholism or consistent drug use Current untreated major psychiatric illness as defined by the DSM-V criteria Medications that decrease alertness (that cannot be held on the days of testing) History of recent major head trauma Current pregnancy Diagnosis of diabetes Current or recent smoker (i.e. >2 cigarettes/week during past year) History of metal in body (shrapnel, metal slivers, unremovable metal adornments, clips, top braces, pacemaker) Use of glucocorticoid medications

Ages Eligible for Study
-----------------
Minimum Age: 7 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prader-Willi Syndrome<br>24 children and adolescents (7-16 years) with diagnosed Prader-Willi Syndrome will be recruited | |
| Controls<br>24 children and adolescents (7-16 years) without diagnosed Prader-Willi Syndrome will be matched for age, sex, and BMI-percentile to the Prader-Willi group | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuronal activity during the food cue reactivity task | To compare neuronal activity between PWS and controls during the food cue task | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationships between appetite hormone response and neuronal activity during the food cue task | To compare how appetite hormones correlate with neuronal activity in PWS compared to controls | 2 years | 
| Relationships between cortisol and neuronal activity during the food cue reactivity task | To compare how stress correlates with neuronal activity in PWS compared to controls | 2 years | 
| Neuronal activity during the emotional processing task | To compare neuronal activity between PWS and controls during the emotional processing task | 2 years | 
| Neuronal activity during resting state | To compare neuronal activity between PWS and controls during resting state | 2 years | 
| Neuronal activity during the response inhibition task | To compare neuronal activity between PWS and controls during the response inhibition task | 2 years | 
| Relationships between neuropsychological function and neuronal activity during the emotional processing task | To compare how neuropsychological function correlate with neuronal activity in PWS compared to controls | 2 years | 
| Relationships between cortisol and neuronal activity during the emotional processing task | To compare how stress correlates with neuronal activity in PWS compared to controls | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prader-Willi Syndrome, Magnetoencephalography, Food Cue Reactivity, Stress