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.

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.

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

Prader-Willi Syndrome (PWS) is characterized by hyperphagia, although the degree of food seeking can vary between individuals. The characteristic endocrine and metabolic dysfunction in PWS is indicative of abnormalities in the hypothalamus, and other brain systems. In addition to the hyperphagia and risk for obesity, anxiety is a prominent feature of PWS