Stress and Brain Response Using MEG in PWS

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prader-Willi Syndrome

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.

• Study Type: Observational
• Enrollment (Anticipated): 48

Contacts and Locations

• Study Contact: Name: Jill K Hamilton, MD; Phone Number: 205115 416-813-5115; Email: jill.hamilton@sickkids.ca
• Study Contact Backup: Name: Barkha Patel, PhD; Phone Number: 201915 416-813-7654; Email: barkha.patel@sickkids.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • Recruiting
      • The Hospital for Sick Children
      • Contact: Barkha Patel, PhD; Phone Number: 201915 416-813-7654; Email: barkha.patel@sickkids.ca
      • Principal Investigator: Jill Hamilton, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • The Hospital for Sick Children
      • Principal Investigator: Jill Hamilton, MD
      • Contact: Jill Hamilton, MD; Phone Number: (416) 913-5115; Email: jill.hamilton@sickkids.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Prader-Willi Syndrome; 24 children and adolescents (7-16 years) with diagnosed Prader-Willi Syndrome will be recruited
Controls; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationships between neuropsychological function and neuronal activity during the food cue reactivity task	To compare how neuropsychological function correlate with neuronal activity in PWS compared to controls	2 years
Relationships between neuropsychological function and neuronal activity during the response inhibition task	To compare how neuropsychological function correlate with neuronal activity in PWS compared to controls	2 years

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: University of Western Ontario, Canada; Holland Bloorview Kids Rehabilitation Hospital
• Investigators: Principal Investigator: Jill Hamilton, MD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: July 11, 2019
• First Submitted That Met QC Criteria: July 19, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): September 13, 2022
• Last Update Submitted That Met QC Criteria: September 12, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Stress; Magnetoencephalography; Prader-Willi Syndrome; Food Cue Reactivity
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: 1000061983

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No