Neuroimaging Investigation of Hyperphagia in Prader-Willi Syndrome
Marked hyperphagia (increased appetite for food) and its resultant morbid obesity pose major health risks to people with Prader-Willi Syndrome (PWS), a genetic disorder characterized by excessive eating and food-seeking. Further study of hyperphagia and food perception in PWS is essential to better treatment in PWS.
Preliminary findings from Dr. Elisabeth Dykens’ ongoing study “Prader-Willi Syndrome: Correlates of Compulsivity,” suggest that individuals with PWS show altered brain electrical activity in EEG/ERP responses to certain food images, such as contaminated food and inappropriate combinations of food. These preliminary data reveal differences in food perception and discrimination in PWS relative to healthy controls, and across the two primary genetic subtypes of PWS, uniparental disomy (UPD) and deletion (Del) PWS. Individuals with PWS-Del tend to initially discriminate food on the basis of quantity over appropriateness, while those with PWS-UPD are more similar to healthy controls in focusing on suitability for eating when viewing images. These data suggest novel differences in food cue processing at the neural level between individuals with the two primary genetic subtypes of PWS. The next step in understanding the neural basis of these preliminary ERP findings is to use functional MRI (fMRI) to examine regional brain activation in persons with PWS and obese controls while viewing similar food-cue paradigms.
We will use fMRI to study 10 PWS subjects (5 PWS-UPD and 5 PWS-Del subjects) and 10 healthy overweight subjects to examine regional brain activation in persons with PWS and healthy controls while viewing food-cue paradigms similar to those used in Dr. Dykens’ studies. Patterns of brain activation in response to food items, such as cereal, ice cream, and pizza, shown in various states of palatability will be contrasted to control images. Participants will be asked to view each stimulus and think about whether they would consider eating the presented foods. Our specific aims are to determine how:
- Regional brain activation in response to food scenes differs between obese adults with PWS and otherwise healthy obese adult control subjects.
- Regional brain activation in response to food scenes differs between PWS adults with uniparental disomy (UPD) versus paternal deletions.
Exploratory analyses will be conducted to examine the effects of the various states of palatability on regional brain activity and to compare differences in neural response in PWS relative to controls, and across the two primary genetic subtypes of PWS.