Developing objective biomarkers of hyperphagia in children with PWS

Hyperphagia is one of the distinctive features of Prader-Willi syndrome (PWS), and when not carefully monitored or controlled, can be life threatening. It emerges in early childhood and remains a life-long challenge for individuals with PWS and their caregivers. To effectively manage and, in the future, treat hyperphagia, it is important to be able to accurately detect and characterize it. Yet, evaluating emerging food interest and hyperphagia is challenging because young children are often not able to provide an accurate self-report of their eating behavior. Currently, the main sources of data on hyperphagia in PWS are caregiver questionnaires. While informative, questionnaires remain an indirect, subjective evaluation, which could be affected by the reporter’s personal beliefs and opinions. An increasing number of clinical trials are being developed to evaluate new treatment options for hyperphagia. Thus, new, objective measures of food-related interests in persons with PWS are needed.

This project will evaluate two noninvasive, low-cost measures of food-related interest using physiological processes, such as eye movements and brain activity, in 3-12-year-old children with PWS (n=60). We will use a camera to track children’s eye gaze while they view colorful displays of food and non-food pictures to document spontaneous attention to different image categories. We will also monitor brain responses to these images to evaluate the emotional response to food compared to other pictures. Without the need for a behavioral response, these measures are optimal for use across ages and levels of intellectual ability. They also circumvent any social desirability confounds and are less susceptible to the placebo effects. We will then examine whether the results from the new measures correspond to the caregiver reports of hyperphagia and how they may vary across different nutritional phases. To determine whether the eye tracking and brain activity results are specific to PWS, we will also recruit children without PWS who are overweight/obese or have healthy weight. To facilitate study recruitment and to evaluate the feasibility of implementing the new measures at different clinical and research groups, the study will be conducted at two sites: Vanderbilt Kennedy Center and Case Western Reserve University.

We anticipate that both eye tracking and brain-based measures will be informative about hyperphagia and food-related interests in children with PWS. The results of this study will demonstrate that the proposed measures can serve as direct, objective markers of hyperphagia, suitable for use in clinical and research settings. Documenting spontaneous attention and emotional reactions to food will provide new insights into hyperphagia in PWS. Because our eye tracking and brain-based tests do not require children to follow any specific directions, they can be used repeatedly, across ages, and the results are less likely to be affected by the placebo effect or by learning. Therefore, the long-term goals will be to examine the emergence and progression of hyperphagia by following individuals over time and to use these new measures in clinical trials to evaluate hyperphagia.

Funded Year:


Awarded to:

Alexandra Key, PhD




Vanderbilt University


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