Neural mechanisms underlying hyperphagia in Prader-Willi syndrome

Abstract

Objective: Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group.

Research methods and procedures: Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data.

Results: Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks.

Discussion: Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

Figure 1

Regions of interest analysis: results of the food vs. baseline contrast in the post-meal condition, comparing patterns of activation in HWC and PWS groups. Results are depicted in the coronal perspective, centered on (A) the medial PFC (4,54,35) and (B) the amygdala (22,−9,−16). Event-related averaging of all time-points across all blocks, separately for each group, is depicted to the left. PWS group participants (red) showed greater activation to food stimuli than the HWC group (green) for regions of interest in the medial PFC and in the right amygdala after eating.