| Prader-Willi syndrome (PWS) is associated with extreme hyperphagia that results in morbid obesity. We used fMRI to investigate the neural mechanisms associated with response to visual stimuli of food, both before and after eating, in eight individuals with PWS (age 10--24) and eight age-matched typically developing individuals. Participants were scanned once before (pre-meal) and once after (post-meal) a standardized meal. Visual stimuli of food, animals, and blurred control images were presented for passive viewing in a block design format during acquisition of whole-brain functional MRI data. Individuals with PWS exhibited an abnormal and blunted pattern of activation to food before eating, although this group did exhibit normal increases in activation in the amygdala. During the pre-meal session, typically developing individuals responded similarly to individuals in previous studies, showing increased activation in food motivation regions such as the orbitofrontal cortex, amygdala, insula, and prefrontal cortex. After eating, the PWS group exhibited very large increases in several food motivation areas, including the orbitofrontal cortex, amygdala, insula, and medial prefrontal cortex. Conversely, typically developing individuals responded as expected during the post-meal session, with increased response to food stimuli only in the medial prefrontal cortex. These results indicate a distinct neural mechanism associated with hyperphagia in PWS. Dysfunction appears to involve connections between hyperactive limbic and paralimbic regions that drive eating behavior (such as the amygdala) and overactive regions that suppress food intake (such as the prefrontal cortex) in PWS. This lack of inhibition is likely tied to low levels of gamma-aminobutyric acid (GABA) in the prefrontal cortex in PWS that results from deletion of GABA-A receptor subunit genes. |
