Abnormal Food Motivation in Prader-Willi Syndrome: Relationship between Neural Dysfunction and Obesity using fMRI

Laura Holsen¹, Jennifer Zarcone*¹, Mary Anderson¹, Jamie Young¹, Merlin Butler², Travis Thompson³, and Cary Savage¹

¹University of Kansas Medical Center, ²Children’s Mercy Hospitals and Clinics and University of Missouri - Kansas City, and ³Minnesota Autism Center and University of Minnesota

*presenting author 

The behavioral phenotype of Prader-Willi syndrome (PWS) includes hyperphagia and obsessive-compulsive disorder (OCD).  It is proposed that the interaction of these behaviors may be related to regional brain dysfunction.  Based on a model of OCD and abnormal food motivation, it was predicted that specific areas of the brain that respond to food-related images (i.e., orbitofrontal cortex, insula, limbic cortex and anterior cingulate gyrus) may differ from areas of activation during viewing of non-food images.  Further, it is predicted that different states of motivation (pre-meal vs. post-meal) may predict specific sites of activation (LeBar et al., 2001).  This study examined the relationship between hyperphagic and food-related compulsive behaviors and localized brain activity in Prader-Willi syndrome. 

Data are reported for eight individuals with PWS (7 females, 1 male; mean age = 15.4 years, SD = 5.2) who have undergone functional magnetic resonance imaging (fMRI) scanning sessions in a Siemens 3T Allegra scanner. Images of food and animals were presented in counterbalanced blocks interspersed with blurred baseline image blocks.  Visual stimuli were projected through 3D limited view goggles.  Participants completed two scanning sessions: one just before and one immediately after eating a meal. The meal was standardized across subjects for micro- and macronutrient content.  Data from a total of 24 studies (from 8 subjects) were analyzed using multi-study general linear model analysis through BrainVoyager; reported regions of interest (ROIs) are significant at the p<.0000001 level.

Group analysis during the pre-meal condition showed decreased activation in response to food images in multiple brain territories, corresponding to the hippocampal formation, orbitofrontal cortex, and anterior cingulate cortex, and increased activation in the temporal pole.  In comparison, activation increased during the post-meal condition in response to food images in the peri-amygdaloid complex, insula, anterior cingulate cortex, hippocampal formation, and fusiform gyrus.

In contrast to normal-weight individuals, for whom pictures of food activate specific areas of the brain to a greater degree when a person is hungry (versus during a state of satiation; LeBar et al., 2001), our recent findings using fMRI demonstrate that individuals with PWS display greater activation post-meal than pre-meal.  These findings may indicate a specific neural contribution to the gene-brain-behavior interaction in hyperphagic behaviors in PWS, as well as possible delineation of neural mechanisms of obesity. 

LeBar, K. S., Gitelman, D. R., Parrish, T. B., Kim, Y., Nobre, A. C., & Mesulam, M. M. (2001). Hunger selectivity modulates corticolimbic activation to food stimuli in humans. Behavioral Neuroscience, 115, 493-500.

June 2004