Anastasia Dimitropoulos¹, R. T. Schultz^2,3

Department of Psychology, Case Western Reserve University, Cleveland, Ohio¹, Developmental Neuroimaging Laboratory, Child Study Center, Yale University School of Medicine, New Haven, Connecticut², Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut³ 

Introduction: Prader-Willi syndrome (PWS) is a neurodevelopmental disorder associated with missing material from the paternal chromosome 15 (q11-q13), derived either by deletion on the paternal copy or by receipt of two copies of the maternal chromosome. It is characterized by hyperphagia and intense food preoccupations. Associated behaviors often include persistent hunger, food obsessions and compulsions, and food foraging, all resulting in an increased likelihood of obesity. Although dysfunction of the hypothalamus is thought to have a critical role in PWS-induced hyperphagia, it is only one of several regions involved in the regulation of eating behavior. The purpose of this research was to identify food-related neural circuitry in PWS-induced hyperphagia during a hunger state. Although recent studies have shown preliminary evidence of a satiation deficit, the hunger circuitry has not been systematically examined.  We hypothesize that abnormally strong hunger states by themselves can contribute to hyperphagia, and as a first step we test for differences in hunger state neural activation between those with PWS and matched controls. 

Method: We used functional magnetic resonance imaging (fMRI) to examine neural circuitry during a hunger state in 9 participants with PWS (3 male, mean age = 21.6 years) and in 10 participants (4 male, mean age = 22.9 years) matched on IQ and body mass index (BMI) while they made perceptual judgments on pairs of high- or low-calorie foods and objects in a block design task. T1-weighted 3D structural images (1 mm³), and EP images (TR = 1950, TE = 30 ms, flip angle = 60) were acquired on a Siemens 3.0T Trio scanner. Averaged group data sets were examined using a random effects GLM analysis contrasting the experimental conditions. Regions of interest included the hypothalamus, thalamus, insular cortex, amygdala, fusiform gyrus, and select portions of the orbitofrontal cortex (OFC).  

Results and Discussion: Individuals with PWS showed hyperactivation to high-calorie foods in contrast to low-calorie foods and nonfood objects in neural circuitry known to mediate food-related behavior and showed significantly more activation of these circuits when directly compared to the MR/DD controls. Significant differences were found in several a priori ROIs, including the hypothalamus (6, -3, -3; -6, -4, -3), insula (38, -1, 19; -36, 0 19), and OFC (21, 38, -8). Our findings suggest that the food neural circuitry for PWS is abnormally activated during hunger and this may mediate abnormally strong hunger states and therefore play a significant role in PWS-induced hyperphagia. A better understanding of the mechanisms of this eating disorder should allow for future development of more effective treatment options for individuals with PWS and potentially provide insight into the mechanisms of food-related obesity in the general population.

edited: 02/09/2012