Medical student Perelman School of Medicine at the University of Pennsylvania
Introduction: Prader-Willi syndrome (PWS) is a multisystem, neurodevelopmental genetic disorder. A key manifestation of PWS is hyperphagia – an extreme, life-threatening form of uncontrolled eating. In a cohort of obese, binge-prone individuals, our group previously demonstrated both decreased right-sided ventromedial prefrontal cortex (vmPFC) thickness and feasibility of responsively stimulating vmPFC interconnections directly within the nucleus accumbens (NAc) to reduce binge-eating. If analogous vmPFC differences exist in PWS, this vmPFC-NAc impulse-control circuitry may be a potential target for hyperphagia control. Here, we investigated whether PWS patients also exhibit differences in vmPFC thickness and aimed to define a target for modulation of vmPFC-NAc interconnections in this population.
Methods: We processed T1-weighted anatomical MRI images from nine patients and eight sibling controls and diffusion-weighted images that were available for six subjects in each group. Advanced Normalization Tools (ANTs) was used for co-registration of vmPFC and NAc masks from MNI-based atlases to subject images and calculation of mean vmPFC thickness in all subjects. Probabilistic tractography was used to generate a PWS-specific map of vmPFC interconnections within the NAc. K-means clustering was used to subdivide the NAc based on distribution of these interconnections.
Results: Mean right vmPFC thickness was significantly decreased (p < .05) in PWS patients (3.5 mm) versus sibling controls (3.9 mm). Mean left vmPFC thickness was not significantly different between groups (p=.19). The PWS-specific NAc probabilistic maps of vmPFC interconnections allowed subdivision of the NAc into shell and core subregions. The NAc shell contained significantly more vmPFC interconnections than the NAc core bilaterally (p < .05).
Conclusion : Decreased right-sided vmPFC thickness in PWS, analogous to that previously observed in binge-prone individuals, suggests vmPFC derangement may contribute to hyperphagia in PWS patients. vmPFC-NAc interconnections are more densely located in the NAc shell in PWS and represent a potential opportunity to target vmPFC circuitry with responsive deep brain stimulation to address hyperphagia.
