Lack of response to disgusting food in the hypothalamus and related structures in Prader Willi syndrome

Objective To investigate, based on a putative abnormal neural processing of disgusting signals in Prader Willi syndrome (PWS) patients, the brain response to visual representations of disgusting food in PWS using functional MRI (fMRI). Methods Twenty-one genetically-confirmed PWS patients, 30 age- and sex-matched and 28 BMI-matched control subjects viewed a movie depicting disgusting food-related scenes interspersed with scenes of appetizing food while fMRI was acquired. Brain activation maps were compared between groups and correlated with disgust and hunger ratings. Results At the cortical level, the response to disgusting food representations in PWS patients was qualitatively similar to that of control subjects, albeit less extensive, and engaged brain regions typically related to visually-evoked disgust, such as the anterior insula/frontal operculum, the lateral frontal cortex and visual areas. By contrast, activation was almost absent in limbic structures directly concerned with the regulation of instinctive behavior robustly activated in control subjects, such as the hypothalamus, amygdala/hippocampus and periaqueductal gray. Conclusions Our study provides novel insights into the neural substrates of appetite control in a genetically-mediated cause of obesity. The presence of significant cortical changes further indicates that PWS patients consciously process disgusting stimuli, but the virtual absence of response in deep, limbic structures suggests that disgusting signals do not adequately reach the primary brain system for the appetite control.
Highlights • We report an abnormal pattern of brain response to images of disgusting food in PWS. • The activation demonstrated by PWS patients was restricted to the cerebral cortex. • Higher subjective disgust ratings were associated with greater insula activation. • In contrast, the neural response was almost absent in deep subcortical structures. • Disgusting signals may not adequately reach a main brain system for appetite control.