Abstract
Narcolepsy Type 1 is a chronic sleep disorder caused by a deficiency of the hypothalamic neuropeptide orexin (hypocretin). In addition to sleep regulation, orexin signaling is important for motivational processes. Weight gain and obesity are common in narcolepsy. We recently showed that food-specific satiety had reduced effects on food choices and caloric intake in narcolepsy patients, suggesting an important functional role for orexin in human food-related motivation. However, the neurocognitive processes associated with food-related motivation and overeating in orexin-deficient patients are unknown. We explored the neural correlates of attention to food in narcolepsy type 1 patients (n=23), healthy BMI-matched controls (n=20), and idiopathic hypersomnia patients (n=15); the latter serving as a control group with excessive daytime sleepiness but normal orexin levels. Attentional bias to food words was measured with a Food Stroop task during fMRI. Relative to healthy controls and idiopathic hypersomnia patients, narcolepsy patients showed enhanced ventral medial prefrontal cortex (vmPFC) responses when colornaming food versus neutral words. Narcolepsy patients relative to healthy controls also displayed stronger vmPFC-motor cortex connectivity. In addition, the vmPFC responses for food versus neutral words were predictive of spontaneous snack intake after scanning, which was greater in narcolepsy patients than in healthy controls and idiopathic hypersomnia patients. Our results show that orexin deficiency is associated with enhanced vmPFC responses during food-driven attention, predicting increases in food intake.
