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Abstract

Narcolepsy type 1 is a chronic sleep disorder caused by a deficiency of the orexin (hypocretin) neuropeptides. In addition to sleep regulation, orexin is important for motivated control processes. Weight gain and obesity are common in narcolepsy. However, the neurocognitive processes associated with food-related control and overeating in narcolepsy are unknown. We explored the neural correlates of general and food-related attentional control in narcolepsy-type-1 patients (n = 23) and healthy BMI-matched controls (n = 20). We measured attentional bias to food words with a Food Stroop task and general executive control with a Classic Stroop task during fMRI. Moreover, using multiple linear regression, we assessed the relative contribution of neural responses during Food Stroop and Classic Stroop to spontaneous snack intake. Relative to healthy controls, narcolepsy patients showed enhanced ventral medial prefrontal cortex responses and connectivity with motor cortex during the Food Stroop task, but attenuated dorsal medial prefrontal cortex responses during the Classic Stroop task. Moreover, the former activity but not the latter, was a significant predictor of spontaneous snack intake. These findings demonstrate that narcolepsy, characterized by orexin deficiency, is associated with decreased dorsal medial prefrontal cortex responses during general executive control and enhanced ventral medial prefrontal cortex responses during food-driven attention.