Emotional Processing in Narcolepsy

Abstract

Human narcolepsy with cataplexy (NC) is a major sleep-wake disorder caused by a deficiency in hypocretins (Hcrt or orexins). Recent data suggest that the pathophysiology of NC may also involve emotional dysfunctions: emotions trigger cataplexy in NC patients; most anticataplectic medications are antidepressants; NC patients seem less likely to become addicted to stimulant medications; and depression and psychosocial dysfunctions are common in NC. In this chapter, I review data from animal physiology and from human clinical and neuroimaging studies that converge to show a role of the Hcrt system in emotional functions. Specifically, recent data indicate that the Hcrt system may modulate activity in emotion- and reward-related brain regions (e.g., amygdala, medial prefrontal cortex, ventral midbrain, striatum), and that these functions of the Hcrt system may be impaired in NC patients. Human NC could thus be associated with abnormal brain responses to emotions caused by Hcrt deficiency. This hypothesis is supported by three fMRI studies reported in the present chapter, in which we measured changes of regional brain activity in NC patients compared to healthy matched controls. The first study investigated brain responses to positive emotions using humorous pictures; the second study assessed changes in amygdala activity during aversive conditioning; the third study used a game-like paradigm to activate reward brain circuits. The results from these studies revealed functional abnormalities in the hypothalamus, amygdala, ventral tegmental area (VTA), striatum, and medial prefrontal cortex (mPFC) during affective processing in NC patients. These findings suggest that Hcrt activity modulates emotional states in addition to consolidating sleep-wake states. These fMRI data also help bridge the gap between molecular/cellular studies in animals and clinical symptoms of NC patients. (PsycINFO Database Record (c) 2016 APA, all rights reserved)