Humor processing in human narcolepsy with cataplexy

Abstract

In narcolepsy-cataplexy (NC) patients, cataplexy attacks (sudden loss of muscle tone) are most often triggered by strong emotional experiences, in particular positive emotions such as laughter or joking. While muscle atonia associated with cataplexy is thought to implicate ponto-medullary mechanisms, the suprapontine brain mechanisms associated with the cataplectic effects of emotions in human NC remain essentially unknown. Recent animal data suggest that the hypocretin (Hcrt; also called orexin) system, which is deficient in NC patients, is involved not only in the regulation of sleep-wake states but also in emotional and reward processes. Emotion-triggered cataplexy could thus represent an affective consequence of Hcrt deficiency in human NC. In this chapter, we present evidence suggesting that the Hcrt system may play a key modulating role in hypothalamic-limbic circuits that are involved in the integration of emotion, reward, and sleep processes. We show that this hypothesis can be successfully tested using modern functional brain imaging techniques in NC patients. We report recent functional magnetic resonance imaging (fMRI) results showing that humorous pictures elicit reduced hypothalamic response together with enhanced amygdala response in NC patients. We also discuss the implications of these recent findings for current models of cataplexy. © 2010 Springer-Verlag New York.