The Brain Correlates of Laugh and Cataplexy in Childhood Narcolepsy

Abstract

The brain suprapontine mechanisms associated with human cataplexy have not been clarified. Animal data suggest that the amygdala and the ventromedial prefrontal cortex are key regions in promoting emotion-induced cataplectic attacks. Twenty-one drug-naive children/adolescent (13 males, mean age 11 years) with recent onset of narcolepsy type 1 (NT1) were studied with fMRI while viewing funny videos using a "naturalistic" paradigm. fMRI data were acquired synchronously with EEG, mylohyoid muscle activity, and the video of the patient's face. Whole-brain hemodynamic correlates of (1) a sign of fun and amusement (laughter) and of (2) cataplexy were analyzed and compared. Correlations analyses between these contrasts and disease-related variables and behavioral findings were performed.Emotion-induced laughter occurred in 16 patients, and of these 10 showed cataplexy for a total of 77 events (mean duration ϭ 4.4 s). Cataplexy was marked by brief losses of mylohyoid muscle tone and by the observation of episodes of facial hypotonia, jaw drop, and ptosis. During laughter (without cataplexy) an increased hemodynamic response occurred in a bilateral network involving the motor/ premotor cortex and anterior cingulate gyrus. During cataplexy, suprapontine BOLD signal increase was present in the amygdala, frontal operculum-anterior insular cortex, ventromedial prefrontal cortex, and the nucleus accumbens; BOLD signal increases were also observed at locus ceruleus and in anteromedial pons. The comparison of cataplexy versus laugh episodes revealed the involvement of a corticolimbic network that processes reward and emotion encompassing the anterior insular cortex, the nucleus accumbens, and the amygdala.

Narcolepsy

“…38 Cataplexy is triggered by signals related to strong, positive emotions that may be relayed through the medial prefrontal cortex and amygdala to activate circuits in the pons that cause muscle paralysis. [39][40][41] Orexin signaling also increases metabolism, sympathetic tone, and rewarding behaviors such as drug seeking. It is possible that dysfunction in these pathways contributes to the obesity and depression that occur in many people with narcolepsy.…”

Emotion stimulus processing in narcolepsy with cataplexy

“…Due to loss of hypocretinergic neurons, anatomical and functional abnormalities in the hypothalamus were found in a meta‐study performed by Dang‐Vu (), who reviewed various brain imaging studies including fMRI studies in NC. According to one of the latest fMRI studies in narcolepsy caused by hypocretin deficiency, cataplexy is associated with an increase in neural activity in the amygdala, the nucleus accumbens, and the ventromedial prefrontal cortex – areas responsible for emotion and reward processing (Meletti et al ., ). These findings confirm other recent data obtained in the hypocretin knockout mice, and suggest that the absence of hypothalamic hypocretin control on mesolimbic reward centres is crucial in determining cataplexy induced by emotions (Burgess et al ., ).…”

Orexin/Hypocretin and Organizing Principles for a Diversity of Wake-Promoting Neurons in the Brain

“…Thus, a vital flexibility of arousal is lost without orexin/hypocretin. In terms of robustness, it is well known that without orexin/hypocretin arousal can dip to inappropriately low levels (unconsciousness) upon disturbances such as laughter in humans or sight of delicious food in animals [2,117,118]. Without orexin/hypocretin, there is no appropriate tracking/adjustment of arousal state to internal and external state.…”