The brain correlates of laugh and cataplexy in childhood narcolepsy

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=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