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.
SIGNIFICANCE STATEMENT: In this study we reported for the first time in humans the brain structures whose neural activity is specifically and consistently associated with emotion-induced
cataplexy. To reach this goal
drug-naive children and adolescents with recent onset
narcolepsy type 1 were investigated. In
narcolepsy caused by
hypocretin/
orexin deficiency,
cataplexy is associated with a marked increase in neural activity in the amygdala, the nucleus accumbens, and the ventromedial prefrontal cortex, which represent suprapontine centers that physiologically process emotions and reward. These findings confirm recent data obtained in the
hypocretin knock-out mice and suggest that the absence of hypothalamic
hypocretin control on mesolimbic reward centers is crucial in determining
cataplexy induced by emotions. 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.