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.


CONCLUSIONS
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.
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy, N.O.C.S.A.E. Hospital, AUSL 41100 Modena, Italy, giuseppe.plazzi@unibo.it stefano.meletti@unimore.it.
Stefano
S
Meletti
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy, N.O.C.S.A.E. Hospital, AUSL 41100 Modena, Italy.
Anna Elisabetta
AE
Vaudano
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy, IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, 40123 Bologna, Italy, and.
Fabio
F
Pizza
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Andrea
A
Ruggieri
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy, IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, 40123 Bologna, Italy, and.
Stefano
S
Vandi
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Alberto
A
Teggi
Department of Clinical and Experimental Medicine, University of Parma, 43121 Parma, Italy.
Christian
C
Franceschini
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy.
Francesca
F
Benuzzi
Department of Biomedical, Metabolic, and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy, N.O.C.S.A.E. Hospital, AUSL 41100 Modena, Italy.
Paolo Frigio
http://orcid.org/0000-0001-9756-6796
PF
Nichelli
Department of Biomedical and Neuromotor Sciences, University of Bologna, 40123 Bologna, Italy, IRCCS Istituto delle Scienze Neurologiche, AUSL di Bologna, 40123 Bologna, Italy, and giuseppe.plazzi@unibo.it stefano.meletti@unimore.it.
Giuseppe
G
Plazzi
D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D002385:Cataplexy / Q000503:physiopathology*; D002648:Child; D005152:Facial Muscles / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007845:Laughter; D008279:Magnetic Resonance Imaging; D008297:Male; D009290:Narcolepsy / Q000517:prevention & control*; D009415:Nerve Net / Q000503:physiopathology; D013223:Statistics as Topic
cataplexy; emotion; fMRI; humor; narcolepsy; sleep disorders