Hypocretin-deficient narcolepsy patients have abnormal brain activation during humor processing

Hilde T Juvodden; Dag Alnæs; Martina J Lund; Espen Dietrichs; Per M Thorsby; Lars T Westlye; Stine Knudsen

doi:10.1093/sleep/zsz082

Hypocretin-deficient narcolepsy patients have abnormal brain activation during humor processing

Sleep. 2019 Jul 8;42(7):zsz082. doi: 10.1093/sleep/zsz082.

Authors

Hilde T Juvodden^{1

2}, Dag Alnæs³, Martina J Lund^{3

4}, Espen Dietrichs⁵, Per M Thorsby⁶, Lars T Westlye^{3

7}, Stine Knudsen¹

Affiliations

¹ Norwegian Centre of Expertise for Neurodevelopmental Disorders and Hypersomnias (NevSom), Department of Rare Disorders, Oslo University Hospital, Ullevål, Norway.
² Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
³ NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Ullevål, Norway.
⁴ NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Neurology, Oslo University Hospital & University of Oslo, Oslo, Norway.
⁶ Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Norway.
⁷ Department of Psychology, University of Oslo, Oslo, Norway.

PMID: 30923809
DOI: 10.1093/sleep/zsz082

Abstract

Study objectives: To assess brain activation patterns in response to fun-rated and neutral-rated movies we performed functional magnetic resonance imaging (fMRI) during a humor-paradigm in narcolepsy type 1 (NT1) patients with cataplexy (muscle atonia triggered by emotions) and controls.

Methods: The fMRI-humor-paradigm consisted of short movies (25/30 with a humorous punchline; 5/30 without a humorous punchline [but with similar build-up/anticipation]) rated by participants based on their humor experience. We included 41 NT1 patients and 44 controls. Group-level inferences were made using permutation testing.

Results: Permutation testing revealed no group differences in average movie ratings. fMRI analysis found no group differences in brain activations to fun-rated movies. Patients showed significantly higher activations compared to controls during neutral-rated movies; including bilaterally in the thalamus, pallidum, putamen, amygdala, hippocampus, middle temporal gyrus, cerebellum, brainstem and in the left precuneus, supramarginal gyrus, and caudate. We found no brain overactivation for patients during movies without a humorous punchline (89.0% neutral-rated). Group analyses revealed significantly stronger differentiation between fun-rated and neutral-rated movies in controls compared with patients (patients showed no significant differentiation), including bilaterally in the inferior frontal gyrus, thalamus, putamen, precentral gyrus, lingual gyrus, supramarginal gyrus, occipital areas, temporal areas, cerebellum and in the right hippocampus, postcentral gyrus, pallidum, and insula.

Conclusion: Patients showed significantly higher activations in several cortical and subcortical regions during neutral-rated movies, with no differentiation from activations during fun-rated movies. This lower threshold for activating the humor response (even during neutral-rated movies), might represent insight into the mechanisms associated with cataplexy.

Keywords: cataplexy; fMRI; humor; hypocretin; narcolepsy type 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / physiopathology*
Brain Mapping / methods
Cataplexy / physiopathology*
Emotions
Female
Humans
Magnetic Resonance Imaging / methods
Male
Narcolepsy / physiopathology*
Orexins / deficiency*
Young Adult

Substances

HCRT protein, human
Orexins