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Brain Advance Access originally published online on December 19, 2007
Brain 2008 131(2):514-522; doi:10.1093/brain/awm292
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abnormal activity in hypothalamus and amygdala during humour processing in human narcolepsy with cataplexy

Sophie Schwartz1, Aurélie Ponz1, Rositsa Poryazova2, Esther Werth2, Peter Boesiger3, Ramin Khatami2 and Claudio L. Bassetti2

1Laboratory for Neurology and Imaging of Cognition, Department of Clinical Neurology & Department of Neurosciences, University Medical Center, Michel-Servet 1, 1211 Geneva, Switzerland, 2Neurologische Klinik und Poliklinik, Zurich University Hospital, Frauenklinikstrasse 26, 8091 Zurich, Switzerland and 3Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, 8092 Zurich, Switzerland

Correspondence to: Sophie Schwartz, Neurology and Imaging of Cognition, Department of Neurosciences, University Medical Center, Michel-Servet 1, 1211 Geneva, Switzerland E-mail: sophie.schwartz{at}medecine.unige.ch

Narcolepsy with cataplexy (NC) is a complex sleep–wake disorder, which was recently found to be associated with a reduction or loss of hypocretin (HCRT, also called orexin). HCRT is a hypothalamic peptide implicated in the regulation of sleep/wake, motor and feeding functions. Cataplexy refers to episodes of sudden and transient loss of muscle tone triggered by strong, mostly positive emotions, such as hearing or telling jokes. Cataplexy is thought to reflect the recruitment of ponto-medullary mechanisms that normally underlie muscle atonia during REM-sleep. In contrast, the suprapontine brain mechanisms associated with the cataplectic effects of emotions in human narcolepsy with cataplexy remain essentially unknown. Here, we used event-related functional MRI to assess brain activity in 12 NC patients and 12 controls while they watched sequences of humourous pictures. Patients and controls were similar in humour appreciation and activated regions known to contribute to humour processing, including limbic and striatal regions. A direct statistical comparison between patients and controls revealed that humourous pictures elicited reduced hypothalamic response together with enhanced amygdala response in the patients. These results suggest (i) that hypothalamic HCRT activity physiologically modulates the processing of emotional inputs within the amygdala, and (ii) that suprapontine mechanisms of cataplexy involve a dysfunction of hypothalamic–amygdala interactions triggered by positive emotions.

Key Words: narcolepsy with cataplexy; functional MRI; hypocretin/orexin; amygdala; emotion

Abbreviations: HCRT, hypocretin; NC, narcolepsy with cataplexy; REM, rapid eye movement sleep

Received July 15, 2007. Revised October 20, 2007. Accepted November 8, 2007.


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