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Abnormal activity in reward brain circuits in human narcolepsy with cataplexy

Ponz, Aurelie
Khatami, Ramin
Poryazova, Rositsa
Werth, Esther
Boesiger, Peter
Bassetti, C. L.
Published in Annals of Neurology. 2010, vol. 67, no. 2, p. 190-200
Abstract OBJECTIVE: Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. METHODS: We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. RESULTS AND INTERPRETATION: Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.
Keywords AdultAnalysis of VarianceBrain/blood supply/*physiopathology*Brain MappingCase-Control StudiesEmotions/physiologyFemaleGames, ExperimentalHumansImage Processing, Computer-Assisted/methodsMaleMotivation/physiologyNarcolepsy/*pathologyNeural Pathways/physiopathologyOxygen/bloodReaction Time/physiology*Reward
PMID: 20225193
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Research group Neuroimagerie du Sommeil et de la Cognition (832)
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PONZ, Aurelie et al. Abnormal activity in reward brain circuits in human narcolepsy with cataplexy. In: Annals of neurology, 2010, vol. 67, n° 2, p. 190-200. https://archive-ouverte.unige.ch/unige:10390

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Deposited on : 2010-08-06

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