Abnormal activity in reward brain circuits in human narcolepsy with cataplexy

Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Bassetti, Claudio L.; Schwartz, Sophie

doi:10.1002/ana.21825

Cited by 97 publications

(72 citation statements)

References 60 publications

(107 reference statements)

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“…It is possible that hypocretin-deficient patients may process reward via a different mechanism, not solely involving the mesolimbic pathway. Recent fMRI findings by Ponz et al 39 suggest that in contrast to controls, in nonmedicated narcoleptics with cataplexy, activity in the ventral tegmental area is not modulated by high reward expectancy, and activity in the ventral striatum is reduced during winning. Interestingly, in the 12 hypocretin-deficient patients studied, there was reward-associated increased activity in the amygdala and dorsal striatum.…”

Section: Hypocretin Deficiency and Addictionmentioning

confidence: 97%

Reward-Seeking Behavior in Human Narcolepsy

Dimitrova

Fronczek

Ploeg

et al. 2011

Journal of Clinical Sleep Medicine

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Study Objectives: The hypocretin system enhances signaling in the mesolimbic pathways regulating reward processing and addiction. Because individuals with narcolepsy with cataplexy have low hypocretin levels, we hypothesized that they may be less prone to risk-and reward-seeking behaviors, including substance abuse. Design: Endpoints were performance on an array of psychometric tests (including the Eysenck Impulsiveness Scale, the Zuckerman Sensation Seeking Scale, the Gormally Binge Eating Scale, and the Beck Depression and Anxiety Inventory) and on the Balloon Analogue Risk Task (BART). Setting: Tertiary narcolepsy referral centers in Leiden (The Netherlands) and Boston (USA). Patients: Subjects with narcolepsy with cataplexy (n = 30), narcolepsy without cataplexy (n = 15), and controls (n = 32) matched for age, sex, and smoking behavior. Interventions: None. Measurements and Results: There was no difference in risktaking behavior between narcolepsy with or without cataplexy and the control group, as measured using the BART and the array of questionnaires. However, subjects in the narcolepsy with cataplexy group had significantly higher scores on the Eysenck Impulsiveness Scale (p < 0.05), with 10.0% categorized as impulsive, compared to 6.7% of the narcolepsy without cataplexy group and none of the controls. Narcoleptics with cataplexy also scored significantly higher than controls on the Binge Eating Scale (p < 0.05), with moderate or severe binge eating in 23%. On the depression and anxiety scales, all narcolepsy patients, especially those with cataplexy, scored significantly higher than controls. Conclusions:We found that narcoleptics with or without cataplexy generally have normal risk-taking behavior, but narcoleptics with cataplexy were more impulsive and more prone to binge eating than patients without cataplexy and controls. Our findings shed new light on the relation between sleepiness and impulsiveness. Furthermore, rates of depression and anxiety were higher in all narcoleptic subjects. However, using the current methods, no evidence could be found to support the hypothesis that hypocretin deficiency would affect reward-processing in humans. Keywords: Narcolepsy, cataplexy, hypocretin, orexin, risktaking, addiction, reward-seeking, substance abuse, sleep, sleepiness Citation: Dimitrova A; Fronczek R; Van der Ploeg J; Scammell T; Gautam S; Pascual-Leone A; Lammers GJ. Rewardseeking behavior in human narcolepsy. S C I E N T I F I C I N V E S T I G A T I O N SN arcolepsy with cataplexy is caused by an extensive loss of the neurons producing the hypocretin (orexin) neuropeptides. 1,2 Loss of these essential signaling molecules results in chronic daytime sleepiness, cataplexy, and other REM sleep associated phenomena. 3 In addition, considerable research indicates that the hypocretin system enhances signaling in the mesolimbic pathways that regulate reward processing and addiction, and hypocretin is now considered a key factor in of the neural mechanisms of drug addiction. 4,5 In response to drugs of a...

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Section: Hypocretin Deficiency and Addictionmentioning

confidence: 97%

Reward-Seeking Behavior in Human Narcolepsy

Dimitrova

Fronczek

Ploeg

et al. 2011

Journal of Clinical Sleep Medicine

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“…Although these results counter the hypothesis that orexin deficiency affects reward processing, these investigators suggested that orexin-deficient subjects use a different neurological mechanism for these behaviors (Dimitrova et al, 2011). In fact, a recent functional magnetic resonance imaging study suggests altered activity in brain reward circuits in patients exhibiting narcolepsy with cataplexy (Ponz et al, 2010).…”

Section: A Central Modulation Of Behavior and Physiology By Orexin Smentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXVI. Orexin Receptor Function, Nomenclature and Pharmacology

et al. 2012

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“…Two task-based fMRI studies using emotional processing elicited by humorous stimuli demonstrated an abnormal activation of the hypothalamus and an increase in the activation of limbic system particularly in amygdala as well as other cortical regions in narcoleptics with cataplexy (Reiss et al, 2008;Schwartz et al, 2008;Dang-Vu and Schwartz, 2013). The reward processing task fMRI showed abnormal activation of the nucleus accumbens (NAcc) and the ventral midbrain tegmental region in hypocretin-deficient narcoleptic patients with cataplexy (Ponz et al, 2010;Dang-Vu and Schwartz, 2013). Brain proton magnetic resonance spectroscopy (MRS) can be performed using protons to report changes in either the concentration or distribution of chemical substances.…”

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confidence: 99%