Decision Making in Narcolepsy with Cataplexy

Bayard, Sophie; Abril, Beatriz; Yu, Hui; Scholz, Sabine; Carlander, Bertrand; Dauvilliers, Yves

doi:10.1093/sleep/34.1.99

Cited by 59 publications

(38 citation statements)

References 33 publications

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“…This parallels our animal studies showing activation of Hcrt neurons during positively motivated tasks, but not during negatively motivated tasks 5 . The current results, in concert with these prior animal and human studies suggest that depression and reported difficulties with social interaction in narcolepsy and Parkinson’s 35 may be related to the loss of Hcrt cells in both of these conditions 2, 14, 36 . However, we cannot eliminate the indirect role of the disability that accompanies these disorders in generating depression in humans.…”

Section: Discussionsupporting

confidence: 77%

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction

et al. 2013

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The neurochemical changes underlying human emotions and social behavior are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 (Hcrt-1) and melanin concentrating hormone (MCH), measured in the human amygdala. We show that Hcrt-1 levels are maximal during positive emotion, social interaction, and anger, behaviors that induce cataplexy in human narcoleptics. In contrast, MCH levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. MCH levels increase at sleep onset, consistent with a role in sleep induction, whereas Hcrt-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.

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Section: Discussionsupporting

confidence: 77%

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction

et al. 2013

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“…Cognitive performance has been difficult to assay in narcolepsy due to the confounding effect of sleepiness. Sleep, however, remains restorative and phasic arousal is preserved in patients (70), and sleepiness-independent deficits were reported, including impaired perceptual encoding of stimuli, attention deficits in executive tasks, and impaired decision making (70)(71)(72). Neural substrates underlying sleepiness and subjective perception of sleep propensity while awake are largely unknown.…”

Section: Tdw State Heterogeneity: Hcrt Loss Finely Alters the Tdw Oscmentioning

confidence: 99%

Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need

Vassalli

Franken

2017

Proc. Natl. Acad. Sci. U.S.A.

121

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Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrt ko/ko mice respond to 6-h sleep deprivation (SD) with a slowwave sleep (SWS) EEG δ (1.0 to 4.0 Hz) power rebound like WT littermates, spontaneous waking fails to induce a δ power reflecting prior waking duration. This correlates with impaired θ (6.0 to 9.5 Hz) and fast-γ (55 to 80 Hz) activity in prior waking. We algorithmically identify a theta-dominated wakefulness (TDW) substate underlying motivated behaviors and typically preceding cataplexy in Hcrt ko/ko mice. Hcrt ko/ko mice fully implement TDW when waking is enforced, but spontaneous TDW episode duration is greatly reduced. A reformulation of the classic sleep homeostasis model, where homeostatic pressure rises exclusively in TDW rather than all waking, predicts δ power dynamics both in Hcrt ko/ko and WT mouse baseline and recovery SWS. The low homeostatic impact of Hcrt ko/ko mouse spontaneous waking correlates with decreased cortical expression of neuronal activityrelated genes (notably Bdnf, Egr1/Zif268, and Per2). Thus, spontaneous TDW stability relies on Hcrt to sustain θ/fast-γ network activity and associated plasticity, whereas other arousal circuits sustain TDW during SD. We propose that TDW identifies a discrete global brain activity mode that is regulated by contextdependent neuromodulators and acts as a major driver of sleep homeostasis. Hcrt loss in Hcrt ko/ko mice causes impaired TDW maintenance in baseline wake and blunted δ power in SWS, reproducing, respectively, narcolepsy excessive daytime sleepiness and poor sleep quality.hypocretin/orexin | narcolepsy | sleep homeostasis | brain theta oscillations | waking substate W akefulness encompasses a wide spectrum of arousal levels, sensorimotor processing modes, and behaviors, reflected in the electroencephalogram (EEG) by a great variety of signal patterns (1). Fourier transform decomposes the signal into multiple frequency ranges, defining δ, θ (5 to 10 Hz), and γ (>30 Hz) oscillatory components. However, although the EEG has been used to define wakefulness and distinguish it from slow-wave and paradoxical sleep (SWS and PS) for decades, a formal cartography of waking substates, associated EEG features, and their significance for the animal is largely lacking. Likewise, definition of the relation between waking quality and subsequent sleep content has evolved little since enunciation of the twoprocess model of sleep regulation (2) in which a sleep/wakedependent homeostatic "process S," reflected in EEG δ power during SWS, regulates sleep propensity as a function of prior waking duration regardless of waking quality. Later studies described behaviors (3, 4) or EEG components (5, 6) that disproportionally affect the sleep homeostat. Different procedural, cognitive, or emotional experience differentially impacts subsequent SWS δ powe...

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“…Other studies have found that patients with narcolepsy have particular difficulties in tasks that put high demands on monitoring and manipulation of information (ie, in tasks that require a high degree of executive control) [17,18]. Recent investigations have pointed to changes in decision-making, information sampling, and reward sensitivity [21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Subjective deficits of attention, cognition and depression in patients with narcolepsy

et al. 2015

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Decision Making in Narcolepsy with Cataplexy

Cited by 59 publications

References 33 publications

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction

Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction

Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need

Subjective deficits of attention, cognition and depression in patients with narcolepsy

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