Evidence of a Perceptual-Encoding Deficit in Narcolepsy?

Henry, George K.; Satz, Paul; Heilbronner, Robert L.

doi:10.1093/sleep/16.2.123

Cited by 43 publications

(31 citation statements)

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“…Experiments are currently being conducting along these lines. We are also investigating the recent finding that narcoleptics exhibit a perceptual encoding deficit in cognitive experiments by examining dynamic pupitlary responses and pupillary noise during cognitive tasks (Henry et al 1993). Preliminary results indicate that the narcoleptic pupil has a larger dilation associated with memory tasks and, supporting the noise finding in the present study, regressions of pupil diameter on cognitive memory load show narcoleptics having smaller residuals (less noise) than controls.…”

Section: Discussionsupporting

confidence: 77%

Neurological pupillary noise in narcolepsy

O'Neill¹,

Oroujeh²,

Keegan³

et al. 1996

Journal of Sleep Research

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SUMMARY Pupillometry has a long but inconclusive history as a means of measuring human alertness. Spontaneous pupillary oscillations in narcoleptics and the sleep deprived are a recognized but quantitatively elusive indication of alertness. Stimulation of the pupillary light reflex (PLR) has provided contradictory or confusing indications of alertness levels. Results from 10 diagnosed narcoleptics and 10 control subjects in which the PLR system was stimulated and a reliable (90%) discriminator derived for classifying narcoleptics and controls was reported. Random pupillary oscillations, which is called pupillary noise to distinguish these oscillations from spontaneous ones, were estimated from continuous pupil diameter recordings using a recursive least squares method applied to a subject-specific PLR system model. Pupillary noise sum of squares indicate that narcoleptics have significantly (P

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Section: Discussionsupporting

confidence: 77%

Neurological pupillary noise in narcolepsy

O'Neill¹,

Oroujeh²,

Keegan³

et al. 1996

Journal of Sleep Research

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“…The potent effects on the perforant path-evoked potential suggest the ORX-LC pathway could play a significant role in the neural plasticity that underlies learning and memory and provides a mechanism for hypothalamic modulation of cognition. These results may have clinical relevance, as in narcolepsy, in which there is an ORX deficit, memory impairments (Henry et al, 1993), and difficulties with vigilance and attention tasks (Rogers and Rosenberg, 1990;Rieger et al, 2003).…”

Section: Discussionmentioning

confidence: 97%

Orexin-A Infusion in the Locus Ceruleus Triggers Norepinephrine (NE) Release and NE-Induced Long-Term Potentiation in the Dentate Gyrus

Walling¹,

Nutt²,

Lalies³

et al. 2004

J. Neurosci.

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The orexins (ORX-A/ORX-B) are neuroactive peptides known to have roles in feeding and sleep. Evidence of dense, excitatory projections of ORX-A neurons to the noradrenergic pontine nucleus, the locus ceruleus (LC), suggests ORX-A also participates in attention and memory. Activation of LC neurons by glutamate produces a ␤-adrenergic receptor-mediated long-term potentiation (LTP) of the perforant path-evoked potential in the dentate gyrus, a target structure of the LC that has been implicated in memory. We asked whether ORX-A also activates norepinephrine (NE)-induced LTP by initiating NE release in the hippocampus. Here, we show that ORX-A infusion (0.25-25 fmol) into the LC produces a robust, ␤-adrenergic receptor-dependent, long-lasting potentiation of the perforant path-evoked dentate gyrus population spike in the anesthetized rat. Pharmacological inactivation of the LC with an ␣ 2 -adrenergic receptor agonist, before ORX-A infusion, prevents this potentiation. Analysis of NE concentrations in the hippocampus after ORX-A infusion into the LC reveals a transient, but robust, increase in NE release. Thus, this study demonstrates that the dense orexinergic projection to the LC promotes the induction of NE-LTP in the dentate gyrus. ORX-A modulation of LC activity may provide important support for the cognitive processes of attention and memory.

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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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Evidence of a Perceptual-Encoding Deficit in Narcolepsy?

Cited by 43 publications

References 0 publications

Neurological pupillary noise in narcolepsy

Neurological pupillary noise in narcolepsy

Orexin-A Infusion in the Locus Ceruleus Triggers Norepinephrine (NE) Release and NE-Induced Long-Term Potentiation in the Dentate Gyrus

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

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