Circadian-Modulated Thresholds for Sleep Patterns in Aging and Narcolepsy
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In the two-process model of sleep-wake regulation, circadian-modulated thresholds time every sleep onset and awakening, yet they remain free parameters rather than quantities derived from neuronal dynamics. This limitation leaves the framework unable to predict how sleep patterns change when neuromodulatory drive is altered, as in aging and narcolepsy. Here we close that gap by deriving closed-form, circadian-modulated threshold expressions from the Phillips-Robinson model with explicit orexinergic excitation of the wake-promoting population. Within this single threshold geometry, aging and narcolepsy appear as opposite deformations along the orexinergic axis: age-related hyperexcitability of orexin neurons elevates the sleep-onset boundary and creates a fragility regime in which minor nocturnal disturbances trigger premature awakenings, whereas orexin loss depresses the same boundary toward the wake-onset threshold and produces the rapid state fragmentation of narcolepsy. Concurrently, reduced circadian amplitude compresses the inter-threshold corridor, advancing sleep onset and shortening sleep duration. These results convert the classical two-process thresholds from descriptive conveniences into mechanistic organizers of sleep–wake dynamics across healthy aging and orexin deficiency.
Author summary
The classical two-process model of sleep relies on a pair of switching thresholds that have been imposed by hand rather than derived from the neurons that actually stabilize sleep and wakefulness. Here we remove this limitation: starting from a biophysical mean-field model of the sleep- and wake-promoting populations, and adding the orexin system that stabilizes arousal, we derive the sleep-onset and awakening thresholds analytically from the bifurcation geometry of the underlying dynamical system. These closed-form thresholds depend explicitly on circadian phase, homeostatic state, and orexinergic tone, revealing that aging and narcolepsy are opposite deformations of a single threshold corridor along one orexinergic axis. In aging, orexin hyperexcitability raises the sleep-onset barrier past a sharp “arousal fragility boundary,” beyond which a minor disturbance triggers irreversible awakening; in narcolepsy, orexin loss collapses the same barrier and fragments sleep while paradoxically preserving total sleep time. We further find, contrary to common assumption, that orexin sustains wakefulness chiefly by raising the barrier to falling asleep rather than by resisting awakening. This work turns phenomenological sleep thresholds into physics-derived organizers of behavior, providing a mechanistic bridge from neuronal circuitry to whole-organism sleep dynamics.
