Dissociating the intensity and phase origins of sleepiness through a threshold-distance model of sleep-wake dynamics – Myna Lim

In this Journal club, we will discuss the paper “Dissociating the intensity and phase origins of sleepiness through a threshold-distance model of sleep-wake dynamics”, Yi Yao Zijun Ning et al., bioRxiv, 2026.

Abstract:

Sleepiness is a leading proximate cause of drowsy-driving fatalities, medical errors and industrial accidents, yet it has resisted mechanistic prediction; although it arises from well-characterized sleep-wake physiology, it is experienced as a subjective state and has lacked a quantitative link to the underlying dynamics. We previously showed that subjective sleepiness maps linearly, with a protocol-invariant form, onto the signed distance H − H⁺ between the homeostatic pressure H and the circadian-modulated sleep-onset threshold H⁺. This single quantity predicts sleepiness accurately but is mechanistically ambiguous: the same value can arise either because H sits far from the boundary or because the threshold H⁺(t) has shifted with circadian phase, and these two origins call for entirely different interpretations and interventions. Here we resolve this ambiguity by decomposing H − H⁺ into two mechanistically separable axes–intensity and phase. The intensity axis is the time-averaged margin ⟨ H − H⁺⟩, set by how far, on average, H sits from the sleep boundary: slowed homeostatic accumulation accounts for the paradoxically blunted sleepiness of older adults, and pharmacological suppression of H accounts for the dose-dependent alerting effect of caffeine. The phase axis is set by the circadian modulation of H⁺(t): under a forced-desynchrony protocol, in which the pacemaker free-runs and the homeostatic and circadian processes are experimentally decoupled, sleepiness tracks the circadian profile of H⁺(t) across all phases while the intensity mapping itself remains unchanged–a clean dissociation of the two axes. By resolving felt sleepiness into these two physiological degrees of freedom, this framework renders previously isolated phenomena–aging, caffeine and circadian misalignment–commensurable within a single theory and provides a physiologically interpretable basis for prospective fatigue-risk prediction.