A unified clearance-based model of homeostatic drive across acute and chronic sleep loss

Comprehensive dynamical models of sleep homeostasis must provide a mechanistic framework capable of reproducing a broad range of sleep–wake conditions, including normal sleep, total sleep deprivation (TSD), and chronic sleep restriction (CSR) of varying severity. Traditionally, such models have been evaluated using behavioural performance measures, particularly psychomotor vigilance test (PVT) outcomes obtained under controlled laboratory sleep curtailment protocols. However, accurately capturing the progressive, multi-day impairments observed during chronic sleep restriction—while simultaneously accounting for the rapid deterioration seen during total sleep deprivation—has proven difficult within a single mechanistic architecture. In the present work, we propose a unified homeostatic model that integrates coupled fast and slow clearance processes with a wake-dependent stress state that accumulates during sustained wakefulness and dissipates during sleep. Latent physiological states are mapped to behavioral performance, enabling direct comparison with empirical PVT trajectories. The model was jointly fit to independent datasets spanning both TSD and CSR scenarios and subsequently evaluated in cross-paradigm simulations of independent sleep restriction protocols, accounting for approximately 90% of variance across all conditions. By combining physiologically interpretable clearance dynamics with multi-timescale accumulation and state-dependent vulnerability, this framework identifies the minimal structural components required to reconcile acute and chronic sleep loss within a single mechanistic model.