Objective sleep assessment relies on polysomnography (PSG), yet clinical impact is often better reflected in patient-reported outcomes (PROs) such as sleepiness and fatigue. Existing summary indices, including the Apnea-Hypopnea Index (AHI), provide limited insight into the multidomain physiology underlying functional recovery. We propose an interpretable, causal-discovery-guided framework for deriving a hierarchical Sleep Recovery Score (SRS) from multimodal PSG. Using two large population cohorts (MESA: n=1,540; MrOS: n=825), we apply directed acyclic graph (DAG) learning to identify candidate physiological drivers spanning respiratory burden, hypoxic burden, sleep fragmentation, sleep architecture, and autonomic regulation. Although derived from clinical PSG, these domains map naturally to sensing streams increasingly available in connected health technologies, including wearable ECG, oximetry, and sleep-stage estimation devices. To preserve mechanistic plausibility, we introduce a two-stage screening process that combines physiology-based constraints with constrained LLM-assisted auditing to identify and remove structural confounders and construct-overlapping variables. Across cohorts, these five domains emerge as recurrent physiological domains associated with recovery, and the resulting SRS shows up to 3.4× stronger alignment with perceived recovery than AHI. By linking multimodal sleep physiology to patient-centered outcomes through an interpretable, bias-aware, and domain-structured framework, this work provides a practical foundation for recovery modeling across both clinical sleep studies and emerging smart and connected health settings.
Sleep occupies roughly one-third of human life, yet many aspects of its physiology remain poorly understood. Large polysomnography (PSG) datasets offer new opportunities to study sleep and its links to disease, but extracting insight from these recordings requires substantial expert effort and remains difficult for general-purpose AI systems. We developed AI Sleep Co-Scientist, an expert-guided environment in which human scientists direct specialist agents for hypothesis development, signal preprocessing, and statistical analysis, reviewing intermediate outputs. Each reported result is linked to the executable code that produced it. Across four cohorts of approximately 124,000 PSG recordings and more than 50 TB of raw signals, we conducted five case studies spanning how sleep physiology relates to future disease, how it distinguishes clinical phenotypes, and how sleep is organized and regulated. Diminished network-level physiological coupling during sleep was associated with incident Parkinson's disease (HR 1.48) and Alzheimer's disease (HR 1.38). A physiologically structured late-fusion sleep-age model outperformed an unconstrained early-fusion approach, and its age residual was associated with incident disease across multiple organ systems. Arousal dynamics characterized comorbid insomnia and sleep apnoea as an intermediate phenotype skewed towards obstructive sleep apnoea, distinguished by prolonged post-arousal wakefulness. Rapid eye movement (REM) bout duration tracked preceding non-REM sleep more closely than intervening wakefulness. Transient-oscillation analysis identified a fast-sigma deficit and excess centrofrontal theta activity in narcolepsy type 1. Together, these findings connect sleep to disease risk, clinical classification, and its own regulation, and show how agentic AI can support large-scale, multimodal discovery.
Sleep is essential for health, yet studying its dynamics requires manual sleep staging, a labor-intensive step in research and clinical care. Across centers, polysomnography (PSG) recordings are traditionally scored in 30-s epochs for pragmatic, not physiological, reasons and vary in electrode count, montage, and subject characteristics. These constraints challenge harmonized multi-center studies and the discovery of robust biomarkers on shorter timescales. We present AnySleep, a deep neural network that scores sleep from any electroencephalography (EEG) or electrooculography (EOG) data at adjustable temporal resolutions. We trained and validated the model on over 20,000 overnight recordings (> 200,000 hours of EEG and EOG) from 28 datasets across multiple clinics to promote robust generalization across sites. The model attains state-of-the-art performance and surpasses or equals established baselines at 30-s epochs. Performance improves with more channels, yet remains strong when EOG is absent or only EOG or single EEG derivations (frontal, central, or occipital) are available. On sub-30-s timescales, the model captures short wake intrusions consistent with arousals and improves prediction of pathophysiological conditions (obstructive sleep apnea, narcolepsy type 1, insomnia) over 30-s scoring. We make the model publicly available to facilitate large-scale studies with heterogeneous electrode setups and accelerate biomarker discovery in sleep.
Sleep physiology arises from the coordinated dynamics of the central nervous system (CNS) and autonomic nervous system (ANS), as reflected by multimodal polysomnography signals including EEG, EOG, EMG, ECG, and respiration. However, existing sleep foundation models often fuse heterogeneous biosignals in a topology-agnostic manner, overlooking their physiological organization. We introduce Omni-Sleep, a sleep foundation model that uses the CNS/ANS partition as a physiological prior for topology-constrained representation learning. Omni-Sleep learns structured representations through three objectives: intra-system consistency, which captures shared subsystem-level factors within neural and cardio-respiratory signals; inter-system synchronization, which aligns subsystem trajectories to model brain--body dynamics; and latent-space masked temporal modeling, which captures long-horizon sleep dynamics. Pre-trained on over 100,000 hours of multi-center multimodal PSG data, Omni-Sleep is evaluated on sleep staging and multi-disease classification. Across datasets and modality-ablation settings, Omni-Sleep outperforms strong foundation-model baselines, showing improved label efficiency, cross-dataset generalization, and robustness to missing modalities. These results highlight the value of physiological hierarchy for generalizable sleep representation learning. Code is available at https://github.com/AutoBrain-sleep/OmniSleep.