Multicomponent Analysis of Sleep Using Electrocortical, Respiratory, Autonomic and Hemodynamic Signals Reveals Distinct Features of Stable and Unstable NREM and REM Sleep.

A new concept of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep is proposed, that of multi-component integrative states that define stable and unstable sleep, respectively, NREMS, NREMUS REMS, and REMUS. Three complementary data sets are used: obstructive sleep apnea (20), healthy subjects (11), and high loop gain sleep apnea (50). We use polysomnography (PSG) with beat-to-beat blood pressure monitoring, and electrocardiogram (ECG)-derived cardiopulmonary coupling (CPC) analysis to demonstrate a bimodal, rather than graded, characteristic of NREM sleep. Stable NREM (NREMS) is characterized by high probability of occurrence of the <1 Hz slow oscillation, high delta power, stable breathing, blood pressure dipping, strong sinus arrhythmia and vagal dominance, and high frequency CPC. Conversely, unstable NREM (NREMUS) has the opposite features: a fragmented and discontinuous <1 Hz slow oscillation, non-dipping of blood pressure, unstable respiration, cyclic variation in heart rate, and low frequency CPC. The dimension of NREM stability raises the possibility of a comprehensive integrated multicomponent network model of NREM sleep which captures sleep onset (e.g., ventrolateral preoptic area-based sleep switch) processes, synaptic homeostatic delta power kinetics, and the interaction of global and local sleep processes as reflected in the spatiotemporal evolution of cortical "UP" and "DOWN" states, while incorporating the complex dynamics of autonomic-respiratory-hemodynamic systems during sleep. Bimodality of REM sleep is harder to discern in health. However, individuals with combined obstructive and central sleep apnea allows ready recognition of REMS and REMUS (stable and unstable REM sleep, respectively), especially when there is a discordance of respiratory patterns in relation to conventional stage of sleep.

Estimation of adaptive ventilation success and failure using polysomnogram and outpatient therapy biomarkers.

Study Objectives: Adaptive servo-ventilation (ASV) devices provide anticyclic pressure support for the treatment of central and/or complex sleep apnea, including heart failure patients. Variability in responses in the clinic and negative clinical trials motivated assessment of standard and novel signal biomarkers for ASV efficacy. Methods: Multiple clinical databases were queried to assess potential signal biomarkers of ASV effectiveness, including the following: (1) attended laboratory adaptive ventilation titrations: 108, of which 66 had mainstream ETCO2 measurements; (2) AirView data in 98 participants, (3) complete data, from diagnostic polysomnogram (PSG) through review and prospective analysis of on-therapy data using SleepyHead freeware in 44 participants; and (4) hemodynamic data in the form of beat-to-beat blood pressure during ASV titration, using a Finometer in five participants. Results: Signal biomarkers of reduced ASV efficacy were noted as follows: (1) an arousal index which markedly exceeded the respiratory event index during positive pressure titration; (2) persistent pressure cycling during long-term ASV therapy, visible in online review systems or reviewing data using freeware; (3) the ASV-associated pressure cycling induced arousals, sleep fragmentation, and blood pressure surges; and (4) elevated ratios of 95th percentile to median tidal volume, minute ventilation, and respiratory rate were associated with pressure cycling. High intraclass coefficients (>0.8) for machine apnea-hypopnea index and other extractable metrics were consistent with stability of patterns over multiple nights of use. Global clinical outcomes correlated negatively with pressure cycling. Conclusions: Potential polysomnographic- and device-related signal biomarkers of ASV efficacy are described and may allow improved estimation of therapeutic effectiveness of adaptive ventilation.

Cardiopulmonary coupling spectrogram as an ambulatory clinical biomarker of sleep stability and quality in health, sleep apnea, and insomnia.

STUDY OBJECTIVES: Ambulatory tracking of sleep and sleep pathology is rapidly increasing with the introduction of wearable devices. The objective of this study was to evaluate a wearable device which used novel computational analysis of the electrocardiogram (ECG), collected over multiple nights, as a method to track the dynamics of sleep quality in health and disease. METHODS: This study used the ECG as a primary signal, a wearable device, the M1, and an analysis of cardiopulmonary coupling to estimate sleep quality. The M1 measures trunk movements, the ECG, body position, and snoring vibrations. Data from three groups of patients were analyzed: healthy participants and people with sleep apnea and insomnia, obtained from multiple nights of recording. Analysis focused on summary measures and night-to-night variability, specifically the intraclass coefficient. RESULTS: Data were collected from 10 healthy participants, 18 people with positive pressure-treated sleep apnea, and 20 people with insomnia, 128, 65, and 121 nights, respectively. In any participant, all nights were consecutive. High-frequency coupling (HFC), the signal biomarker of stable breathing and stable sleep, showed high intraclass coefficients (ICCs) in healthy participants and people with sleep apnea (0.83, 0.89), but only 0.66 in people with insomnia. The only statistically significant difference between weekday and weekend in healthy subjects was HFC duration: 242.8 ± 53.8 vs. 275.8 ± 57.1 minutes (89 vs. 39 total nights), F(1,126) = 9.86, p = .002. CONCLUSIONS: The M1 and similar wearable devices provide new opportunities to measure sleep in dynamic ways not possible before. These measurements can yield new biological insights and aid clinical management.

Large-Scale Automated Sleep Staging.

Study Objectives: Automated sleep staging has been previously limited by a combination of clinical and physiological heterogeneity. Both factors are in principle addressable with large data sets that enable robust calibration. However, the impact of sample size remains uncertain. The objectives are to investigate the extent to which machine learning methods can approximate the performance of human scorers when supplied with sufficient training cases and to investigate how staging performance depends on the number of training patients, contextual information, model complexity, and imbalance between sleep stage proportions. Methods: A total of 102 features were extracted from six electroencephalography (EEG) channels in routine polysomnography. Two thousand nights were partitioned into equal (n = 1000) training and testing sets for validation. We used epoch-by-epoch Cohen's kappa statistics to measure the agreement between classifier output and human scorer according to American Academy of Sleep Medicine scoring criteria. Results: Epoch-by-epoch Cohen's kappa improved with increasing training EEG recordings until saturation occurred (n = ~300). The kappa value was further improved by accounting for contextual (temporal) information, increasing model complexity, and adjusting the model training procedure to account for the imbalance of stage proportions. The final kappa on the testing set was 0.68. Testing on more EEG recordings leads to kappa estimates with lower variance. Conclusion: Training with a large data set enables automated sleep staging that compares favorably with human scorers. Because testing was performed on a large and heterogeneous data set, the performance estimate has low variance and is likely to generalize broadly.