Background Changes in autonomic control cause regular breathing during NREM sleep to fluctuate during REM. Piezoelectric cage-floor sensors have been used to successfully discriminate sleep and wake states in mice based on signal features related to respiration and other movements. This study presents a classifier for noninvasively classifying REM and NREM using a piezoelectric sensor. New Method Vigilance state was scored manually in 4-second epochs for 24-hour EEG/EMG recordings in twenty mice. An unsupervised classifier clustered piezoelectric signal features quantifying movement and respiration into three states: one active; and two inactive with regular and irregular breathing respectively. These states were hypothesized to correspond to Wake, NREM, and REM respectively. States predicted by the classifier were compared against manual EEG/EMG scores to test this hypothesis. Results Using only piezoelectric signal features, an unsupervised classifier distinguished Wake with high (89% sensitivity, 96% specificity) and REM with moderate (73% sensitivity, 75% specificity) accuracy, but NREM with poor sensitivity (51%) and high specificity (96%). The classifier sometimes confused light NREM sleep—characterized by irregular breathing and moderate delta EEG power—with REM. A supervised classifier improved sensitivities to 90, 81, and 67% and all specificities to over 90% for Wake, NREM, and REM respectively. Comparison with Existing Methods Unlike most actigraphic techniques, which only differentiate sleep from wake, the proposed piezoelectric method further dissects sleep based on breathing regularity into states strongly correlated with REM and NREM. Conclusions This approach could facilitate large-sample screening for genes influencing different sleep traits, besides drug studies or other manipulations.

Physiological closed-loop controlled medical devices automatically adjust therapy delivered to a patient to adjust a measured physiological variable. In critical care scenarios, these types of devices could automate, for example, fluid resuscitation, drug delivery, mechanical ventilation, and/or anesthesia and sedation. Evidence from simulations using computational models of physiological systems can play a crucial role in the development of physiological closed-loop controlled devices; but the utility of this evidence will depend on the credibility of the computational model used. Computational models of physiological systems can be complex with numerous nonlinearities, time-varying properties, and unknown parameters, which leads to challenges in model assessment. Given the wide range of potential uses of computational patient models in the design and evaluation of physiological closed-loop controlled systems, and the varying risks associated with the diverse uses, the specific model as well as the necessary evidence to make a model credible for a use case may vary. In this review, we examine the various uses of computational patient models in the design and evaluation of critical care physiological closed-loop controlled systems (e.g., hemodynamic stability, mechanical ventilation, anesthetic delivery) as well as the types of evidence (e.g., verification, validation, and uncertainty quantification activities) presented to support the model for that use. We then examine and discuss how a credibility assessment framework (American Society of Mechanical Engineers Verification and Validation Subcommittee, V&V 40 Verification and Validation in Computational Modeling of Medical Devices) for medical devices can be applied to computational patient models used to test physiological closed-loop controlled systems.

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