Comparison of Drug-Induced Sleep Endoscopy and Natural Sleep Endoscopy in the Assessment of Upper Airway Pathophysiology During Sleep: Protocol and Study Design

Study Objectives: Obstructive sleep apnea (OSA) is increasingly recognized as a complex and heterogenous disorder. As a result, a “one-size-fits-all” management approach should be avoided. Therefore, evaluation of pathophysiological endotyping in OSA patients is emphasized, with upper airway collapse during sleep as one of the main features. To assess the site(s) and pattern(s) of upper airway collapse, natural sleep endoscopy (NSE) is defined as the gold standard. As NSE is labor-intensive and time-consuming, it is not feasible in routine practice. Instead, drug-induced sleep endoscopy (DISE) is the most frequently used technique and can be considered as the clinical standard. Flow shape and snoring analysis are non-invasive measurement techniques, yet are still evolving. Although DISE is used as the clinical alternative to assess upper airway collapse, associations between DISE and NSE observations, and associated flow and snoring signals, have not been quantified satisfactorily. In the current project we aim to compare upper airway collapse identified in patients with OSA using endoscopic techniques as well as flow shape analysis and analysis of tracheal snoring sounds between natural and drug-induced sleep.Methods: This study is a blinded prospective comparative multicenter cohort study. The study population will consist of adult patients with a recent diagnosis of OSA. Eligible patients will undergo a polysomnography (PSG) with NSE overnight and a DISE within 3 months. During DISE the upper airway is assessed under sedation by an experienced ear, nose, throat (ENT) surgeon using a flexible fiberoptic endoscope in the operating theater. In contrast to DISE, NSE is performed during natural sleep using a pediatric bronchoscope. During research DISE and NSE, the standard set-up is expanded with additional PSG measurements, including gold standard flow and analysis of tracheal snoring sounds.Conclusions: This project will be one of the first studies to formally compare collapse patterns during natural and drug-induced sleep. Moreover, this will be, to the authors' best knowledge, the first comparative research in airflow shape and tracheal snoring sounds analysis between DISE and NSE. These novel and non-invasive diagnostic methods studying upper airway mechanics during sleep will be simultaneously validated against DISE and NSE.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04729478.

The Biomechanical Mechanism of Upper Airway Collapse in OSAHS Patients Using Clinical Monitoring Data during Natural Sleep

Obstructive sleep apnea hypopnea syndrome (OSAHS) is a common sleep disorder characterized by repeated pharyngeal collapse with partial or complete obstruction of the upper airway. This study investigates the biomechanics of upper airway collapse of OSASH patients during natural sleep. Computerized tomography (CT) scans and data obtained from a device installed on OSASH patients, which is comprised of micro pressure sensors and temperature sensors, are used to develop a pseudo three-dimensional (3D) finite element (FE) model of the upper airway. With consideration of the gravity effect on the soft palate while patients are in a supine position, a fluid–solid coupling analysis is performed using the FE model for the two respiratory modes, eupnea and apnea. The results of this study show that the FE simulations can provide a satisfactory representation of a patient’s actual respiratory physiological processes during natural sleep. The one-way valve effect of the soft palate is one of the important mechanical factors causing upper airway collapse. The monitoring data and FE simulation results obtained in this study provide a comprehensive understanding of the occurrence of OSAHS and a theoretical basis for the individualized treatment of patients. The study demonstrates that biomechanical simulation is a powerful supplementation to clinical monitoring and evaluation.

Urethane Anesthesia Exhibits Neurophysiological Correlates of Unconsciousness and is Distinct from Sleep

Urethane is a general anesthetic widely used in animal research. It is unique among anesthetics because urethane anesthesia alternates between macroscopically distinct electrographic states: a slow-wave state that resembles NREM sleep (NREMure), and an activated state with features of both REM sleep and wakefulness (REMure). However, the relationship between urethane anesthesia and physiological sleep is still unclear. In this study, electroencephalography (EEG) and electromyography were recorded in chronically prepared rats during natural sleep-wake states and during urethane anesthesia. We subsequently analyzed the EEG signatures associated with the loss of consciousness and found that, in comparison to natural sleep-wake states, the power, coherence, directed connectivity and complexity of brain oscillations are distinct during urethane. We also demonstrate that both urethane states have clear EEG signatures of general anesthesia. Thus, despite superficial similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anesthesia differ from physiological sleep states.

Stability of neocortical synapses across sleep and wake states during the critical period in rats

Sleep is important for brain plasticity, but its exact function remains mysterious. An influential but controversial idea is that a crucial function of sleep is to drive widespread downscaling of excitatory synaptic strengths. Here we used real-time sleep classification, ex vivo measurements of postsynaptic strength, and in vivo optogenetic monitoring of thalamocortical synaptic efficacy to ask whether sleep and wake states can constitutively drive changes in synaptic strength within the neocortex of juvenile rats. We found that miniature EPSC amplitudes onto L4 and L2/3 pyramidal neurons were stable across sleep and wake dense epochs in both primary visual (V1) and prefrontal cortex (PFC). Further, chronic monitoring of thalamocortical synaptic efficacy in V1 of freely behaving animals revealed stable responses across even prolonged periods of natural sleep and wake. Together these data demonstrate that sleep does not drive widespread downscaling of synaptic strengths during the highly plastic critical period in juvenile animals. Whether this remarkable stability across sleep and wake generalizes to the fully mature nervous system remains to be seen.

The Sleep Modeling in the Human Organism

There are three alternating states of vigilance throughout our lives: wakefulness, NREM, and REM sleep. We usually yawn before falling asleep. Yawning is an ancient reaction, an instinctive action, manifested in a person by drowsiness or boredom. Yawning is often associated with the need for stretching. Yawning is a less strong territorial reflex. During deep sleep muscular tone is sharply reduced. Relaxation of the muscles and the lowering of their tone, howeever, are not constant and necessary components of sleep. Analysis of EEG recordings soon revealed that sleep is by no means a uniform process, but can be divided into at least two sharply separated states: one is characterized by slow waves in the EEG that are completely separate from the activity of wakefulness: this so-called slow wave sleep; the other is the so-called paradoxical sleep. Hypnopedia, as a discipline, deals with the input of fixed information introduced during the period of natural sleep, also known as sleep learning. Our hypnopedia researches was a pleasant surprise, because they were able to reproduce texts they did not know with an efficiency of approx. 25%.

Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways

Non-rapid eye movement (NREM) sleep, characterized by slow-wave electrophysiological activity, underlies several critical functions, including learning and memory. However, NREM sleep is heterogeneous, varying in duration, depth, and spatially across the cortex. While these NREM sleep features are thought to be largely independently regulated, there is also evidence that they are mechanistically coupled. To investigate how cortical NREM sleep features are controlled, we examined the astrocytic network, comprising a cortex-wide syncytium that influences population-level neuronal activity. We quantified endogenous astrocyte activity in mice over natural sleep and wake, then manipulated specific astrocytic G-protein-coupled receptor (GPCR) signaling pathways in vivo. We find that astrocytic Gi- and Gq-coupled GPCR signaling separately control NREM sleep depth and duration, respectively, and that astrocytic signaling causes differential changes in local and remote cortex. These data support a model in which the cortical astrocyte network serves as a hub for regulating distinct NREM sleep features.