Multi-night home assessment of sleep structure in OSA with and without insomnia.

OBJECTIVE: To explore sleep structure in participants with obstructive sleep apnea (OSA) and comorbid insomnia (COMISA) and participants with OSA without insomnia (OSA-only) using both single-night polysomnography and multi-night wrist-worn photoplethysmography/accelerometry. METHODS: Multi-night 4-class sleep-staging was performed with a validated algorithm based on actigraphy and heart rate variability, in 67 COMISA (23 women, median age: 51 years) and 50 OSA-only (15 women, median age: 51) participants. Sleep statistics were compared using linear regression models and mixed-effects models. Multi-night variability was explored using a clustering approach and between- and within-participant analysis. RESULTS: Polysomnographic parameters showed no significant group differences. Multi-night measurements, during 13.4 ± 5.2 nights per subject, demonstrated a longer sleep onset latency and lower sleep efficiency for the COMISA group. Detailed analysis of wake parameters revealed longer mean durations of awakenings in COMISA, as well as higher numbers of awakenings lasting 5 min and longer (WKN≥5min) and longer wake after sleep onset containing only awakenings of 5 min or longer. Within-participant variance was significantly larger in COMISA for sleep onset latency, sleep efficiency, mean duration of awakenings and WKN≥5min. Unsupervised clustering uncovered three clusters; participants with consistently high values for at least one of the wake parameters, participants with consistently low values, and participants displaying higher variability. CONCLUSION: Patients with COMISA more often showed extended, and more variable periods of wakefulness. These observations were not discernible using single night polysomnography, highlighting the relevance of multi-night measurements to assess characteristics indicative for insomnia.

Performance of cardiorespiratory-based sleep staging in patients using beta blockers.

STUDY OBJECTIVES: Automatic sleep staging based on cardiorespiratory signals from home sleep monitoring devices holds great clinical potential. Using state-of-the-art machine learning, promising performance has been reached in patients with sleep disorders. However, it is unknown whether performance would hold in individuals with potentially altered autonomic physiology, for example under the influence of medication. Here, we assess an existing sleep staging algorithm in patients with sleep disorders with and without the use of beta blockers. METHODS: We analyzed a retrospective dataset of sleep recordings of 57 patients with sleep disorders using beta blockers and 57 age-matched patients with sleep disorders not using beta blockers. Sleep stages were automatically scored based on electrocardiography and respiratory effort from a thoracic belt, using a previously developed machine-learning algorithm (CReSS algorithm). For both patient groups, sleep stages classified by the model were compared to gold standard manual polysomnography scoring using epoch-by-epoch agreement. Additionally, for both groups, overall sleep parameters were calculated and compared between the two scoring methods. RESULTS: Substantial agreement was achieved for four-class sleep staging in both patient groups (beta blockers: kappa = 0.635, accuracy = 78.1%; controls: kappa = 0.660, accuracy = 78.8%). No statistical difference in epoch-by-epoch agreement was found between the two groups. Additionally, the groups did not differ on agreement of derived sleep parameters. CONCLUSIONS: We showed that the performance of the CReSS algorithm is not deteriorated in patients using beta blockers. Results do not indicate a fundamental limitation in leveraging autonomic characteristics to obtain a surrogate measure of sleep in this clinically relevant population. CITATION: Hermans L, van Meulen F, Anderer P, et al. Performance of cardiorespiratory-based sleep staging in patients using beta blockers. J Clin Sleep Med. 2024;20(4):575-581.

Heart rate response to cortical arousals in patients with isolated obstructive sleep apnea and with comorbid insomnia (COMISA).

PURPOSE: Comorbid insomnia often occurs in patients with obstructive sleep apnea (OSA), referred to as COMISA. Cortical arousals manifest as a common feature in both OSA and insomnia, often accompanied by elevated heart rate (HR). Our objective was to evaluate the heart rate response to nocturnal cortical arousals in patients with COMISA and patients with OSA alone. METHODS: We analyzed data from patients with COMISA and from patients with OSA matched for apnea-hypopnea index. Sleep staging and analysis of respiratory events and cortical arousals were performed using the Philips Somnolyzer automatic scoring system. Beat-by-beat HR was analyzed from the onset of the cortical arousal to 30 heartbeats afterwards. HR responses were divided into peak and recovery phases. Cortical arousals were separately evaluated according to subtype (related to respiratory events and spontaneous) and duration (3-6 s, 6-10 s, 10-15 s). RESULTS: A total of 72 patients with COMISA and 72 patients with OSA were included in this study. There were no overall group differences in the number of cortical arousals with and without autonomic activation. No significant differences were found for spontaneous cortical arousals. The OSA group had more cortical arousals related to respiratory events (21.0 [14.8-30.0] vs 16.0 [9.0-27.0], p = 0.016). However, the COMISA group had longer cortical arousals (7.2 [6.4-7.8] vs 6.7 [6.2-7.7] s, p = 0.024) and the HR recovery phase was prolonged (52.5 [30.8-82.5] vs 40.0 [21.8-55.5] beats/min, p = 0.017). Both the peak and the recovery phase for longer cortical arousals with a duration of 10-15 s were significantly higher in patients with COMISA compared to patients with OSA (47.0 [27.0-97.5] vs 34.0 [21.0-71.0] beats/min, p = 0.032 and 87.0 [47.0-132.0] vs 71.0 [43.0-103.5] beats/min, p = 0.049, respectively). CONCLUSIONS: The HR recovery phase after cortical arousals related to respiratory events is prolonged in patients with COMISA compared to patients with OSA alone. This response could be indicative of the insomnia component in COMISA.

Sleep structure in patients with COMISA compared to OSA and insomnia.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and insomnia frequently co-occur, making diagnosis and treatment challenging. We investigated differences in sleep structure between patients with OSA, insomnia, and comorbid insomnia and sleep apnea (COMISA) to identify characteristics that can be used to improve the diagnosis of COMISA. METHODS: We obtained polysomnography data of 326 patients from the Sleep and OSA Monitoring with Non-Invasive Applications database. The group included patients with OSA (n = 199), insomnia (n = 47), and COMISA (n = 80). We compared statistics related to sleep structure between the 3 patient groups. RESULTS: Wake after sleep onset was significantly shorter for the OSA group (median: 60.0 minutes) compared to the COMISA (median: 83.3 minutes, P < .01) and the insomnia (median: 83.5 minutes, P = .01) groups. No significant differences were found in the total number of awakenings and the number of short (up to and including 2 minutes) and medium-length awakenings (2.5 up to and including 4.5 minutes). However, the number of long awakenings (5 minutes or longer) and wake after sleep onset containing only long awakenings was significantly lower for patients with OSA (median: 2 awakenings and 25.5 minutes) compared to patients with COMISA (median: 3 awakenings, P < .01 and 43.3 minutes, P < .001) or with insomnia (median: 3 awakenings, P < .01 and 56.0 minutes, P < .001). Total sleep time was significantly longer and sleep efficiency was significantly higher for the OSA group (median: 418.5 minutes and 84.4%) compared to both the COMISA (median: 391.5 minutes, P < .001 and 77.3%, P < .001) and the insomnia (median: 381.5 minutes, P < .001 and 78.2%, P < .001) groups. The number of sleep-stage transitions during the night for patients with COMISA (median: 194.0) was lower compared to that for patients with OSA (median: 218.0, P < .01) and higher compared to that for patients with insomnia (median: 156.0, P < .001). Other sleep architectural parameters were not discriminative between the groups. CONCLUSIONS: Patients with COMISA show specific characteristics of insomnia, including prolonged awakenings. This variable is distinctive in comparison to patients with OSA. The combination of prolonged awakenings and the presence of sleep-disordered breathing leads to increased sleep disturbance compared to patients having only 1 of the sleep disorders. CITATION: Wulterkens BM, Hermans LWA, Fonseca P, et al. Sleep structure in patients with COMISA compared to OSA and insomnia. J Clin Sleep Med. 2023;19(6):1051-1059.

Interpretation and further development of the hypnodensity representation of sleep structure.

Objective.The recently-introduced hypnodensity graph provides a probability distribution over sleep stages per data window (i.e. an epoch). This work explored whether this representation reveals continuities that can only be attributed to intra- and inter-rater disagreement of expert scorings, or also to co-occurrence of sleep stage-dependent features within one epoch.Approach.We proposed a simplified model for time series like the ones measured during sleep, and a second model to describe the annotation process by an expert. Generating data according to these models, enabled controlled experiments to investigate the interpretation of the hypnodensity graph. Moreover, the influence of both the supervised training strategy, and the used softmax non-linearity were investigated. Polysomnography recordings of 96 healthy sleepers (of which 11 were used as independent test set), were subsequently used to transfer conclusions to real data.Main results.A hypnodensity graph, predicted by a supervised neural classifier, represents the probability with which the sleep expert(s) assigned a label to an epoch. It thus reflects annotator behavior, and is thereby only indirectly linked to the ratio of sleep stage-dependent features in the epoch. Unsupervised training was shown to result in hypnodensity graph that were slightly less dependent on this annotation process, resulting in, on average, higher-entropy distributions over sleep stages (Hunsupervised= 0.41 versusHsupervised= 0.29). Moreover, pre-softmax predictions were, for both training strategies, found to better reflect the ratio of sleep stage-dependent characteristics in an epoch, as compared to the post-softmax counterparts (i.e. the hypnodensity graph). In real data, this was observed from the linear relation between pre-softmax N3 predictions and the amount of delta power.Significance.This study provides insights in, and proposes new, representations of sleep that may enhance our comprehension about sleep and sleep disorders.

Self-Organizing Maps for Contrastive Embeddings of Sleep Recordings.

Nowadays, high amounts of data can be acquired in various applications, spurring the need for interpretable data representations that provide actionable insights. Algorithms that yield such representations ideally require as little a priori knowledge about the data or corresponding annotations as possible. To this end, we here investigate the use of Kohonen's Self-Organizing Map (SOM) in combination with data-driven low-dimensional embeddings obtained through self-supervised Contrastive Predictive Coding. We compare our approach to embeddings found with an auto-encoder and, moreover, investigate three ways to deal with node selection during SOM optimization. As a challenging experiment we analyze nocturnal sleep recordings of healthy subjects, and conclude that - for this noisy real-life data - contrastive learning yields a better low-dimensional embedding for the purpose of SOM training, compared to an auto-encoder. In addition, we show that a stochastic temperature-annealed SOM-training outperforms both a deterministic and a non-temperature-annealed stochastic approach. Clinical relevance - The hypnogram has for decades been the clinical standard in sleep medicine despite the fact that it is a highly simplified representation of a polysomnography recording. We propose a sensor-agnostic algorithm that is able to reveal more intricate patterns in sleep recordings which might teach us about sleep structure and sleep disorders.

Representations of temporal sleep dynamics: Review and synthesis of the literature.

Sleep is characterized by an intricate variation of brain activity over time. Measuring these temporal sleep dynamics is relevant for elucidating healthy and pathological sleep mechanisms. The rapidly increasing possibilities for obtaining and processing sleep registrations have led to an abundance of data, which can be challenging to analyze and interpret. This review provides a structured overview of approaches to represent temporal sleep dynamics, categorized based on the way the source data is compressed. For each category of representations, we describe advantages and disadvantages. Standard human-defined 30-s sleep stages have the advantages of standardization and interpretability. Alternative human-defined representations are less standardized but offer a higher temporal resolution (in case of microstructural events such as sleep spindles), or reflect non-categorical information (for example spectral power analysis). Machine-learned representations offer additional possibilities: automated sleep stages are useful for handling large quantities of data, while alternative sleep stages obtained from clustering data-driven features could aid finding new patterns and new possible clinical interpretations. While newly developed sleep representations may offer relevant insights, they can be difficult to interpret in for example a clinical context. Therefore, there should always be a balance between developing these sophisticated sleep analysis techniques and maintaining clinical explainability.

Validation of the Dutch translation of the Paris Arousal Disorders Severity Scale for non-REM parasomnias in a 1-year and 1-month version.

STUDY OBJECTIVES: We created a Dutch version of the Paris Arousal Disorders Severity Scale (PADSS), which assesses non-rapid eye movement (NREM) parasomnia symptoms over the past year (PADSS-year). This questionnaire was previously validated in patients with sleep walking and/or sleep terrors (SW/ST). We validated the questionnaire in SW/ST patients, and in a broader population, including patients with confusional arousals, comorbidities, and medication users ("other NREM parasomnias"). Furthermore, we introduced a version covering the past month (PADSS-month), with the potential purpose of evaluating symptom evolution and treatment response. METHODS: We compared PADSS scores among 54 SW/ST patients, 34 age-matched controls, and 23 patients with other NREM parasomnias. We evaluated discriminative capacity, internal consistency, and construct validity. Furthermore, we assessed the test-retest reliability and treatment response of PADSS-month. RESULTS: Healthy controls scored significantly lower than both patient groups. We found an excellent diagnostic accuracy (area under the curve PADSS-year 0.990, PADSS-month 0.987) and an acceptable internal consistency. Exploratory factor analysis identified 3 components: "behaviors outside the bed," "behaviors in/around the bed," and "violent behaviors," with the former 2 factors reflecting the distinction between SW and ST. PADSS-month showed an acceptable test-retest reliability (0.75). Additionally, PADSS-month significantly decreased after pharmaceutical and/or behavioral treatment. This change was correlated with the clinical impression of the caregiver, implying that PADSS-month is sensitive to treatment effects. CONCLUSIONS: The Dutch PADSS questionnaire can be used as a screening tool in a broad population of patients with NREM parasomnia, not only SW/ST. Furthermore, we validated a PADSS-month version to assess the evolution of symptoms and treatment effect. CITATION: van Mierlo P, Hermans L, Arnulf I, Pijpers A, Overeem S, van Gilst M. Validation of the Dutch translation of the Paris Arousal Disorders Severity Scale for non-REM parasomnias in a 1-year and 1-month version. J Clin Sleep Med. 2022;18(4):1135-1143.

It is All in the Wrist: Wearable Sleep Staging in a Clinical Population versus Reference Polysomnography.

PURPOSE: There is great interest in unobtrusive long-term sleep measurements using wearable devices based on reflective photoplethysmography (PPG). Unfortunately, consumer devices are not validated in patient populations and therefore not suitable for clinical use. Several sleep staging algorithms have been developed and validated based on ECG-signals. However, translation from these techniques to data derived by wearable PPG is not trivial, and requires the differences between sensing modalities to be integrated in the algorithm, or having the model trained directly with data obtained with the target sensor. Either way, validation of PPG-based sleep staging algorithms requires a large dataset containing both gold standard measurements and PPG-sensor in the applicable clinical population. Here, we take these important steps towards unobtrusive, long-term sleep monitoring. METHODS: We developed and trained an algorithm based on wrist-worn PPG and accelerometry. The method was validated against reference polysomnography in an independent clinical population comprising 244 adults and 48 children (age: 3 to 82 years) with a wide variety of sleep disorders. RESULTS: The classifier achieved substantial agreement on four-class sleep staging with an average Cohen's kappa of 0.62 and accuracy of 76.4%. For children/adolescents, it achieved even higher agreement with an average kappa of 0.66 and accuracy of 77.9%. Performance was significantly higher in non-REM parasomnias (kappa = 0.69, accuracy = 80.1%) and significantly lower in REM parasomnias (kappa = 0.55, accuracy = 72.3%). A weak correlation was found between age and kappa (ρ = -0.30, p<0.001) and age and accuracy (ρ = -0.22, p<0.001). CONCLUSION: This study shows the feasibility of automatic wearable sleep staging in patients with a broad variety of sleep disorders and a wide age range. Results demonstrate the potential for ambulatory long-term monitoring of clinical populations, which may improve diagnosis, estimation of severity and follow up in both sleep medicine and research.

Sleep-Wake Survival Dynamics in People with Insomnia.

INTRODUCTION: Assessing objective measures of sleep fragmentation could yield important features reflecting impaired sleep quality in people with insomnia. Survival analysis allows the specific examination of the stability of NREM sleep, REM sleep and wake. The objective of this study was to assess the differences between survival dynamics of NREM sleep, REM sleep and wake between people with insomnia and healthy controls. METHODS: We analyzed retrospective polysomnography recordings from 86 people with insomnia and 94 healthy controls. For each participant, survival dynamics of REM sleep, NREM sleep and wake were represented using Weibull distributions. We used lasso penalized parameter selection in combination with linear regression to analyze the difference between participant groups with respect to the Weibull scale and shape parameters, while correcting for age, sex, total sleep time and relevant interaction effects. RESULTS: Significant effects of group were found for the NREM scale parameter, and for the wake scale and shape parameters. Results indicated that people with insomnia had less stable NREM sleep and more stable wake after sleep onset compared to healthy controls. Additionally, the altered distribution of wake segment lengths indicated an increased difficulty to fall asleep after longer awakenings in the insomnia group. However, these differences were mainly observed in younger participants. Significant effects of group for the survival parameters of REM sleep were not found. CONCLUSION: As illustrated by our results, survival analysis can be very useful for disentangling different types of sleep fragmentation in people with insomnia. For instance, the current findings suggest that people with insomnia have an increased fragmentation of NREM sleep, but not necessarily of REM sleep. Additional research into the underlying mechanisms of NREM sleep fragmentation could possibly lead to a better understanding of impaired sleep quality in people with insomnia, and consequently to improved treatment.

Assessing sleep-wake survival dynamics in relation to sleep quality in a placebo-controlled pharmacological intervention study with people with insomnia and healthy controls.

RATIONALE: The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed. OBJECTIVES: The aim of this study is to explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality. METHODS: We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors. RESULTS: In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16, p = 0.32; treatment F = 8.89, p < 0.01; group x treatment F = 0.44, p = 0.65), while the segment length of wake was decreased (group F = 1.48, p = 0.23; treatment F = 11.49, p < 0.01; group x treatment F = 0.36, p = 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08, p < 0.01, treatment F = 10.8, p < 0.01, group x treatment F = 2.49, p = 0.09; model-estimated F = 1.70, p = 0.19, treatment F = 16.1, p < 0.001, group x treatment F = 0.60, p = 0.55). The prediction error was not altered (group F = 1.62, p = 0.20; treatment F = 0.20, p = 0.65; group x treatment F = 1.01, p = 0.37). CONCLUSIONS: Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.

Modeling sleep onset misperception in insomnia.

OBJECTIVES: To extend and validate a previously suggested model of the influence of uninterrupted sleep bouts on sleep onset misperception in a large independent data set. METHODS: Polysomnograms and sleep diaries of 139 insomnia patients and 92 controls were included. We modeled subjective sleep onset as the start of the first uninterrupted sleep fragment longer than Ls minutes, where parameter Ls reflects the minimum length of a sleep fragment required to be perceived as sleep. We compared the so-defined sleep onset latency (SOL) for various values of Ls. Model parameters were compared between groups, and across insomnia subgroups with respect to sleep onset misperception, medication use, age, and sex. Next, we extended the model to incorporate the length of wake fragments. Model performance was assessed by calculating root mean square errors (RMSEs) of the difference between estimated and perceived SOL. RESULTS: Participants with insomnia needed a median of 34 minutes of undisturbed sleep to perceive sleep onset, while healthy controls needed 22 minutes (Mann-Whitney U = 4426, p < 0.001). Similar statistically significant differences were found between sleep onset misperceivers and non-misperceivers (median 40 vs. 20 minutes, Mann-Whitney U = 984.5, p < 0.001). Model outcomes were similar across other subgroups. Extended models including wake bout lengths resulted in only marginal improvements of model outcome. CONCLUSIONS: Patients with insomnia, particularly sleep misperceivers, need larger continuous sleep bouts to perceive sleep onset. The modeling approach yields a parameter for which we coin the term Sleep Fragment Perception Index, providing a useful measure to further characterize sleep state misperception.

Sleep onset (mis)perception in relation to sleep fragmentation, time estimation and pre-sleep arousal.

STUDY OBJECTIVE: To elucidate the contribution of time estimation and pre sleep arousal to the component of sleep onset misperception not explained by sleep fragmentation. METHODS: At-home ambulatory polysomnograms (PSGs) of 31 people with insomnia were recorded. Participants performed a time estimation task and completed the Pre Sleep Arousal Scale (PSAS). Based on previous modelling of the relationship between objectively measured sleep fragmentation and sleep onset misperception, the subjective sleep onset was estimated for each participant as the start of the first uninterrupted sleep bout longer than 30 min. Subsequently, the component of misperception not explained by sleep fragmentation was calculated as the residual error between estimated sleep onset and perceived sleep onset. This residual error was correlated with individual time estimation task results and PSAS scores. RESULTS: A negative correlation between time estimation task results and the residual error of the sleep onset model was found, indicating that participants who overestimated a time interval during the day also overestimated their sleep onset latency (SOL). No correlation was found between PSAS scores and residual error. CONCLUSIONS: Interindividual variations of sleep architecture possibly obscure the correlation of sleep onset misperception with time estimation and pre sleep arousal, especially in small groups. Therefore, we used a previously proposed model to account for the influence of sleep fragmentation. Results indicate that time estimation is associated with sleep onset misperception. Since sleep onset misperception appears to be a general characteristic of insomnia, understanding the underlying mechanisms is probably important for understanding and treating insomnia.

Sleep EEG characteristics associated with sleep onset misperception.

STUDY OBJECTIVE: To study sleep EEG characteristics associated with misperception of Sleep Onset Latency (SOL). METHODS: Data analysis was based on secondary analysis of standard in-lab polysomnographic recordings in 20 elderly people with insomnia and 21 elderly good sleepers. Parameters indicating sleep fragmentation, such as number of awakenings, wake after sleep onset (WASO) and percentage of NREM1 were extracted from the polsysomnogram, as well as spectral power, microarousals and sleep spindle index. The correlation between these parameters during the first sleep cycle and the amount of misperceived sleep was assessed in the insomnia group. Additionally, we made a model of the minimum duration that a sleep fragment at sleep onset should have in order to be perceived as sleep, and we fitted this model to subjective SOLs of both subject groups. RESULTS: Misperception of SOL was associated with increased percentage of NREM1 and more WASO during sleep cycle 1. For insomnia subjects, the best fit of modelled SOL with subjective SOL was found when assuming that sleep fragments shorter than 30 min at sleep onset were perceived as wake. The model indicated that healthy subjects are less sensitive to sleep interruptions and perceive fragments of 10 min or longer as sleep. CONCLUSIONS: Our findings suggest that sleep onset misperception is related to sleep fragmentation at the beginning of the night. Moreover, we show that people with insomnia needed a longer duration of continuous sleep for the perception as such compared to controls. Further expanding the model could provide more detailed information about the underlying mechanisms of sleep misperception.