Georg Gruber

An E-Health Solution for Automatic Sleep Classification according to Rechtschaffen and Kales: Validation Study of the Somnolyzer 24 × 7 Utilizing the Siesta Database

To date, the only standard for the classification of sleep-EEG recordings that has found worldwide acceptance are the rules published in 1968 by Rechtschaffen and Kales. Even though several attempts have been made to automate the classification process, so far no method has been published that has proven its validity in a study including a sufficiently large number of controls and patients of all adult age ranges. The present paper describes the development and optimization of an automatic classification system that is based on one central EEG channel, two EOG channels and one chin EMG channel. It adheres to the decision rules for visual scoring as closely as possible and includes a structured quality control procedure by a human expert. The final system (Somnolyzer 24 × 7™) consists of a raw data quality check, a feature extraction algorithm (density and intensity of sleep/wake-related patterns such as sleep spindles, delta waves, SEMs and REMs), a feature matrix plausibility check, a classifier designed as an expert system, a rule-based smoothing procedure for the start and the end of stages REM, and finally a statistical comparison to age- and sex-matched normal healthy controls (Siesta Spot Report™). The expert system considers different prior probabilities of stage changes depending on the preceding sleep stage, the occurrence of a movement arousal and the position of the epoch within the NREM/REM sleep cycles. Moreover, results obtained with and without using the chin EMG signal are combined. The Siesta polysomnographic database (590 recordings in both normal healthy subjects aged 20–95 years and patients suffering from organic or nonorganic sleep disorders) was split into two halves, which were randomly assigned to a training and a validation set, respectively. The final validation revealed an overall epoch-by-epoch agreement of 80% (Cohen’s kappa: 0.72) between the Somnolyzer 24 × 7 and the human expert scoring, as compared with an inter-rater reliability of 77% (Cohen’s kappa: 0.68) between two human experts scoring the same dataset. Two Somnolyzer 24 × 7 analyses (including a structured quality control by two human experts) revealed an inter-rater reliability close to 1 (Cohen’s kappa: 0.991), which confirmed that the variability induced by the quality control procedure, whereby approximately 1% of the epochs (in 9.5% of the recordings) are changed, can definitely be neglected. Thus, the validation study proved the high reliability and validity of the Somnolyzer 24 × 7 and demonstrated its applicability in clinical routine and sleep studies.

Sleep spindle-related activity in the human EEG and its relation to general cognitive and learning abilities.

Stage 2 sleep spindles have been previously viewed as useful markers for the development and integrity of the CNS and were more currently linked to ‘offline re‐processing’ of implicit as well as explicit memory traces. Additionally, it had been discussed if spindles might be related to a more general learning or cognitive ability. In the present multicentre study we examined the relationship of automatically detected slow (< 13 Hz) and fast (> 13 Hz) stage 2 sleep spindles with: (i) the Ravens Advanced Progressive Matrices (testing ‘general cognitive ability’); as well as (ii) the Wechsler Memory scale‐revised (evaluating memory in various subdomains). Forty‐eight healthy subjects slept three times (separated by 1 week) for a whole night in a sleep laboratory with complete polysomnographic montage. Whereas the first night only served adaptation and screening purposes, the two remaining nights were preceded either by an implicit mirror‐tracing or an explicit word‐pair association learning or (corresponding) control task. Robust relationships of slow and fast sleep spindles with both cognitive as well as memory abilities were found irrespectively of whether learning occurred before sleep. Based on the present findings we suggest that besides being involved in shaping neuronal networks after learning, sleep spindles do reflect important aspects of efficient cortical‐subcortical connectivity, and are thereby linked to cognitive‐ and memory‐related abilities alike.

Interrater reliability for sleep scoring according to the Rechtschaffen & Kales and the new AASM standard

Interrater variability of sleep stage scorings has an essential impact not only on the reading of polysomnographic sleep studies (PSGs) for clinical trials but also on the evaluation of patients’ sleep. With the introduction of a new standard for sleep stage scorings (AASM standard) there is a need for studies on interrater reliability (IRR). The SIESTA database resulting from an EU‐funded project provides a large number of studies (n = 72; 56 healthy controls and 16 subjects with different sleep disorders, mean age ± SD: 57.7 ± 18.7, 34 females) for which scorings according to both standards (AASM and R&K) were done. Differences in IRR were analysed at two levels: (1) based on quantitative sleep parameter by means of intraclass correlations; and (2) based on an epoch‐by‐epoch comparison by means of Cohen’s kappa and Fleiss’ kappa. The overall agreement was for the AASM standard 82.0% (Cohen’s kappa = 0.76) and for the R&K standard 80.6% (Cohen’s kappa = 0.68). Agreements increased from R&K to AASM for all sleep stages, except N2. The results of this study underline that the modification of the scoring rules improve IRR as a result of the integration of occipital, central and frontal leads on the one hand, but decline IRR on the other hand specifically for N2, due to the new rule that cortical arousals with or without concurrent increase in submental electromyogram are critical events for the end of N2.

Artifact processing in computerized analysis of sleep EEG - a review.

Quantitative analysis of sleep EEG data can provide valuable additional information in sleep research. However, analysis of data contaminated by artifacts can lead to spurious results. Thus, the first step in realizing an automatic sleep analysis system is the implementation of a reliable and valid artifact processing strategy. This strategy should include: (1) high-quality recording techniques in order to minimize the occurrence of avoidable artifacts (e.g. technical artifacts); (2) artifact minimization procedures in order to minimize the loss of data by estimating the contribution of different artifacts in the EEG recordings, thus allowing the calculation of the ‘corrected’ EEG (e.g. ocular and ECG interference), and finally (3) artifact identification procedures in order to define epochs contaminated by remaining artifacts (e.g. movement and muscle artifacts). Therefore, after a short description of the types of artifacts in the sleep EEG and some typical examples obtained in different sleep stages, artifact minimization and identification procedures will be reviewed.

Is there a link between sleep changes and memory in Alzheimer's disease?

Aging and Alzheimers disease (AD) are both characterized by memory impairments and sleep changes. We investigated the potential link between these disturbances, focusing on sleep spindles, involved in memory consolidation. Two episodic memory tasks were given to young and old healthy participants, as well as to AD patients. Postlearning sleep was recorded. Sleep spindles were globally reduced in aging and AD. AD patients also exhibited a further decrease in fast spindles. Besides, mean intensity of fast spindles was positively correlated, in AD patients, with immediate recall performance. Our results are the first report of a specific decrease in fast spindles in AD, associated with learning abilities. They also give further hints for a functional differentiation between slow and fast spindles.

Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double‐blind, placebo‐controlled investigations on the effects of a novel estrogen–progestogen combination (Climodien®, Lafamme®) versus estrogen alone

Differences in sleep and awakening quality between 51 insomniac postmenopausal syndrome patients and normal controls were evaluated. In a subsequent double‐blind, placebo‐controlled, comparative, randomized, three‐arm trial (Climodien 2/3 = estradiol valerate 2 mg + the progestogen dienogest 3 mg = regimen A, estradiol valerate 2 mg = regimen EV, and placebo = regimen P), the effects of 2 months of hormone replacement therapy were investigated, followed by a 2‐month open‐label phase in which all patients received Climodien® 2/2 (EV 2 mg + dienogest 2 mg = regimen A*). Polysomnography at baseline demonstrated significantly deteriorated sleep initiation and maintenance, increased S1 and decreased S2 in patients. Subjective sleep and awakening quality, well‐being, morning drive, wakefulness, memory and reaction time performance were deteriorated too. Treatment with both regimen A and regimen EV induced a moderate, although nonsignificant, improvement in the primary efficacy variable wakefulness during the total sleep period compared with baseline, while under placebo no changes occurred. Secondary efficacy variables concerning sleep initiation and maintenance, and sleep architecture showed similar findings. The apnea and apnea–hypopnea indices improved significantly under regimen A, compared with both baseline and placebo. Subjective sleep and awakening quality improved significantly after regimen A and EV compared with baseline, with the drug‐induced changes being superior to those induced by placebo. In the open‐label phase, subjective sleep quality improved further, significantly in the former regimen A group. Awakening quality, somatic complaints and morning thymopsyche did not yield any significant findings. Concerning morning noopsychic performance, memory improved significantly after regimen A compared with baseline, fine motor activity after regimen EV. Reaction time performance increased with all three compounds. In conclusion, Climodien significantly improved subjective sleep quality, the apnea and apnea–hypopnea indices of insomniac postmenopausal syndrome patients, while it only marginally improved variables concerning objective sleep and awakening quality.

Computer-assisted sleep classification according to the standard of the American Academy of Sleep Medicine: validation study of the AASM version of the Somnolyzer 24 × 7.

Background: In 2007, the AASM Manual for the Scoring of Sleep and Associated Events was published by the American Academy of Sleep Medicine (AASM). Concerning the visual classification of sleep stages, these new rules are intended to replace the rules by Rechtschaffen and Kales (R&K). Methods: We adapted the automatic R&K sleep scoring system Somnolyzer 24 × 7 to comply with the AASM rules and subsequently performed a validation study based on 72 polysomnographies from the Siesta database (56 healthy subjects, 16 patients, 38 females, 34 males, aged 21–86 years). Scorings according to the AASM rules were performed manually by experienced sleep scorers and semi-automatically by the AASM version of the Somnolyzer. Manual scorings and Somnolyzer reviews were performed independently by at least 2 out of 8 experts from 4 sleep centers. Results: In the quality control process, sleep experts corrected 4.8 and 3.7% of the automatically assigned epochs, resulting in a reliability between 2 Somnolyzer-assisted scorings of 99% (Cohen’s kappa: 0.99). In contrast, the reliability between the 2 manual scorings was 82% (kappa: 0.76). The agreement between the 2 Somnolyzer-assisted and the 2 visual scorings was between 81% (kappa: 0.75) and 82% (kappa: 0.76). Conclusion: The AASM version of the Somnolyzer revealed an agreement between semi-automated and human expert scoring comparable to that published for the R&K version with a validity comparable to that of human experts, but with a reliability close to 1, thereby reducing interrater variability as well as scoring time to a minimum.

Sleep in the Unresponsive Wakefulness Syndrome and Minimally Conscious State

The goal of our study was to investigate different aspects of sleep, namely the sleep-wake cycle and sleep stages, in the vegetative state/unresponsive wakefulness syndrome (VS/UWS), and minimally conscious state (MCS). A 24-h polysomnography was performed in 20 patients who were in a UWS (n=10) or in a MCS (n=10) because of brain injury. The data were first tested for the presence of a sleep-wake cycle, and the observed sleep patterns were compared with standard scoring criteria. Sleep spindles, slow wave sleep, and rapid eye movement sleep were quantified and their clinical value was investigated. According to our results, an electrophysiological sleep-wake cycle was identified in five MCS and three VS/UWS patients. Sleep stages did not always match the standard scoring criteria, which therefore needed to be adapted. Sleep spindles were present more in patients who clinically improved within 6 months. Slow wave sleep was present in eight MCS and three VS/UWS patients but never in the ischemic etiology. Rapid eye movement sleep, and therefore dreaming that is a form of consciousness, was present in all MCS and three VS/UWS patients. In conclusion, the presence of alternating periods of eyes-open/eyes-closed cycles does not necessarily imply preserved electrophysiological sleep architecture in the UWS and MCS, contrary to previous definition. The investigation of sleep is a little studied yet simple and informative way to evaluate the integrity of residual brain function in patients with disorders of consciousness with possible clinical diagnostic and prognostic implications.

Slow sleep spindle activity, declarative memory, and general cognitive abilities in children.

STUDY OBJECTIVES Functional interactions between sleep spindle activity, declarative memory consolidation, and general cognitive abilities in school-aged children. DESIGN Healthy, prepubertal children (n = 63; mean age 9.56 ± 0.76 y); ambulatory all-night polysomnography (2 nights); investigating the effect of prior learning (word pair association task; experimental night) versus nonlearning (baseline night) on sleep spindle activity; general cognitive abilities assessed using the Wechsler Intelligence Scale for Children-IV (WISC-IV). MEASUREMENTS AND RESULTS Analysis of spindle activity during nonrapid eye movement sleep (N2 and N3) evidenced predominant peaks in the slow (11-13 Hz) but not in the fast (13-15 Hz) sleep spindle frequency range (baseline and experimental night). Analyses were restricted to slow sleep spindles. Changes in spindle activity from the baseline to the experimental night were not associated with the overnight change in the number of recalled words reflecting declarative memory consolidation. Children with higher sleep spindle activity as measured at frontal, central, parietal, and occipital sites during both baseline and experimental nights exhibited higher general cognitive abilities (WISC-IV) and declarative learning efficiency (i.e., number of recalled words before and after sleep). CONCLUSIONS Slow sleep spindles (11-13 Hz) in children age 8-11 y are associated with inter-individual differences in general cognitive abilities and learning efficiency.

Perception of sleep: Subjective versus objective sleep parameters in patients with Parkinson's disease in comparison with healthy elderly controls Sleep perception in Parkinson's disease and controls

AbstractIntroductionSubjective sleep perception, as measured against objective parameters such as those obtained by polysomnography, have not been examined thoroughly to date. Little is known about subjective sleep perception in patients with chronic somatic diseases.Patients and methodsPatients with Parkinson’s disease (PD) and healthy elderly controls filled in a sleep log over 14 days, which included a self–rating questionnaire concerning sleep and quality of time awake, sleep times and somatic complaints. All participants underwent polysomnography in the sleep lab on nights 7 and 8, and slept all other nights at home.ResultsSeventeen patients with PD (64 ± 6 years, 6 female, Hoehn and Yahr median = 2), and 62 healthy controls of the same age without sleep disturbances (64 ± 8 years, 36 female) were included. Patients with PD showed reduced subjective sleep (p = 0.001) and quality of time awake (p = 0.02), decreased sleep duration (p = 0.01) and reduced sleep efficiency (p = 0.004) compared with the controls. Subjective sleep efficiency at home was no different from that in the sleep lab for both groups. Patients with PD reported more somatic complaints (p = 0.001) than controls but did not show a firstnight effect.ConclusionIn summary, patients with PD have subjectively and objectively disturbed sleep as compared to healthy controls of the same age. However, they may not rate this poor sleep as much changed from their baseline sleep at home, and they have more somatic complaints. Increasing sleep efficiency might be of importance in PD patients, as it shows an association with subjective quality of time awake in the morning.