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.     

Sleep extension in humans: sleep stages, EEG power spectra and body temperature

In eight male subjects the electroencephalogram (EEG) and core body temperature (Tcore) were recorded during long sleep episodes from 0000 to 1,500 hr. EEGs were visually scored and subjected to spectral analysis by fast Fourier transform. Slow-wave sleep [SWS, i.e. stages 3 + 4 of non-rapid eye movement (NREM) sleep and slow wave activity (SWA, mean EEG power density in the range of 0.75-4.5 Hz)] in NREM sleep attained highest values in the first 3 hr of sleep and lowest values in the morning hours when rapid eye movement (REM) sleep was at its maximum. Wakefulness was significantly enhanced in the last 3 hr of the recording period. Occasional NREM episodes containing SWS were observed in the late morning and early afternoon. However, no significant increase in SWS or SWA in the last 3 hr of the sleep episode over any of the preceding 3-hr intervals was present and SWA in this interval was significantly below the values observed at the beginning of sleep. The duration of NREM episodes varied significantly over the sleep episode. Analysis of the dynamics of SWA within NREM episodes revealed that SWA gradually rose during the episode. Consequently, SWA averaged per episode was positively correlated with episode duration. Tcore dropped in the initial part of sleep, rose during the morning hours and reached values in the afternoon that were higher than at the beginning of sleep. Thus the time course of Tcore dissociated from the time course of SWA. This indicates that SWA in NREM sleep is not directly related to the variation in core body temperature.     

Spontaneous baroreflex analysis in non-apneic snoring individuals during NREM sleep.

The primary purpose of this study was to measure baroreceptor sensitivity (BS) during wakefulness and non-rapid eye movement (NREM) sleep in non-apneic snoring individuals. To achieve this purpose continuous and simultaneous measurements of snoring, oxygen saturation, sleep stages, arterial blood pressure and heart rate were obtained from seven non-apneic snoring subjects. After obtaining these measures, a computer program was employed to detect concomitant increases or decreases in systolic blood pressure and R-R interval duration during sequences of three or more consecutive beats that occurred during stage II and slow wave sleep (SWS). The values recorded from a given sequence were plotted and the slope of the regression line fit to the data was used as a measure of BS. The results showed that mean arterial pressure and heart rate during stage II and SWS of NREM sleep were not significantly different from wakefulness. In contrast, the BS measured during NREM sleep was significantly lower than values recorded during wakefulness. In addition, linear regression analysis showed that an inverse and significant correlation existed between snoring frequency and the decrease in BS during sleep. We conclude that the decrease in blood pressure and heart rate normally observed during NREM sleep in healthy non-snoring individuals is attenuated or abolished in non-apneic snoring individuals and that these cardiovascular alterations may be partially mediated by a decrease in BS.     

Arousals and sleep stages in patients with obstructive sleep apnoea syndrome: changes under nCPAP treatment

Nocturnal arousals are the essential cause of disturbed sleep structure in patients with obstructive sleep apnoea syndrome (OSAS). The aim of this study was to analyse the relationship between sleep stages, respiratory (type-R) and movement (type-M) related EEG arousals. Furthermore, the value of these arousals as a criterion for the efficiency of nCPAP treatment was estimated. We examined 38 male patients aged between 30 and 71 (49.1±20.9 SD) y. All patients suffered from OSAS. The mean respiratory disturbance index (RDI) was 47.3±27.8 per h. Polysomnographic monitoring was carried out on 4 subsequent nights: baseline night, 2 nights of nCPAP titration and nCPAP control night. Sleep was visually scored and EEG arousals were classified into type R and M, depending on whether changes of respiration or movement caused the arousal. The RDI, the R index (type-R/h), the M index (type-M/h) and the R and M indices in different sleep stages were calculated. During the baseline night a deficit of slow wave sleep (SWS) and REM sleep was found. Furthermore there were more type-R than type-M arousals registered (17.4 h^?1[3.6–43.6] vs. 5.9 h^?1[1.6–11.8]) ( P <0.01). They occurred during stages NREM 1, NREM 2 and REM ( P <0.01). An SWS sleep rebound and a reduction of the SWS and REM latencies were already found during the first CPAP night. The R index was reduced during the first CPAP night in all sleep stages ( P <0.01) and remained approximately the same in the following 2 nights (3. CPAP night: 1.1 h^?1[0.3–5.0]). Type M arousals occurred more in stages 1 and 2 ( P <0.01), and remained unchanged under nCPAP. We concluded that differentiation of nocturnal arousals may provide more detailed information regarding the influence of breathing disturbances on sleep. Respiratory related, not movement related, arousals may be a useful additional tool in judging the efficiency of OSAS.     

Hypersynchronous delta sleep EEG activity and sudden arousals from slow-wave sleep in adults without a history of parasomnias: clinical and forensic implications

STUDY OBJECTIVES: To determine the frequency of classical markers of non-rapid eye movement (NREM) parasomnias--hypersynchronous delta sleep (HSD) electroencephalogram waves and sudden arousals from slow-wave sleep (SWS)--in patients without histories of somnambulism or other NREM parasomnias. DESIGN: Retrospective review. SETTING: Sleep disorders center laboratory. PATIENTS: 82 consecutive patients without a history of parasomnias who underwent diagnostic polysomnograms; 57 men and 25 women, mean age 48+/-13.3 years, were included without regard to diagnosis or findings. All patients had at least 30 seconds of stage 3 or 4 sleep during the polysomnogram. MEASUREMENTS AND RESULTS: The primary diagnosis of all but 4 patients was obstructive sleep apnea (mean respiratory disturbance index, 30 +/- 23.6 [range, 2.7-117] per hour of sleep). Polysomnograms were then reviewed for the presence of HSD and SWS arousals. A total of 235 arousals (mean, 2.9 +/- 2.7; range, 0-14) from stage 3 or 4 sleep were noted. Eight-five percent of all patients had at least 1 SWS arousal and 45% had 3 or more SWS arousals; 85.1% of all arousals from SWS were secondary to sleep-disordered breathing, and 5.9% were secondary to leg movements. At least 1 episode of HSD (mean, 1.4 +/- 1.6; range, 0-9) was noted in 65.8% of patients. CONCLUSIONS: HSD and SWS arousals were a common finding in patients without clinical histories of sleepwalking or other parasomnias but who were found to have frequent respiratory-related arousals during sleep. HSD and SWS arousals thus have a low specificity for NREM parasomnias and, without further research, are not useful for the objective confirmation of parasomnias in clinical evaluations and in the forensic evaluation of sleepwalking as a legal defense.     

The distribution of slow-wave sleep across the night: a comparison for infants, children, and adults.

This study describes the temporal distribution of slow-wave sleep (SWS) (defined as the visually scored stages 3 + 4) across the night for 16 infants aged between 20 weeks and 1 year, 17 children between 1 and 6 years, and 17 adults between 20 and 36 years. In all three groups the amounts of SWS peaked during the first nonrapid eye movement (NREM) episode. SWS decreased across the night for adults and children, but not for infants. In infants the amounts of SWS remained at a fairly constant level from the second cycle onward, although many cycles were observed with zero SWS. The latter was evident from the very low tendency for SWS to appear in consecutive NREM/REM cycles. Rather, SWS was observed in alternate cycles. In children this phenomenon was less prominent but still well visible, and the tendency for SWS to appear in consecutive cycles had increased. In adults SWS occurred predominantly in consecutive cycles. The results suggest that whereas REM recurrence time increases twofold from infancy to adulthood, SWS recurrence time remains of similar length in infants, children, and adults.     

The impact of slow wave sleep proximity on evoked K-complex generation

During human stage 2 non-rapid eye movement (NREM) sleep, spontaneous K-complexes are more likely to occur prior to transitions to stage 3 or stage 4 sleep (referred to as slow wave sleep or SWS) compared to transitions to REM sleep, suggesting that the K-complex may be the 'forerunner' of SWS. The present study investigated the impact of SWS or REM sleep proximity on the probability of evoking a K-complex (pKC) during stage 2 and on components of the NREM sleep averaged evoked potential. Ten subjects spent three nights in the laboratory. On either the second or third night tones were presented continuously during sleep. Evoked K-complexes and sleep-evoked potentials were assessed for the 10 min of stage 2 prior to SWS (SWS-10) or REM (REM-10) sleep episodes as well as for all of SWS. pKC did not differ between SWS-10 (0.88) and SWS (0.91) but was significantly larger in SWS-10 than REM-10 (0.63). Amplitude effects were seen for the P2, N350, P900 NREM sleep-evoked potential components but not for the K-complex related N550. In each case where amplitude effects were found, SWS-10 was larger than REM-10. No latency differences were seen between conditions for the earlier components (P2, N350) however, both N550 and P900 were significantly shorter during SWS-10 compared to REM-10. These results are consistent with previous spontaneous K-complex studies and are supportive of a relationship between the K-complex and delta activity. They also indicate that stage 2 may consist of a continuum of microstates between SWS and REM sleep that are indicative of different brain stem, diecephalic and cortical patterns of activation.     

The relationships between memory systems and sleep stages

Sleep function remains elusive despite our rapidly increasing comprehension of the processes generating and maintaining the different sleep stages. Several lines of evidence support the hypothesis that sleep is involved in the off-line reprocessing of recently-acquired memories. In this review, we summarize the main results obtained in the field of sleep and memory consolidation in both animals and humans, and try to connect sleep stages with the different memory systems. To this end, we have collated data obtained using several methodological approaches, including electrophysiological recordings of neuronal ensembles, post-training modifications of sleep architecture, sleep deprivation and functional neuroimaging studies. Broadly speaking, all the various studies emphasize the fact that the four long-term memory systems (procedural memory, perceptual representation system, semantic and episodic memory, according to Tulving's SPI model; Tulving, 1995) benefit either from non-rapid eye movement (NREM) (not just SWS) or rapid eye movement (REM) sleep, or from both sleep stages. Tulving's classification of memory systems appears more pertinent than the declarative/non-declarative dichotomy when it comes to understanding the role of sleep in memory. Indeed, this model allows us to resolve several contradictions, notably the fact that episodic and semantic memory (the two memory systems encompassed in declarative memory) appear to rely on different sleep stages. Likewise, this model provides an explanation for why the acquisition of various types of skills (perceptual-motor, sensory-perceptual and cognitive skills) and priming effects, subserved by different brain structures but all designated by the generic term of implicit or non-declarative memory, may not benefit from the same sleep stages.     

The dynamics of the first sleep cycle.

Eight subjects participated in an experiment in which sleep stages and electroencephalographic (EEG) power density during the first sleep cycles (and where such appeared, also second cycles) were studied in a design involving 8, 4, 2 or 0 hr of progressively postponed night-time sleep. Each of these four manipulations was followed by a day-time sleep beginning at 1100 hr. No significant changes in the duration of the first sleep cycle appeared. As the prior sleep loss increased both SWE (slow-wave energy; accumulated EEG delta power density) and SWA (slow-wave activity; EEG delta power per minute) increased during the 1100-hr sleeps. This was observed for the entire cycles, the nonrapid eye movement (NREM) periods, and the SWS periods, respectively. SWS latency decreased and SWS duration increased, respectively, markedly with prior waking. Also, for the progressively postponed sleeps (started at 2300 hr, 0300 hr, 0500 hr and 1100 hr) there were changes, but not as clear. After 28 hr of continuous waking there was a marked increase of SWA during SWS. Also, at this level there was a spill over of SWA to the second cycle. It is suggested that there might be a limit to the amount and intensity of SWS that can be accommodated in the first sleep cycle and that this limit is reached before the appearance of REM sleep.     

A field study of age and gender differences in habitual adult sleep

The sleep of 52 healthy paid subjects (23 male) divided into three age-bands (20–34, 35–49 and 50–70 y) were recorded at night in their homes for a total of 190 subject-nights while following their normal daily activities and habitual sleep-wake schedule. There was a shortening in both nocturnal total sleep period and total sleep time (TST) with age, the oldest group sleeping 46 min less than the youngest. Also, the mid-point of sleep occurred 32 min earlier in the oldest group compared with the youngest group. The reduction in TST with age was due, in part, to increased wake periods within sleep. The youngest subjects showed more Movement Time which progressively decreased with age while the amount of stage 1 increased with age. The amount of slow-wave sleep (SWS, stages 3+4) was reduced, stage 4 was more than halved, while REM was slightly reduced with age. There were far fewer significant gender differences in the sleep variables: males, particularly in the middle and oldest age bands, had more stage 1 than females, while females had more SWS, particularly stage 3, than males. In general, despite relatively limited subject selection criteria, there was good agreement with previous laboratory-based normative sleep values for the effect of age and gender.     

Purpose of REM sleep: endogenous anti-epileptogenesis in man -- a hypothesis

Neuro-scientists, worldwide, are endeavoring to elucidate the purpose of sleep which still remains largely elusive. There is, however, consensus on many aspects of sleep functions; one such aspect is its relationship with seizures/epilepsy. There is unequivocal agreement on increased susceptibility to epilepsy during nonrapid eye movement (NREM, slow-wave) sleep. Large number of studies have shown increased frequency of seizures and interictal epileptiform discharges in epileptic patients during NREM sleep (esp., stages I and II) which is associated with EEG synchronization. Similarly, there is widespread acceptance of de-synchronized brain-activity states being associated with rarity/total absence of epileptic potentials, one such state being rapid eye movement (REM) sleep. Certain drugs and substances which inhibit NREM sleep have been found to possess anti-convulsant properties. Not surprisingly, drugs/chemicals which enhance/promote NREM sleep or suppress/inhibit REM sleep are associated with increased susceptibility to seizures and are contraindicated in epilepsy. The manner and pattern in which REM phase occurs in sleep are also naturally programmed to exert anti-epileptogenic influence. This hypothesis-article highlights and conceptualizes the primary function of REM-sleep as endogenous anti-epileptogenic system in the body akin to the endogenous analgesia and immune systems man is born with.     

Sleep disturbances in men with asymptomatic human immunodeficiency (HIV) infection.

During the clinical latency phase of human immunodeficiency virus (HIV) disease the central nervous system may be infected and begin to manifest subtle dysfunction. Our early investigations demonstrated persistent alterations in the sleep architecture of HIV-infected asymptomatic men. The major aims of this study were to delineate alterations of sleep architecture in asymptomatic HIV-infected men, to identify and describe sleep behavior complaints and to seek a correlation between objective sleep parameters and subjective complaints of sleep behavior. The study sample consisted of 24 men, 14 HIV-infected and 10 HIV-negative, age-matched controls. The protocol included a comprehensive history and physical, two polysomnograms, urine toxicity, detailed written sleep questionnaire, the Pittsburgh Sleep Quality Index, the Spielberger State-Trait Anxiety Test and the Beck Depression Inventory. Our results indicated that sleep architecture differed from controls in that wakefulness, slow-wave sleep [SWS-stage 3 and 4 nonrapid eye movement (NREM) sleep] and stage rapid eye movement (REM) sleep were more evenly dispersed throughout the night. In particular, SWS was prevalent during the second half of recorded sleep. The observed changes in the NREM/REM cycle could not be explained on the basis of underlying psychopathology. Just as the course of individuals with HIV infection varies, it is expected that sleep abnormalities will vary. Considering the known relationships between NREM stage 3 and 4 and immune system function, it is possible that the observed alterations in the NREM/REM cycle are related to coincident changes in immunologic function. Quantitative measures of NREM sleep, especially SWS and REM sleep, are perhaps of greater significance than relative measures of sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)     

Heart rate variability during waking and sleep in healthy males and females

STUDY OBJECTIVES: The study goal was to investigate autonomic activity with heart rate variability analysis during different sleep stages in males and females. DESIGN: The study utilized a 2 Groups (males, females) x 4 States (waking, stage 2 sleep, stage 4 sleep, rapid-eye movement sleep) mixed design with one repeated, within-subjects factor (i.e., state). SETTING: The study was carried out in the sleep laboratory of the Thomas N. Lynn Institute for Healthcare Research. PARTICIPANTS: Twenty-four healthy adults (fourteen females and ten males). INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: All participants underwent polysomnographic monitoring and electrocardiogram recordings during pre-sleep waking and one night of sleep. Fifteen-minute segments of beat-to-beat heart rate intervals during waking, stage 2 sleep, stage 4 sleep, and REM sleep were subjected to spectral analysis. Compared to NREM sleep, REM sleep was associated with decreased high frequency (HF) band power, and significantly increased low frequency (LF) to (HF) ratio. Compared to females, males showed significantly elevated LF/HF ratio during REM sleep. Males also demonstrated significantly decreased HF band power during waking when compared to females. No significant sleep- or gender-related changes in LF band power were found. CONCLUSIONS: The results confirmed changes in autonomic activity from waking to sleep, with marked differences between NREM and REM sleep. These changes were primarily due to stage-related alterations in vagal tone. REM sleep was characterized by increased sympathetic dominance, secondary to vagal withdrawal. The data also suggested gender differences in autonomic functioning during waking and sleep, with decreased vagal tone during waking and increased sympathetic dominance during REM sleep in the males.     

Inter-rater reliability for identification of REM sleep in Parkinson's disease

Recently described functional connections between basal ganglia and brainstem circuits provide a neurobiologic basis for the absence of REM sleep atonia in Parkinson's disease (PD). However, identifying atypical REM sleep in PD may be problematic. Reliable sleep staging has never been demonstrated in such patients. In this study, 3 experienced scorers independently evaluated overnight polysomnograms from 10 (PD) patients. Results indicated good agreement for distinguishing REM from NREM sleep and waking. Reliable differentiation among NREM stages was more difficult to achieve. The results suggest that, despite suspension of REM sleep atonia accompanying PD, trained scorers can distinguish REM from wakefulness and NREM sleep.     

Arousal thresholds during human tonic and phasic REM sleep

The goal of the present study was to investigate arousal thresholds (ATs) in tonic and phasic episodes of rapid eye movement (REM) sleep, and to compare the frequency spectrum of these sub‐states of REM to non‐REM (NREM) stages of sleep. We found the two REM stages to differ with regard to behavioural responses to external acoustic stimuli. The AT in tonic REM was indifferent from that in sleep stage 2, and ATs in phasic REM were similar to those in slow‐wave sleep (stage 4). NREM and REM stages of similar behavioural thresholds were distinctly different with regard to their frequency pattern. These data provide further evidence that REM sleep should not be regarded a uniform state. Regarding electroencephalogram frequency spectra, we found that the two REM stages were more similar to each other than to NREM stages with similar responsivity. Ocular activity such as ponto‐geniculo‐occipital‐like waves and microsaccades are discussed as likely modulators of behavioural responsiveness and cortical processing of auditory information in the two REM sub‐states.     

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction

The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.     

The sleep EEG topography in children and adolescents shows sex differences in language areas

The topographic distribution of slow wave activity (SWA, EEG power between 0.75 and 4.5 Hz) during non-rapid eye movement (NREM) sleep was proposed to mirror cortical maturation with a typical age-related pattern. Here, we examined whether sex differences occur in SWA topography of children and adolescents (22 age-matched subjects, 11 boys, mean age 13.4 years, range: 8.7–19.4, and 11 girls, mean age 13.4 years, range: 9.1–19.0 years). In females, SWA during the first 60 min of NREM sleep was higher over bilateral cortical areas that are related to language functions, while in males SWA was increased over the right prefrontal cortex, a region also involved in spatial abilities. We conclude that cortical areas governing functions in which one sex outperforms the other exhibit increased sleep SWA and, thus, may indicate maturation of sex-specific brain function and higher cortical plasticity during development.     

Effects of sleep restriction on the sleep electroencephalogram of adolescents

Study ObjectivesThis report describes findings from an ongoing longitudinal study of the effects of varied sleep durations on wake and sleep electroencephalogram (EEG) and daytime function in adolescents. Here, we focus on the effects of age and time in bed (TIB) on total sleep time (TST) and nonrapid eye movement (NREM) and rapid eye movement (REM) EEG.MethodsWe studied 77 participants (41 male) ranging in age from 9.9 to 16.2 years over the 3 years of this study. Each year, participants adhered to each of three different sleep schedules: four consecutive nights of 7, 8.5, or 10 h TIB.ResultsAltering TIB successfully modified TST, which averaged 406, 472 and 530 min on the fourth night of 7, 8.5, and 10 h TIB, respectively. As predicted by homeostatic models, shorter sleep durations produced higher delta power in both NREM and REM although these effects were small. Restricted sleep more substantially reduced alpha power in both NREM and REM sleep. In NREM but not REM sleep, sleep restriction strongly reduced both the all-night accumulation of sigma EEG activity (11–15 Hz energy) and the rate of sigma production (11–15 Hz power).ConclusionsThe EEG changes in response to TIB reduction are evidence of insufficient sleep recovery. The decrease in sigma activity presumably reflects depressed sleep spindle activity and suggests a manner by which sleep restriction reduces waking cognitive function in adolescents. Our results thus far demonstrate that relatively modest TIB manipulations provide a useful tool for investigating adolescent sleep biology.