Visual and computer-based detection of slow eye movements in overnight and 24-h EOG recordings.

OBJECTIVE: The present work aimed to evaluate the performance of an automatic slow eye movement (SEM) detector in overnight and 24-h electro-oculograms (EOG) including all sleep stages (1, 2, 3, 4, REM) and wakefulness. METHODS: Ten overnight and five 24-h EOG recordings acquired in healthy subjects were inspected by three experts to score SEMs. Computerized EOG analysis to detect SEMs was performed on 30-s epochs using an algorithm based on EOG wavelet transform, recently developed by our group and initially validated by considering only pre-sleep wakefulness, stages 1 and 2. RESULTS: The validation procedure showed the algorithm could identify epochs containing SEM activity (concordance index k=0.62, 80.7% sensitivity, 63% selectivity). In particular, the experts and the algorithm identified SEM epochs mainly in pre-sleep wakefulness, stage 1, stage 2 and REM sleep. In addition, the algorithm yielded consistent indications as to the duration and position of SEM events within the epoch. CONCLUSIONS: The study confirmed SEM activity at physiological sleep onset (pre-sleep wakefulness, stage 1 and stage 2), and also identified SEMs in REM sleep. The algorithm proved reliable even in the stages not used for its training. SIGNIFICANCE: The study may enhance our understanding of SEM meaning and function. The algorithm is a reliable tool for automatic SEM detection, overcoming the inconsistency of manual scoring and reducing the time taken by experts.     

The use of two-channel electro-oculography in automatic detection of unintentional sleep onset

An automatic method was developed for detecting unintentional sleep onset. The automatic method is based on a two-channel electro-oculography (EOG) with left mastoid (M1) as reference. An automatic estimation of slow eye movements (SEM) was developed and used as the main criterion to separate sleep stage 1 (S1) from wakefulness. Additionally synchronous electroencephalographic (EEG) activity of sleep stages 1 and 2 was detected by calculating cross-correlation and amplitude difference in the 1.5-6 Hz theta band between the two EOG channels. Alpha power 8-12 Hz and beta power 18-30 Hz were used to determine wakefulness. Unintentional sleep onsets were studied using data from four separate maintenance of wakefulness test (MWT) sessions of 228 subjects. The automatic scoring of 30s sleep onset epochs using only EOG was compared to standard visual sleep stage scoring. The optimal detection thresholds were derived using data from 114 subjects and then applied to the data from different 114 subjects. Cohen's Kappa between the visual and the new automatic scoring system in separating wakefulness and sleep was substantial (0.67) with epoch by epoch agreement of 98%. The sleep epoch detection sensitivity was 70% and specificity 99%. The results are provided with a 1s delay for each 30s epoch. The developed method has to be tested in field applications. The advantage of the automatic method is that it could be applied during online recordings using only four disposable self-adhesive self-applicable electrodes.     

Time trends and periodic cycles in REM sleep eye movements.

Eye movements during REM sleep episodes were tabulated in 16 young adults. REM episodes were then broken down into four ranges according to length in min: (1) 11.0-21.3; (2) 21.7-29.7; (3) 30.0-42.3; (4) 42.7 or longer. These data were then analyzed for linear and quadratic trends. Eight episodes had a significant linear trend, 10 had a significant quadratic trend, 7 had both linear and quadratic trends, while 12 had no trend. The residuals from the best-fitting polynomial curve were then subject to a spectral analysis. In addition, 2 long periods of pre-sleep wakefulness (approximately 2 h each) were also analyzed. In general, the spectral analysis revealed the dominant presence of a slow cycle (period of 10 min to about 30 min) the exact period of which varied according to the length of the REM episode. A binomial probability test indicated that the presence of slow cycles was significant in REM episodes except for those in the 21-30 min range. For the episodes of wakefulness, a dominant slow cycle was found in both cases. The results give the impression of similarity in the periodic organization of eye movements during REM sleep and waking. The data also indicated that an ultradian (70-150 min) cycle was present in eye movements during sleep and waking. Further, the finding of a decrease in eye movements before sleep onset, coupled with previous reports of an increase in eye movement after sleep onset, indicate the presence of a circadian cycle.     

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects

Saccade-like eye movements are the most prominent phasic component of rapid eye movement (REM) sleep. Eye movement density (EMD) appears to be negatively related to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a) whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is increased by daytime naps; and (c) whether EMD patterns across sleep cycles differ in the two age groups. Subjects participated in four separate 2-day recording sessions, each consisting of a baseline night, a daytime nap, and post nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM. EMD was not correlated with rate of non rapid eye movement (NREM) delta production (power/min) in the baseline sleep of either group. Changes in EMD and delta power/min on post nap nights also were uncorrelated. These data indicate that very strong changes in sleep depth (state) are required to overcome the individual stability (traits) of NREM delta and eye movement density. ANOVA for EMD across REM periods 1-4 showed a significant cycle effect and a significant age x cycle interaction. These effects were mainly due to YNs having depressed EMD in the first REM period, likely due to the low arousal level early in sleep in these subjects. Compared with waking saccades the saccade eye movements of REM sleep have received little investigation. Further study of these movements could shed new light on neurophysiology of REM sleep. Such studies might also be clinically useful because the density of these movements appears to be related to depression and (independently) to cognitive function in individuals with brain impairment.     

The effect of small differences in electrode position on EOG signals: application to vigilance studies

The primary aim of the study was to determine the best electrode positions for EOG signals in vigilance studies. Two-channel recordings were conducted in analogy to the Rechtschaffen and Kales (1968) system. Twenty electrodes (10 electrode pairs) were compared. Both EOG amplitudes and amplitude asymmetries within an electrode pair were studied.The amplitude of the EOG signal is sensitive to relatively small differences in electrode position. This concerns especially distance from the eye, the direction of eye movement and the effect of the upper eye lid movement. Larger and more symmetrical EOG amplitudes were obtained for different eye movements by placing the electrodes more medially than in the conventionally used system. EOG asymmetry in different electrode positions was dependent on the eye movement direction and even on the starting and end points of a movement with equal angular degrees.Most of the data could be explained by a simple monopolar model when combined with the effects of the upper eye lid movements. The most unexpected finding was that the EOG amplitudes of the horizontal and oblique eye movements were significantly larger when the eye were moving towards an electrode than when they were moving to the opposite direction.     

Nocturnal and diurnal sleep in Macaca sylvana.

In Macaca sylvana restrained in chairs, continuous 24 h recordings were obtained of scalp EEG, neck EMG, bilateral EOG, motility of the head and lever manipulation. A total of 32 days were studied in 8 monkeys. Recordings were divided into epochs of 30 sec and analyzed in a PDP-12 computer. Four stages of sleep and 5 stages of wakefulness were identified by combination of the above data. Results were as follows: (1) During the night, there was 21% wakefulness and during the day 20% sleep, including a considerable amount of REM. (2) Recordings of spontaneous motility of head and hands proved an excellent indicator of sleep-wakefulness cycles. (3) Spectral analysis revealed the cyclic characteristics of non-REM sleep, with peaks at 360, 149, 72, and 55 min. (4) Stages of wakefulness had ultradian cycles, and stage W-2 was the most important in number and duration of occurrences. (5) Night wakefulness had characteristics different from day wakefulness. (6) Study of sequences showed that stage II was the least differentiated being transitional among the other stages, while stage III-IV was never preceded by wakefulness or REM, and almost always it followed stage II (99.0% of the time). (7) The high statistical significance of results obtained under restraint in different monkeys suggests that this situation has great potential value in the investigation of physiological mechanisms of ultradian rhythms.     

Mental activity after early afternoon nap awakenings in healthy subjects

Despite the common misconception that rapid eye movement (REM) sleep is a unique correlate of dreaming, reports of mental activity can be elicited after awakenings from any stage of nocturnal sleep. We extended the investigation to naps and tried to explore the relationship between recall length and level of sleep stage and depth preceding the awakening. We hypothesized that dream report length would be related to arousal level. In 10 healthy young adults, sleep EEG and EOG were recorded for four non-consecutive early afternoon naps. Dream recalls were recorded following 10 s, 1 min, and 6 min of NREM Stage 2 and after 5 min of first REM period. We measured mental recall with total word count (TWC) method, sleep stages by using EEG visual scoring and Delta and Beta activity by period amplitude (PAA) and power spectral (PSA) analyses. All awakening conditions were followed by a dream report. TWC was significantly greater after REM than after 10 s and 1 min of NREM, and TWC did not differ among the NREM awakenings. Delta activity after REM was significantly lower compared to the NREM 6 and 1 min while Beta activity did not differ across the conditions. Assuming that arousal level decreased with increased NREM duration and increasing Delta EEG activity, the constant TWC across the three NREM awakenings indicates that arousal level cannot be the only factor affecting dream report length. Some other factor such as memory processing may explain the longer dream reports following REM sleep, or it may be that the EEG is an imperfect indicator of arousal level.     

Midlatency auditory evoked responses: differential effects of sleep in the human

Middle latency responses (MLRs) in the 10-100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuous presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2-4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5-8 msec, Pa, 30-40 msec, Nb, 45-55 msec, and P1, 55-80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.     

Automatic detection of slow wave sleep using two channel electro-oculography

An automatic method was developed for detecting slow wave sleep (SWS). The automatic method is based on a two-channel electro-oculography (EOG) with left mastoid (M1) as reference. Synchronous electroencephalographic (EEG) activity was detected by calculating cross-correlation between the two EOG channels by using 0.5-6 Hz band. An amplitude criterion was used for detecting slow waves and beta power 18-30 Hz was used to exclude artefacts. The automatic scoring was compared to a standard visual sleep scoring based on EOG, central EEG and submental EMG. Sleep EEG and EOG were recorded from 265 subjects. The optimal cross-correlation, amplitude and beta thresholds were derived using data from 133 training subjects and then applied to the data from different 132 validation subjects. Results were most sensitive to the changes in the amplitude criteria. Cohen's Kappa between the visual and the new developed automatic scoring in separating non-SWS and SWS was substantial (0.70) with epoch-by-epoch agreement of 93%. SWS epoch detection sensitivity was 75% and specificity was 96%. Also the total amount of slow waves, slow wave time (SWT), was estimated. The advantage of the automatic method is that it could be applied during online recordings using only four disposable self-adhesive electrodes.     

GABAergic neurons in prepositus hypoglossi regulate REM sleep by its action on locus coeruleus in freely moving rats.

GABA in locus coeruleus modulates REM sleep. Apart from the presence of interneurons, locus coeruleus also receives GABAergic inputs from prepositus hypoglossi in the medulla, where the presence of REM-ON-like neurons have been reported. Therefore, it was hypothesized that GABAergic projections from prepositus hypoglossi to locus coeruleus may modulate REM sleep. The experiments were conducted on chronic rats prepared for recording EEG, EOG, and EMG in freely moving conditions. Bipolar stimulating electrodes were implanted in prepositus hypoglossi bilaterally, while chemitrodes were implanted bilaterally in locus coeruleus. The prepositus hypoglossi were bilaterally stimulated (3 Hz, 250 microsec, 100 microA) for 8 h in the presence and absence of picrotoxin (0.25 microg/250 nl) microinjection bilaterally in locus coeruleus, followed by poststimulation recording for 4 h. It was observed that stimulation of prepositus hypoglossi alone significantly increased REM sleep primarily by increasing the REM sleep duration per episode. However, when it was stimulated in the presence of picrotoxin in LC, REM sleep decreased, predominantly due to decreased REM sleep duration per episode. The results of this study suggest that GABAergic inputs from prepositus hypoglossi act on locus coeruleus and regulate REM sleep, possibly by inhibition of REM-OFF neurons.     

A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

ObjectivesTo investigate electroencephalographic (EEG), electrooculographic (EOG) and micro-sleep abnormalities associated with rapid eye movement (REM) sleep behavior disorder (RBD) and REM behavioral events (RBEs) in Parkinson's disease (PD).MethodsWe developed an automated system using only EEG and EOG signals. First, automatic macro- (30-s epochs) and micro-sleep (5-s mini-epochs) staging was performed. Features describing micro-sleep structure, EEG spectral content, EEG coherence, EEG complexity, and EOG energy were derived. All features were input to an ensemble of random forests, giving as outputs the probabilities of having RBD or not (P (RBD) and P (nonRBD), respectively). A patient was classified as having RBD if P (RBD)≥P (nonRBD). The system was applied to 107 de novo PD patients: 54 had normal REM sleep (PDnonRBD), 26 had RBD (PD + RBD), and 27 had at least two RBEs without meeting electromyographic RBD cut-off (PD + RBE). Sleep diagnoses were made with video-polysomnography (v-PSG).ResultsConsidering PDnonRBD and PD + RBD patients only, the system identified RBD with accuracy, sensitivity, and specificity over 80%. Among the features, micro-sleep instability had the highest importance for RBD identification. Considering PD + RBE patients, the ones who developed definite RBD after two years had significantly higher values of P (RBD) at baseline compared to the ones who did not. The former were distinguished from the latter with sensitivity and specificity over 75%.ConclusionsOur method identifies RBD in PD patients using only EEG and EOG signals. Micro-sleep instability could be a biomarker for RBD and for proximity of conversion from RBEs, as prodromal RBD, to definite RBD in PD patients.     

Minute eye movement during sleep.

The minute eye movements of 4 sleeping subjects were studied with a piezo-electric strain-gauge transducer. The frequency and amplitude of ocular microtremor activity diminished during sleep. Activity increased after auditory stimulation and with the appearance of a K complex in the EEG. The ocular microtremor activity also increased with the onset of rapid eye movement (REM). Low amplitude 'micronystagmoid' movements were observed at intervals throughout sleep. In contrast to the changes observed during sleep, ocular microtremor activity did not diminish during hypnosis. The transducer was far more sensitive than the conventional EOG recording system.     

The effects of time constant on electrooculographic recording of slow eye movements during the wake-sleep transition

Abstract This study examines distortions in electrooculogram (EOG) wave form of slow eye movements (SEM) during the wake-sleep transition. Distortions in AC-coupled EOG, which were evaluated by computing Pearson's product-moment correlation coefficient between DC- and AC-coupled EOG, decreased as a function of time constants (0.3, 3 and 6 s) and showed SEM-dependent changes. Time constants of longer than 3.0 s should be chosen to reliably recognize SEM.     

Longitudinal change in REM sleep components in a patient with multiple system atrophy associated with REM sleep behavior disorder: paradoxical improvement of nocturnal behaviors in a progressive neurodegenerative disease

A 60-year-old patient with multiple system atrophy (MSA) who presented with rapid eye movement (REM) sleep behavior disorder was investigated longitudinally by all-night polysomnography. REM sleep components, i.e. rapid eye movements and chin muscle activity, were analyzed together with the frequency of behaviors/movements on the videorecording. Decreased frequency of elaborate motor activity during REM sleep with time in this patient was compatible with the observation by his wife, and this change seemed to correlate with predominant tonic chin electromyogram with relatively suppressed phasic chin muscle activity, but the reduction of the REM sleep behavior disorder (RBD) episodes could be interpreted as being due to the increased rigidity along with MSA progression. The chronological change in REM sleep components in RBD with neurological disorders is worth studying in large follow-up series to enlarge our knowledge about the mechanism of behavioral manifestation of RBD in humans.     

Polysomnographic studies of Lesch–Nyhan syndrome

Three cases of Lesch–Nyhan syndrome (LNS) were examined by polysomnography to assess the brainstem function, and to determine the causes of the neurological manifestations and sudden death in this syndrome. In the two older cases, the amount of slow wave and rapid eye movement (REM) sleep, the REM density and the frequency of REM bursts were decreased. In the youngest case, symmetrical phasic movements of all four limbs were observed at all sleep stages other than REM sleep. Although movements other than these symmetrical body movements appeared to be normal in this case, the frequency of twitch movements showed an abnormal pattern in each sleep stage in the two older cases. These findings suggest that in the brainstems of younger cases with LNS the REM-non REM generator as well as multiple neurotransmitter systems influencing body movements during sleep remain relatively normal, but become progressively impaired in adult cases. Severe obstructive apnea was observed in one case with hypothyroidism, but there were no respiratory abnormalities in other two cases.     

Eye movement patterns in REM sleep.

Eye movements in 6 healthy men and women were studied for recurrent patterns during REM sleep. The REM periods of nocturnal polysomnograms, on 2 consecutive nights, were analyzed in each subject. A discrete scale from 1 to 8 was used to record each eye position. The total number of recorded eye positions for the 2 nights of testing varied from 1314 to 3006. The distributions of eye movement were similar for males and females, for both nights of testing for each subject, among individual REM periods, and between subjects. This was in spite of marked differences in the number and length of REM periods, and in the number of eye movements per minute of REM sleep. In 5 of 6 subjects there was a marked tendency for the eyes to move between the 2 opposite lateral positions. Regardless of the eye position, the opposite movement was generally most likely, with an underlying tendency to return to the most opposite of the two lateral positions. In the remaining subject the opposite movement was also favored, but in this subject eye movements were more likely to be vertical rather than horizontal. Our data suggest that eye movements in REM sleep are organized in complex recurring patterns, with marked similarities between subjects. The significance of these patterns and the significance of deviations from these patterns require further study.     

Periodic limb movements both in non-REM and REM sleep: Relationships between cerebral and autonomic activities

ObjectiveTo investigate the temporal relationship between cerebral and autonomic activities before and during periodic limb movements in NREM and REM sleep (PLMS).MethodsPatterns of EEG, cardiac and muscle activities associated with PLMS were drawn from polysomnographic recordings of 14 outpatients selected for the presence of PLMS both in NREM and REM sleep. PLMS were scored during all sleep stages from tibial EMG. Data from a bipolar EEG channel were analyzed by wavelet transform. Heart rate (HR) was evaluated from the electrocardiogram. EEG, HR and EMG activations were detected as transient increase of signal parameters and examined by analysis of variance and correlation analysis independently in NREM and REM sleep. Homologous parameters in REM and NREM sleep were compared by paired t-test.ResultsThe autonomic component, expressed by HR increase, took place before the motor phenomenon both in REM and NREM sleep, but it was significantly earlier during NREM. In NREM sleep, PLM onset was heralded by a significant activation of delta-EEG, followed by a progressive increase of all the other bands. No significant activations of delta EEG were found in REM sleep. HR and EEG activations positively correlated with high frequency EEG activations and negatively (in NREM) with slow frequency ones.ConclusionsOur findings suggested a heralding role for delta band only in NREM sleep and for HR during both NREM and REM sleep. Differences in EEG and HR activation between REM and NREM sleep and correlative data suggested a different modulation of the global arousal response.SignificanceIn this study, time–frequency analysis and advanced statistical methods enabled an accurate comparison between brain and autonomic changes associated to PLM in NREM and REM sleep providing indications about interaction between autonomic and slow and fast EEG components of arousal response.     

Comparison between eye movement latency and REM sleep parameters in major depression

Alterations of sleep can be observed polysomnographically in approximately 90 percent of depressed patients. Most of the registered sleep abnormalities in depression also occur in other psychiatric disorders. Only some types of REM sleep alterations – short REM latency, increase of REM density and shortening of mean latency of eye movements – were reported as more specific for affective disorders. In the present study polysomnograms of 21 medication free patients with major depressive disorder (assessed with a structured interview for DSM-III-R and Hamilton Scale) and 21 healthy controls were analysed. REM latency (LREM), REM density (RD), latencies of eye movements (LEM) and mean latency of eye movements (M-LEM) were calculated for both groups. Depressed patients (compared with healthy controls) showed increased RD (38.2% vs. 28.2%, p < 0.0001), shortened M-LEM (35.7 s vs. 48.3 s, p < 0.04) and shortening of LEM in the 1st (28.9 s vs. 48.9 s, p < 0.007) and 4th (27.0 s vs. 59.1 s, p < 0.043) REM sleep periods. LREM was not shortened significantly in depressives (78.5 min vs. 91.3 min, ns). In healthy subjects a negative correlation between M-LEM and RD was found (rho = − 0.47, p < 0.03). Since in the current study depressed patients differed from healthy controls, especially concerning phasic activity during REM sleep, presented data support the essential role of REM density for the assessment of sleep in depression. As a quick and easy manner to compute measurement, M-LEM is suggested as additional parameter for the assessment of phasic activity during REM sleep. Received: 23 March 1999 / Accepted: 23 November 1999     

脑卒中后抑郁状态的多导睡眠图研究

目的：探讨脑卒中后抑郁状态患者的睡眠图异常改变及与抑郁症之间的差异。方法：采用多导睡眠图对６２例脑卒中和３０例抑郁症患者进行整夜睡眠描记，并与对照组比较。结果：卒中后抑郁组与对照组和非抑郁组比较多项睡眠指标均有显著性差异（Ｐ＜０．０５～０．０１）；卒中后抑郁组的ＲＥＭ睡眠时间和密度明显低于抑郁症组，差异有显著性（Ｐ＜０．０１）。结论：卒中后抑郁状态病人除具有睡眠障碍在多导睡眠图改变外，ＲＥＭ睡眠时间和密度是一个较为特征性的改变，卒中后抑郁状态的发生可能与脑内５－ＴＨ递质改变有关。     

REM sleep abnormalities in severe athetoid cerebral palsy

Various abnormalities of sleep have been reported in extrapyramidal diseases in adults. We have investigated the disturbances of REM sleep (SREM) in severe athetoid cerebral palsy (ACP) originating perinatally. Ten ACP patients, 5 males and 5 females ranging from 15 to 30 years old, were studied by means of all-night polygraphic examination. Three cases showed a marked decrease in rapid eye movements in SREM. Moreover, the tone of submental muscle in SREM was also disturbed in three. Regarding body movements during sleep, gross movements and twitch movements of the submental muscle were analyzed. In most of the patients, an abnormal distribution of body movements according to sleep stages was observed, the rate being significantly reduced in SREM. REMs, atonia and body movements are considered to be related to the brainstem function in animals. The results of the present study suggest that perinatal extrapyramidal diseases could also coincide with brainstem dysfunctions.