Can short-wavelength depleted bright light during single simulated night shifts prevent circadian phase shifts?

In single night shifts, extending habitual wake episodes leads to sleep deprivation induced decrements of performance during the shift and re-adaptation effects the next day. We investigated whether short-wavelength depleted (=filtered) bright light (FBL) during a simulated night shift would counteract such effects. Twenty-four participants underwent a simulated night shift in dim light (DL) and in FBL. Reaction times, subjective sleepiness and salivary melatonin concentrations were assessed during both nights. Daytime sleep was recorded after both simulated night shifts. During FBL, we found no melatonin suppression compared to DL, but slightly faster reaction times in the second half of the night. Daytime sleep was not statistically different between both lighting conditions (n = 24) and there was no significant phase shift after FBL (n = 11). To conclude, our results showed positive effects from FBL during simulated single night shifts which need to be further tested with larger groups, in more applied studies and compared to standard lighting.

Exogenous melatonin in periodic limb movement disorder: an open clinical trial and a hypothesis.

STUDY OBJECTIVES: The etiology of Periodic Limb Movement Disorder (PLMD) as well as the precise role of melatonin in human physiology remains poorly understood. Inspired by a single case observation we performed the presented study in order to obtain first evidence for the hypothesis that exogenous melatonin would decrease PLM's and thereby improves symptoms of PLMD patients. DESIGN: N/A. SETTING: N/A. PATIENTS/PARTICIPANTS: Nine patients with first time diagnosis of PLMD without RLS were treated over a six-week period with 3 mg melatonin, taken between 10 and 11 p.m. INTERVENTIONS: N/A. RESULTS: Melatonin improved well-being in 7 of the 9 patients. Polysomnography, performed prior and at the end of melatonin treatment, demonstrated a significant reduction of investigated movement parameters, such as PLMs, PLM index, PLMs with arousals and PLM-arousal index. Actigraphy, measured over 14 nights prior and during the last 14 days of melatonin treatment, showed a significant reduction in movement rate and minutes with movements during Time in Bed. CONCLUSIONS: The temporal distribution of PLMs, as well as the coupling of PLMs with the phase position of circadian temperature curve, suggest an involvement of the circadian timing system in the pathophysiology of PLMD. Locomotor activity in animals clearly exhibits a circadian pattern and can be strongly influenced by exogenous melatonin. Results suggest a chronobiotic effect of exogenous melatonin in PLMD. More specifically, we hypothesize that the mode of action of melatonin in the presented PLMD patients might have been an increase of output-amplitude of the circadian timing system, thereby enhancing the circadian rhythmicity of locomotor activity with a reduction of sleep motor activity.

Melatonin as a therapy in REM sleep behavior disorder patients: an open-labeled pilot study on the possible influence of melatonin on REM-sleep regulation.

REM sleep behavior disorder (RBD) is clinically impressive by virtue of its vigorous sleep behaviors usually accompanying vivid, striking dreams. The main feature of the disorder, REM sleep without muscle atonia, has been shown in a variety of diseases; therefore, the disorder might possibly be underestimated. In an open-labeled trial, we treated six consecutive RBD patients over a 6-week period with 3 mg melatonin given within 30 minutes before bedtime. There was a dramatic clinical improvement in five of the six patients within a week which extended beyond the end of treatment for weeks or months. A second polysomnogram performed 6 weeks after the beginning of treatment showed a significant tendency toward normalization of the percentage of REM sleep, a significant reduction of 30-second epochs, scored as REM sleep without muscle atonia, a significant reduction of stage-shifts in REM, and a significant reduction in epochs considered as movement time in REM. All other sleep parameters were not changed consistently. We hypothesize that internal desynchrony might be a part of the underlying pathophysiology in RBD. Our data might give first evidence to the hypothesis that exogenous melatonin, administered to patients with internal desynchrony at the time of the maximal rise of melatonin secretion, might increase the overall amplitude of the circadian pacemaker by reentraining the suprachiasmatic nucleus and thereby restore circadian driven rhythms, one of them being the circadian modulation of REM sleep.

On pineal calcification and its relation to subjective sleep perception: a hypothesis-driven pilot study.

We classified the degree of pineal calcification (DOC) into seven groups using cranial Computer Tomography (cCT) and then correlated pineal DOC to chronic subjective sleep-related disturbances as measured by a sleep questionnaire in 36 patients. Analysed by logistic regression models, age and sex were not, but higher pineal DOC was significantly associated with the presence of daytime tiredness (OR = 4.15, 95% CI: 1.63, 10.54) and sleep disturbance (OR = 1.74, 95% CI: 1.10, 2.74). This study provides initial confirmation of the hypothesis that the increasing degree of pineal calcification (DOC) might indicate a decrease of melatonin production, which consecutively might lead to a disturbed circadian rhythmicity in the sleep-wake cycle, with the principal symptom being daytime tiredness.

On the use of neural network techniques to analyse sleep EEG data. First communication: application of evolutionary and genetic algorithms to reduce the feature space and to develop classification rules.

To automate sleep stage scoring, the system sleep analysis system to challenge innovative artificial networks (SASCIA) has been developed and implemented. The aims of our investigation were twofold: In addition to automatic sleep stage scoring the hypothesis was tested that the information of only 1 EEG channel (C4-A2) should be sufficient to automatically generate sleep profiles which are comparable with profiles made by sleep experts on the basis of at least 3-channel EEG (C4-A2), EOG and EMG, as EOG and EMG are seen as epiphenomena during sleep and the full information about the sleep stage should--according to our hypothesis--be available in the EEG. The main components of the SASCIA sleep analysis system are designed to meet the requirements of flexible adaptation to the interindividual differences of the sleep EEG. The core of the SASCIA sleep analysis system consists of neural networks. Supervised learning was implemented and the experts' scorings were included into the learning set and test set. The feature selections out of a large number (118) are performed by genetic algorithms and the topologies of the networks are optimized by evolutionary algorithms. Different mathematical procedures were used to evaluate and optimize the efficiency of the system. The profiles generated by SASCIA are in reasonable agreement with the sleep stages scored by experts according to RKR. The development of the system is communicated in three parts: the first communication deals with the application of the neural network techniques using evolutionary and genetic algorithms and with the selection of feature space. The second communication shows the training of these evolutionary optimized network techniques with multiple subjects and the application of context rules, while the third communication shows an improvement in the robustness by the simultaneous application of 9 different networks obtained from 9 subject types which were used in combination with context rules.

Melatonin effects in a patient with severe REM sleep behavior disorder: case report and theoretical considerations.

REM sleep behavior disorder (RBD) is so far a possibly underestimated yet well-described sleep disorder. Its major impact is the vigorous sleep behavior that often results in injuries to the patient himself or to people sleeping nearby. We treated a 64-year-old male with a clinically and polysomnographically confirmed diagnosis of RBD with 3 mg melatonin, which led to a significant reduction of motor activity during sleep, as measured by actigraphy (p < 0.0001 in all analyzed movement parameters), and a full clinical recovery over a 5-month treatment period. RBD phenomena gradually returned after melatonin administration was stopped. After 2 months' treatment, polysomnography showed no major changes except an increase of REM sleep (13 vs. 17% of sleep period time) and a better preservation of REM-sleep-associated muscle atonia. Our results suggest that melatonin might be able to reinforce REM sleep in RBD patients by enhancing its active inhibition of motor activity.

The diurnal distribution of sleep propensity: experimental data about the interaction of the propensities for slow-wave sleep and REM sleep.

The aim of the present study was to assess the diurnal variation of sleep propensity by evaluating the temporal distribution of sleep onset latency (SOL) and REM- and slow-wave sleep (SWS) parameters in systematically scheduled daytime naps for 12 young males. To reduce the effect of prior SWS on subsequent REM sleep, a double-nap technique was used, i.e. two adjacent naps A and B, which were separated by a 10-min break. Nap duration was adjusted in such a way that nap A allowed 30 min of sleep and nap B one complete NREM-REM cycle. EEG slow wave activity (SWA, power density from 0.5-4 Hz) was estimated from nap A and REM sleep parameters from nap B. The time span between 08.00 hours and 24.00 hours was covered by nine double-naps at 2 h intervals. The order of the nap sessions was systematically varied within and across subjects. For each subject, the time between successive double-nap recordings was at least three days. SOL was shortest in the time interval 12.00 hours to 16.00 hours and significantly longer between 20.00 hours and 24.00 hours. REM sleep duration and the percentage of sleep onset REM episodes decreased continuously from 08.00 hours to the interval 18.00-20.00 hours and increased thereafter, with a time course inversely related to the one of body temperature, which was also measured continuously. SWA showed a steady, threefold increase from 08.00 hours to 24.00 hours. The study offers new data on the diurnal variation of sleep propensity which seems to be a composite function of the drives for SWS and REM sleep.

Dynamics of EEG background activity level within quiet sleep in successive cycles in infants.

We investigated in infants the emergence of the trends of the EEG synchronization throughout quiet sleep (QS) as a function of the QS rank. The night sleep of 3 groups with 6 subjects each (aged respectively 9-18 weeks, 21-47 weeks, and 16-45 years) was recorded. A parameter value reflecting the degree of synchronization of the EEG background activity for successive epochs was computed by automatic analysis. For each QS phase 3 indicators of the dynamics of the time course of the EEG parameter activity were determined: the range (difference between the EEG parameter value at the beginning of the QS episode and that at the trough), the trough latency (after QS onset), and the rate of synchronization (range/trough latency). The range and the trough latency increased with age, whereas the rate of synchronization decreased. The range and the rate of synchronization decreased in the successive cycles, whereas the trough latency increased. These results provide further support for the hypothesis of the early emergence of the process S mechanisms and suggest that the framework of the 2-process model could account also for the development of both the EEG background activity dynamics and the sleep-wake organization.

Electromyographic activity and sleep states in infants.

The electromyographic (EMG) activity in infants was studied in relationship to sleep states and age using an automatic method. One night of sleep in 23, healthy, full-term infants was recorded. Based on 10-second measures of chin EMG activity, two parameters were derived: 1) the tonic EMG and 2) the EMG instability (corresponding to phasic events). Age comparisons were made between young (2-11 weeks) and older infants (21-47 weeks) and between two subgroups of young infants (2-3 weeks and 7-11 weeks). State comparisons were made between paradoxical sleep (PS) and quiet sleep (QS) and, for the older infants, between QS with and without slow-wave sleep. QS tonic level did not differ either between age groups or between QS+ and QS- phases. The EMG instability was larger in PS than in QS for all age groups, and larger in the young than in the older infants, although within the group of young infants no differences between age subgroups were found.

Trends in electroencephalographic synchronization across nonrapid eye movement sleep in infants.

The trend of synchronized (high-voltage, low-frequency) electroencephalographic (EEG) activity was determined across nonrapid eye movement (NREM) sleep periods of night sleep in two groups of infants (eight "young infants", age 2-19 weeks; eight "older infants", age 21-54 weeks) and, a reference, in a group of eight adults (age 16-45 years). By automatic analysis of the sleep EEG, a parameter was derived that represents the degree of synchronized (high-amplitude, low-frequency) EEG activity for successive 30-second epochs. For each subject, the average level of EEG synchronization for each NREM period and the time of the NREM period midpoints were determined. In all three groups, synchronized EEG activity tended to decrease across successive NREM periods. This trend was weaker for infants than for adults and, surprisingly, weaker for older than for young infants. This suggests that the decreasing trend typical for adults is already present in the first months after birth. The difference in trend between infants and adults may be caused by differences in the 24-hour sleep-wakefulness distribution, whereas the distinction between young and older infants could be related to a restructuring of sleep in the second semester, in particular to the emergence of slow-wave sleep and its peculiar distribution across NREM periods of night sleep.

A computerized method for detecting episodes of wakefulness during sleep based on the alpha slow-wave index (ASI).

A method for the automatic detection of episodes of wakefulness during sleep is presented. The algorithm is based on the evaluation of the alpha slow-wave index (ASI), a measure that has been developed to detect fluctuations of vigilance in daytime pharmaco-electroencephalogram studies. Its application to sleep data was validated with polysomnographic recordings from 16 elderly insomniacs and 16 young healthy subjects. The rate of agreement between the computerized procedure and the visual scoring of wakefulness was 94.0% for the insomniacs and 96.9% for the healthy subjects. The decision criterion used by the computer allowed the definition of a subject-adapted threshold for the detection of wake episodes. The method opens new perspectives for the automatic analysis of continuous 24-hour sleep-wake recordings.

The role of slow-wave sleep on the duration of quiet sleep in infants.

The duration of quiet sleep (QS) phases has been shown to increase during the first year of life. Slow-wave sleep (SWS) appears in about half of the QS phases beyond 20 weeks. In order to evaluate the role of SWS in the lengthening of QS phase duration during the first year of life, we looked at 48 normal full-term infants (aged between 1 and 54 weeks), recorded for a whole-night period. Records included electro-encephalogram (EEG) and other polygraphic parameters. Infants were separated into two groups: (1) those who did not show SWS episodes at all, and (2) those who show both QS phases with (QS SWS+) and without (QS SWS-) SWS episodes. In group 2 the duration of QS SWS+ was longer than that of QS SWS, as well as longer than that of QS of group 1. Group 1 had a duration of QS phases similar to that of QS SWS-. The duration of QS SWS+ depended both on the SWS latency and SWS duration. The lengthening of QS phases with age is accounted for by those phases containing SWS episodes, reflecting a maturational restructuring of QS.

Respiration and heart rate variation in normal infants during quiet sleep in the first year of life.

Forty-three all-night sleep recordings have been performed on 19 control infants of the ages 6 weeks, 6 months and 1 year. During eight hour periods 22 physiological parameters were sampled by a personal computer based monitoring system and stored on an optical disk. This paper reports on spectral analysis of breathing and heart rate patterns during the first and last episode of quiet sleep at three different age groups. The results demonstrate that the respiratory rate during quiet sleep decreases (6 weeks: 37.2 +/- 5.4; 6 months: 30.1 +/- 4.9; 1 year: 24.1 +/- 1.8; adults (mean age 25.1 +/- 2.8 years; n = 10): 14.8 +/- 1.8; values are means +/- one standard deviation in breaths/min) and the respiratory coefficient Pm/Ps (higher values of Pm/Ps indicate lower respiratory variability) increases with age (6 weeks: 2.3 +/- 0.7; 6 months: 3.2 +/- 1.1; 1 year: 3.4 +/- 1.0; adults: 4.5 +/- 1.0). The calculation of the heart rate in beats per minute (bpm) and heart rate variability (%) revealed the following results: 6 weeks: 127.4 +/- 11.5 bpm, 3.8 +/- 1.5%; 6 months: 119.4 +/- 17.3 bpm, 4.2 +/- 1.7%; 1 year: 110.3 +/- 21.5 bpm, 5.8 +/- 2.3%; adults: 59.2 +/- 8.5 bpm, 4.3 +/- 2.2%. A comparison of the cardiorespiratory data from the first and last quiet sleep period showed no significant differences within either age group.

Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients. A double-blind study.

The influence of delta sleep-inducing peptide (DSIP) on sleep was studied in 16 chronic insomniac patients according to a double-blind matched-pairs parallel-groups design. Subjects slept for 5 consecutive nights in the laboratory. Night 1 was used for adaptation, night 2 for baseline measurements. In the afternoon before the 3rd, 4th and 5th night, half of the patients received intravenously 25 nmol/kg body weight DSIP, and half of the patients a glucose solution (placebo). Measures for sleep structure, objective (polysomnography) and subjective sleep quality and for subjective tiredness were assessed. The results for objective sleep quality indicated higher sleep efficiency and shorter sleep latency with DSIP as compared to placebo. One measure of subjectively estimated tiredness decreased within the DSIP group. Data analysis suggested, however, that the statistically significant effects were weak and in part could be due to an incidental change in the placebo group. As none of the other measures, including subjective sleep quality, showed any change, it was concluded that short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit.

Oxygen consumption during sleep in children under continuous and cyclic nutrition.

The present study investigated the effects of two modalities of parenteral nutrition (continuous nutrition over the 24-hour period vs. cyclic nutrition, i.e., administered only during the night) on O2 consumption during sleep in children affected by severe gastrointestinal diseases. In both feeding modalities O2 consumption was always highest in REM sleep, intermediate in stage 2 and lowest in SWS. The trends during the night of O2 consumption (an increase from the second to the third part of the night) for different sleep stages were comparable in both feeding modalities. These results suggest that O2 consumption is not affected by the feeding modalities investigated, but is dependent on both sleep stages and time of night.

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.

Developmental changes in the clustering pattern of sleep rapid eye movement activity during the first year of life: a Markov-process approach.

Findings are presented in support of the hypothesis that the tendency of sleep rapid eye movement (REM) activity to group into burst structures changes with age during the first year of life in normal infants. Specifically, by assuming a markovian model for the generation of 1 sec long units of REM activity, it is shown that the propensity of those units to develop a sustained clustering pattern may increase during the first 2 months, possibly reaching a plateau at about 4 months. On the other hand, the overall density of REM activity units may continue to increase beyond that point in time.

24-hour behavioural states distribution in continuously fed infants.

This study compared the 24-h sleep states distribution in infants fed orally with separate meals with that in infants continuously fed from birth. Sleep was polygraphically recorded for 24 h in 12 infants (aged between 6 weeks and 14 months) continuously fed since birth through an intracaval catheter, and in 12 age-paired control infants. The amount of sleep states in each six 4-h epoch of the 24-h day was evaluated. A clear decrease of the sleep amount, concerning both Paradoxical Sleep and Quiet Sleep, was observed during the day-time in infants older than 4 months, independently from the feeding condition. This result does not support the role of feeding rhythm upon the early development of sleep pattern circadian distribution.

Time course of night sleep EEG in the first year of life: a description based on automatic analysis.

The aim of this study is to describe the time course of night sleep in the first year of life. Forty-eight infants aged between 1 and 54 weeks were polygraphically recorded for 1 night. The central occipital EEG derivation was processed with a lab computer in order to obtain every 30 sec an EEG parameter value. The parameter is based on the joint frequency-amplitude distribution of the EEG and displays fluctuations between 2 extreme levels, high voltage low frequency (HVLF) and low voltage high frequency (LVHF). The range of the fluctuations between HVLF and LVHF increases from the period of 1-6 weeks to the period of 7-14 weeks. A further increase of the parameter range occurs after 24 weeks, which remains restricted to the first half of the night. The recurrence time of LVHF and HVLF episodes (possibly corresponding to quiet sleep paradoxical sleep cycles) is about 56 min and does not change with age in the first year of life.