Sleep organization in the first year of life: developmental trends in the quiet sleep-paradoxical sleep cycle

The night sleep of 48 healthy drug-free infants, aged 1-54 weeks, was recorded and analysed in order to show how cycles contribute to sleep episode organization and how the balance among different sleep states (i.e. quiet sleep, paradoxical sleep and ambiguous sleep) within cycles changes as a function of age. A greater proportion of time spent in cycles (TCT) on total sleep time (TST), as a result of the lengthening of sleep cycles, was found in older infants, whereas sleep out of cycles decreases with age. The internal structure of the sleep cycles also changes with age, because of the increase in the proportion of quiet sleep (QS), the appearance of slow wave sleep (SWS) from the 21st week onwards, and the decrease in ambiguous sleep. The proportion of paradoxical sleep (PS), however, remains stable throughout the first year of age. The improvement of sleep organization across the first year of life is paralleled by an internal restructuring of the cycle, involving mainly changes in QS. We may speculate that both changes, one involving the lengthening of cycle and the other involving the increase in QS component, contribute to the improvement of biological and psychological sleep functions during development.     

The microstructure of active and quiet sleep as cortical delta activity emerges in infant rats

STUDY OBJECTIVES: Previous investigators have suggested that quiet sleep (QS) in rats develops rapidly upon the emergence of cortical delta activity around postnatal day (P)11 and that the presence of "half-activated" active sleep (AS) suggests that infant sleep is initially disorganized. To address these issues, we examined the temporal organization of sleep states during the second postnatal week in rats as delta activity emerges. DESIGN: Subjects were P9, P11, and P13 Sprague-Dawley rats. Electroencephalogram and nuchal electromyogram electrodes were implanted, and data were recorded at thermoneutrality for 2 hours. RESULTS: At all ages, using electromyogram and behavioral criteria, QS (defined as nuchal atonia and behavioral quiescence) dominated the first third of each sleep period, whereas AS (defined as nuchal atonia accompanied by myoclonic twitching) dominated the last third. When delta activity, which was first detected at P11, could be added to the definition of QS, gross assessments of sleep-state organization were not altered, although it was now possible to identify brief periods of QS interposed between periods of AS. No evidence of "half-activated" AS was found. Finally, "slow activity transients" were detected and were primarily associated with QS; their rate of occurrence declined as delta activity emerged. CONCLUSIONS: When delta activity emerges at P11, it integrates smoothly with periods of QS, as defined using electromyogram and behavioral criteria alone. Delta activity helps to refine estimates of QS duration but does not reflect a significant alteration of sleep-state organization. Rather, this organization is expressed much earlier in ontogeny as fluctuations in muscle tone and associated phasic motor activity.     

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.     

A comparative study of quiet sleep, active sleep, and waking on the first 2 days of life.

Direct behavioral observation and motility monitoring procedures provide reliable data, and both are appropriate for sleep/wake state measurements starting immediately after birth. Using these procedures, newborn rats, rabbits, and humans were found to have a greater amount of quiet sleep on the day of birth rather than 24 hr later. Changes in active sleep and wake were inconsistent across the 2 days. The quiet sleep findings are contrary to the developmental course which increases with age. The findings are interpreted as a temporary adaptive response to the stress of the birth process.     

Beta EEG reflects sensory processing in active wakefulness and homeostatic sleep drive in quiet wakefulness

Markers of sleep drive (<10 Hz; slow‐wave activity and theta) have been identified in the course of slow‐wave sleep and wakefulness. So far, higher frequencies in the waking electroencephalogram have not been examined thoroughly as a function of sleep drive. Here, electroencephalogram dynamics were measured in epochs of active wake (wake characterized by high muscle tone) or quiet wake (wake characterized by low muscle tone). It was hypothesized that the higher beta oscillations (15–35 Hz, measured by local field potential and electroencephalography) represent fundamentally different processes in active wake and quiet wake. In active wake, sensory stimulation elevated beta activity in parallel with gamma (80–90 Hz) activity, indicative of cognitive processing. In quiet wake, beta activity paralleled slow‐wave activity (1–4 Hz) and theta (5–8 Hz) in tracking sleep need. Cerebral lactate concentration, a measure of cerebral glucose utilization, increased during active wake whereas it declined during quiet wake. Mathematical modelling of state‐dependent dynamics of cortical lactate concentration was more precisely predictive when quiet wake and active wake were included as two distinct substates rather than a uniform state of wakefulness. The extent to which lactate concentration declined in quiet wake and increased in active wake was proportionate to the amount of beta activity. These data distinguish quiet wake from active wake. Quiet wake, particularly when characterized by beta activity, is permissive to metabolic and electrophysiological changes that occur in slow‐wave sleep. These data urge further studies on state‐dependent beta oscillations across species.     

Spontaneous arousals during quiet sleep in piglets: a visual and wavelet-based analysis

STUDY OBJECTIVES: The objectives of the study were to characterize spontaneous arousals during NREM sleep in piglets and to compare two methods of identifying these events: a "visual" technique using spectral analysis and an automated technique using wavelets. Our goal was to understand the benefits and limits of these methods when applied to sleep in human infants. DESIGN: Arousals were identified by evaluating rapid changes in EEG low frequency activity, blood pressure (BP), and heart rate (HR). A cortical arousal was defined as a rapid decrease in EEG low frequency activity. An autonomic arousal was defined by a transient increase in heart rate or a transient change in mean arterial BP (MAP). SETTING: Laboratory study in sleeping and awake piglets. PARTICIPANTS: Five 1-2 week old piglets. INTERVENTIONS: Chronically instrumented with a femoral arterial line, EEG, EOG, EMG electrodes, and a micro-dialysis probe with its tip located in the rostral ventral medulla. Artificial CSF (aCSF) was dialyzed into the RVM throughout the experiments Measurements: For the visual analysis, the average delta power (0.5-4 Hz) for each 5-second epoch was determined using spectral analysis. MAP and HR were analyzed in 1-second bins. Video images were analyzed for body movements and eye openings. Transient changes in blood pressure, HR, and delta power were then visually identified. For the wavelet analysis, a quantitative, automated technique with a defined "wakefulness threshold" was used to identify rapid decreases in EEG low frequency activity and the rate of change of MAP. RESULTS: Using the visual method, 117 episodes associated with stereotypical hemodynamic, EEG, and behavioral changes (startle) were identified. Seventy five events occurred in isolation or were first in a series of "multiple" events, 41 "multiple" events were defined as events occurring <20 seconds following a previous event. Eighteen events were associated with the termination of apnea. In isolated events or those occurring first in a series, the onset of changes in HR and BP clearly preceded the decrease in EEG amplitude and delta power. Using wavelet analysis, 73 EEG arousals and 115 MAP transients were identified independently; 62% of the EEG events were associated with a transient change in MAP and HR, and in these cases the onset of the hemodynamic events preceded EEG arousals. EEG arousals and MAP transients, however, also occurred alone and not associated with a stereotypical pattern of a startle, changes in MAP and HR and the EEG. CONCLUSIONS: Many of these spontaneous arousals represent integrated EEG, hemodynamic, and behavioral processes similar to arousal phenomena described in adult rats and human infants, but the pattern of spontaneous arousals appears to be more heterogeneous than has been described for arousals induced by exogenous stimuli. Both the visual and wavelet analysis identified these events, but the wavelet technique has the potential advantage of better time resolution and automation of the analysis.     

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.     

Heart rate variability during sleep as a function of the sleep cycle

In this work, in order to evaluate whether autonomic differences distinguish REM sleep and NREM sleep through the whole sleeping period, statistical analysis on spectral power associated with low frequency and high frequency bands were performed on the whole polysomnographic recording, considering the sleep cycle as a unit of sleep. Our results from nine subjects show that power associated with low frequency is higher in REM sleep than in NREM sleep, while power associated with high frequency is significantly higher in NREM sleep than in REM sleep. Differences between REM sleep and NREM sleep are not of the same magnitude within the whole sleep episode and, independent of sleep stages, specific trends are observable in the autonomic control of heart rate during the night.     

Renin as a biological marker of the NREM-REM sleep cycle: effect of REM sleep suppression

SUMMARY  We have previously described that, in normal man, the nocturnal oscillations of plasma renin activity (PRA) exactly reflect the rapid eye movement (REM)–non(N)REM sleep cycles, with increasing PRA levels during NREM sleep and decreasing levels during REM sleep. This study was carried out to determine whether REM sleep suppression affects nocturnal renin profiles and to define which sleep stage is essential for renin release.
In a first experimental series, REM sleep was suppressed by using clomipramine, a tricyclic antidepressant. Seven healthy young men were studied once during a night when a placebo was given and once during a night following a single dose of 50 mg clomipramine. Blood was collected every 10 min from 23.00 hours to 07.00 hours. PRA was measured by radio-immunoassay and the nocturnal profiles were analysed using the pulse detection program ULTRA. Clomipramine suppressed REM sleep in all subjects but one, but did not affect the number of SWS episodes nor their duration. Similar PRA profiles were observed in both experimental conditions. Neither the mean levels, nor the number and the amplitude of the oscillations were modified and the normal relationship between slow wave sleep and increasing PRA levels was preserved.
In a second experimental series, REM sleep was prevented by rapidly awakening the subjects as soon as they fell into REM sleep. The four subjects studied attempted several times to go into REM sleep, but only when PRA levels were decreasing. The interruption of REM sleep by short waking periods did not disturb PRA for which the oscillations remained unaffected. Again, the relationship between SWS and increasing PRA levels was preserved.
These results provide evidence that mechanisms increasing slow-wave activity are principally involved in increasing PRA levels and that replacing REM sleep by waking periods and light sleep does not modify nocturnal PRA oscillations.     

Serotonin and the sleep/wake cycle: special emphasis on microdialysis studies

Several areas in the brainstem and forebrain are important for the modulation and expression of the sleep/wake cycle. Even if the first observations of biochemical events in relation to sleep were made only 40 years ago, it is now well established that several neurotransmitters, neuropeptides, and neurohormones are involved in the modulation of the sleep/wake cycle. Serotonin has been known for many years to play a role in the modulation of sleep, however, it is still very controversial how and where serotonin may operate this modulation. Early studies suggested that serotonin is necessary to obtain and maintain behavioral sleep (permissive role on sleep). However, more recent microdialysis experiments provide evidence that the level of serotonin during W is higher in most cortical and subcortical areas receiving serotonergic projections. In this view the level of extracellular serotonin would be consistent with the pattern of discharge of the DRN serotonergic neurons which show the highest firing rate during W, followed by a decrease in slow wave sleep and by virtual electrical silence during REM sleep. This suggests that during waking serotonin may complement the action of noradrenaline and acetylcholine in promoting cortical responsiveness and participate to the inhibition of REM-sleep effector neurons in the brainstem (inhibitory role on REM sleep). The apparent inconsistency between an inhibitory and a facilitatory role played by serotonin on sleep has at least two possible explanations. On the one hand serotonergic modulation on the sleep/wake cycle takes place through a multitude of post-synaptic receptors which mediate different or even opposite responses; on the other hand the achievement of a behavioral state depends on the complex interaction between the serotonergic and other neurotransmitter systems. The main aim of this commentary is to review the role of brain serotonin in relation to the sleep/wake cycle. In particular we highlight the importance of microdialysis for on-line monitoring of the level of serotonin in different areas of the brain across the sleep/wake cycle.     

睡眠监护技术的发展

睡眠医学已经发展成为医学中一门新的边缘学科,近年来取得了快速的发展.睡眠障碍是许多疾病形成和发展的重要因素,尤其阻塞性睡眠呼吸暂停是心血管疾病一个独立的危险因素,如何能有效监测病人的睡眠状况,为病人疾病的早期诊断提供依据,已引起人们的重视.本文综述了睡眠中的一些常见疾病,以及近年来在睡眠监护中临床和试验研究中所用到的一些方法.     

Coordination of the EEG and the heart rate of preterm neonates during quiet sleep

Aim of this study was to confirm that EEG bursts are associated with heart rate (HR) accelerations, and to investigate the synchronicity between quadratic phase couplings (QPC) courses of the EEG and HR before and during burst activity during quiet sleep in preterm newborns. The time-courses of QPC between frequency components of the EEG ([0.25–1.0 Hz] ↔ [4.0–6.0 Hz]) as well as between the Mayer–Traube–Hering (MTH) wave and the frequency component of the HR associated to the respiratory sinus arrhythmia (RSA) ([0.02–0.15 Hz] ↔ [0.4–1.5 Hz]) were investigated in five preterm neonates. During quiet sleep, the EEG alternates between burst and interburst activity. The burst onsets were used to trigger an averaging procedure for the EEG, HR, and QPC courses. It can be demonstrated that the envelopes of the EEG rise after the burst onset accompanied by an acceleration of HR before or at the burst maximum. The QPC courses show that the HR's QPC increases before or at the burst onset whereas the increase of the EEG's QPC is delayed. The synchronous changes of EEG and HR as well as of the corresponding QPC courses indicate a coupling between cortical, thalamocortical and neurovegetative brain structures. Such a coupling might be mediated by the MTH waves in the blood pressure.     

Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report

Five patients with endogenous depression were asked to participate in a phase-advance procedure consisting in advancing by 5 h the time schedule of the major external synchronizers such as light/dark, sleep/wake, meal time and social activity cycles. Clinical and biological parameters were observed throughout this 2-week process which followed one night of partial sleep deprivation. All patients improved with partial sleep deprivation and four of the five showed continuing remission during the phase-advance process. The antidepressant effects of the phase-advance process are discussed in light of different chronobiological models for depression.     

Use of the oculocardiac reflex to assess vagal reactivity during quiet sleep in neonates

Arousal from sleep can be a protective response to life-threatening stimuli. Hence, faults within state-switching processes may lead to fatal events. To investigate the role of the nervous system during cardiac failure triggered by phasic, vagally mediated stimulation, we analysed autonomic and behavioural reactions in 50 premature neonates during quiet sleep (QS) -- a sleep state characterized by a preponderance of tonic, parasympathetic activity. Bradycardia was induced with a standardized ocular compression test. Neither awakening nor behavioural escape reactions were observed during or after an episode of bradycardia. Eighty-six per cent of the provoked bradycardic episodes induced central apnoea. During QS, the neonates' respiratory response and arousability were found to be time-dependent: when the test was performed early in the QS episode, apnoea was more frequent (94%), and no sleep state change occurred. When ocular compression was performed in the later part of the QS episode, a transition towards active sleep was observed, together with significantly fewer episodes of apnoea (64%). These results indicate that a progressive decrease in the respiratory system's responsiveness to phasic, parasympathetic stimulation occurs during QS, whereas arousability increases. Our study suggests that newborns could be more vulnerable to potentially fatal events during the initial portion of a QS episode.     

Basophil activation tests: time for a reconsideration

Challenges in in vitro allergy diagnostics lie in the development of accessible and reliable assays allowing identification of all offending allergens and cross-reactive structures. Flow-assisted analysis and quantification of in vitro activated basophils serves as a diagnostic instrument with increasing applications developed over the years. From the earliest days it was clear that the test could constitute a diagnostic asset in basophil-mediated hypersensitivity. However, utility of the basophil activation test should be reassessed regarding difficulties with preparation, characterization and validation of allergen extracts; availability and the potential of more accessible diagnostics. Today, the added value mainly lies in diagnosis of immediate drug hypersensitivity. Other potential indications are monitoring venom-immunotherapy and follow-up of natural history of food allergies. However, results in these nondiagnostic applications are preliminary. We review the most relevant clinical applications of the basophil activation test. Some personal comments and views about perspectives and challenges about flow-assisted allergy diagnosis are made.     

Anticipation in schizophrenia: a review and reconsideration

There have been several reports on anticipation and schizophrenia, and the purpose of the present article is to review the literature and present data from an ongoing family study of schizophrenia. The published data find on average a 10-year difference in the age of onset between the parental and offspring generation in family sets that have been ascertained for a genetic linkage study. The biases inherent in such studies include the biases of ascertainment that were described by Penrose [1948]. Several investigators have searched for evidence of enlarged triplet repeats, and some find evidence consistent with expanded triplet repeats, whereas others do not. In any event the phenomenon of anticipation in schizophrenia appears to be consistently found and an explanation is needed. Data are presented from pairwise analyses using intergenerational pairs from 61 pedigrees with schizophrenia showing evidence of anticipation as well as the fertility bias. Anticipation was found in aunt:niece/nephew pairs (14.5 years) but not in uncle:niece/nephew pairs (0.5 years). The sex difference in age of onset was accentuated in uncles versus aunts (8.5 years), present in parents (4.5 years), but absent in the proband generation. Therefore, there appears to be an interaction within families between age of onset and sex that deserves further investigation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:686-693, 1999.