Polygraphic studies of kitten development: respiratory rate and variability during sleep-waking states.

The developmental course of respiration rate and variability during sleep states and waking was measured in chronically prepared kittens. Kittens had higher respiration rates during active sleep (AS) as compared to quiet sleep (QS) at all ages, with rates declining developmentally in both sleep states. Compared to waking, respiration rate and variability were decreased during sleep. The decrease was greatest in the youngest animals and during QS. Minute-to-minute respiratory variability declined from 10 to 40 days of age for each state, whereas breath-to-breath variability declined during the same period only during QS. Respiratory variability was higher in AS than QS in older kittens. Heart rate and variability were found to be correlated with respiratory parameters only during QS. These observations support the hypothesis that the control and development of respiration during sleep is achieved by different processes in QS and AS.     

Sleep and waking states in infancy: normative studies

Twelve-hour polygraphic recordings were obtained in 20 normal healthy term infants at 1 week of age, at monthly intervals up to 4 months, and at 6 months of age. Each minute of these recordings was coded into active sleep (AS), quiet sleep (QS), wakefulness (AW), or indeterminate (IN) based on polygraphic and behavioral variables. For each state, a dozen variables were computed with the help of a laboratory computer. Together these variables describe trends in the development of sleep and wakefulness in the laboratory: an increase in QS and a concomitant decrease in AS, an increase in sustained episodes of these states, and continuous sleep onset in AS throughout this time span. Considerable variability appears to characterize immature sleep patterns, but a reduction in variability was noted between 3 and 4 months of age. The number of sustained sleep-state episodes and the percentage of AS and IN proved to be stable characteristics of individual infants. The large variability among and within infants sheds doubt on the usefulness of polygraphic monitoring of sleep states for early detection of abnormalities.     

Postnatal development of spontaneous neuronal discharges in the pontine reticular formation of free-moving rats during sleep and wakefulness

Summary A developmental study has been made of spontaneous neuronal activity within the pontine reticular formation (giant cell field: FTG) of the rat between one week and one month after birth. Through day 14, the recorded FTG neurons discharged more frequently during quiet sleep (QS) than was generally true in older animals. In addition, they were active to the same extent during active-sleep (AS) as during waking-with-movements (AW). In contrast, most of the cells recorded from day 15 on were considerably more active during AS and AW, relative to the QS level, than had hitherto been the case. This new class of neurons, in turn, fell into two sub-groups, one of which was most active during AW while the other was more active during AS. Clomipramine selectively suppressed AS along with the neuronal activity patterns associated with it, and in many cases the QS firing level was even lower than it had been prior to the injection. It is concluded that FTG unit activity is an excellent monitor for controlling the effectiveness of experimental manipulations of AS but is probably not involved in its generation.     

Comparison of postnatal development of heart rate responses to trigeminal stimulation in sleeping preterm and term infants

Autonomic dysfunction has been regarded as a possible cause of the sudden infant death syndrome (SIDS) and it has been suggested that preterm infants, who are at a greater risk of SIDS than term infants, may have immature autonomic control. Our aim was to compare the maturation of cardiac autonomic control during sleep in preterm and term infants by examining heart rate responses to arousing and non-arousing trigeminal stimuli. Preterm infants (n = 15) and term infants (n = 24) were studied longitudinally with daytime polysomnography. Air-jet stimulation of the nares was delivered in both active sleep (AS) and quiet sleep (QS), and heart rate (HR) changes recorded for both arousal and non-arousal responses. Changes in HR (DeltaHR%) were calculated as the relative differences between baseline HR (BHR) and either MaxHR (arousal) or MinHR (non-arousal). Comparisons of HR changes between sleep states and postnatal ages were made with two-way anova for repeated measures and between groups with two-way anova. The increase in HR (DeltaHR%) was greater in term than preterm infants (P < 0.05), but only at 2-3 weeks corrected postnatal age (CPA). In preterm infants, there were no differences in BHR between sleep states, whereas in term infants, BHR was higher in AS than in QS at 2-3 weeks and 2-3 months of age. The smaller DeltaHR% to arousing stimuli in preterm infants compared with term infants at 2-3 weeks suggests that cardiac sympathetic activity in preterm infants may be lower than in term infants. This mechanism may account for the increased risk for SIDS of preterm infants.     

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.     

Polysomnographic sleep and waking states are similar in subsequent siblings of SIDS and control infants during the first six months of life

Twenty-five subsequent siblings of infants who died of Sudden Infant Death Syndrome (SIDS) underwent 12-h overnight polygraphic recordings during the first week of life and at 1, 2, 3, 4, and 6 months of age. The polygraphic tracings from these infants were compared with those from 25 infants without a family history of SIDS. One dozen sleep and waking parameters were examined including state transition probabilities, the ratio between quiet sleep (QS) and active sleep (AS), the incidence and duration of sustained states and the stability of an infant's sleep and waking during the first half year of life. Variability within and between infants was marked with a reduction of variability in measures of QS at 3 months and of AS at 4 months of age. The similarities between subsequent siblings of SIDS and control infants far outweighted the differences. However, subsequent siblings exhibited a tendency, once asleep, to remain asleep longer than controls. This finding was observed in a comparison of 20 infants in each group. When five infants were added to each group, infants in both groups tended to awaken equally from QS, but once in AS the subsequent siblings tended to proceed into QS instead of awaken as the controls did.     

Neonatal Acoustically-Elicited Cardiac Response: Modulation by State and Antecedent Stimulation

This study investigated modulation of the acoustic cardiac reflex (ACR) in human neonates. Three groups of 16 human neonates born at term were presented an abrupt cardioacceleratory auditory stimulus during awake (AW), quiet sleep (QS), and active sleep (AS) states of wakefulness. On 3/4 of the trials this stimulus was preceded by a continuous pure tone at lead times of either 100, 250, or 4000 ms. Across state, prestimulation modified the amplitude and pattern of the neonatal ACR. Relative to trials without prestimulation, the 100-ms lead inhibited, whereas the 250-ms and the 4000-ms lead stimului enhanced the ACR. During AS, neonates exhibited a triphasic ACR that returned to baseline within 9 s in contrast to the sustained responses in AW and QS states. The results demonstrate central inhibitory and facilatatory control over the ACR early in postnatal life. The pattern of results is consistent with the adult pattern of acoustic startle modulation, as is the absence of significant state effects. Given data from 2-month-old infants suggesting an absence of inhibitory effects in acoustic modulation of cardiac startle, it appears that there are non-linear changes in this basic sensory processing mechanism during the first months after birth.     

Methodological issues in coding sleep states in immature infants

Thirty-five healthy, premature infants, ranging from 30–39 weeks postconceptional age, were observed continuously for 6 to 24 hr. Behavioral state and electroencephalographic patterns were coded for each minute. Using these data, three questions regarding coding of states of sleep were addressed: What is the concordance between behavioral codes and specific EEG patterns? Does the concordance between behavioral codes and EEG patterns change with postconceptional age? What range of error can be expected when observation periods shorter than 24-hr are used to estimate the daily distribution of quiet sleep (QS) and active sleep (AS)? With behavioral codes as the standard, concordances of EEG patterns for QS and AS were 72.5 and 92.1% respectively. With EEG patterns as the standard, behavioral codes for QS and AS agreed 83.0 and 88.9%. Agreement between behavioral codes and EEG patterns for QS increased with age. Finally, variation in estimates of the daily distribution of QS and AS decreased dramatically as the length of observation increased from 3 to 24 hr. © 1995 John Wiley & Sons, Inc.     

Autoregulation of the cerebral circulation during sleep in newborn lambs

Autoregulation is a vital protective mechanism that maintains stable cerebral blood flow as cerebral perfusion pressure changes. We contrasted cerebral autoregulation across sleep–wake states, as little is known about its effectiveness during sleep. Newborn lambs ( n = 9) were instrumented to measure cerebral blood flow (flow probe on the superior sagittal sinus) and cerebral perfusion pressure, then studied during active sleep (AS), quiet sleep (QS) and quiet wakefulness (QW). We generated cerebral autoregulation curves by inflating an occluder cuff around the brachiocephalic artery thereby lowering cerebral perfusion pressure. Baseline cerebral blood flow was higher ( P < 0.05) and cerebral vascular resistance lower ( P < 0.05) in AS than in QW (76 ± 8% and 133 ± 15%, respectively, of the AS value, mean ± s.d. ) and in QS (66 ± 11% and 158 ± 30%). The autoregulation curve in AS differed from that in QS and QW in three key respects: firstly, the plateau was elevated relative to QS and QW ( P < 0.05); secondly, the lower limit of the curve (breakpoint) was higher ( P < 0.05) in AS (50 mmHg) than QS (45 mmHg); and thirdly, the slope of the descending limb below the breakpoint was greater ( P < 0.05) in AS than QS (56% of AS) or QW (56% of AS). Although autoregulation functions in AS, the higher breakpoint and greater slope of the descending limb may place the brain at risk for vascular compromise should hypotension occur.     

Of sleep state and postnatal age on arousal responses induced by mild hypoxia in infants

STUDY OBJECTIVES: It has been suggested that mild hypoxia may not be a potent stimulus for arousal during sleep in infants because infants frequently fail to arouse from quiet sleep (QS). Our aim was to characterize arousal responses of sleeping infants in both active sleep (AS) and QS under normoxic and mildly hypoxic (15% O2) conditions over the first 6 months of life. PARTICIPANTS: Five healthy term and 6 healthy preterm infants were each studied at 2 to 5 weeks, 2 to 3 months, and 5 to 6 months postterm. All infants underwent daytime polysomnography during which nasal airflow was monitored using a purpose-built pneumotachograph. All infants were studied under both normoxic (21% O2) and hypoxic (15% O2, balance N2) conditions (presentation order randomized) in each sleep state at each study age. Tests were terminated at arousal, O2 saturation falling below 85%, or 5 minutes (failure to arouse). MEASUREMENTS: Probability of failure to arouse and mean arousal latency were compared between each experimental condition, with each infant serving as its own control. RESULTS: Infants aroused more frequently under hypoxic conditions than under normoxic conditions. Overall, arousal latencies were shorter during hypoxia compared to normoxia in both sleep states at each age. Arousal latencies were longer in QS compared to AS in both hypoxic and normoxic conditions. CONCLUSION: In sleeping infants, mild hypoxia serves as a stimulus for arousal in both AS and QS. Of particular significance is our finding that arousal from AS is readily elicited by mild hypoxia.     

Development of sleep states in normal premature and full-term newborns

The aims of our study were: 1) to answer the question "Do sleep states exist in normal premature infants;" 2) to analyze the development of sleep cycle and sleep state characteristics in premature and full-term newborns. Polygraph recordings were done on 38 normal, appropriate for gestational age newborns, born at 30 to 41 weeks (w) of gestation. All infants fell asleep in active sleep (AS). Postwaking AS was significantly shorter than the next AS. Mean sleep cycle duration increased from approximately 46 min at 31-34 w of conceptional age (CA) to 70 min. at 35-36 w CA. In all infants we observed stable, greater than 5 min AS and quiet sleep (QS) periods, as defined by EEG and REM criteria. Indeterminate sleep was about 30% of the total sleep cycle at 31-34 w; it decreased to 12% at 35-36 w. Both duration and percentage of AS and QS significantly increased at 35-36 w and remained stable up to 39-41 w CA. Values of QS were significantly reduced when defined by additional criteria (respiratory rate, tonic chin EMG or motility). Concordance of QS criteria was not significantly better in older versus younger groups of infants. At all ages, AS values were insensitive to changes in the criteria chosen to define them. The contrast, starting from 31-34 w CA, between AS and QS as defined by EEG and REM criteria could account for state differences in the control of many physiological variables in prematures.     

Behavioural and EEG responses to auditory stimuli during sleep in newborn infants and in infants aged 3 months

Two studies were conducted in order to assess EEG and behavioural responsiveness to auditory stimuli as a function of sleep state in infants. The subjects in the first experiment were 11 infants aged 3 months, and in the second study the responsiveness of 8 infants aged 3 months was compared with that of 8 newborn infants. The stimuli ranged in intensity from 36 to 90 dB and were presented using a modification of the method of constant stimuli. The occurrence and intensity of behavioural responses were recorded by a trained observer. Electroencephalogram (EEG) responses were defined as EEG desynchronization and were identified by a Fast Fourier Transform algorithm. The results of the two studies showed that infants were more responsive during active sleep (AS) than during quiet sleep (QS) and gave behavioural responses at lower stimulus intensities than EEG responses. Behavioural responsiveness and EEG responsiveness during AS increased as a function of age, while EEG responsiveness during QS decreased. The marked suppression of EEG responsiveness during QS at 3 months of age is thought to be a consequence of developmental changes in sleep mechanisms--an effect which may have clinical implications.     

Maturation of the initial ventilatory response to hypoxia in sleeping infants

In infants most previous studies of the hypoxic ventilatory response (HVR) have been conducted only during quiet sleep (QS) and arousal responses have not been considered. Our aim was to quantify the maturation of the HVR in term infants during both active sleep (AS) and QS over the first 6 months of life. Daytime polysomnography was performed on 15 healthy term infants at 2-5 weeks, 2-3 and 5-6 months after birth and infants were challenged with hypoxia (15% O2, balance N2). Tests in AS always resulted in arousal; in QS tests infants either aroused or did not arouse. A biphasic HVR was observed in non arousing tests at all three ages studied. The fall in SpO2 was more rapid in arousal tests at all three ages. At 2-5 weeks, in non-arousing QS tests, there was a greater fall in respiratory frequency (f) despite a smaller fall in SpO2 compared with 2-3 and 5-6 months. When infants aroused there was no difference in the HVR between sleep states or with postnatal age. However, when infants failed to arouse from QS, arterial desaturation was less in the younger infants despite a poorer HVR. We suggest that arousal in response to hypoxia, particularly in AS, is a vital survival mechanism throughout the first 6 months of life.     

The evolution of sleep: a reconsideration of the development of the quiet sleep/active sleep cycle

Quiet sleep (QS) is usually assumed to have evolved before active sleep (AS), because early studies of the primitive mammal echidna indicated that it experiences QS only. Theories designed to account for the development of AS therefore usually focused on the adaptive advantages of a QS/AS cycle over QS alone. There are several conceptual and empirical problems with those theories, however. Moreover, recent data indicate that a QS/AS cycle is extant in all mammals and birds. Empirical and conceptual evidence supporting the notion that AS developed earlier than previously thought, and that AS could have preceded QS in evolution, are discussed here.     

In vivo microdialysis measures of extracellular norepinephrine in the rat amygdala during sleep-wakefulness

Norepinephrine (NE)-containing locus ceruleus (LC) has been known to participate in the regulation of the sleep-wake cycle according to the differential firing rate. The aim of this study was to know the change of extracellular NE level in the rat amygdala, which are reciprocally connected with LC, during sleep-wakefulness. Extracellular NE levels in the rat amygdala were investigated during different stages of the sleep-waking cycle using in vivo microdialysis and polygraphic recording. Dialysates were collected every 5 min and correlated with the results of polygraphic recording. The content of NE was measured by high-performance liquid chromatography with electrochemical detection. NE level was the highest in active waking (AW) and, when compared to AW, NE level was progressively lower in quiet waking (QW; 86%), quiet sleep (QS; 72%), and active sleep (AS or REM sleep; 61%). This result suggests that the rat amygdala also participates in the regulation of the sleep-wake cycle according to the differential NE release.     

Postnatal development of ventilatory and arousal responses to hypoxia in human infants

During the first year of life there is significant maturation of the hypoxic ventilatory response (HVR) in human infants. Compared with adults, healthy term infants have an immature HVR until at least 6 months of age. There are few studies in infants on the effects of sleep state on the HVR but these suggest that at early postnatal ages there is initially no sleep-state related difference; this is followed by a developmental trend towards the adult situation in which the response is depressed in REM sleep compared with NREM. Maternal cigarette smoking is a major risk factor for SIDS and the mechanism for this may involve a depressed HVR in the exposed infant; however studies are limited and the wide variation in cigarette consumption makes interpretation of results difficult. Arousal responses to hypoxia are of vital importance and a failure to arouse has been implicated in SIDS. Sleeping infants frequently fail to arouse in response to hypoxia in QS, whereas in AS they invariably arouse; furthermore arousal latency is longer in QS compared with AS. The oxygen saturation at which infants arouse is not different between sleep states, suggesting that desaturation is more rapid in AS. In QS younger infants arouse more readily than at older ages and arousal is depressed by maternal smoking. These findings suggest that depression of the arousal response to hypoxia in AS may have life-threatening consequences. Infants at increased risk for SIDS have been shown to have both depressed ventilatory and arousal responses to hypoxia, thus they may be at even greater risk.     

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.     

Prone sleeping impairs circulatory control during sleep in healthy term infants: implications for SIDS

STUDY OBJECTIVES: To determine the effects of sleeping position on development of circulatory control in infants over the first 6 months of postnatal age (PNA). DESIGN: Effects of sleeping position, sleep state and PNA on beat-beat heart rate (HR) and mean arterial pressure (MAP) responses to a head-up tilt (HUT) were assessed during sleep in infants at 2-4 wks, 2-3 mo and 5-6 mo PNA. MEASUREMENTS: Daytime polysomnography was performed on 20 full-term infants (12 F/8 M) and MAP was recorded continuously and noninvasively (Finometer). HUTs of 15 degrees were performed during active sleep (AS) and quiet sleep (QS) in both the prone and supine sleeping positions. MAP and HR data were expressed as the percentage change from baseline, and responses were divided into initial, middle and late phases. RESULTS: In the supine position HUT usually resulted in an initial increase (P < 0.05) in HR and MAP, followed by decreases (P < 0.05) in HR and MAP in the middle phase; subsequently HR and MAP returned to baseline in the late phase. By contrast, in the prone position the initial HUT-induced rises in HR and MAP were usually absent, and at 2-3 mo MAP actually decreased (P < 0.05); subsequently HR but not MAP returned to baseline. At 2-3 mo, MAP was lower (P < 0.05) in prone than supine sleeping throughout the HUT. CONCLUSIONS: Prone sleeping alters MAP responses to a HUT during QS at 2-3 mo PNA. Decreased autonomic responsiveness may contribute to the increased risk for SIDS of infants sleeping in the prone position.     

Scatterplot analysis of EEG slow-wave magnitude and heart rate variability: an integrative exploration of cerebral cortical and autonomic functions

STUDY OBJECTIVES: To explore interactions between cerebral cortical and autonomic functions in different sleep-wake states. DESIGN: Active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) of adult male Wistar-Kyoto rats (WKY) on their daytime sleep were compared. PARTICIPANTS: Ten WKY. INTERVENTIONS: All rats had electrodes implanted for polygraphic recordings. One week later, a 6-hour daytime sleep-wakefulness recording session was performed. MEASUREMENTS AND RESULTS: A scatterplot analysis of electroencephalogram (EEG) slow-wave magnitude (0.5-4 Hz) and heart rate variability (HRV) was applied in each rat. The EEG slow-wave-RR interval scatterplot from all of the recordings revealed a propeller-like pattern. If the scatterplot was divided into AW, PS, and QS according to the corresponding EEG mean power frequency and nuchal electromyogram, the EEG slow wave-RR interval relationship became nil, negative, and positive for AW, PS, and QS, respectively. A significant negative relationship was found for EEG slow-wave and high-frequency power of HRV (HF) coupling during PS and for EEG slow wave and low-frequency power of HRV to HF ratio (LF/HF) coupling during QS. The optimal time lags for the slow wave-LF/HF relationship were different between PS and QS. CONCLUSIONS: Bradycardia noted in QS and PS was related to sympathetic suppression and vagal excitation, respectively. The EEG slow wave-HRV scatterplot may provide unique insights into studies of sleep, and such a relationship may delineate the sleep-state-dependent fluctuations in autonomic nervous system activity.     

Non-nutritive swallowing and respiration coordination in full-term newborn lambs

Swallowing is a powerful inhibitor of respiratory rhythm in infants. The present study was aimed at investigating the influence of states of alertness on non-nutritive swallowing (NNS) frequency, on NNS and respiration coordination, and on bursts of NNS frequency in newborn lambs. Six full term newborn lambs were instrumented for electroencephalogram, eye movement, diaphragm and thyroarytenoid muscle electromyogram, nasal flow and electrocardiogram. Polysomnographic recordings were performed in non-sedated lambs, using radiotelemetry. NNS frequency was significantly higher during quiet wakefulness (W) and active sleep (AS) than during quiet sleep (QS). NNS mainly interrupted inspiration and the transition phases between expiration and inspiration, especially in W and AS. Bursts of NNS occurred significantly more often during AS. This study highlights the relevance of the ovine model to study ontogeny of NNS during sleep, and documents the influence of sleep on NNS and respiration coordination.