Sleep and wakefulness in the green iguanid lizard (Iguana iguana)

The reptile Iguana iguana exhibits four states of vigilance: active wakefulness (AW), quiet wakefulness (QW), quiet sleep (QS) and active sleep (AS). Cerebral activity decreases in amplitude and frequency when passing from wakefulness to QS. Both parameters show a slight increase during AS. Heart rate is at a maximum during AW (43.8+/-7.9 beats/min), decreases to a minimum in QS (25.3+/-3.2 beats/min) and increases in AS (36.1+/-5.7 beats/min). Tonical and phasical muscular activity is present in wakefulness, decreases or disappears in QS and reappears in AS. Single or conjugate ocular movements are observed during wakefulness, then disappear in QS and abruptly reappear in AS. Although these reptiles are polyphasic, their sleep shows a tendency to concentrate between 20:00 and 8:00 h. Quiet sleep occupies the greater percentage of the total sleep time. Active sleep episodes are of very short duration, showing an average of 21.5+/-4.9 (mean+/-SD). Compensatory increment of sleep following its total deprivation was significant only for QS. Reaction to stimuli decreased significantly when passing from wakefulness to sleep. It is suggested that the lizard I. iguana displays two sleep phases behaviorally and somatovegetatively similar to slow wave sleep and paradoxical sleep in birds and mammals.     

Development of the nocturnal sleep electroencephalogram in human infants

The development of nocturnal sleep and the sleep electroencephalogram (EEG) was investigated in a longitudinal study during infancy. All-night polysomnographic recordings were obtained at home at 2 wk and at 2, 4, 6, and 9 mo after birth (analysis of 7 infants). Total sleep time and the percentage of quiet sleep or non-rapid eye movement sleep (QS/NREMS) increased with age, whereas the percentage of active sleep or rapid eye movement sleep (AS/REMS) decreased. Spectral power of the sleep EEG was higher in QS/NREMS than in AS/REMS over a large part of the 0.75- to 25-Hz frequency range. In both QS/NREMS and AS/REMS, EEG power increased with age in the frequency range <10 Hz and >17 Hz. The largest rise occurred between 2 and 6 mo. A salient feature of the QS/NREMS spectrum was the emergence of a peak in the sigma band (12-14 Hz) at 2 mo that corresponded to the appearance of sleep spindles. Between 2 and 9 mo, low-frequency delta activity (0.75-1.75 Hz) showed an alternating pattern with a high level occurring in every other QS/NREMS episode. At 6 mo, sigma activity showed a similar pattern. In contrast, theta activity (6.5-9 Hz) exhibited a monotonic decline over consecutive QS/NREMS episodes, a trend that at 9 mo could be closely approximated by an exponential function. The results suggest that 1) EEG markers of sleep homeostasis appear in the first postnatal months, and 2) sleep homeostasis goes through a period of maturation. Theta activity and not delta activity seems to reflect the dissipation of sleep propensity during infancy.     

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.     

Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation

Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of N(omega)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.     

Transient ventilatory response to CO2 as a function of sleep state in full-term infants

The influence of sleep state on the transient (i.e., initial 60 s) and steady-state ventilatory responses to 2% CO2 inhalation was studied in 19 healthy full-term infants. A nasal mask pneumotachometer was used to measure ventilation and end-tidal CO2 partial pressure (PCO2) and enabled abrupt changes in the inspired gas concentration to be made. The magnitude of the change in minute ventilation for both the transient and steady-state responses to CO2 was not statistically different between active (AS) and quiet (QS) sleep. Nonetheless the greater variability in minute ventilation during AS compared with QS continued throughout the period of CO2 inhalation and was associated with a more variable change in ventilation in the individual infants during AS. There was a greater increase in end-tidal PCO2 over the first 60 s during AS (3.3 +/- 0.3 vs. 2.6 +/- 0.2 Torr, in AS and QS, respectively, P less than 0.03). This may indicate a smaller initial increase in alveolar ventilation, relative to CO2 delivery to the lungs, in response to CO2 inhalation during AS. Asynchronous chest wall movements were more common during AS than QS (P less than 0.005) and did not change with CO2. The inconsistent transient ventilatory response to CO2 during AS compared with QS may be important in the behavior of infants to spontaneous episodes of hypercapnia occurring during AS.     

Time of night effects on heart rate variation in normal neonates

Circadian patterns have been observed in infants as early as the first few postnatal days. We hypothesized that, in each sleep-waking state, heart rate variation in several distinct frequency bands would show consistent variations across a night in newborn infants. Twelve-hour night-time recordings of EEG, ECG, EOG, digastric EMG, respiratory movements, and CO2 were obtained from 25 normal full-term infants at 2-7 days postnatal age. The extents of three types of heart rate variation were determined for all epochs identified as quiet sleep, rapid eye movement (REM) sleep, and waking during each 4-hr period of the night. In particular states, the extent of all three types of heart rate variation decreased from the evening (7-11pm) to the late night (11pm-3am). Heart rate variation at the respiratory frequency showed such a time-of-night effect in quiet sleep only, resulting in a significant sleep state effect on respiratory sinus arrhythmia during the evening that disappeared later in the night. Previous studies have indicated that respiratory sinus arrhythmia is enhanced during quiet sleep, relative to other states, after 3 mo of age; the present findings suggest that the tendency for enhancement during quiet sleep is present even in the neonate, although this tendency is only expressed during the evening. Results indicate that time-of-night effects on heart rate variation are not constant across physiological states in neonates, and heart rate variation during the waking state is particularly unresponsive to these time-of-night influences.     

Effects of sleep deprivation on respiratory events during sleep in healthy infants

This study was designed to determine the effects of sleep deprivation on respiratory events during sleep in healthy infants. Ten unsedated full-term infants (1-6 mo) were monitored polygraphically during "afternoon naps" on a control day and on the day after sleep deprivation. Respiratory events, i.e., central apnea, obstructive apnea and hypopnea, and periodic breathing were tabulated. Results for respiratory events were expressed as 1) indexes of the total number of respiratory events and of specific respiratory events per hour of total sleep (TST), "quiet" sleep (QS) and "active" sleep (AS) times; 2) total duration of total and specific respiratory events, expressed as a percentage of TST, QS, and AS times. After sleep deprivation, significant increases were observed for 1) respiratory event (P less than 0.001), central apnea (P less than 0.05), and obstructive respiratory event (P less than 0.01) indexes; 2) respiratory event time as a percentage of TST (P less than 0.002) and as a percentage of AS time (P less than 0.001); 3) obstructive respiratory event time as a percentage of TST (P less than 0.01), QS (P less than 0.05), and AS times (P less than 0.002). The present study shows that short-term sleep deprivation in healthy infants increases the number and timing of respiratory events, especially obstructive events in AS.     

The effect of short-term sleep fragmentation produced by intense auditory stimuli on the arousal response to upper airway obstruction in lambs

Upper airway obstruction is recognized to cause apnoea in newborns as well as in adults. However, very little is known about factors that influence the arousal response from sleep during upper airway obstruction in newborns. Experiments were therefore done to investigate the effect of short-term sleep fragmentation on the arousal response to upper airway obstruction in six lambs aged 8 to 14 days. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of systemic arterial blood pressure and oxygen saturation (fiberoptic catheter oximeter). A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. Experiments were not done before the third postoperative day. During a study, a 5F balloon tipped catheter was inserted into the tube so that airflow could be obstructed by inflating the balloon. Measurements were made during 30 s control periods and during experimental periods of upper airway obstruction in at least three epochs of quiet sleep and active sleep in each animal. These measurements were made following a period of uninterrupted sleep and repeated following a 36-42 h period of sleep fragmentation. Sleep fragmentation was produced by 30 s of noise separated by 2 min of quiet. Sleep fragmentation produced small but statistically significant increases in the time to arousal and decreases in the haemoglobin oxygen saturation at arousal during upper airway obstruction in quiet sleep but not active sleep. However, these changes, although consistent, were small and are of questionable biological significance. Therefore, I believe it is unlikely that short-term sleep fragmentation per se significantly impairs the arousal response to respiratory stimuli in newborns.     

Sleep in mammals

Quiet sleep (QS) was correlated with a different set of constitutional variables from those associated with active sleep (AS), in a sample of 69 species of mammals. The time spent in quiet sleep was negatively correlated with body size and basal metabolic rate. The latter relationship remained even after controlling for the effects of body weight. Neither the total time spent in active sleep, nor active sleep as a percentage of total sleep time was significantly correlated with body weight or metabolic rate. Altricial species spend more time in active sleep than do precocial species. The time between the onset of successive episodes of active sleep, the AS-QS cycle length, was positively correlated with body weight. For their body sizes, species that live in temperate regions have shorter AS-QS cycles than those living in tropical or sub-tropical regions. Correlations between patterns of sleep and adult brain weight probably result from the confounding effects of body weight. These findings were used to evaluate several explanations for interspecific differences in patterns of sleep among mammals.     

Fetal breathing and behavior measured through a double-wall Plexiglas window in sheep

The inability to see the fetus makes the assessment of fetal behavior difficult. To circumvent this problem we implanted a Plexiglas window in the left flank of the ewe. Fetuses were instrumented for measurements of sleep, breathing, and swallowing. Ten fetal sheep were studied on 32 occasions. Six fetuses were delivered through the window at term, and postnatal behavior was compared with intrauterine behavior. Fetuses observed during resting conditions alternated between periods of quiet sleep [high-voltage electrocortical activity (ECoG)] and active or rapid-eye-movement sleep (low-voltage ECoG). In quiet sleep, movements were absent except for periodic generalized electromyographic discharges. Eye and breathing movements were rare or absent. Swallowing was also absent. In active sleep, movements were increased with powerful breathing and swallowing activity. Fetal wakefulness defined by open eyes and purposeful movements of the head was never seen in utero but was clearly observed after delivery. We conclude that fetal wakefulness as defined postnatally was not able to be demonstrated in utero.     

Behavioral state transition and local cerebral blood flow in fetal sheep.

Local cerebral blood flow in four near term fetal sheep was evaluated continuously before and after natural alternations in fetal behavioral state. Measurements were made in fetuses several days following an aseptic surgery to place electrodes for behavioral state recordings as well as heated and reference thermojunctions in cortical and subcortical tissue. These thermojunctions were used to qualitatively assess local cerebral blood flow. The time of transition between rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) was based on visual inspection of strip chart recordings of electrocortical, electroocular, and neck electromyographic activity and application of published criteria for their assessment. To confirm that transition had occurred, the amplitude of the spectrum of the electrocorticogram in one-third octave bands centered around 1 Hz and 20 Hz was measured before and after the transition point. Mean cerebral blood flow rose significantly by 24 s (P less than 0.05) after the transition from NREMS to REMS and fell by 12 s after the transition from REMS to NREMS (P less than 0.05).     

Sleep-related sympathovagal imbalance in SHR

The role of the autonomic nervous system in spontaneous hypertension during each stage of the sleep-wake cycle remains unclear. The present study attempted to evaluate the differences in cardiac autonomic modulations among spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) across sleep-wake cycles. Continuous power spectral analysis of electroencephalogram, electromyogram, and heart rate variability was performed in unanesthetized free moving rats during daytime sleep. Frequency-domain analysis of the stationary R-R intervals (RR) was performed to quantify the high-frequency power (HF), low-frequency power (LF)-to-HF ratio (LF/HF), and normalized LF (LF%) of heart rate variability. WKY and SD had similar mean arterial pressure, which is significantly lower than that of SHR during active waking, quiet sleep, and paradoxical sleep. Compared with WKY and SD, SHR had lower HF but similar RR, LF/HF, and LF% during active waking. During quiet sleep, SHR developed higher LF/HF and LF% in addition to lower HF. SHR ultimately exhibited significantly lower RR accompanied with higher LF/HF and LF% and lower HF during paradoxical sleep compared with WKY. We concluded that significant cardiac sympathovagal imbalance with an increased sympathetic modulation occurred in SHR during sleep, although it was less evident during waking.     

The Relationship between CPAP Usage and Corneal Thickness

The purpose of this study was to determine whether there is a correlation between CPAP usage and corneal thickness in patients with sleep disordered breathing. Full-night polysomnography (PSG) recordings were collected. Ten patients had undergone PSG recordings with continuous positive airway pressure (CPAP), and seven patients had undergone PSG recordings without CPAP. We measured corneal thickness by ultrasonic pachymeter before sleep and ten minutes after waking. We also measured visual acuity with a routine ophthalmologic eye chart before and after sleep. We asked patients to fill out a post-sleep questionnaire to get their subjective opinions. In the without-CPAP group, corneal thickness increased significantly during sleep in both eyes (left, p = 0.0025; right, p<0.0001). In the with-CPAP group, corneal thickness did not increase significantly (p>0.05 for both left and right cornea). There was no significant difference in visual acuity tests (p>0.05 for both left and right eye) between the two groups. According to our results, there is a significant increase in corneal thickness in the without-CPAP group. Our data show that a low percentage of Rapid Eye Movement (REM) sleep may cause an increase in corneal thickness, which can indicate poor corneal oxygenation. In fact, many sleep-disordered breathing (SDB) patients have low REM. Since a contact lens may cause low corneal oxygenation, SDB patients with contact lenses should be monitored carefully for their corneal thickness.     

Unit activity of neurons of the posterior ventral nucleus of the thalamus for various waking stages in the normal cat

Using the electrocortical activity in the sensorimotor cortex as an index, three distinct levels of motionless waking can be identified in the cat, all three different from active waking and from slow sleep (attentive waking, quiet waking and drowsiness). It has now been shown that spontaneous and evoked single unit activities in n. ventralis posterior of the thalamus undergo significant changes when passing from one level of waking into another one.     

Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior

Noradrenergic, serotonergic, and histaminergic neurons are continuously active during waking, reduce discharge during NREM sleep, and cease discharge during REM sleep. Cataplexy, a symptom associated with narcolepsy, is a waking state in which muscle tone is lost, as it is in REM sleep, while environmental awareness continues, as in alert waking. In prior work, we reported that, during cataplexy, noradrenergic neurons cease discharge, and serotonergic neurons greatly reduce activity. We now report that, in contrast to these other monoaminergic "REM-off" cell groups, histamine neurons are active in cataplexy at a level similar to or greater than that in quiet waking. We hypothesize that the activity of histamine cells is linked to the maintenance of waking, in contrast to activity in noradrenergic and serotonergic neurons, which is more tightly coupled to the maintenance of muscle tone in waking and its loss in REM sleep and cataplexy.     

Comparison of calibration methods for respiratory inductive plethysmography in infants

In infants under the age of 6 mo respiratory inductive plethysmograph (RIP)-calculated tidal volumes (VT) were compared with simultaneously measured volumes using a pneumotachograph (PNT) to 1) assess whether using multiple points (MP) along the inspiratory profile of a breath is superior to using only VT when calculating volume-motion (VM) coefficients, 2) verify the assumption of independent contributions of the abdomen and rib cage to VT, which was accomplished by extending the normal RIP model to include a term representing interaction between these two compartments, and 3) investigate whether VM coefficients are sleep-state dependent. Neither use of multiple points nor inclusion of the interacting term improved the performance of the RIP over that observed using a simple two-compartment model with VT measurements. However, VM coefficients obtained during quiet sleep (QS) were not reliable when used during rapid-eye-movement (REM) sleep, suggesting that coefficients obtained during one sleep state may not be applicable to another state where there is a substantial change in the relative abdominal/rib cage contributions to VT.     

Effect of sleep state and hypercapnia on alae nasi and diaphragm EMGs in preterm infants

A coordinated activation of upper airway and chest wall muscles may be crucial in maintaining airway patency and ventilation. The alae nasi (AN) and diaphragm (DIA) electromyograms (EMG) were recorded with surface electrodes in 17 unsedated healthy preterm infants during both active (AS) and quiet sleep (QS). Airflow was measured via a nasal mask pneumotachograph and integrated to obtain tidal volume. Studies were performed during inhalation of room air and mixtures of 2 and 4% CO2 in air. In room air, phasic AN EMG accompanied 45 +/- 7% of breaths during AS compared with 14 +/- 5% of breaths during QS (P less than 0.001); however, with inhalation of 4% CO2 the incidence of AN EMG increased to comparable levels in both sleep states. During room air breathing onset of AN EMG preceded that of the DIA EMG and inspiratory airflow by 41 +/- 8 ms (P less than 0.01) and 114 +/- 29 ms (P less than 0.05), respectively. Peak AN activity preceded peak DIA activity by 191 +/- 36 ms (P less than 0.01). Alteration in sleep state or increasing chemical drive did not significantly alter these temporal relationships. Nevertheless, with each increase in end-tidal CO2, peak DIA EMG and tidal volume increased while peak AN EMG only showed a consistent increase during 4% CO2 inhalation. We conclude that although there exists a mechanism that temporally coordinates AN and DIA activation, the amount of AN EMG activity with each breath is not clearly correlated with DIA activation, which may contribute to the high incidence of respiratory dysrhythmias in preterm neonates.     

Sleep states alter ventral medullary surface responses to blood pressure challenges

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.     

Quantifying the Interactions between Maternal and Fetal Heart Rates by Transfer Entropy

Evidence of the short term relationship between maternal and fetal heart rates has been found in previous studies. However there is still limited knowledge about underlying mechanisms and patterns of the coupling throughout gestation. In this study, Transfer Entropy (TE) was used to quantify directed interactions between maternal and fetal heart rates at various time delays and gestational ages. Experimental results using maternal and fetal electrocardiograms showed significant coupling for 63 out of 65 fetuses, by statistically validating against surrogate pairs. Analysis of TE showed a decrease in transfer of information from fetus to the mother with gestational age, alongside the maturation of the fetus. On the other hand, maternal to fetal TE was significantly greater in mid (26–31 weeks) and late (32–41 weeks) gestation compared to early (16–25 weeks) gestation (Mann Whitney Wilcoxon (MWW) p<0.05). TE further increased from mid to late, for the fetuses with RMSSD of fetal heart rate being larger than 4 msec in the late gestation. This difference was not observed for the fetuses with smaller RMSSD, which could be associated with the quiet sleep state. Delay in the information transfer from mother to fetus significantly decreased (p = 0.03) from mid to late gestation, implying a decrease in fetal response time. These changes occur concomitant with the maturation of the fetal sensory and autonomic nervous systems with advancing gestational age. The effect of maternal respiratory rate derived from maternal ECG was also investigated and no significant relationship was found between breathing rate and TE at any lag. In conclusion, the application of TE with delays revealed detailed information on the fetal-maternal heart rate coupling strength and latency throughout gestation, which could provide novel clinical markers of fetal development and well-being.     

Sleep EEG as a nonlinear dynamic process: a comparison of global correlation dimension of human EEG and measures of linear interdependence between channels

The goal of this work was to study (1) whether the estimation of correlation dimension (D2) using spatial embedding distinguishes between sleep stages and (2) whether information gained from the application of global D2 is redundant to measures of linear interdependence between channels. Twenty one-channel EEG segments of 12 healthy male subjects recorded during waking and sleep stages REM, I, II, and III-IV (according to the Rechtshaffen and Kales criteria) were analyzed with global (multichannel) D2, mean square correlation coefficients (MS) and proportion of variance accounted for by the first principal component (PC1). D2 was found to decrease progressively from stage I to stage III-IV with D2 values of waking and REM being close to those of stages I and II. MS and PC1 did not distinguish among sleep stages but yielded significant differences between waking and sleep. The results suggest that global D2 extracts information from human EEG. That sort of evidence cannot be obtained with measures of linear interdependence between channels.