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Aims: This study sought to determine whether not sleeping soundly in early infancy predicted poor development. This complemented earlier studies of children aged 12 months or older. Methods: Sleep/wake patterns of 35 Japanese infants (23 males) with a gestational age of 37< weeks were recorded at home using actigraphy. Families were registered with a laboratory-based database for infant research. Follow-up recordings were conducted at 3, 4, 6, 12, and 24 months. Crawling was rated by mothers at 12 months and used to create regular and irregular crawling groups. Temperament was scaled using the Japanese Infant Behaviour Questionnaire-Revised Questionnaire and the Japanese Early Childhood Behaviour Questionnaire. Results: At 4 months, infants with regular crawling style had shorter night-time sleep than infants with irregular crawling style. However, at 12 months, the former had longer motionless sleep at night compared to the latter. Before 6 months, infants with regular crawling style showed lower sleep efficiency, especially during the day, compared to those with irregular crawling style. In addition, the amount of night-time active sleep at 3 and 4 months were positively correlated with day-time activity, but not at 6 months. Conclusion: Short fragmental sleep in early infancy did not always predict poor development. [ABSTRACT FROM AUTHOR]

• Higher power of cortical bursts after postnatal day 3 predicted worse cognitive, language and motor outcomes. • Association between cortical bursts and outcome was independent of structural MRI findings. • EEG may provide additional information by indexing persistent active mechanisms that support recovery or exacerbate damage. Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. We identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. Higher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. Clinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. These findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future. [ABSTRACT FROM AUTHOR]

The objective of the present study was to confirm the link between spontaneous smiling and active sleep in newborns, and to identify the role of the cortex in the generation of spontaneous smiles. A total of 12 healthy newborns born at term and three infants with major congenital abnormalities (two with hydranencephaly and one with a left hemispherectomy) were evaluated by video and polysomnography during a 3‐hr sleep period. Smiles were graded and their association with isolated rapid eye movements and grouped rapid eye movements was analysed. In all, 383 smiles were recorded of which 377 occurred during active sleep. Smiles were shown to be significantly associated with active sleep (p <.0001) and with grouped rapid eye movements (p <.0001). Bilateral smiles were more frequent than asymmetrical smiles. Among asymmetrical smiles, left‐sided smiles were more frequent than right‐sided smiles (p <.0001). Maternal stimulation during active sleep did not increase smiles. Smiling was absent during active sleep only in the infant with total hydranencephaly in whom nearly all cortical tissue was absent. In conclusion, smiling occurs in healthy newborns, almost exclusively in active sleep and is associated with grouped rapid eye movements. In infants with major congenital abnormalities, smiling is abolished only when nearly all of the cerebral cortex is absent. These results support the hypothesis of the role of active sleep in the stimulation of neuronal circuits responsible for spontaneous smiling and emphasise the importance of cortical areas in newborn smiling. [ABSTRACT FROM AUTHOR]

Delta and theta power across fronto-central regions is lower during phasic (saccadic eye movements) than tonic rapid eye movement (active) sleep in full-term infants (n = 15). This indicates that the behavioural-electrophysiological pillars of rapid eye movement sleep micro-architecture are in place at birth. [ABSTRACT FROM AUTHOR]

There is a growing realization that proper sleep during pregnancy is essential for the health of the mother and the offspring. However, there are no reports on the effects of maternal sleep restriction on the sleep-wake profiles of newborns. So, this study was conducted to evaluate the effects of sleep restriction during the third term of pregnancy on the sleep-wake profiles of neonates born to them. The female pregnant Wistar rats were sleep restricted for 5 h/day on gestational days 15–20 by gentle handling. Sleep-wake profiles of the pups born to them and to the control rats were recorded on postnatal days 1–21. Pups of sleep restricted dams had higher active sleep (AS) and lower quiet sleep (QS) as well as wakefulness. Higher ratio of AS to QS, longer duration of sleep cycles, lesser bout frequency and reduced EEG delta power were also observed in these pups, all of which indicated brain immaturity. All these signs of delayed maturation, usually found in premature babies, were observed in the pups of sleep restricted mothers, who had longer gestation period. This report not only shows the importance of sleep during pregnancy, but it also suggests that neonatal sleep monitoring can be used as a tool for early assessment of retarded brain development. [ABSTRACT FROM AUTHOR]

In this short review, I would like to share some personal memories about the insights and achievements of Michel Jouvet in the field of sleep ontogeny. The first time I met Michel Jouvet was in 1972 when he accepted to chair my thesis on sleep, the research work being preformed in Howard Roffwarg's lab in New York. From then on we had many discussions together about the mechanisms and nature of neonatal Paradoxical Sleep, notably its characteristic muscular "twitches". The idea emerged of a genetically programmed pattern of motor activation responsible for this state of "seismic" sleep. Such a pattern would underlie, for example, the facial mimics displayed during sleep in early life, whose function would be to "pre-practice" a specific behavior. Later on, in the 1980's Michel Jouvet had the masterful insight to extend this role of Paradoxical Sleep to the theory of genetic programming for maintaining psychological individualism. Michel Jouvet's scientific curiosity and generosity led to his exceptional accomplishments, and he will remain as an immense figure in the culture of sleep science. [ABSTRACT FROM AUTHOR]

Morphology and late components of evoked potentials change depending on wake-sleep stages in adults. Visual Evoked potentials (VEPs) have been frequently studied in newborns to identify abnormal development of visual pathways; however, large variability has been reported and there is uncertainty as to the effect of sleep stages on VEPs in neonates. Objective To describe the characteristics of VEPs in one month old, healthy full-term newborns during active sleep (AS) and quiet sleep (QS), defined by simultaneous polysomnography (PSG). Methods VEPs were obtained by monocular LEDs stimulation of each eye during AS and QS, in 20 healthy full-term newborns (gestational age 37–40 weeks) with normal birth weights and normal prenatal Doppler ultrasound indices. Latencies and amplitudes of N2, P2 and N3 components in AS and QS were compared, and their association with absolute power of EEG frequency bands, assessed. Results There were no significant differences in VEP morphology, latencies and amplitudes between sleep states. Typical wave forms were obtained in all newborns in AS; however, no VEPs could be identified clearly in 3 newborns in QS; QS VEPs were less reliable than in AS: more averaging was required; correlation was significantly lower between the VEP averages; and a larger number of babies needed more than two averages to obtain replicable responses needed for clinical purposes. Conclusions These results indicate that changes in amplitude and latency of some VEP components observed in NREM and REM sleep in adults are not yet present in one month old newborns probably due to immaturity of cortical and sleep mechanisms. VEPs are more reliable during AS than QS in newborns. Systematic VEP recording during AS, and polysomnographic control to identify this stage, are highly recommended as methods that can increase there liability of neonatal VEPs. [ABSTRACT FROM AUTHOR]

Aim of this study was to investigate the preferential looking behaviour, subsequent to a familiarization task (8-min) with a previously responsive or motionless face, before and after a sleep cycle. Moreover, the role of the active sleep in memory consolidation of the responsive or motionless faces was explored. Hypotheses were that the newborns undergoing a motionless familiarization will exhibit a novelty effect (preference for the novel face) whereas the newborns undergoing a responsive familiarization will show a familiarity effect (preference for the known face) before and after the sleep cycle; moreover, the amount of active sleep will be associated with the looking time at the known face after a sleep cycle. Forty-five healthy full-term newborns were randomly assigned to two groups (group 1: motionless-familiarization and group 2: responsive-familiarization); in both groups newborns were video-recorded during four post-familiarization face-preference tasks, two of them performed before and two after a sleep cycle. During the pre-sleep-trials, there was not a significant preference for one face in both groups. During the post-sleep trials, the newborns showed a clear preference for the novel face. This effect was more evident in group 1. Only in group 2 there was a significant positive correlation between the active sleep duration and the looking duration at the known-face during the post-sleep trials (r=0.41; p=0.040). Multiple regression confirmed that only in the group 2 the total duration of the active sleep was associated with the looking duration at the known-face during the post-sleep trials (Adjusted R2=0.13; β=0.41; t=2.2; p=0.040). Findings showed that in newborns the face representation can be recalled after a sleep cycle. Moreover, the amount of the active sleep predicted the post-sleep looking toward the known-face only in the newborns who interactively familiarized with the face. [ABSTRACT FROM AUTHOR]

As an approach of unobtrusive assessment of neonatal sleep state we aimed at an automated sleep state coding based only on heart rate variability obtained from electrocardiography used for regular patient monitoring. We analyzed active and quiet sleep states of preterm infants between 30 and 37weeks postmenstrual age. To determine the sleep states we used a nonlinear kernel support vector machine for sleep state separation based on known heart rate variability features. We used unweighted and weighted misclassification penalties for the imbalanced distribution between sleep states. The validation was performed with leave-one-out-cross-validation based on the annotations of three independent observers. We analyzed the classifier performance with receiver operating curves leading to a maximum mean value for the area under the curve of 0.87. Using this sleep state separation methods, we show that automated active and quiet sleep state separation based on heart rate variability in preterm infants is feasible. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite the ubiquitous nature of sleep, its functions remain a mystery. In an attempt to address this, many researchers have studied behavioural and electrophysiological phenomena associated with sleep in a diversity of animals. The great majority of vertebrates and invertebrates display a phase of immobility that could be considered as a sort of sleep. Terrestrial mammals and birds, both homeotherms, show two sleep states with distinct behavioural and electrophysiological features. However, whether these features have evolved independently in each clade or were inherited from a common ancestor remains unknown. Unfortunately, amphibians and reptiles, key taxa in understanding the evolution of sleep given their position at the base of the tetrapod and amniote tree, respectively, remain poorly studied in the context of sleep. This review presents an overview of what is known about sleep in amphibians and reptiles and uses the existing data to provide a preliminary analysis of the evolution of behavioural and electrophysiological features of sleep in amphibians and reptiles. We also discuss the problems associated with analysing existing data, as well as the difficulty in inferring homologies of sleep stages based on limited data in the context of an essentially mammalian-centric definition of sleep. Finally, we highlight the importance of developing comparative approaches to sleep research that may benefit from the great diversity of species with different ecologies and morphologies in order to understand the evolution and functions of sleep. [ABSTRACT FROM AUTHOR]

The cerebellum is a critical sensorimotor structure that exhibits protracted postnatal development in mammals. Many aspects of cerebellar circuit development are activity dependent, but little is known about the nature and sources of the activity. Based on previous findings in 6-day-old rats, we proposed that myoclonic twitches, the spontaneous movements that occur exclusively during active sleep (AS), provide generalized as well as topographically precise activity to the developing cerebellum. Taking advantage of known stages of cerebellar cortical development, we examined the relationship between Purkinje cell activity (including complex and simple spikes), nuchal and hindlimb EMG activity, and behavioral state in unanesthetized 4-, 8-, and 12-day-old rats. AS-dependent increases in complex and simple spike activity peaked at 8 days of age, with 60% of units exhibiting significantly more activity during AS than wakefulness. Also, at all three ages, approximately one-third of complex and simple spikes significantly increased their activity within 100 ms of twitches in one of the two muscles from which we recorded. Finally, we observed rhythmicity of complex and simple spikes that was especially prominent at 8 days of age and was greatly diminished by 12 days of age, likely due to developmental changes in climbing fiber and mossy fiber innervation patterns. All together, these results indicate that the neurophysiological activity of the developing cerebellum can be used to make inferences about changes in its microcircuitry. They also support the hypothesis that sleep-related twitches are a prominent source of discrete climbing and mossy fiber activity that could contribute to the activity-dependent development of this critical sensorimotor structure. [ABSTRACT FROM AUTHOR]

During adulthood, electroencephalogram (EEG) recordings are used to distinguish wake, non–rapid eye movement sleep, and rapid eye movement sleep states. The close association between behavioral states and EEG rhythms is reached late during development, after birth in humans and by the end of the second postnatal week in rats and mice. This critical time is also when cortical activity switches from a discontinuous to a continuous pattern. We review the major cellular and network changes that can account for this transition. After this close link is established, new evidence suggests that the slow waves of non–rapid eye movement sleep may function as markers to track cortical development. However, before the EEG can be used to identify behavioral states, two distinct sleep phases—quiet sleep and active sleep—are identified based on behavioral criteria and muscle activity. During this early phase of development, cortical activity is far from being disorganized, despite the presence of long periods of neuronal silence and the poor modulation by behavioral states. Specific EEG patterns, such as spindle bursts and gamma oscillations, have been identified very early on and are believed to play a significant role in the refinement of brain circuits. Because most early EEG patterns do not map to a specific behavioral state, their contribution to the presumptive role of sleep in brain maturation remains to be established and should be a major focus for future research. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of the study is to understand the relationship between sleep development and crying episodes during early infancy more accurately by longitudinal and objective sleep evaluations. Design: The study is designed as a prospective longitudinal study of infants in the first 4months of life. Methods: This study included 31 healthy term infants. At approximately 4- to 6-week intervals, when the infants were aged 4–6weeks, 8–10weeks, and 14–16weeks, their mothers recorded the duration of crying/fussy behavior of infants in a timetable and attached an actigraph to the infants for 3days. The relationship between 24-h crying/fussy behavior duration and actigraphic sleep measures was examined from both a cross-sectional (age group) and longitudinal (within-infants) perspective. Interactions with diverse covariates were studied by multiple regression analysis. Results: A significant correlation was found between 24-h crying/fussy behavior duration and proportion of active sleep in infants at 14–16weeks and in within-infant relationships. Among potential covariates, gestational age and co-sleeping had a significant impact on proportion of active sleep. Results of multiple regression analysis showed that gestational age and co-sleeping were positively associated with proportion of active sleep, whereas 24-h crying/behavior duration was not associated with proportion of active sleep. Conclusions: Subsiding of early crying and decreasing of proportion of active sleep are parallel phenomena in some infants. However, this association was thought to be attributable to the influence of covariates, including co-sleeping or gestational age. The underlying mechanisms regulating these developmental processes might overlap with one another, as covariates that affect one process could affect the other. [Copyright &y& Elsevier]

Abstract: The present study was designed to elucidate the neuronal projections from the amygdala to the nucleus pontis oralis (NPO). We propose that glutamatergic cells in the central nucleus of the amygdala (CNA) activate neurons in the NPO, which is the critical brainstem site that is responsible for the generation and maintenance of active (REM) sleep. Phaseolus vulgaris-leucoagglutinin (PHA-L), an anterograde transported neuronal tracer, was iontophoresed into the CNA of adult male Sprague-Dawley rats. After a survival time of 7–8 days, the animals were perfused with a fixative and brain tissue was prepared for histological analysis. Sections of the NPO and CNA, which were immunostained with an antibody against PHA-L, were examined with light microscopy. In addition, in order to identify the phenotype of PHA-L-labeled fibers and terminals in the NPO, a double immunohistochemical technique was employed with antibodies against PHA-L and the vesicular glutamate transporter type 2 (VGluT2). Numerous PHA-L-labeled axons and terminals were found in the NPO ipsilateral to the injection site in the CNA. Within the NPO, the majority of labeled fibers were located in the dorsolateral portion of the caudal part of the nucleus. Double-labeling immunostaining studies revealed that PHA-L-labeled axons and terminals in the NPO were glutamatergic. The present demonstration of direct, excitatory (glutamatergic) projections from the CNA to the NPO provide an anatomical basis for the amygdalar control of active sleep. [Copyright &y& Elsevier]

Abstract: Many studies have investigated infant smiling behaviour during wake and active sleep. In the majority of studies authors agreed that two month-old infants exhibit social smiles. However it is not clear if newborns exhibit different kinds of smiles during wake and active sleep to two month-old infants and if the communicative context can affect the quantity and quality of these smiles. The aim of this study was to test if different kinds of communication affects the amount and the quality of smiles during different behavioural states. Smiling behaviour was analyzed during interactive wake (IW) and active sleep (AS), in 40 newborns randomly assigned to 4 groups of 10 newborns each: continuous tactile communication group, discontinuous non periodic tactile communication group, discontinuous periodic tactile communication group, absent communication group. In the total sample the open/closed mouth (social/non social) smiles ratio was 38/5 during IW and 1/28 during AS (p <.001). Moreover these ratios were different between the four groups. Different kinds of tactile communication affect amount and quality of the smiles of newborns during IW and AS. Moreover the morphological difference of the smiles during IW and AS suggested that for newborns the smiling behaviour during IW could have a social meaning, as it does for two month-old infants. [Copyright &y& Elsevier]

Sleep pressure and rebound comprise the two compensatory or "homeostatic" responses to sleep deprivation. Although sleep pressure is expressed by infant rats as early as postnatal day (P)5, sleep rebound does not appear to emerge until after P11. We reexamined the developmental expression of these sleep-regulatory processes in P2 and P8 rats by depriving them of sleep for 30 mm using a cold, arousing stimulus delivered to a cold-sensitive region of the snout. This method effectively increased sleep pressure over the 30-mm period (i.e., increases in the number of arousing stimuli presented over time). Moreover, sleep rebound (i.e., increased sleep during the recovery period) is demonstrated for the first time at these ages. Next, we showed that precollicular transections in P2 rats prevent sleep rebound without affecting sleep pressure, suggesting that the brainstem is sufficient to support sleep pressure, but sleep rebound depends on neural mechanisms that lie rostral to the transection. Finally, again in P2 rats, we used c-fos immunohistochemistry to examine neural activation throughout the neuraxis during sleep deprivation and recovery. Sleep deprivation and rebound were accompanied by significant increases in neural activation in both brainstem and hypothalamic nuclei, including the ventrolateral preoptic area and median preoptic nucleus. This early developmental expression of sleep pressure and rebound and the apparent involvement of brainstem and hypothalamic structures in their expression further solidify the notion that sleep-wake processes in newborns-defined at these ages without reference to state-dependent EEG activity-provide the foundation on which the more familiar processes of adults are built. [ABSTRACT FROM AUTHOR]

Aims: To investigate the correlation between the ‘perfusion index’ (PI) and other commonly used estimates of cutaneous blood flow [heart rate (HR), surface temperatures (ST) and central-to-peripheral thermal gradients (C-P grad)] and to use this new non-invasive tool to compare differences between prone and supine sleep position in low birth weight (LBW) infants. Methods: Six-hour continuous recordings of pulse oximetry, cardiac activity and absolute ST from three sites (flank, forearm and leg), along with minute-to-minute assessment of behavioural states were performed in 31 LBW infants. Infants were randomly assigned to the prone or supine position for the first 3 h and then reversed for the second 3 h. PI data were correlated with HR and C-P grad, and compared across sleep positions during quiet sleep (QS) and active sleep (AS). Results: Perfusion index correlated significantly with HR (r2 = 0.40) and flank-to-forearm thermal gradient (r2 = 0.28). In the prone position during QS, infants exhibited higher PI (3.7 ± 0.9 vs. 3.1 ± 0.7), HR (158.4 ± 8.9 vs. 154.1 ± 8.8 bpm), SpO2 (95.8 ± 2.6 vs. 95.2 ± 2.6%), flank (36.7 ± 0.4 vs. 36.5 ± 0.4°C), forearm (36.1 ± 0.6 vs. 35.5 ± 0.4°C) and leg (35.4 ± 0.7 vs. 34.7 ± 0.7°C) temperatures and narrower flank-to-forearm (0.6 ± 0.4 vs. 0.9 ± 0.3°C) and flank-to-leg (1.3 ± 0.6 vs. 1.8 ± 0.7°C) gradients, compared to those of the supine position. Similar differences were observed during AS. Conclusion: Perfusion index is a good non-invasive estimate of tissue perfusion. Prone sleeping position is associated with a higher PI, possibly reflecting thermoregulatory adjustments in cardiovascular control. The effects of these position-related changes may have important implications for the increased risk for sudden infant death syndrome in prone position. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Infant rats cycle rapidly between periods of high muscle tone (indicative of wakefulness) and periods of atonia (indicative of sleep). Here, the influence of air temperature on sleep in 8-day-old rats was examined by testing pups at thermoneutrality (35 °C) and during moderate (28 °C) and extreme (20 °C) cold challenge; also, pups were tested 1, 4, and 8 hr after infusion of milk to assess the effects of food deprivation on sleep. Whereas moderate cooling slightly reduced sleep durations and altered the temporal patterning of myoclonic twitching, extreme cooling substantially decreased sleep durations and inhibited twitching. In contrast, food deprivation had little effect. Therefore, thermoregulatory mechanisms engaged during moderate cooling sustain sleep, whereas extreme cooling overwhelms these mechanisms, thereby promoting arousal. [ABSTRACT FROM AUTHOR]

Abstract: Muscle atonia is a central feature of adult REM sleep which has recently been demonstrated to be a component of sleep in rats as young as 2 days of age (P2). The neural generation of atonia, which depends on mesopontine and medullary structures, is not fully understood in adults and has never been described in infants. In the present experiments we used electrical stimulation in decerebrated pups to identify an inhibitory area within the medial medulla of P7-10 rats. Muscle tone inhibition was consistently found on or near the midline within the ventromedial medulla, dorsal to the inferior olive, in an area that includes the nucleus gigantocellularis, nucleus paramedianus, and raphe obscurus. Chemical infusions in the same region revealed inhibitory responses to quisqualic acid but not to carbachol or corticotropin-releasing factor. Next, extracellular recordings within the medullary inhibitory area revealed neurons with atonia-on profiles; tone-on neurons were also found, typically at more lateral sites. Finally, in non-decerebrated pups, chemical lesions within the inhibitory area resulted in significant reductions in atonia durations, as well as decoupling of atonia from a second component of infant sleep, myoclonic twitching; specifically, twitches occasionally occurred during periods of high muscle tone, a condition reminiscent of “REM without atonia” as described in adults. In summary, we document the existence of an area within the ventromedial medulla of infant rats that (i) causes atonia when stimulated; (ii) contains units that exhibit atonia-related discharge profiles during sleep-wake cycling; and (iii) when lesioned, results in the partial loss of atonia and decoupling of the components of sleep. All together, these findings demonstrate that muscle atonia is actively regulated very early in ontogeny. [Copyright &y& Elsevier]

Neonatal electroencephalography (EEG) presents some of the most difficult challenges in EEG interpretation, II differs significantly in many ways from EEG of older children and adults. Technologically, acquisition of a neonatal EEG is significantly more difficult and different than an adult EEG. There are numerous features that are age-specific and change almost week-to-week in the preterm infant. Some features may be normal at one age and abnormal If they persist for several weeks. Many of these features also have different implications in neonates as compared to older individuals. These issues mandate a different approach to neonatal EEG interpretation. In this article an overview of neonatal EEG is presented. After a brief discussion of relevant technical issues, various normal EEG features encountered in neonates are discussed. This is followed by a discussion of the ontogeny of EEG, starting from the age of viability to the first few months of life. A description of various abnormalities follows. Finally an approach to analysis of a neonatal EEG is presented. [ABSTRACT FROM AUTHOR]

Loss of muscle tone during active (rapid-eye-movement, REM) sleep is due to the inhibition of motoneurons. This inhibition is manifest in high-gain intracellular electrophysiological records as hyperpolarizing synaptic noise, which includes large amplitude active sleep-specific inhibitory postsynaptic potentials (IPSPs). We report here evidence that the large active sleep-specific IPSPs are comprised of a small number of minimal unitary potentials that are characterized by fast rise-times (10–90% rise-times ≤0.75 ms); they are present in high-gain records during quiet sleep or during active sleep where they are intermingled with larger active sleep-specific IPSPs with 10–90% rise-times ≥1.00 ms and amplitudes that are integer multiples of the minimal unitary potentials. In hypoglossal motoneurons, the amplitude of these minimal unitary potentials averaged 0.33±0.04 mV (mean±S.D., n=6). It is concluded that the large IPSPs with slow rise-times that are observed in motoneurons during active sleep are due to the nearly simultaneous arrival of multiple (≤5) minimal unitary potentials. We hypothesize that the same inhibitory interneurons that produce small IPSPs with fast rise-times during quiet sleep are also responsible for the large amplitude active sleep-specific IPSPs. [Copyright &y& Elsevier]

Infant mammals cycle rapidly between sleep and wakefulness and only gradually does a more consolidated sleep pattern develop. The neural substrates responsible for this consolidation are unknown. To establish a reliable measure of sleep-wake cyclicity in infant rats, nuchal muscle tone was measured in 2-, 5-, and 8-day-old rats, as were motor behaviors associated with sleep (i.e. myoclonic twitching) and wakefulness (e.g. kicking, stretching). Sleep–wake cycles of 2-day-old rats were characterized by short periods of muscle atonia followed by equally short periods of high tone. In 8-day-olds, sleep periods lengthened significantly and disproportionately in relation to awake periods. Next, locus coeruleus (LC) lesions in 8-day-olds resulted in rapid sleep–wake cycling similar to that exhibited by 2-day-olds; in addition, LC lesions had no effect on the duration of awake periods. Finally, transections caudal, but not rostral, to the anterior hypothalamus also reinstated rapid cycling in 8-day-olds, again without affecting the duration of awake periods. This last finding implicates neural structures within the anterior hypothalamus (e.g. ventrolateral preoptic area) in the modulation of sleep–wake cyclicity. The temporal coherence of atonia and myoclonic twitching was not disrupted by any of the manipulations.These results suggest the presence of a bistable mesopontine circuit governing rapid sleep–wake cycling that does not include the LC and that comes increasingly under hypothalamic control during the first postnatal week. This circuit may represent a basic building block with which other sleep components become integrated during ontogeny. [Copyright &y& Elsevier]

Cholinergic and γ-aminobutyric acid (GABA) mechanisms in the dorsolateral pontomesencephalic tegmentum have been implicated in the control of active (REM) sleep and wakefulness. To determine the relationships between neurons that contain these neurotransmitters in this region of the brainstem in adult cats, combined light and electron microscopic immunocytochemical procedures were employed. Light microscopic analyses revealed that choline acetyltransferase (ChAT) and GABA immunoreactive neurons were distributed throughout the laterodorsal and pedunculopontine tegmental nuclei (LDT and PPT). Surprisingly, approximately 50% of the ChAT immunoreactive neurons in these nuclei also contained GABA. Using electron microscopic pre-embedding immunocytochemistry, GABA immunoreactivity was observed in somas, dendrites and axon terminals in both the LDT and PPT. Most of the GABA immunoreactive terminals formed symmetrical synapses with non-immunolabeled dendrites. Electron microscopic double-immunolabeling techniques revealed that ChAT and GABA were colocalized in axon terminals in the LDT/PPT. Approximately 30% of the ChAT immunoreactive terminals were also GABA immunoreactive, whereas only 6–8% of the GABA immunoreactive terminals were ChAT immunoreactive. Most of the ChAT/GABA immunoreactive terminals formed symmetrical synapses with non-immunolabeled dendrites; however, ChAT/GABA immunoreactive terminals were also observed that contacted ChAT immunoreactive dendrites. With respect to ChAT immunoreactive postsynaptic profiles, approximately 40% of the somas and 50% of the dendrites received synaptic contact from GABA immunoreactive terminals in both the LDT and PPT. These findings (a) indicate that there are fundamental interactions between cholinergic and GABAergic neurons within the LDT/PPT that play an important role in the control of active sleep and wakefulness and (b) provide an anatomical basis for the intriguing possibility that a mechanism of acetylcholine and GABA co-release from the terminals of LDT/PPT neurons is involved in the regulation of behavioral states. [Copyright &y& Elsevier]

The amplitude of electrically-evoked mass action potentials recorded in the spinal cord and brainstem has been reported to decrease only during eye movement events of active sleep. In contrast, we have reported that the response of trigeminal sensory neurons to peripheral stimuli is modulated throughout the behavioral state of active sleep. It is unclear whether eye movement events contribute to the modulation of trigeminal sensory neuron activity during active sleep. In the present study, eye movement events were demarcated in order to investigate how these events affect peripheral input to trigeminal sensory neurons in chronic, intact, behaving cats. When compared with wakefulness, the mean response of 45 trigeminal sensory neurons to low-intensity electrical stimulation of the canine tooth pulp was significantly suppressed by 28% during periods of active sleep where no eye movement activity was present and by 41% during periods of active sleep with eye movement events. Hence, during active sleep, tooth pulp-evoked responses were significantly decreased by 16% during eye movement events when compared with non-eye movement active sleep. To investigate whether presynaptic inhibition played a role in this phenomenon, the excitability of eight individual tooth pulp afferent terminals during eye movement periods was compared with non-eye movement periods of active sleep. No evidence of eye movement-related depolarization of tooth pulp terminals was detected. When compared to wakefulness, the responses of six trigeminal sensory neurons to air puff stimulation of facial hair mechanoreceptors were significantly increased by 96% during periods of active sleep where no eye movement activity was present but were significantly decreased by 15% during eye movement events when compared with non-eye movement active sleep. The results of the present study indicate that neuronal responses to both tooth pulp and facial hair mechanoreceptor stimulation are significantly attenuated during eye movement events of active sleep. [Copyright &y& Elsevier]

SUMMARY Newborn mammals spend as much as 90% or more of their time in a sleep state characterized by frequent twitches, rapid eye movements (REMs), and irregular respiratory cycles. These motor and respiratory patterns resemble the phasic motor/respiratory components of adult REM sleep, and as a consequence, this sleep state is traditionally viewed as an immature form of REM sleep. An alternative view is that a significant portion of what has been called REM sleep in these species is a form of spontaneous activity typical of the immature nervous system. In this review, we compare and contrast these two opposing views about the ontogenetic origins of REM sleep, and review the evidence most often cited to support the idea that REM sleep is present in newborn altricial mammals. Critical review of this evidence indicates that REM sleep may not be present at birth in these species; rather, it appears that all mammals early in development exhibit spontaneous, dissociated activity that progressively becomes organized into the distinct states of REM and non-rapid eye movement sleep. [ABSTRACT FROM AUTHOR]

The pedunculopontine tegmental nucleus (PPT) has been implicated in the generation and/or maintenance of both active sleep (AS) and wakefulness (W). GABAergic neurons are present within this nucleus and recent studies have shown that these neurons are active during AS . In order to examine the role of mesopontine GABAergic processes in the generation of AS, the GABAA agonist muscimol and the GABAA antagonist bicuculline were microinjected into the PPT of chronic cats that were prepared for recording the states of sleep and wakefulness. Muscimol increased the time spent in AS by increasing the frequency and duration of AS episodes; this increase in AS was at the expense of the time spent in wakefulness. A decrease in PGO density during AS was also observed following the microinjection of muscimol. On the other hand, bicuculline decreased both AS and quiet sleep and increased the time spent in wakefulness. These data suggest that GABA acts on GABAA receptors within the PPT to facilitate the generation of AS by suppressing the activity of waking-related processes within this nucleus. [Copyright &y& Elsevier]

There are suggestions in the literature that the electroencephalographic (FIG) desynchronization response is in the newborn's repertoire. The present investigation was designed to examine that possibility under stringent experimental conditions. Sixteen normal neonates were presented with a 1-sec pure tone or white noise during one episode of quiet sleep and one episode of active sleep. Flat activity during stimulated quiet sleep was compared with spontaneous periods of low voltage activity during a nonstimulated quiet sleep episode. Comparisons were also made between responses in quiet sleep with and without prior stimulation in active sleep. Habituation and dishabituation were studied by presenting the nonfamiliar stimulus after repetition of the original stimulus. Increased EEG desynchronization to stimulation was found but the response appears to be a complex function of the type of stimulus, recording location, stimulus repetition, and the prior experience variable. The results have implications for differential maturation of the brain, the perceptual capacities of the neonate, and the controversy over orientation in the newborn. [ABSTRACT FROM AUTHOR]

The present study investigated the applicability of the Law of Initial Value (LIV) for heart rate (HR) responses evoked by a nociceptive stimulus in neonatal sleep states. Ten infants were tested during Quiet and Active Sleep. In concordance with the LIV there was a significant inverse correlation for all Ss in Active Sleep between HR change and prestimulus HR values; the average correlation was -.76, the average slope -.48. In Quiet Sleep, which had a small prestimu1us HR range, this relationship was significant only for some Ss. Equating for prestimulus HR values, no significant difference existed in the magnitude of average HR response in Active Sleep vs Quiet Sleep. It was concluded that for nociceptive stimuli the initial HR value is a better predictor than the behavioral sleep state of the magnitude of HR response. It is suggested that the LIV depends largely on the modality and strength of the stimulus and the width of the prestimulus HR range. [ABSTRACT FROM AUTHOR]

In a pilot study, 34 fetuses were stimulated daily with a maternal spoken nursery rhyme from week 34 of gestation onward and re-exposed two and five weeks after birth to this familiar, as well as to an unfamiliar rhyme, both spoken with the maternal and an unfamiliar female voice. During auditory stimulation, newborns were continuously monitored with polysomnography using video-monitored hdEEG. Afterward, changes in sleep–wake-state proportions during familiar and unfamiliar voice stimulation were analyzed. Our preliminary results demonstrate a general calming effect of auditory stimulation exclusively in infants who were prenatally "familiarized" with a spoken nursery rhyme, as evidenced by less waking states, more time spent in quiet (deep) sleep, and lower heartrates. A stimulation naïve group, on the other hand, demonstrated no such effects. Stimulus-specific effects related to the familiarity of the prenatally replayed voice or rhyme were not evident in newborns. Together, these results suggest "fetal learning" at a basic level and point to a familiarization with auditory stimuli prior to birth, which is evident in the first weeks of life in behavioral states and heartrate physiology of the newborn. [ABSTRACT FROM AUTHOR]