Sleep organization in normal premature newborn infants. Polygraphic study

Polygraphic recordings including EEG, eye movements (REMs) and limb movements (recorded by piezo-electric crystals), chin EMG and respiratory rate, were performed in 23 normal neonates of 31 to 38 weeks conceptional age (CA). The concordance between various parameters characteristic for sleep states was analysed. For all infants, it was possible to define periods (greater than 7 min) of active (AS) and quiet sleep (QS) according to EEG and REM criteria. Mean duration of the 1st sleep cycle (including both AS and QS) lasted 57 to 65 min; no significant difference regarding CA was observed. According to EEG and REM criteria, AS accounted for 47 to 52% of each sleep cycle; QS rose from 27% at 31-34 wCA to 33% at 35-36 wCA (P less than 0.05); indeterminate sleep (IS) decreased from 32% at 31-34 wCA to 10% at 35-36 wCA (P less than 0.01). At all ages studied, the observed duration of AS was not modified when other criteria were considered in addition to EEG and REMs. On the contrary, the observed duration of QS was frequently shortened and scattered with interruptions (indeterminate sleep) when respiration and body motility were considered; but the tonic EMG remained for 80% of QS. The concordance between different criteria characteristic for QS was not better at 37-38 wCA compared to 31-34 wCA.     

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects

Saccade-like eye movements are the most prominent phasic component of rapid eye movement (REM) sleep. Eye movement density (EMD) appears to be negatively related to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a) whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is increased by daytime naps; and (c) whether EMD patterns across sleep cycles differ in the two age groups. Subjects participated in four separate 2-day recording sessions, each consisting of a baseline night, a daytime nap, and post nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM. EMD was not correlated with rate of non rapid eye movement (NREM) delta production (power/min) in the baseline sleep of either group. Changes in EMD and delta power/min on post nap nights also were uncorrelated. These data indicate that very strong changes in sleep depth (state) are required to overcome the individual stability (traits) of NREM delta and eye movement density. ANOVA for EMD across REM periods 1-4 showed a significant cycle effect and a significant age x cycle interaction. These effects were mainly due to YNs having depressed EMD in the first REM period, likely due to the low arousal level early in sleep in these subjects. Compared with waking saccades the saccade eye movements of REM sleep have received little investigation. Further study of these movements could shed new light on neurophysiology of REM sleep. Such studies might also be clinically useful because the density of these movements appears to be related to depression and (independently) to cognitive function in individuals with brain impairment.     

Developmental changes in phasic sleep parameters as reflections of the brain-stem maturation: polysomnographical examinations of infants, including premature neonates.

To gain understanding of brain-stem maturation during the early stages of life, we used polysomnography to examine 32 normal infants aged 33-184 conceptional weeks. Our study focused on the developmental aspects of the phasic sleep parameters, REM density and body movement, and the executive system. REM densities were highest in infants aged 36-38 conceptional weeks. The numbers of gross movements and localized movements (LMs) on chin muscle decreased with age; whereas, those of the twitch movements (TMs) on chin muscle increased. Ratios of the TMs to the total number of LMs and TMs (tentatively designated dissociation indexes because of the close relation between LMs and TMs on surface electromyograms) showed significant increases that paralleled the increase in age. We speculate that the dissociation index is a quantitative reliable sleep parameter which reflects brain-stem maturation.     

Loss of REM sleep features across nighttime in REM sleep behavior disorder

ObjectivesMelatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects.MethodsAn overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD−), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity.ResultsFrom the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change.ConclusionsPatients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity.     

Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep.

Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells. Twelve hour polygraphic recordings were obtained in 18 cats before and 1-2 weeks after bilateral electrolytic or radio frequency lesions of either: (1) PPT, which contains the dorsolateral pontine cholinergic cell column; (2) laterodorsal tegmental nucleus (LDT), which contains the dorsomedial pontine cholinergic cell column; (3) locus ceruleus (LC), which contains mostly noradrenergic cells; or (4) subceruleus (LC alpha, peri-LC alpha and the lateral tegmental field), which also contains predominantly noncholinergic cells. There were three main findings: (i) Only lesions of PPT and subceruleus significantly affected REM sleep time. These lesions produced comparable reductions in REM sleep time but influenced REM sleep components quite differently: (ii) PPT lesions, estimated to damage 90 +/- 4% of cholinergic cells, reduced the number of REM sleep entrances and phasic events, including ponto-geniculooccipital (PGO) spikes and rapid eye movements (REMs), but did not prevent complete atonia during REM sleep: (iii) Subceruleus lesions eliminated atonia during REM sleep. Mobility appeared to arouse the cat prematurely from REM sleep and may explain the brief duration of REM sleep epochs seen exclusively in this group. Despite the reduced amount of REM sleep, the total number of PGO spikes and REM sleep entrances increased over baseline values. Collectively, the results distinguish pontine loci regulating phasic events vs atonia. PPT lesions reduced phasic events, whereas subceruleus lesions created REM sleep without atonia. Severe REM sleep deficits after large pontine lesions, including PPT and subceruleus, might be explained by simultaneous production of both REM sleep syndromes. However, extensive loss of ACh neurons in the PPT does not disrupt REM sleep atonia.     

Functional microstates within human REM sleep: first evidence from fMRI of a thalamocortical network specific for phasic REM periods

High thalamocortical neuronal activity characterizes both, wakefulness and rapid eye movement (REM) sleep, but apparently this network fulfills other roles than processing external information during REM sleep. To investigate thalamic and cortical reactivity during human REM sleep, we used functional magnetic resonance imaging with simultaneous polysomnographic recordings while applying acoustic stimulation. Our observations indicate two distinct functional substates within general REM sleep. Acoustic stimulation elicited a residual activation of the auditory cortex during tonic REM sleep background without rapid eye movements. By contrast, periods containing bursts of phasic activity such as rapid eye movements appear characterized by a lack of reactivity to sensory stimuli. We report a thalamocortical network including limbic and parahippocampal areas specifically active during phasic REM periods. Thus, REM sleep has to be subdivided into tonic REM sleep with residual alertness, and phasic REM sleep with the brain acting as a functionally isolated and closed intrinsic loop.     

Sleep and treatment response in depression: new findings using power spectral analysis

This study examined quantitative measures of sleep electroencephalogram (EEG) and phasic rapid eye movements (REM) as correlates of remission and recovery in depressed patients. To address correlates of remission, pre-treatment EEG sleep studies were examined in 130 women outpatients with major depressive disorder treated with interpersonal psychotherapy (IPT). To address correlates of recovery, baseline and post-treatment EEG sleep studies were examined in 23 women who recovered with IPT alone and 23 women who recovered with IPT+fluoxetine. Outcomes included EEG power spectra during non-rapid eye movement (NREM) sleep and REM sleep and quantitative REMs. IPT non-remitters had increased phasic REM compared with remitters, but no significant differences in EEG power spectra. IPT+fluoxetine recoverers, but not IPT recoverers, showed increases in phasic REM and REM percentage from baseline to recovery. In NREM sleep, the IPT+fluoxetine group showed a decrease in alpha power from baseline to recovery, while the IPT group showed a slight increase. The number of REMs was a more robust correlate of remission and recovery than modeled quantitative EEG spectra during NREM or REM sleep. Quantitative REMs may provide a more direct measure of brainstem function and dysfunction during REM sleep than quantitative sleep EEG measures.     

Sleep architecture and its clinical correlates in first episode and neuroleptic-naive patients with schizophrenia

The goal of the present study was to characterize sleep organization in first episode and neuroleptic-naive patients with schizophrenia and to evaluate relationships between those sleep parameters and clinical symptoms. Eleven patients with acute schizophrenia never treated with neuroleptics were compared to 11 healthy controls. Sleep stages and phasic events (sleep spindles and rapid-eye-movements during REM sleep (REMs) were visually identified. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). Compared to controls, patients with schizophrenia had difficulty initiating sleep, decreased stage 4 duration, reduced rapid eye movement (REM) sleep latency, and normal sleep spindles and REMs densities. Positive symptoms correlated negatively with REM sleep latency. The BPRS total score correlated negatively with REM sleep duration and REMs density. The present results indicate that first episode and neuroleptic-naive patients with schizophrenia have difficulties initiating, but not maintaining, sleep. These results also confirm that the duration of stage 4 and REM sleep latency are reduced in first episode and neuroleptic-naive patients with schizophrenia. The fact that measures of REM sleep correlate with clinical scales of schizophrenia suggests that REM sleep physiology shares common substrates with symptoms of this disease.     

Comparison between eye movement latency and REM sleep parameters in major depression

Alterations of sleep can be observed polysomnographically in approximately 90 percent of depressed patients. Most of the registered sleep abnormalities in depression also occur in other psychiatric disorders. Only some types of REM sleep alterations – short REM latency, increase of REM density and shortening of mean latency of eye movements – were reported as more specific for affective disorders. In the present study polysomnograms of 21 medication free patients with major depressive disorder (assessed with a structured interview for DSM-III-R and Hamilton Scale) and 21 healthy controls were analysed. REM latency (LREM), REM density (RD), latencies of eye movements (LEM) and mean latency of eye movements (M-LEM) were calculated for both groups. Depressed patients (compared with healthy controls) showed increased RD (38.2% vs. 28.2%, p < 0.0001), shortened M-LEM (35.7 s vs. 48.3 s, p < 0.04) and shortening of LEM in the 1st (28.9 s vs. 48.9 s, p < 0.007) and 4th (27.0 s vs. 59.1 s, p < 0.043) REM sleep periods. LREM was not shortened significantly in depressives (78.5 min vs. 91.3 min, ns). In healthy subjects a negative correlation between M-LEM and RD was found (rho = − 0.47, p < 0.03). Since in the current study depressed patients differed from healthy controls, especially concerning phasic activity during REM sleep, presented data support the essential role of REM density for the assessment of sleep in depression. As a quick and easy manner to compute measurement, M-LEM is suggested as additional parameter for the assessment of phasic activity during REM sleep. Received: 23 March 1999 / Accepted: 23 November 1999     

The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication.

BACKGROUND: Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. METHODS: Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. RESULTS: Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. CONCLUSIONS: Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.     

Eye movements in the human fetus and newborn

The human oculomotor system becomes active long before birth. At about 16 weeks (post-menstrual age) the first slow changes of eye position can be observed with the aid of real time ultrasonography. At 18-20 weeks more rapid eye movements are detectable. There is a gradual decline in the percentage of time spent in rapid and slow eye movements from 32-40 weeks. These eye movements are organized in episodes of activity, divided by episodes of quiescence which are at first unrelated to cyclical changes in other variables (such as breathing movements, body movements and fetal heart rate patterns). At about 36 weeks gestation, REM and non-REM episodes become linked with other changes and then represent behavioural states identical to those seen in the newborn infant. This organization of behavioral states in the fetus is identical with that found in preterm infants of comparable age. Opening of eyelids is difficult to see before birth but the existence of episodes of wakefulness seems most probable. Hence fetal eye movements will be in part related to wakefulness. In the newborn at term, the interval distributions of REMs during sleep and of scanning eye movements during wakefulness are statistically different.     

Rem sleep in depressed patients: Different attempts to achieve adaptation

Twenty-seven depressed patients and 10 healthy subjects were investigated in the sleep laboratory during two to three consecutive nights. Eleven of the 27 patients demonstrated the “first night effect” (group I) and 11 other patients demonstrated a clear absence of the “first night effect” (group II). Five of the 27 depressed patients were omitted from the study because they did not fit criteria for first night effect. The 10 healthy controls demonstrated a first night effect. In group I, the duration of the first rapid eye movement (REM) sleep episode was increased on the first night and on the second night the REM sleep latency was decreased, whereas REM sleep duration and eye movement (EM) density was increased. The number of the short sleep cycles (less than 40 minutes) was greater in group I versus group II and the percentage of slow-wave sleep (SWS) was also higher in group I. In depressed patients with the “first night effect” the enhanced REM sleep requirement is satisfied not only by an increased REM sleep duration but also by the improved REM sleep quality that is crucial for adaptation. The adaptive role of the increased first REM period and the increased EM density in this period is very limited.     

Polysomnographic studies of Lesch–Nyhan syndrome

Three cases of Lesch–Nyhan syndrome (LNS) were examined by polysomnography to assess the brainstem function, and to determine the causes of the neurological manifestations and sudden death in this syndrome. In the two older cases, the amount of slow wave and rapid eye movement (REM) sleep, the REM density and the frequency of REM bursts were decreased. In the youngest case, symmetrical phasic movements of all four limbs were observed at all sleep stages other than REM sleep. Although movements other than these symmetrical body movements appeared to be normal in this case, the frequency of twitch movements showed an abnormal pattern in each sleep stage in the two older cases. These findings suggest that in the brainstems of younger cases with LNS the REM-non REM generator as well as multiple neurotransmitter systems influencing body movements during sleep remain relatively normal, but become progressively impaired in adult cases. Severe obstructive apnea was observed in one case with hypothyroidism, but there were no respiratory abnormalities in other two cases.     

Rapid eye movement sleep behavior disorder and rapid eye movement sleep without atonia in narcolepsy

Narcolepsy is a rare disabling hypersomnia disorder that may include cataplexy, sleep paralysis, hypnagogic hallucinations, and sleep-onset rapid eye movement (REM) periods, but also disrupted nighttime sleep by nocturnal awakenings, and REM sleep behavior disorder (RBD). RBD is characterized by dream-enacting behavior and impaired motor inhibition during REM sleep (REM sleep without atonia, RSWA). RBD is commonly associated with neurodegenerative disorders including Parkinsonisms, but is also reported in narcolepsy in up to 60% of patients. RBD in patients with narcolepsy is, however, a distinct phenotype with respect to other RBD patients and characterized also by absence of gender predominance, elementary rather than complex movements, less violent behavior and earlier age at onset of motor events, and strong association to narcolepsy with cataplexy/hypocretin deficiency. Patients with narcolepsy often present dissociated sleep features including RSWA, increased density of phasic chin EMG and frequent shift from REM to NREM sleep, with or without associated clinical RBD. Most patients with narcolepsy with cataplexy lack the hypocretin neurons in the lateral hypothalamus. Tonic and phasic motor activities in REM sleep and dream-enacting behavior are mostly reported in presence of cataplexy. Narcolepsy without cataplexy is a condition rarely associated with hypocretin deficiency. We proposed that hypocretin neurons are centrally involved in motor control during wakefulness and sleep in humans, and that hypocretin deficiency causes a functional defect in the motor control involved in the development of cataplexy during wakefulness and RBD/RSWA/phasic motor activity during REM sleep.     

REM sleep eye movement activity and CSF concentrations of 5-hydroxyindoleacetic acid in psychiatric patients

The relationship between rapid-eye-movement (REM) sleep tonic and phasic activity measures and the pre- and postprobenecid cerebrospinal fluid (CSF) concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) was examined in a sample of 14 unmedicated psychiatric patients. The average duration of an eye movement burst and the average number of eye movements within a burst were found to be inversely related to the probenecid corrected accumulation of 5-HIAA in the CSF. These results are interpreted as indicating an association between REM burst eye movement activity and serotonin turnover in psychiatric subjects.     

Rapid eye movements, muscle twitches and sawtooth waves in the sleep of narcoleptic patients and controls

Seventeen unmedicated patients with narcolepsy-cataplexy and 17 age- and sex-matched controls were recorded polygraphically for 3 consecutive nights. Rapid eye movements (REMs), m. mentalis twitches and sawtooth waves in the EEG were visually scored. REM and twitch densities during REM sleep were significantly higher in the patients than in the controls. The distribution pattern of REMs and twitches was altered in the patients: twitch density peaked in the first REM period and density of REMs showed an even distribution across all the REM periods of the night. In the controls both REM and twitch density increased from the first to the second REM period. We therefore assume that in the narcoleptics phasic activity of REM sleep is disinhibited. Densities of REMs, twitches and sawtooth waves did not correlate with one another in patients and controls. They appear to be independently regulated. The REM periods of the patients contained 3 times as many waking epochs as those of the controls. This suggests that in narcolepsy the transition REM/waking is selectively facilitated. The REM/NREM ratio of twitch and sawtooth wave densities was the same in patients and controls.     

Motor disturbance during REM sleep in group A xeroderma pigmentosum

We investigated motor phenomena during rapid eye movement (REM) sleep in 13 patients with group A xeroderma pigmentosum aged from 11 to 39 months, and compared them with those obtained from 12 age-matched controls. At the time of sleep study, they had no abnormality on routine electrophysiological examinations. The amount of REM sleep and the incidence of motor phenomena during REM sleep in patients were similar to those in age-matched controls. However, using the newly designated indices, we demonstrated disturbance on both the tonic motor inhibition occurring during the whole REM sleep period and the phasic one acting simultaneously with horizontal rapid eye movements in these patients. Since the motor inhibition during REM sleep is mediated by the subcortical structures, our study indicate that these structures are functionally impaired in group A xeroderma pigmentosum even during the early stage of the illness.     

Sleep in children with episodic sleep phenomena: a comparison with the normal child]

(1) The sleep pattern of 23 children, aged 5-12 years, with episodic nocturnal phenomena (night-terrors, somnambulism, rhythmic movements) was recorded during two successive nights. It was compared with that of a group of 21 normal children of the same age. (2) In the pathological group, slow wave sleep (SLP, stages 3 and 4) was significantly shortened during the 2 nights. This deficit mainly involved the first 3h of sleep. (3) As for the slow wave sleep, REM sleep (SP) modifications prevailed during the first hours of sleep. The first REM period was delayed and preceded by more numerous and atypical partial REM periods. The duration of the first REM period increased faster as a function of its latency than in the normal child. (4) In contrast with this difficulty for REM sleep to occur during the first part of the night, the subsequent REM sleep pattern was similar in the 2 groups (total REM sleep duration, mean REM period duration, mean REM cycle duration). For equal latencies, REM periods had similar duration. Finally, the total REM sleep amount was a linear function of the total sleep time, with more or less identical coefficients for the two groups. (5) The part played by these modifications during the first hours of sleep in the occurrence of night terrors and somnambulism is discussed.     

Quantification of electromyographic activity during sleep: a phasic electromyographic metric.

Recording of electromyographic (EMG) activity is considered essential for defining rapid eye movement (REM) sleep and for quantifying certain types of movements in sleep, such as periodic leg movements in sleep (PLMS). However, routine analyses of EMG activity beyond such purposes is performed rarely and quantified seldom, and normative data are lacking. In this study, the authors examined systematic application of a visual scoring system for short-duration (approximately 100-millisecond) phasic EMG activity recorded from five different muscle groups (submentalis, left/right anterior tibialis, left/right brachioradialis) recorded from two different age groups of normal subjects and a group of patients with Parkinson's disease. Quantification of this activity was labeled as a phasic electromyographic metric (PEM). PEM data were compiled separately by REM and non-REM sleep. Results indicated that PEM is a normal part of REM sleep in all muscle groups, more specifically constituting about 5% (SD = 3.1%) of 2.5-second intervals of REM sleep in the mentalis in healthy young adults. It occurs at higher rates in patients with Parkinson's disease, and its quantification in the legs may be influenced to some degree by the presence of PLMS. PEM may be a useful metric amenable to quantification with digital techniques. It may have particular relevance for the identification of neurodegenerative conditions in which disinhibition of midbrain dopaminergic pathways results in excessive motor discharge during sleep.     

Longitudinal change in REM sleep components in a patient with multiple system atrophy associated with REM sleep behavior disorder: paradoxical improvement of nocturnal behaviors in a progressive neurodegenerative disease

A 60-year-old patient with multiple system atrophy (MSA) who presented with rapid eye movement (REM) sleep behavior disorder was investigated longitudinally by all-night polysomnography. REM sleep components, i.e. rapid eye movements and chin muscle activity, were analyzed together with the frequency of behaviors/movements on the videorecording. Decreased frequency of elaborate motor activity during REM sleep with time in this patient was compatible with the observation by his wife, and this change seemed to correlate with predominant tonic chin electromyogram with relatively suppressed phasic chin muscle activity, but the reduction of the REM sleep behavior disorder (RBD) episodes could be interpreted as being due to the increased rigidity along with MSA progression. The chronological change in REM sleep components in RBD with neurological disorders is worth studying in large follow-up series to enlarge our knowledge about the mechanism of behavioral manifestation of RBD in humans.