Rapid Eye Movement Sleep Stage Research Articles

Expression of inducible nitric oxide synthase (iNOS) and period 1 (PER1) clock gene products in different sleep stages of patients with cognitive impairment

Circadian and sleep disturbances are common behavioural and psychological symptoms of dementia; circadian rhythm–related molecules may be altered in dementia patients. This study investigated the expression of the period 1 clock gene product (PER1), which is involved in circadian rhythms, and inducible nitric oxide synthase (iNOS), thought to generate nitric oxide, important in rapid eye movement (REM) sleep regulation. Specifically, we investigated the difference in expression of these two genes between patients with cognitive impairment and controls. We studied iNOS and PER1 mRNA expression using real-time polymerase chain reaction in peripheral leukocytes during REM sleep, non-REM sleep and wake stages in patients with Alzheimer’s disease (AD, n = 5), patients with mild cognitive impairment (MCI, n = 8) and controls ( n = 9) during polysomnography examination. Expression of iNOS significantly increased during REM sleep in AD patients compared to MCI patients and controls. There were no significant differences in PER1 expression between the three groups, but an increase in PER1 expression during the wake stage was observed for all participants. Increased expression of iNOS during REM sleep of patients with AD might be a compensation mechanism for maintaining REM sleep. However, the precise role of nocturnal expression of iNOS in patients with AD requires further investigation.

Sleep Stage Transitions in Healthy Humans Altered by Central Monoaminergic Antagonist

Sleep stage transitions constitute one of the key components of the dynamical aspect of sleep. However, neural mechanisms of sleep stage transitions have not, to date, been fully elucidated. We investigate the effects of administrating risperidone, a central serotonergic and dopaminergic antagonist, on sleep stage transitions inhumans, and also on ultradian rapid-eye-movement (REM) sleep rhythms. Ten healthy young male volunteers (age: 22 ± 3.7 years) participated in this study. The subjects spent three nights in a sleep laboratory. The first was the adaptation night, and the second was the baseline night. On the third night, the subjects received risperidone (1 mg tablet) 30 min before the polysomnography recording. We measured and investigated transition probabilities between waking, REM and non-REM (stages I-IV) sleep stages. We found that the probability of transition from stage II to stage III was significantly greater for the risperidone night than for the baseline night. We also found that risperidone administration prolonged REM-onset intervals, when compared to the baseline night. We demonstrate that central serotonergic and/or dopaminergic neural transmissions are involved in the regulation of sleep stage transitions from light (stage II) to deep (stage III) sleep, and also in determining ultradian REM sleep rhythms.

Artificial Neural Network and Wavelet Based Automated Detection of Sleep Spindles, REM Sleep and Wake States

Backpropagation artificial neural network (ANN) has been designed to classify sleep-wake stages. Four hours continuous three channel polygraphic signals such as EEG (electroencephalogram), EOG (electrooculogram) and EMG (electromyogram) from conscious subjects were digitally recorded and stored in computer. EOG and EMG signals were used for manual identification of sleep states before training and testing of ANN. The percentages power of the 2 s epochs of the digitized EEG signals from each of three sleep-wake patterns, sleep spindles (SS), rapid eye movement (REM) sleep and awake (AWA) sates, were calculated and analyzed to select the manually confirmed sleep-wake states for each epoch. Further, second order Daubechies mother wavelet has been used to get the wavelet coefficients for the selected EEG epochs. The wavelet coefficients for the EEG epochs (64 data) were selected as inputs for the training the network and to classify SS, REM sleep and AWA stages. The ANN architecture used (64-14-3) in present study shows overall very good agreement with manual sleep stage scoring with an average of 95.35% for all the 1,140 samples tested from SS, REM and AWA stages. This architecture of ANN was also found effectively differentiating the EEG power spectra from different sleep-wake states (96.84% in SS, 93.68% in REM sleep, 95.52% in AWA state). The high performance observed with the system based on wavelet coefficients along with the ANN, highlights the need of this computational tool into the field of sleep research.

Sleep of excessively crying infants: a 24-Hour Ambulatory Sleep Polygraphy study.

Parents' reports suggest that excessively crying or colicky infants sleep less compared with control subjects. The aim of this study was to determine the sleep-wake structure of excessively crying infants throughout a 24-hour cycle. A 24-hour sleep polygraphy study was conducted at home for 24 excessively crying infants and 23 control subjects at the age of 6 weeks. In addition, parental diaries were kept for 4 days. In sleep polygraphy recordings, no major differences between study groups were observed in either the duration or the structure of the 24-hour sleep. In the diaries, the parents overestimated the amount of sleep in both study groups. The parents of the control infants overestimated the amount of sleep more than the parents of excessively crying infants (69.8 minutes [standard deviation: 79.3] compared with 27.1 minutes [standard deviation: 65.4], respectively). In excessively crying infants, the proportion of rapid eye movement sleep was higher during the 3-hour period from the beginning of the first long sleep in the evening and lower during the preceding 3-hour period compared with the control group. The results of this study suggest that diary-based studies are prone to be biased as the parents of the control infants are more likely to overestimate the amount of infant's sleep and, therefore, report more sleep than the parents of the crying infants. Although no differences in the total amount of sleep or proportions of sleep stages were observed, excessively crying infants may be characterized by a disturbance that affects rapid eye movement and non-rapid eye movement sleep stage proportion during evening hours.

Some factors affecting cerebral tissue saturation during obstructive sleep apnoea.

Measurement of cerebral tissue saturation during obstructive sleep apnoea (OSA) may provide additional information to conventional peripheral oxygen saturation. Thirteen subjects with OSA (mean apnoea/hypopnoea index 65.7+/-27.9) were monitored using full polysomnography and monitoring of near-infrared cerebral tissue oxygenation index (TOI). One-thousand and thirty-six apnoeas and hypopnoeas were analysed, in terms of duration, sleep stage, arterial oxygen saturation (Sa,O2) dip, minimum Sa,O2, TOI dip and minimum TOI. Cerebral TOI is a measure of cerebral tissue saturation of haemoglobin with oxygen, calculated using near-infrared spatially resolved spectroscopy, which has been shown to have a high specificity for intracranial changes. Decreases in cerebral oxygenation were observed during apnoeas and hypopnoeas. Baseline TOI ranged from 50.1-73.0% and mean apnoea/hypopnoea related TOI dips ranged from 1.43-6.85%. Mean Sa,O2 dips varied from 3.8-21.7%. In regression analysis, factors significantly predicting the magnitude of the TOI dip were Sa,O2 dip, minimum Sa,O2, apnoea duration and rapid eye movement sleep stage. The effect of apnoea duration and sleep stage remained significant after Sa,O2 was included in the regression equation. Near-infrared spectroscopy provides a noninvasive technique for monitoring cerebral tissue saturation during obstructive sleep apnoea.

Human sleep EEG analysis using the correlation dimension.

Sleep electroencephalograms (EEG) were analyzed by non-linear analysis. Polysomnography (PSG) of nine healthy male subjects was analyzed and the correlation dimension (D2) was calculated. The D2 characterizes the dynamics of the sleep EEG, estimates the degrees of freedom, and describes the complexity of the signal. The mean D2 decreased from the awake stage to stages 1, 2, 3 and 4 increased during rapid eye movement (REM) sleep. The D2 during each REM sleep stage were high and those during each slow wave sleep stage were low, respectively, for each sleep cycle. The mean D2 of the sleep EEG in the second half of the night was significantly higher than those in the first half of the night. Significant changes were also observed during sleep stage 2, but were not seen during REM sleep and sleep stages 3 and 4. The D2 may be a useful method in the analysis of the entire sleep EEG.

Sleep in Critically Ill Patients Requiring Mechanical Ventilation

To objectively measure sleep in critically ill patients requiring mechanical ventilation and to define selection criteria for future studies of sleep continuity in this population. Prospective cohort analysis. University teaching hospital medical-surgical ICU. Twenty critically ill (APACHE II [acute physiology and chronic health evaluation II] acute physiology score [APS], 10 +/- 5), mechanically ventilated adults (male 12, female 8, age 62 +/- 15 years) with mild to moderate acute lung injury (lung injury score, 1.8 +/- 0.9) 10 +/- 7 days after admission to the ICU. Patients were divided into three groups based on 24-h polysomnography (PSG) findings. No patient demonstrated normal sleep. In the "disrupted sleep" group (n = 8), electrophysiologic sleep was identified and was distributed throughout the day (6:00 AM to 10:00 PM; 4.0 +/- 2.9 h) and night (10:00 PM to 6:00 AM; 3.0 +/- 1.9 h) with equivalent proportions of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Nocturnal sleep efficiency was severely reduced (38 +/- 24%) with an increased proportion of stage 1 NREM sleep (40 +/- 28% total sleep time [TST]) and a reduced proportion of REM sleep (10 +/- 14% TST). Severe sleep fragmentation was reflected by a high frequency of arousals (20 +/- 17/h) and awakenings (22 +/- 25/h). Electrophysiologic sleep was not identifiable in the PSG recordings of the remaining patients. These were classified either as "atypical sleep" (n = 5), characterized by transitions from stage 1 NREM to slow wave sleep with a virtual absence of stage 2 NREM and reduced stage REM sleep, or "coma" (n = 7), characterized by > 50% delta or theta EEG activity with (n = 5) and without (n = 2) evidence of EEG activation either spontaneously or in response to deep painful stimuli. The combined atypical sleep and coma groups had a higher APS (13 +/- 4 vs 6 +/- 4) and higher doses of sedative medications than the disrupted sleep group. Sleep, as it is conventionally measured, was identified only in a subgroup of critically ill patients requiring mechanical ventilation and was severely disrupted. We have proposed specific criteria to select patients for future studies to evaluate potential causes of sleep disruption in this population.

Cardiac autonomic function during sleep in psychogenic and organic erectile dysfunction.

The present study investigated the sympathetic/parasympathetic balance during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep in patients with psychogenic and organic erectile dysfunction. The cardiac autonomic balance was assessed from the power of the low frequency (LF) and high frequency (HF) spectral components of heart-rate variability in 11 patients with psychogenic erectile dysfunction and 11 patients with organic erectile dysfunction as determined by monitoring sleep-related erections. Spectral analysis of heart-rate variability was calculated for at least four successive 4-min epochs of electrocardiogram recordings during NREM sleep and for all available 4-min epochs during REM sleep. Statistical analysis revealed that organic patients had a significantly higher LF/HF ratio (P < 0.01) during both stages of sleep, which resulted from a significantly lower power in the HF component (P < 0.004) and higher power in the LF component (P < 0.01) in these patients, in both REM and NREM sleep stages. These results demonstrate that patients complaining of daytime sexual dysfunction and found by sleep-related erection monitoring to suffer from organic erectile dysfunction, have altered cardiac autonomic balance during both stages of sleep.

A neuromagnetic view of hippocampal memory functions

Bursts of highly synchronized discharges of 4-7Hz sinusoidal wave activity can be recorded from the hippocampus during rapid eye movement (REM) sleep. These rhythmic discharges, the hippocampal theta activity, are generated in the dentate granule cells and the pyramidal cell layers of the CA1 field of the hippocampus. The physiological function of the hippocampal theta activity is elusive. The occurrence of this rhythm throughout the REM sleep stage suggests that it is related to some fundamental neurophysiological phenomena associated with REM sleep, particularly consolidation of memory processes. Synchronous oscillations among a population of neurons are expected to yield stronger, more coherent associated magnetic fields which, through their influence back on the electrical fields via induction, would exert an independent effect on the electrical activity of hippocampal neurons and additionally, could foster and reinforce these oscillations through self-induction. The snail-shaped structure of the hippocampal formation, which resembles a solenoid embedded in the temporal lobe, would be expected to amplify these magnetic fields. Additionally, the discovery of large ferromagnetic particles in the human hippocampus suggests that it may function as a large ironcore electromagnet. It is proposed that memory traces may be encoded or decoded magnetically and analogous to a videotape, each encoding unit (i.e., synape, set of synapses or glial cell) could be magnetized in one direction, or the other through the flow of a strong, AC magnetic field along the hippocampal formation. The encoding of memory traces in the hippocampal formation may ultimately reflect an electromagnetic phenomenon.

Relationship of interictal epileptiform discharges to sleep depth in partial epilepsy

Non-rapid eye movement (NREM) sleep activates interictal epileptiform discharges (spikes) in many epileptic syndromes. To define this phenomenon more precisely, we studied the relationship of spikes to absolute log delta power (LDP), a continuous measure of sleep depth, in 8 patients with partial epilepsy. LDP differed significantly across visually scored sleep stages. Logistic regression analyses of spike occurrence in relation to LDP were carried out on the central-occipital channel contralateral to the dominant spike focus (C4-O2 for left and C3-O1 for right temporal focus). Within NREM sleep, spikes were more likely to occur: (1) at higher levels of LDP, (2) on the ascending limb of LDP, and (3) with more rapid rises in LDP. Spike frequency per minute was 4.6 times higher in NREM than in rapid-eye movement (REM) sleep and diminished with time from sleep onset. When the effect of LDP was controlled for in the analysis, however, there was no significant effect of REM sleep stage or time on spike occurrence. Only 1% of spikes occurred within 10 s of an arousal. These findings suggest that processes underlying the deepening of NREM sleep may contribute to spike activation in partial epilepsy.

Sleep Apnea Syndrome and Cerebral Hemodynamics

The dynamics of cerebral blood flow velocity (CBFV) during sleep were investigated in the right middle cerebral artery of 10 patients with sleep apnea syndrome (SAS) (mean age, 37 years) and 10 healthy control subjects (mean age, 32 years) throughout the entire sleep period. A computer-assisted pulsed (2 MHz) transcranial Doppler ultrasonography system was modified for continuous long-term and on-line recording of cerebral hemodynamics. Concurrently, simultaneous polysomnography, continuous BP recordings, and measurement of the end-expiratory carbon dioxide were undertaken. CBFV showed comparable nocturnal profiles in both groups with decreases during non-rapid eye movement (NREM) sleep and increases during rapid eye movement (REM) sleep, indicating that the general pattern of brain perfusion during normal sleep is maintained in SAS. Sleep stage changes were not regularly accompanied by corresponding changes in CBFV. This reflected a quantitative uncoupling between cerebral electrical activity and cerebral perfusion during sleep and indicated a dissociation in the activity of central regulatory mechanisms. Sleep stage-related analysis showed slightly reduced CBFV in patients with SAS compared with healthy control subjects during wakefulness and the first NREM sleep period, suggesting depressed brain activity in the patient group. The higher CBFV values observed in patients with SAS compared with control subjects during REM sleep and sleep stage 2, both preceding and following REM sleep, underline the influence of dynamically changing sleep patterns on cerebral perfusion in these patients. Reproducible rapid decreases in CBFV were related to EEG arousals. Since apneas are terminated by arousals, these results showed that direct neuronal influences on brain perfusion during apnea are evident.

Effect of sleep stage on somatosensory evoked potentials by median nerve stimulation

The effects of sleep stage on early cortical somatosensory evoked potentials (SEPs) and short-latency components elicited by median nerve stimulation were studied in 12 normal volunteers. The latency of P13 in the awake stage was not significantly different from that in any sleep stage. The latencies of N16, N20 and P20 were significantly prolonged while the amplitude of N20 was decreased during the non-rapid eye movement (NREM) sleep stage. P22, P23 and N24 components showed double peaks (P23a, P23b, N24a, N24b) during the NREM sleep stage in 6 subjects, while N24 showed a single peak and only P22 and P23 showed double peaks in 5 other subjects. The latencies and morphologies of SEPs during rapid eye movement sleep stage were almost the same as those during the awake stage. These findings suggest that NREM sleep affects the latency, amplitude and morphology of N16 and early cortical components.

The distribution of EEG frequencies in REM and NREM sleep stages in healthy young adults.

Period-analyzed electroencephalographic (EEG) activity was evaluated in 11 men and 11 women to explore the distribution of EEG frequencies during sleep and potential gender differences. Significant stage-of-sleep main effects were noted for both incidence and amplitude measures. Power measures seemed to best differentiate between non-rapid eye movement (NREM) stages, although incidence measures showed roughly the same distributions across sleep stages. Beta incidence and amplitude was highest in stage 1 sleep followed in descending order by rapid eye movement (REM), stage 2, and slow-wave sleep (SWS). Delta incidence and amplitude were highest in SWS, with slightly lower values in stage 2. Interestingly, REM was characterized by higher incidence and amplitude delta than those found in stage 1 sleep. EEG variables did not show striking sex differences in any sleep stage, although a global measure of delta power in NREM sleep was higher among women. Hemispheric asymmetries were small throughout REM and NREM stages. These findings suggest that period analysis provides a detailed description of EEG frequency characteristics during sleep but does not reveal dramatic gender differences.

Relationship between enteric migrating motor complex and the sleep cycle

To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.

Autoregressive and bispectral analysis techniques: EEG applications

Some basic properties of autoregressive (AR) modeling and bispectral analysis are reviewed, and examples of their application in electroencephalography (EEG) research are provided. A second-order AR model was used to score cortical EEGs in order. In tests performed on five adult rats to distinguish between different vigilance states such a quiet-waking (QW), rapid-eye-movement (REM), and slow-wave sleep (SWS), SWS activity was correctly identified over 96% of the time, and a 95% agreement rate was achieved in recognizing the REM sleep stage. In a bispectral analysis of the rat EEG, third-order cumulant (TOC) sequences of 32 epochs belonging to the same vigilance state were estimated and then averaged. Preliminary results have shown that bispectra of hippocampal EEGs during REM Sleep exhibit significant quadratic phase couplings between frequencies in the 6-8-Hz range, associated with the theta rhythm.

Asymmetrical Auditory Probe Evoked Potentials During REM and NREM Sleep

Two experiments were conducted to evaluate interhemispheric differences in late auditory evoked potentials (AEPs) during rapid-eye-movement (REM), Stage 2, and Stage 4 sleep. In the first study, 1,000-Hz stimuli [80 db (SPL)] were presented binaurally at a rate of 1/1.1 s. Analyses of variance were computed on the absolute difference in the amplitude of right and left evoked responses. N1 AEPs were significantly more asymmetrical in Stage 4 sleep compared to either REM or Stage 2 sleep. A second study was conducted with a wider topographical electrode distribution. This study used both a long and a short interstimulus interval with 500-Hz 80-db SPL tone pips. The absolute difference in the amplitude of right and left AEPs was compared across sleep stage. Asymmetries were larger in Stage 4 sleep than in either REM or Stage 2. Examination of these data indicated relative hemispheric balance in REM and Stage 2 sleep with largest asymmetries in Stage 4. The results do not support the view that REM and non-REM sleep stages are associated with differential activation of the two cerebral hemispheres. Rather, they suggest that the sleep cycle is characterized by variations in the degree of asymmetry. Asymmetries in Stage 4 sleep were not consistently in favor of the left hemisphere.

Sleep and depression.

Manifestations of sleep disturbances can potentially serve as external criteria for the diagnosis of specific subtypes of major depressive disorder (MDD). Depressed patients generally experience disturbances of sleep continuity and rapid eye movement (REM) sleep. Disturbances in nonrapid eye movement (NREM) sleep (stages III and IV) also occur. Characteristic of primary sleep disturbance in many depressed patients are shortened REM latency periods and instabilities in NREM sleep identified by increases in the number of stage shifts, decreases in the duration of stage III and IV sleep, and a shift towards lighter sleep stages (sleep efficiency disturbances). Treatment modalities for these sleep disturbances include sleep deprivation therapy and antidepressant therapy. Sleep deprivation alone has been only moderately successful, while antidepressant therapy usually results in symptomatic improvement. To restore normative sleep, REM sleep periods and stage III and IV sleep must be returned to normal. Trazodone therapy has been shown to reduce the frequency of arousals, the severity of drowsiness, and the duration of REM sleep, and increase restorative slow wave sleep and stage III and IV NREM sleep.

Altered sleep physiology in chronic alcoholics: reversal with abstinence.

Somnograms obtained from recently abstinent chronic alcoholics reveal gross disruption succinctly described as "fractured" sleep. Sleep onset is delayed and the rhythmic properties of the sleep pattern are markedly disturbed with numerous brief arousals and changes of sleep stage. Excessive stage 1 and stage rapid eye movement sleep are present while the high voltage slow wave sleep is markedly reduced or absent. With continued sobriety (9 mo or more) the sleep stage percentages tend to return to normal levels, but the disruption of the sleep pattern persists after as much as 21 mo of abstinence.

EFFECTS OF INTRAVENTRICULARLY ADMINISTERED POLYAMINES SPERMIDINE AND SPERMINE ON SLEEP-WAKEFULNESS CYCLES IN RATS

Freely moving rats with chronically implanted electrodes were used and the electroencephalogram (EEG) from the occipital cortex and the dorsal hippocampus, the electromyogram (EMG) and the electrooculogram (EOG) were simultaneously recorded. The REM (rapid eye movement) sleep stage was significantly shortened without a marked change of the Non-REM sleep from the 24th to the 32nd hr following injection of 40 microgram of SPD. The waking stage significantly increased, and the Non-REM sleep and REM sleep markedly decreased immediately after the injection of 40 microgram of SPM to the 8th, and from the 24th to the 32nd hr. The amount of total sleep significantly shortened from the 72nd to the 80th hr following injection of 40 microgram of SPD. The administration of 40 microgram of SPM significantly reduced the amount of total sleep in every period measured for 8 hr. Marked change was observed from the 24th to the 32nd hr following injection of 100 microgram of PUT, and Non-REM sleep and total sleep produced a significant decrease. These results show that the intraventricular administration of polyamines including PUT inhibits the amount of normal sleep.

Early components of the averaged electroencephalic response to constant level clicks during rapid eye movement sleep.

The early components of the averaged electroencephalic response (AER) were elicited by click stimuli from each of four subject during completed night of nature sleep. Clicks were presented from a loudspeaker 50 dB above the subject's voluntary threshold at a rate of 4.5/sec continuously throughout the night. Response obtained during sleep stages 2, 3, and 4 were pooled and compared to the responses obtained during rapid eye movement (REM) sleep for each subject. Statistically significant peak-to-peak amplitude difference scores were only obtained for the Pa and Nb peaks. The largest differences, with shorter REM latencies in both cases, were 1.5 msec for Pa and 4.5 msec for Nb. Thus a similar pattern for the early components of the AER was found during REM and non-REM (NREM) sleep. Therefore, the clinical usefulness of the early components was not diminished during stage REM sleep.