Variations in Period-Analysed EEG Asymmetry in REM and NREM Sleep

Monopolar EEG was recorded from lateral frontal and parietal sites with linked ear reference during sleep in 24 adults. Electrode placement followed the 10-20 International system. EEG was quantified using digital period analyses. The absolute difference in interhemispheric EEG parameters was compared for Stage 2, REM, and a slow wave sleep measure. The absolute difference measures reflect the degree of symmetry or asymmetry, regardless of the hemisphere of origin. Theta and delta activity in slow wave sleep was more asymmetrical than in either Stage 2 or REM. REM sleep was associated with the smallest asymmetries. These results do not support a right hemisphere REM, left hemisphere NREM relationship. Rather they suggest that REM sleep is associated with relative hemispheric symmetry whereas asymmetries are most prominent in slow wave sleep. Stage 2 sleep was significantly less asymmetrical than slow wave on a number of theta and delta measures. The significant differences between slow wave and Stage 2 sleep may denote functional differences within NREM sleep stages.     

Comparison of MK-801 and sleep deprivation effects on NREM, REM, and waking spectra in the rat.

In previous studies, we showed that blockade of the cation channel gated by NMDA glutamate receptors with ketamine or MK-801 massively stimulates NREM delta. We now test whether this NREM delta stimulation is physiological by comparing the EEG response following MK-801 to the EEG response following sleep deprivation (SD). Our previous studies measured only NREM 1-4 Hz EEG with period-amplitude analysis (PAA). Here we extended the analysis of MK-801 effects on sleep EEG by applying power spectral analysis (PSA) to examine delta and higher frequency spectra (.2-100 Hz) in NREM and by including REM and waking spectra. The changes in EEG spectra following MK-801 and SD were remarkably similar. Both SD and MK-801 produced their largest changes in NREM delta and REM 10-20 Hz power. There were some differences in the high frequency EEG, but the overall similarity of the PSA spectra in all three vigilance states after MK-801 and SD supports the possibility that MK-801 stimulated physiologic sleep, perhaps by increasing the need for homeostatic recovery from the metabolic effects of NMDA channel blockade.     

Developmental changes in the sleep electroencephalogram of adolescent boys and girls

The sleep electroencephalogram (EEG) changes across adolescence; however, there are conflicting data as to whether EEG changes are regionally specific, are evident in non‐rapid eye movement (NREM) and rapid eye movement (REM) sleep, and whether there are sex differences. The present study seeks to resolve some of these issues in a combined cross‐sectional and longitudinal analysis of sleep EEG in adolescents. Thirty‐three healthy adolescents (18 boys, 15 girls; 11–14 years) were studied on two occasions 6–8 months apart. Cross‐sectional analysis of data from the initial visit revealed significantly less slow‐wave sleep, delta (0.3 to <4 Hz) and theta (4 to <8 Hz) power in both NREM and REM sleep with advancing age. The age–delta power relationship was significant at the occipital site, with age accounting for 26% of the variance. Longitudinal analysis revealed that NREM delta power declined significantly from the initial to follow‐up visit, in association with declining delta amplitude and incidence (P < 0.01), with the effect being greatest at the occipital site. REM delta power also declined over time in association with reduced amplitude (P < 0.01). There were longitudinal reductions in theta, alpha and sigma power in NREM and REM sleep evident at the occipital site at follow‐up (P < 0.01). No sex differences were apparent in the pattern of change with age for NREM or REM sleep. Declines in sleep EEG spectral power occur across adolescence in both boys and girls, particularly in the occipital derivation, and are not state‐specific, occurring in both NREM and REM sleep.     

Sleep states alter activity of suprachiasmatic nucleus neurons

The timing of sleep and wakefulness in mammals is governed by a sleep homeostatic process and by the circadian clock of the suprachiasmatic nucleus (SCN), which has a molecular basis for rhythm generation. By combining SCN electrical activity recordings with electroencephalogram (EEG) recordings in the same animal (the Wistar rat), we discovered that changes in vigilance states are paralleled by strong changes in SCN electrophysiological activity. During rapid eye movement (REM) sleep, neuronal activity in the SCN was elevated, and during non-REM (NREM) sleep, it was lowered. We also carried out selective sleep deprivation experiments to confirm that changes in SCN electrical activity are caused by changes in vigilance state. Our results indicate that the 24-hour pattern in electrical activity that is controlled by the molecular machinery of the SCN is substantially modified by afferent information from the central nervous system.     

Sex differences in delta and alpha EEG activities in healthy older adults

STUDY OBJECTIVES: To examine sex effects on sleep stages and electroencephalogram (EEG) spectral power in older adults. DESIGN: Sleep was polygraphically recorded for 2 consecutive nights, and blood was sampled during the last 24 hours. SETTING: The University of Chicago Clinical Research Center. PARTICIPANTS: Two groups of healthy nonobese older subjects: 10 men (59 +/- 2 years), and 10 postmenopausal women (63 +/- 2 years). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: A spectral analysis of the EEG was performed in the delta and alpha bands. There were no sex differences in sleep stages. Blood sampling resulted in reductions of total sleep time, sleep maintenance, slow-wave sleep, and absolute delta activity that were all larger in women than in men. In absolute values, delta and alpha activities in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep were higher in women than in men, but, for delta activity, the sex differences were larger in REM than in NREM sleep. In women, but not in men, absolute delta activity in REM was decreased during blood sampling and was strongly correlated with absolute delta activity in NREM. Delta activity in REM did not dissipate across the night in either group. When normalized for the activity in REM sleep, the sex difference in delta activity in NREM sleep was reversed, with lower activity in women. CONCLUSIONS: Sex differences in sleep EEG variables are present in older adults. When normalized, delta activity in older women is lower than in older men, which may be more consistent with sex differences in subjective complaints, in fragility of sleep in the presence of environmental disturbances, and in the relationship to growth-hormone release.     

The relationship between fasting-induced torpor,sleep, and wakefulness in laboratory mice

Study ObjectivesTorpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice.MethodsContinuous monitoring of electroencephalogram (EEG), electromyogram (EMG), and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding.ResultsAll animals showed bouts of hypothermia that became progressively deeper and longer as fasting progressed. EEG and EMG were markedly affected by hypothermia, although the typical electrophysiological signatures of non-rapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness enabled us to perform vigilance-state classification in all cases. Consistent with previous studies, hypothermic bouts were initiated from a state indistinguishable from NREM sleep, with EEG power decreasing gradually in parallel with decreasing surface body temperature. During deep hypothermia, REM sleep was largely abolished, and we observed shivering-associated intense bursts of muscle activity.ConclusionsOur study highlights important similarities between EEG signatures of fasting-induced torpor in mice, daily torpor in Djungarian hamsters and hibernation in seasonally hibernating species. Future studies are necessary to clarify the effects on fasting-induced torpor on subsequent sleep.     

Effect of the Delta Sleep-Inducing Peptide (DSIP) on the sleep-wakefulness cycle of cats

The effect of intravenously injected delta sleep-inducing peptide (DSIP) on the sleep-wakefulness cycle of the cat was studied using telemetric EEG and EMG recording in 6-h sessions. A small dose of DSIP (30 nmol kg⁻¹) shortened latency of onset of sleep, reduced waking time, enhanced non-rapid eye movement (NREM) sleep and, even more markedly, rapid eye movement (REM) sleep. In contrast, a higher dose of DSIP (300 nmol kg⁻¹) produced no significant effects. The results suggest that, in the cat, appropriate intravenous doses of DSIP have a facilitatory action on both NREM and REM sleep, an effect which is absent after higher doses.     

Cortical activation patterns herald successful dream recall after NREM and REM sleep

Dreaming pertains to both REM and NREM sleep. However, frequency and regional specific differences in EEG activity remains controversial. We investigated NREM and REM sleep EEG power density associated with and without dream recall in 17 young subjects during a 40-h multiple nap protocol under constant routine conditions. NREM sleep was associated with lower EEG power density for dream recall in the delta range, particularly in frontal derivations, and in the spindle range in centro-parietal derivations. REM sleep was associated with low frontal alpha activity and with high alpha and beta activity in occipital derivations. Our data indicate that specific EEG frequency- and topography changes underlie differences between dream recall and no recall after both NREM and REM sleep awakening. This dual NREM-REM sleep modulation holds strong implications for the mechanistic understanding of this complex ongoing cognitive process.     

Acute deprivation of the terminal four hours of sleep does not increase delta (0-3-Hz) electroencephalograms: a replication

This experiment evaluated further our previous finding that substitution of waking for the terminal 3-4 hr of sleep produces little or no increase in either visually scored or computer measures of delta sleep. Eleven young adults (mean age 24.5 yr) were studied on a baseline night, a night with sleep limited to an average of 188 min, and a recovery night. Visually scored sleep stages, eye movement activity and computer measures of 0-3 Hz were analyzed by nonrapid eye movement periods (NREMPs) and for all recorded sleep in each condition. In addition, we measured the heights, durations and areas under the curve manifested by the cyclic waxing and waning of 0-3-Hz integrated amplitude across sleep. Acute loss of 3.9 hr of sleep did not increase either visual or computer measures of delta electroencephalograms (EEG) on the recovery night, essentially confirming our previous findings. We hypothesize that augmentation of delta EEG above baseline levels after acute (one night's) sleep loss requires that disruption or loss of sleep from the first two NREMPs (or delta cycles). Rapid eye movement (REM) sleep durations on the recovery night were unaffected by the marked loss of REM sleep caused by partial deprivation. Although eye movements as well as stage REM were lost in the deprivation condition, eye movement density was significantly reduced rather than increased on the recovery night. This reduction is consistent with the hypothesis that REM activity varies inversely with sleep depth (or directly with central arousal level). The observations here, taken in association with previous results, suggest that a threshold for eye movement suppression by sleep deprivation in young adults lies in the range of 3-4 hr of prior sleep loss.     

EEG sleep, depression, and aging

—To date little attention has been paid to the posssible age-dependent relationships of EEG sleep measures in depression or to the implications of such relationships for diagnostic sensitivity and specificity. In a study of 108 patients with major depressive disorders (67 inpatients, 41 outpatients), age was shown to be a very powerful determinant of electroencephalographic (EEG) sleep patterns. Thus, among other sleep variables, sleep efficiency, delta sleep percent, and REM latency all showed significant linear declines with increasing age. Similar trends were seen in both inpatients and outpatients. Some variables were without age trends (age-stable), including sleep latency, REM sleep percent, and REM activity. These findings confirm those of an earlier report from our laboratory [45] and suggest that age-corrected sleep variables can be developed for clinical diagnostic application. Thus, using normative data from Gillin et al. [19] for comparison, a sensitivity level of 65% for age-corrected REM latency was demonstrated, together with a specificity of 95% and a diagnostic confidence of 92%. Data from a pilot study comparing EEG sleep measures in depression and dementia are also presented; these data suggest the potential utility of EEG sleep measures in the differential diagnosis of these two disorders, especially in patients with mixed symptoms. Additional areas for further research are reviewed with enumeration of specific testable hypotheses.     

不同行为状态下大鼠脑电时频变化特性的直方图分析

结合应用多分辨率小波分解方法和直方图参数统计方法 ,分析大鼠脑电信号 (Electroencephalogram,EEG)在不同行为状态下的非稳态时频动态变化特性。利用埋植电极记录自由活动大鼠在清醒期、慢波睡眠期和快动眼睡眠期的皮层 EEG,应用小波变换将 EEG分解成 δ、θ、α和 β四个分量 ,求各分量功率对数值直方图和功率百分比值直方图的均值、方差、偏斜度和峭度。结果表明 :EEG功率对数值的分布比较接近正态分布 ,而多数功率百分比值的分布与正态分布差别显著。单因素方差分析结果显示这些直方图统计参数在不同行为状态之间和不同分解分量之间具有显著差别。 EEG在不同时期的某些特征波 (例如 :慢波睡眠期的 δ波、清醒期和快动眼睡眠期的 θ波等 )使功率对数值分布具有较大的偏斜度值和峭度值。由此可见 ,EEG小波分解分量的直方图参数是一种新的描述EEG动态时频变化特性的定量分析指标     

NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes

STUDY OBJECTIVES: To determine whether the frequency spectrum of the sleep EEG is a physiologic correlate of 1) the degree to which individuals with persistent primary insomnia (PPI) underestimate their sleep time compared with the traditionally scored polysomnogram (PSG) and 2) the sleep complaints in PPI subjects who have relatively long traditionally scored PSG sleep times and relatively greater underestimation of sleep time. DESIGN: We compared EEG frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective insomnia sufferers (those with relatively long total sleep time and relative underestimation of sleep time compared with PSG), and objective insomnia sufferers (those with relatively short PSG total sleep time) with EEG frequency spectra in normals. We also studied the correlation between these indices and the degree of underestimation of sleep. Further, we determined the degree to which sleep EEG indexes related to sleep complaints. SETTING: Duke University Medical Center Sleep Laboratory. PARTICIPANTS: Normal (N=20), subjective insomnia (N=12), and objective insomnia (N=18) subjects. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: Lower delta and greater alpha, sigma, and beta NREM EEG activity were found in the patients with subjective insomnia but not those with objective insomnia, compared with the normal subjects. These results were robust to changes in the subtyping criteria. No effects were found for REM spectral indexes. Less delta non- REM EEG activity predicted greater deviation between subjective and PSG estimates of sleep time across all subjects. For the subjective insomnia subjects, diminished low-frequency and elevated higher frequency non- REM EEG activity was associated with their sleep complaints. CONCLUSIONS: NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep.     

EEG sleep, depression, and aging

—To date little attention has been paid to the posssible age-dependent relationships of EEG sleep measures in depression or to the implications of such relationships for diagnostic sensitivity and specificity. In a study of 108 patients with major depressive disorders (67 inpatients, 41 outpatients), age was shown to be a very powerful determinant of electroencephalographic (EEG) sleep patterns. Thus, among other sleep variables, sleep efficiency, delta sleep percent, and REM latency all showed significant linear declines with increasing age. Similar trends were seen in both inpatients and outpatients. Some variables were without age trends (age-stable), including sleep latency, REM sleep percent, and REM activity. These findings confirm those of an earlier report from our laboratory [45] and suggest that age-corrected sleep variables can be developed for clinical diagnostic application. Thus, using normative data from Gillin et al. [19] for comparison, a sensitivity level of 65% for age-corrected REM latency was demonstrated, together with a specificity of 95% and a diagnostic confidence of 92%. Data from a pilot study comparing EEG sleep measures in depression and dementia are also presented; these data suggest the potential utility of EEG sleep measures in the differential diagnosis of these two disorders, especially in patients with mixed symptoms. Additional areas for further research are reviewed with enumeration of specific testable hypotheses.     

Absence of ponto-geniculo-occipital (PGO) spikes in rats

In contrast to the cat, EEG recordings from macroelectrodes in the lateral geniculate nucleus and occipital neocortex of rats (a) failed to show spiking activity during REM sleep, and (b) failed to show spiking activity after reserpine, i.p., during wakefulness or sleep. Other phasic activities during REM sleep, such as eye movements or muscle twitches, were present in rats. The absence of the ponto-geniculo-occipital spikes in rats, at least in the latter two regions, suggests that these monophasic events are not essential or fundamental characteristics of mammalian REM sleep.     

Microinjection of neostigmine into the pontine reticular formation of C57BL/6J mouse enhances rapid eye movement sleep and depresses breathing

STUDY OBJECTIVES: The cholinergic model of rapid eye movement (REM) sleep has contributed significantly to understanding sleep neurobiology and sleep-dependent respiratory depression. The model has been used extensively in cat and rat, but no previous studies have demonstrated cholinergic REM sleep enhancement in mouse. The present study used microinjection of neostigmine into pontine reticular formation of mouse to test the hypothesis that enhancing pontine cholinergic neurotransmission would cause increased REM sleep and sleep disordered breathing. DESIGN: Mice (n=8) were anesthetized and implanted with electrodes for measuring cortical electroencephalogram (EEG). Stainless steel cannulae were stereotaxically implanted to permit subsequent microinjections of 50 nl neostigmine (0.133 microg; 8.8 mM) or saline into the pontine reticular formation. Following recovery, an intensive within-subjects design was used to obtain measures of sleep/wake states, breathing, and locomotor activity. Inferential statistics were provided by t-tests. A probability value of < 0.05 indicated statistical significance. SETTING: NA. PATIENTS OR PARTICIPANTS: NA. INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Behavioral observations and manual scoring of polygraphic recordings showed that neostigmine produced a REM sleep-like state. EEG power analysis using Fast Fourier Transformation confirmed that pontine neostigmine caused EEG activation. Plethysmography demonstrated significantly disordered breathing. Compared to waking, pontine microinjection of neostigmine decreased respiratory rate (-64%) and minute ventilation (-75%). Pontine neostigmine significantly increased duration of inspiration (138%) and expiration (140%) above waking levels and decreased inspiratory flow (-69%). Additional studies showed that pontine neostigmine significantly depressed locomotor activity. CONCLUSIONS: This study is the first to demonstrate cholinergic REM sleep enhancement in unanesthetized, intact mouse. The results encourage future studies to characterize similarities and differences in cholinergic REM sleep enhancement in additional inbred strains and in transgenic mice. Such comparisons will help characterize sleep and breathing as intermediate phenotypes that are determined, in part, by the lower level phenotype of pontine cholinergic neurotransmission.     

Predicting Dream Recall: EEG Activation During NREM Sleep or Shared Mechanisms with Wakefulness?

The common knowledge of a uniqueness of REM sleep as a privileged scenario of dreaming still persists, although consolidated empirical evidence shows that the assumption that dreaming is just an epiphenomenon of REM sleep is no longer tenable. However, the brain mechanisms underlying dream generation and its encoding in memory during NREM sleep are still mostly unknown. In fact, only few studies have investigated on the mechanisms of dream phenomenology related to NREM sleep. For this reason, our study is specifically aimed to elucidate the electrophysiological (EEG) correlates of dream recall (DR) upon NREM sleep awakenings. Under the assumption that EEG activity predicts the presence/absence of DR also during NREM sleep, we have investigated whether DR from stage 2 NREM sleep shares similar brain mechanisms to those involved in the encoding of episodic memory during wakefulness, or it depends on the specific electrophysiological milieu of the sleep period along the desynchronized/synchronized EEG continuum. We collected DR from a multiple nap protocol in a within-subjects design. We found that DR is predicted by an extensive reduction of delta activity during the last segment of sleep, encompassing left frontal and temporo-parietal areas. The results could represent an update on the mechanisms underlying the sleep mentation during NREM sleep. In particular, they support the hypothesis that an increased cortical EEG activation is a prerequisite for DR, and they are not necessarily in conflict with the hypothesis of common wake-sleep mechanisms. We also confirmed that EEG correlates of DR depend on a state-like relationship.     

Effects of a short light-dark cycle on the sleep-wake patterns of the cat.

The purpose of this study was to measure the effect of a short, 106 min, light-dark (LD) cycle on the sleep-wake (SW) patterns of the cat. Eight cats prepared for chronic sleep studies were observed with electrographic tracings for 48 hr on a regular 12:12 hr LD schedule and again after 2 weeks of adaptation to a 27 min light and 79 min dark schedule. Each 1 min of data was scored as either alert, drowsy, slow wave sleep (SWS) or REM sleep. The parameters studied were percent electrographic state, state epoch length, polycyclic SW cycle, and mean vigilance. The short LD cycle caused a significant increase in alert state accompanied by reductions in drowsy, SWS, and REM sleep states. Although the effect was more pronounced during lights-on intervals, the trend was also present in dark intervals. Alert episodes of about all lengths increased. There were decreases in longer episodes of the other three states and a tendency for shorter episodes to increase in number. Episodes of the polycyclic SW cycle did not tend to follow the short LD cycle. The mean length of both sleep and wake episodes increased rather than decreased. However, mean vigilance values increased toward wakefulness at or near the light interval. Analyses showed that both the amplitude and phase relationship of this increase was significantly related to the 27 min light interval in comparison to base-line data. It was hypothesized that both light-dark and dark-light transitions represent alerting cues to the cat. Differences between the SW response of the cat and the rat to LD cycles are discussed.     

A circadian rhythm of hippocampal theta activity in the mouse

Hippocampal theta activity dominates the cortical EEG of the mouse during certain behaviors. We have therefore been able to study the circadian distribution of hippocampal theta activity by means of chronic EEG implantation and computerized EEG state scoring. Observations in six mice indicate consistent and significant circadian patterns of theta-dominated EEG, both during wakefulness (theta-dominated wake, or TDW) and during sleep (REM sleep). The probability of REM rises gradually to a maximum during the sleep period and then falls abruptly at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two episodes of each coincide remarkably, as do their circadian distributions. The probability of TDW rises to a very high level at activity onset and then falls gradually. The complementary circadian patterns of REM and TDW suggest that they may be two halves of a single circadian rhythm of theta probability. This concept would be relevant in interpreting the abnormally phase-advanced pattern of REM sleep observed in human depressives.     

Effects of repeated sleep deprivation in the dark- or light-period on sleep in rats

This study was designed to examine the differences between sleep duration and EEG when sleep was restricted to the rest- or activity-phase for 5 successive days, achieved by repeated sleep deprivation in the dark (DSD) or light-period (LSD). In the DSD-experiment the percentages of the vigilance states were comparable to the level of the baseline light period. In LSD, the amounts of all sleep states increased substantially relative to baseline dark. The sleep episodes were lengthened in DSD and LSD. The duration of NREM-sleep and the sleep episodes remained longer in the light than in the dark, indicating circadian influences. In the first hours after sleep deprivation the delta activity during NREM-sleep was enhanced in LSD and to a lesser extent in DSD. This effect diminished over the consecutive days in both experiments. The EEG energy gained during sleep and its accumulation pattern on each day in DSD and LSD were strikingly similar, thereby reflecting a homeostatic process. After the sleep deprivation days, small changes were observed in the distribution of the vigilance states, the delta activity and EEG energy over the light- and dark-period.