The effects of sleep stages and time of night on NREM sleep ERPs.

Event-related potential (ERP) is one of the best techniques for studying information processing during sleep because it does not require behavioral responses or consciousness awareness. Several ERP components have been identified during non-rapid eye movement (NREM) sleep, but the associated underlying processes of these waveforms remain unclear. The present study examines the effect of sleep stage and time of night on the NREM ERPs to further understand these processes. An oddball paradigm was conducted in 11 healthy subjects to elicit ERPs throughout the night. Polysomnographic recordings were also applied to identify sleep stages. The results showed that P220, N350, and P900 decreased during the second half of the night, when the NREM sleep drive is partially satiated. This finding is consistent with the notion that the NREM ERPs reflect an inhibitory process associated with sleep drive. P220 and P900 were also found to increase as subjects entering deep sleep. However, the N350 was not affected by the deepening of sleep and peaked earlier during stage 1 sleep. Although these components are all related to the process for sleep preservation, the N350 may be more associated with sleep-wake transition and the P220 and P900 with the process of deepening of sleep.     

Enhanced slow-wave activity within NREM sleep in the cortical and subcortical EEG of the cat after sleep deprivation.

Electroencephalograms (EEGs) of the cortex and of seven subcortical structures were recorded during two baseline days and during a recovery day following a 12-hour period of sleep deprivation (SD) in eight cats. The EEGs were analyzed by visual scoring and by spectral analysis. The following subcortical structures were studied: hippocampus, amygdala, hypothalamus, nucleus centralis lateralis of the thalamus, septum, nucleus caudatus and substantia nigra. The EEGs of all brain structures exhibited sleep state-dependent changes. In general, slow-wave activity (SWA, 0.5-4.0 Hz) during nonrapid eye movement (NREM) sleep exceeded that of REM sleep. The power spectra (0.5-24.5 Hz) in NREM, as well as the relationship between the power spectra of NREM and REM sleep, differed between the recording sites. Moreover, the rate of increase of SWA in the course of an NREM episode and the rate of decrease of SWA at the transition from NREM to REM sleep differed between the brain structures. During the first 12 hours following SD, the duration of NREM increased due to a prolongation of the NREM episodes. REM increased by a rise in the number of REM episodes. During the same period, the NREM EEG power density in the delta and theta frequencies was enhanced in all brain structures. Furthermore, in all structures the enhancement of SWA was most pronounced at the beginning of the recovery period and gradually declined thereafter. SD also induced a rise in the rate of increase of SWA in the NREM episodes in all recording sites. This indicates that the enhancement of EEG power density was not only due to prolongation of the NREM episodes. The EEG activity during REM was barely affected by the SD. It is concluded that, in all brain structures studied, the EEG during NREM is characterized by high levels of SWA. Furthermore, in each brain structure, SWA within NREM sleep is enhanced after a prolonged vigil. These data may indicate that SWA reflects a recovery process in cortical and subcortical structures.     

Cardiac activity during sleep onset.

Alterations in a number of measures of cardiac activity were examined during sleep onset in 6 participants over 3 experimental nights. Each sleep onset was divided into four consecutive phases: wakefulness, mixed alpha and theta activity, stage 2 NREM sleep with arousals, and stable stage 2 sleep. The variables measured were heart rate (HR), respiratory sinus arrhythmia (RSA), pre-ejection period (PEP) and T-wave amplitude (TWA). Respiration rate (RR) was also measured. HR and RR were lower in stable Stage 2 sleep compared with wakefulness, whereas PEP, TWA and RSA did not change significantly. During the second and third phases of sleep onset, HR decreased at each transition into sleep and increased following each spontaneous arousal. This increase resolved rapidly, with a return to sleep levels by 12 beats after the arousal. HR changes are discussed with reference to RSA, PEP, TWA and the concept of a waking reflex.     

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.     

Spontaneous arousal activity in infants during NREM and REM sleep

The infant arousal response involves subcortical and cortical responses occurring as a sequence of stereotyped behaviour regardless of the eliciting stimulus. The spontaneous activity of these responses during sleep, however, is uncertain. We examined the spontaneous arousal pattern in normal infants to determine the sequence of responses, and to examine their periodicity and the effects of sleep state. We performed a nap polysomnographic study on 10 normal infants between 2 and 10 weeks of age. Electroencephalographic and electro-oculographic activity, and respiratory airflow and movements were measured, and video recordings were made throughout each study. Different levels of arousal behaviour were examined. We found that spontaneous arousal activity occurred frequently and the majority of responses occurred as a sequence involving an augmented breath followed by a startle and then cortical arousal. Subcortical arousals as reflected by augmented breaths and startles were more common than cortical arousals. Additionally, augmented breaths followed by apnoea were recorded and were not usually associated with other arousal responses. All of the responses occurred periodically either as bursts of activity or as isolated responses. Each of the responses occurred more frequently during rapid eye movement (REM) sleep than during non-rapid eye movement (NREM) sleep. We conclude that there is an endogenous rhythm of spontaneous activity in infants involving excitatory processes from the brainstem, which may or may not be closely followed by cortical excitation. The spontaneous arousal responses occur periodically but with a high level of irregularity and the level of activity is affected by sleep state.     

Effect of rapid eye movement sleep deprivation on rat brain Na-K ATPase activity

Since rapid eye movement (REM) sleep deprivation has been reported to affect the neuronal excitability in the brain, it was hypothesized that a change in the neuronal membrane-bound Na-K ATPase activity might be at least one of the factors inducing such a change. Therefore, in this study rats were deprived of REM sleep by using the platform technique and enzyme activity was estimated in the whole brain, in different regions of the brain and in microsomal preparations. Deprivation was carried out for varying periods and suitable control experiments were conducted to rule out the possibility of nonspecific effects. The observation supported our hypothesis and showed primarily that the deprivation increased the enzyme activity in the rat brain. It showed also that the pons and the medulla were the first sites to be affected by deprivation. The probable mechanism producing such a change is discussed.     

睡眠剥夺相关基因的筛选与生物信息学分析

目的 从分子水平揭示睡眠剥夺对小鼠大脑海马体的影响,为睡眠剥夺相关疾病的基础研究和临床治疗提供新思路。 方法 从基因表达综合数据库(GEO)中下载睡眠剥夺相关基因芯片数据集,利用Qlucore Omics Explorer（QOE）3.0 软件、String、Panther 等工具对睡眠剥夺差异基因进行生物信息学分析。 结果 在101个差异表达基因所编码的蛋白中,有45个存在蛋白与蛋白的相互作用关系;其中涉及主要的生物学通路包括促性腺激素 释放激素受体通路、肾上腺素和去肾上腺素生物合成通路、细胞凋亡信号通路、亨廷顿舞蹈病通路和帕金森病通路等;主要涉及的生物学过程包括代谢过程、生物调节过程、发育过程、细胞定位过程、免疫系统过程和细胞凋亡过程等。 结论 通过生物信息学分析睡眠剥夺相关芯片数据,提示睡眠剥夺能够影响大脑海马体的基因表达,对相关基因的分析可为下一步实验提供有价值的线索。     

Partial REM-sleep deprivation increases the dream-like quality of mentation from REM sleep and sleep onset

STUDY OBJECTIVES: Sleep onset (SO) is cognitively and physiologically similar to rapid eye movement (REM) sleep, supporting the notion that REM sleep-related processes are 'covertly' active at this time. The objective was to determine if SO mentation is sensitive to REM sleep deprivation. DESIGN: Two-group cross-sectional design; sleep recordings for 3 nights. SETTING: Standard sleep laboratory with 24-channel polysomnography recording. PARTICIPANTS: Fourteen female, 13 male healthy volunteers (18-41 yrs, mean=24.8 +/- 6.07). INTERVENTIONS: On Night 2, half were and half were not partially REM sleep-deprived (REMD), recalled REM mentation, and rated it for dream-like quality (DLQ), sleepiness, and sensory attributes. On Night 3, all were awakened from SO substages 4 and 5 for mentation reports and further ratings. REMD measures were derived from scored sleep tracings. MEASUREMENTS AND RESULTS: REMD produced increases in DLQ for both REM and SO reports (P < .05); DLQ scores were higher for REM than for SO mentation (P < .001). Covarying sleepiness preserved the (REMD) effect but abolished the REM/SO difference. Whereas 2 sensory attributes (presence of self, visual intensity) tended to distinguish the REM-mentation reports of REMD and control subjects, only 1, self-movement, distinguished their SO mentation reports (P < .06). Multiple regression revealed that increased DLQ of both REM and SO mentation was associated with increased sleepiness and decreased REM sleep time on Night 2. CONCLUSIONS: SO mentation responds to REMD much like REM mentation does, a finding consistent with other work supporting the notion of covert REM-sleep processes at SO. DLQ may be mediated by both increases in REM-sleep propensity and a circadian process indexed by sleepiness ratings.     

Effect of sleep deprivation on multi‐unit discharge activity of basal forebrain

The basal forebrain (BF) is an important wakefulness/arousal‐promoting structure involved in homeostatic responses to sleep deprivation (SD). However, the effects of SD and subsequent sleep recovery on the BF discharge have not been investigated. Multi‐unit BF activity was recorded on freely moving rats during 8 h of baseline (BL) and, on the following day, during 4 h of SD by gentle handling followed by 4 h of recovery. The effect of SD on the waking discharge was evaluated during the last 10 min of each hour when attentive waking was induced. The wakefulness level was defined based on the ratio between theta and delta electroencephalogram (EEG) powers, and epochs with ratios ≥1 but <2 (T/D‐1) and ≥2 but <4 (T/D‐2) were analysed separately. During T/D‐1 wakefulness, the BF multi‐unit discharge rate increased significantly during the second and third hours of SD and decreased during the third hour of recovery when compared with corresponding hours of BL. Non‐rapid eye movement sleep discharge rate during recovery decreased significantly in the second and third versus the first and last hours. The results suggest that maintenance of the level of vigilance necessary for adequate performance during SD requires increased activation of BF neurones when compared with the BL, whereas the same level of vigilance after several hours of recovery can be maintained with lesser activation of BF neurones.     

Dynamics of slow-wave activity during the NREM sleep of sleepwalkers and control subjects

STUDY OBJECTIVE: To compare the number and distribution of awakenings from slow-wave sleep (SWS) and both the power and dynamics of EEG slow-wave activity (SWA) in sleepwalkers and controls. Somnambulism is considered to be a disorder of arousal from NREM sleep and related to anomalous SWS and SWA. Power spectral analyses have never been used to quantify patients' SWA across sleep cycles. DESIGN: N/A SETTING: N/A PATIENTS: A polysomnographic study was performed on 15 adult sleepwalkers and 15 age- and sex-matched controls. INTERVENTIONS: N/A MEASUREMENTS & RESULTS: Sleepwalkers had a significantly greater number of awakenings from SWS than did control subjects. Controls showed a greater decrease in SWA across NREM cycles. Sleepwalkers had a significantly lower level of SWA during the first NREM period, where most awakenings take place. CONCLUSION: Sleepwalkers appear to suffer from an abnormality in the neural mechanisms responsible for the regulation of SWS.     

Accessing previous mental sleep experience in REM and NREM sleep

This study investigated the processes by which contents previously stored in memory are retrieved and inserted into mental sleep experience (MSE). MSE reports were collected from six subjects awakened three times on each of eight nights in two alternate sequences of awakenings (NREM-REM-NREM; REM-REM-REM). The occurrences of interrelations between contents of report pairs were scored using Clark's (1970) feature matching model. These were greater for same night pairs than for different night pairs, and did not differ with respect to sequence of awakenings or order of report pairs (first-second, second-third, first-third). Contents of previous MSEs, therefore, seem to be accessible in both sleep types for insertion into current MSE. The interrelated units were more frequently lexical than propositional, with more paradigmatic than syntagmatic relationships in report pairs from both sequences of awakenings. Thus, the re-elaboration of contents of previous MSEs seems to occur mainly at the level of single contents in both types of sleep, with similar modalities of processing.     

Cardiac autonomic nervous system activity during presleep wakefulness and Stage 2 NREM sleep

Previous research has found that cardiac parasympathetic nervous system (PNS) activity increases and cardiac sympathetic nervous system (SNS) activity decreases during night-time sleep. This study aimed to examine in greater detail the time course of these changes in cardiac autonomic nervous system (ANS) activity. In the week prior to the experimental night, nine subjects maintained a constant sleep-wake schedule and experienced an adaptation night. Each subject's experimental night consisted of 2 h of presleep wakefulness, followed by a night of sleep, commencing at each subject's normal sleep onset time. One hundred and twenty beat blocks of presleep wakefulness and stable Stage 2 non-rapid eye movement (NREM) sleep across the night were selected. SNS activity was assessed using pre-ejection period, the amplitude of the T-wave in the ECG and the 0.1 Hz peak from the spectral analysis of the ECG. PNS activity was assessed using respiratory sinus arrhythmia (spectral analysis). Heart rate and respiratory rate were also measured. The results indicated a progressive decrease in SNS activity throughout sleep and a rise in PNS activity during the first half of the normal sleep period. The changes in PNS activity were similar, while the changes in SNS activity were altered, compared with a previous study in which stage of sleep was not controlled. This indicates a likely sleep stage influence on SNS activity, but not on cardiac PNS activity. These results are consistent with the concept of a primarily circadian, but not sleep, influence on PNS activity, and primarily a sleep, but not circadian, influence on SNS activity.     

Effect of sleep deprivation on tolerance of prolonged exercise

Summary Acute loss of sleep produces few apparent physiological effects at rest. Nevertheless, many anecdotes suggest that adequate sleep is essential for optimum endurance athletic performance. To investigate this question, heavy exercise performance after 36 h without sleep was compared with that after normal sleep in eight subjects. During prolonged treadmill walking at about 80% of the max, sleep loss reduced work time to exhaustion by an average of 11% (p=0.05). This decrease occurred despite doubling monetary incentives for subjects during work after sleeplessness. Subjects appeared to fall into “resistant” and “susceptible” categories: four showed less than a 5% change in performance after sleep loss, while four others showed decrements in exercise tolerance ranging from 15 to 40%. During the walk, sleep loss resulted in significantly greater perceived exertion (p<0.05), even though exercise heart rate and metabolic rate ( and ) were unchanged. Minute ventilation was significantly elevated during exercise after sleep loss (p<0.05). Sleep loss failed to alter the continuous slow rises in _E and heart rate that occurred as work was prolonged. These findings suggest that the psychological effects of acute sleep loss may contribute to decreased tolerance of prolonged heavy exercise. Supported in part by Public Health Service grant PHS S07 RR 5371, and by Grant DAMD-17-81-C-1023 from the U.S. Army     

Effect of light deprivation on sleep in the rat

The sleep-wake cycles of 24- and 30- day-old rats reared in darkness from 48 hr after birth (E) were polygraphically recorded in 3 3-hr sessions (0900–1200 hr; 1230–1530 hr; 1600–1900 hr) and compared to normally reared controls (C). The total amount of paradoxical sleep (PS) over the 3 3-hr sessions of the light-deprived rats (E₂₄ and E₃₀) was significantly less than in the controls (C₂₄, and C₃₀). The distribution of PS over the 3 sessions was different for the control groups: C₂₄ showed a significantly greater amount of PS and SWS during 1230–1530 hr, and C₃₀ during 1230–1530 and 16–19 hr. Light-deprived groups showed no significant variations neither in PS nor in SWS or W within the three sessions. These data fail to support the hypothesis that PS functions as a compensatory stimulation under conditions of low stimulation.     

睡眠剥夺对大鼠免疫功能的影响

已有实验证明 ,睡眠剥夺或缺失可降低机体的防御能力。Ｂｒｏｗｎ[1 ] 曾发现睡眠剥夺能使小鼠对流感病毒的抵抗力减弱 ,ＩＬ 1或胞壁肽可对抗这一改变。相继的研究显示白细胞介素与肿瘤坏死因子等细胞因子可不同程度地促进睡眠[2 ] 。睡眠是否与免疫有关 ,本文拟通过对睡眠剥夺大鼠Ｔ细胞和Ｂ细胞增殖反应的变化 ,来探讨睡眠对免疫功能的影响。1　材料与方法1 1　主要仪器及药品 :刀豆蛋白Ａ(ＣｏｎＡ) ,北京中山生物公司 ;脂多糖 (ＬＰＳ) ,Ｓｉｇｍａ产品 ;四甲基偶氮唑盐 (ＭＴＴ) ,瑞士ＦＬＵＫＡ产品 ;十二烷基硫酸钠 (ＳＤＳ) ,日本…     

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 min) episodes of isocapnic hypoxia followed by 5 min of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 min of recovery, respectively, for minute ventilation (V(I)), supraglottic pressure (P(SG)), upper airway resistance (R(UA)) and phasic GG electromyogram (EMG(GG)). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG(GG) (202.7+/-24.1% of control, p<0.01) and in V (I) (123.0+/-3.3% of control, p<0.05); however, only phasic EMG(GG) demonstrated a significant persistent increase throughout the recovery. (198.9+/-30.9%, 203.6+/-29.9% and 205.4+/-26.4% of control, at 5, 10, and 20 min of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG(GG) activity during hypoxia were significant predictors of EMG(GG) at recovery 20 min. No significant changes in any of the measured parameters were noted during sham studies. CONCLUSION: (1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without concomitant ventilatory or mechanical LTF. (2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.     

Activity of respiratory neurons during NREM sleep

The purpose of this study was to analyze differences in the activity of medullary respiratory neurons in the unanesthetized, intact cat during wakefulness and non-rapid-eye-movement (NREM) sleep. We studied single respiratory neurons located within a 1-2 mm deep, 8-10 mm long zone that followed, and included in its dorsal aspect, the retrofacial and ambiguus nuclei. The analysis of variance was used to detect respiratory activity, and cycle-triggered histograms were plotted. The respiratory signal strength and consistency of the respiratory activity were quantified with the eta 2 statistic. We determined for each breath in wakefulness and NREM sleep the average discharge rate during the active phase of the cell, the number of action potentials during the active phase of the cell, and durations of both the cycle and inspiration. Differences in discharge rates and in the number of discharges between wakefulness and NREM sleep were tested with the t test. A bimodal distribution of eta 2 values for the population of neurons indicated there were two groups of respiratory cells: those with eta 2 values less than 0.3 and those with values greater than 0.3. The former we call weak respiratory cells; the latter, strong respiratory cells. Strong and weak cells were classified further as inspiratory or noninspiratory on the basis of the shape of their cycle-triggered histograms. Within the class of strong inspiratory cells, those with the highest eta 2 values 1) reached their peak discharge rate early, 2) discharged at high rates throughout inspiration, and 3) were inactive during expiration. The values of these variables diminished progressively in inspiratory cell groups with lower eta 2 values. Most cells were less active in NREM sleep than in wakefulness. Similar proportions of weak and strong cells and inspiratory and noninspiratory cells were affected by sleep. The reduction in sleep of the activity of strong inspiratory cells was consistent with a general relationship between this activity and the duration of inspiration. Lower discharge rates were associated with longer breaths; higher rates with shorter breaths. This relationship existed within both NREM sleep and wakefulness, and the plot of the relationship across these states formed a continuous function. The reduction in discharge rate in sleep was greater for weak than for strong inspiratory cells: the correlation coefficient between percent change in rate and eta 2 values was -0.636 for inspiratory cells, but it was not significant (-0.265) for noninspiratory cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Medullary respiratory neural activity during hypoxia in NREM and REM sleep in the cat

Intact unanesthetized cats hyperventilate in response to hypocapnic hypoxia in both wakefulness and sleep. This hyperventilation is caused by increases in diaphragmatic activity during inspiration and expiration. In this study, we recorded 120 medullary respiratory neurons during sleep in hypoxia. Our goal was to understand how these neurons change their activity to increase breathing efforts and frequency in response to hypoxia. We found that the response of medullary respiratory neurons to hypoxia was variable. While the activity of a small majority of inspiratory (58%) and expiratory (56%) neurons was increased in response to hypoxia, the activity of a small majority of preinspiratory (57%) neurons was decreased. Cells that were more active in hypoxia had discharge rates that averaged 183% (inspiratory decrementing), 154% (inspiratory augmenting), 155% (inspiratory), 230% (expiratory decrementing), 191% (expiratory augmenting), and 136% (expiratory) of the rates in normoxia. The response to hypoxia was similar in non-rapid-eye-movement (NREM) and REM sleep. Additionally, changes in the profile of activity were observed in all cell types examined. These changes included advanced, prolonged, and abbreviated patterns of activity in response to hypoxia; for example, some inspiratory neurons prolonged their discharge into expiration during the postinspiratory period in hypoxia but not in normoxia. Although changes in activity of the inspiratory neurons could account for the increased breathing efforts and activity of the diaphragm observed during hypoxia, the mechanisms responsible for the change in respiratory rate were not revealed by our data.     

The effects of sleep deprivation in humans: topographical electroencephalogram changes in non‐rapid eye movement (NREM) sleep versus REM sleep

Studies on homeostatic aspects of sleep regulation have been focussed upon non‐rapid eye movement (NREM) sleep, and direct comparisons with regional changes in rapid eye movement (REM) sleep are sparse. To this end, evaluation of electroencephalogram (EEG) changes in recovery sleep after extended waking is the classical approach for increasing homeostatic need. Here, we studied a large sample of 40 healthy subjects, considering a full‐scalp EEG topography during baseline (BSL) and recovery sleep following 40 h of wakefulness (REC). In NREM sleep, the statistical maps of REC versus BSL differences revealed significant fronto‐central increases of power from 0.5 to 11 Hz and decreases from 13 to 15 Hz. In REM sleep, REC versus BSL differences pointed to significant fronto‐central increases in the 0.5–7 Hz and decreases in the 8–11 Hz bands. Moreover, the 12–15 Hz band showed a fronto‐parietal increase and that at 22–24 Hz exhibited a fronto‐central decrease. Hence, the 1–7 Hz range showed significant increases in both NREM sleep and REM sleep, with similar topography. The parallel change of NREM sleep and REM sleep EEG power is related, as confirmed by a correlational analysis, indicating that the increase in frequency of 2–7 Hz possibly subtends a state‐aspecific homeostatic response. On the contrary, sleep deprivation has opposite effects on alpha and sigma activity in both states. In particular, this analysis points to the presence of state‐specific homeostatic mechanisms for NREM sleep, limited to <2 Hz frequencies. In conclusion, REM sleep and NREM sleep seem to share some homeostatic mechanisms in response to sleep deprivation, as indicated mainly by the similar direction and topography of changes in low‐frequency activity.