Dreaming during non-rapid eye movement sleep in the absence of prior rapid eye movement sleep

STUDY OBJECTIVES: There is a long-standing controversy surrounding the existence of dream experiences during non-rapid eye movement (NREM) sleep. Previous studies have not answered the question whether this "NREM dream" originates from the NREM sleep mechanism because the subject might simply be recalling experiences from the preceding rapid eye movement (REM) sleep. METHODS: We scheduled 11 healthy men to repeat 20-minute nap trials separated by 40-minute periods of enforced wakefulness across a period of 3 days. At the end of the nap trial, each participant answered questions regarding the formal aspects of his dream experiences during the nap trial, using the structured interviews. RESULTS: We obtained a total of 172 dream reports after naps containing REM sleep (REM naps) and 563 after naps consisting of only NREM sleep (NREM naps). Dream reports from NREM naps were less remarkable in quantity, vividness, and emotion than those from REM naps and were obtained more frequently during the morning hours when the occurrences of REM sleep were highest. CONCLUSIONS: These results suggest that the polysomnographic manifestations of REM sleep are not required for dream experiences but that the mechanisms driving REM sleep alter experiences during NREM sleep in the morning. A subcortical activation similar to REM sleep may occur in human NREM sleep during the morning when REM sleep is most likely to occur, resulting in dream experiences during NREM sleep.     

Differential effects of waking from non-rapid eye movement versus rapid eye movement sleep on cardiovascular activity

The occurrence of cardiovascular events increases in the morning, and while the mechanism responsible is yet to be determined, possible contributors include surges in sympathetic activity and concurrent rises in blood pressure (BP). This study tested the hypothesis that the increase in sympathetic dominance and the surge in BP were greater when waking spontaneously from Stage 2 sleep compared with waking from rapid eye movement (REM) sleep. Twenty healthy young adults had overnight polysomnography, including electrocardiogram measurements. Spectral analysis of heart rate variability (HRV) was conducted on 2-min blocks of stable data selected from the last 30 min of sleep and during 30 min of resting wakefulness (supine) immediately following sleep. Outputs included absolute low frequency (LF) and high frequency (HF) power, the LF/HF ratio, heart rate (HR) and BP. To investigate the effect of waking from Stage 2 or REM sleep on HRV and BP responses, two-way analyses of variance ( anova s) (Stage 2 versus REM) with repeated measures (sleep versus morning wakefulness) were performed. It was found that waking from Stage 2 sleep was associated with significant increases in HR ( P  = 0·002) and BP ( P  < 0·001), as well as a tendency towards an increase in the LF/HF ratio ( P  = 0·08), whereas measurements during REM sleep and subsequent wakefulness were similar ( P  > 0·05). The greater increase in BP and HR when waking from Stage 2 sleep compared with REM sleep suggests that in vulnerable populations, waking from Stage 2 sleep could be an adjunct risk factor of cardiovascular events during the morning period.     

Activation of inactivation process initiates rapid eye movement sleep

Interactions among REM-ON and REM-OFF neurons form the basic scaffold for rapid eye movement sleep (REMS) regulation; however, precise mechanism of their activation and cessation, respectively, was unclear. Locus coeruleus (LC) noradrenalin (NA)-ergic neurons are REM-OFF type and receive GABA-ergic inputs among others. GABA acts postsynaptically on the NA-ergic REM-OFF neurons in the LC and presynaptically on the latter's projection terminals and modulates NA-release on the REM-ON neurons. Normally during wakefulness and non-REMS continuous release of NA from the REM-OFF neurons, which however, is reduced during the latter phase, inhibits the REM-ON neurons and prevents REMS. At this stage GABA from substantia nigra pars reticulate acting presynaptically on NA-ergic terminals on REM-ON neurons withdraws NA-release causing the REM-ON neurons to escape inhibition and being active, may be even momentarily. A working-model showing neurochemical-map explaining activation of inactivation process, showing contribution of GABA-ergic presynaptic inhibition in withdrawing NA-release and dis-inhibition induced activation of REM-ON neurons, which in turn activates other GABA-ergic neurons and shutting-off REM-OFF neurons for the initiation of REMS-generation has been explained. Our model satisfactorily explains yet unexplained puzzles (i) why normally REMS does not appear during waking, rather, appears following non-REMS; (ii) why cessation of LC-NA-ergic-REM-OFF neurons is essential for REMS-generation; (iii) factor(s) which does not allow cessation of REM-OFF neurons causes REMS-loss; (iv) the association of changes in levels of GABA and NA in the brain during REMS and its deprivation and associated symptoms; v) why often dreams are associated with REMS.     

Disruptive effects of rapid eye movement sleep deprivation on long-term memory

The fact that sleep is associated with very active endogenous neural (chemical and electrical) processes, suggests that these processes may be involved in the maintenance of long-term memory storage. The present experiments were designed to examine the hypothesis that rapid eye movement (REM) sleep deprivation will produce impairment of long-term memory. Mice deprived of REM sleep for 3, 5 or 7 continuous days, during the interval between a one-trial inhibitory avoidance training experience and a subsequent retention test, displayed a temporary retrograde amnesia when tested 30 min or three hr following termination of REM deprivation. The mice did not recover from the amnesia if electroconvulsive shock was administered immediately following the interval of REM sleep deprivation. In a further study, the generality of these findings was obtained by depriving mice of REM sleep during the interval between a discrimination training experiment in a black-white T-maze and the subsequent retention test.     

The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep

Sleep deprivation during pregnancy is an emerging concern, as it can adversely affect the development of the offspring brain. This study was conducted to evaluate the effects of deprivation of rapid eye movement (REM) sleep during the third term of pregnancy on the sleep–wake profiles of neonates in the Wistar rat model. Sleep–wake patterns were assessed through electrophysiological measures and behavioural observations during postnatal days 1–21 on pups born to REM sleep‐deprived dams and control rats. Pups of REM sleep‐deprived dams had active sleep that was not only markedly higher in percentage during all the days studied, but also had reduced latency during later postnatal days 15–21. Quiet sleep and wake periods were lower. These factors, along with less frequent but longer sleep–wake cycles, indicated maturational delay in the sleep–wake neural networks. The disruption of time‐bound growth of sleep–wake neural networks was substantiated further by the decreased slope of survival plots in the sleep bouts. Examination of altered sleep–wake patterns during early development may provide crucial information concerning deranged neural development in the offspring. This is the first report, to our knowledge, to show that maternal sleep deprivation during pregnancy can delay and impair the development of sleep–wake profile in the offspring.     

The organization of rapid eye movement activity during rapid eye movement sleep is further impaired in very old human subjects

Rapid eye movement activity (REMA) during rapid eye movement (REM) sleep was studied in seven very old ('old-old') subjects. Beyond global quantitative features (REMA density), we evaluated the organizational aspects of REMA, that is its occurrence in burst mode, which were compared to a group of younger elderly subjects ('young-old'). REMA density in 'old-old' subjects is not significantly different from that of 'young-old' subjects. The same lack of difference in the two groups is found for the number of REMA bursts. By contrast, the duration of REMA bursts is reduced in the 'old-old' subjects, as well as the 'burst state-to-burst-state' probability, i.e. the probability for successive inter-REMA time intervals to be part of the same REMA burst. Our results clearly show that the trend towards an impairment of REMA organizational aspects continues with aging. This is consistent with the hypothesis that sleep disorganization keeps worsening with age. However, it is of interest to observe that the capability of producing REMA bursts is preserved despite aging.     

Human amygdala activation during rapid eye movements of rapid eye movement sleep: an intracranial study

The amygdaloid complex plays a crucial role in processing emotional signals and in the formation of emotional memories. Neuroimaging studies have shown human amygdala activation during rapid eye movement sleep (REM). Stereotactically implanted electrodes for presurgical evaluation in epileptic patients provide a unique opportunity to directly record amygdala activity. The present study analysed amygdala activity associated with REM sleep eye movements on the millisecond scale. We propose that phasic activation associated with rapid eye movements may provide the amygdala with endogenous excitation during REM sleep. Standard polysomnography and stereo‐electroencephalograph (SEEG) were recorded simultaneously during spontaneous sleep in the left amygdala of four patients. Time–frequency analysis and absolute power of gamma activity were obtained for 250 ms time windows preceding and following eye movement onset in REM sleep, and in spontaneous waking eye movements in the dark. Absolute power of the 44–48 Hz band increased significantly during the 250 ms time window after REM sleep rapid eye movements onset, but not during waking eye movements. Transient activation of the amygdala provides physiological support for the proposed participation of the amygdala in emotional expression, in the emotional content of dreams and for the reactivation and consolidation of emotional memories during REM sleep, as well as for next‐day emotional regulation, and its possible role in the bidirectional interaction between REM sleep and such sleep disorders as nightmares, anxiety and post‐traumatic sleep disorder. These results provide unique, direct evidence of increased activation of the human amygdala time‐locked to REM sleep rapid eye movements.     

Painful nocturnal penile erections associated with rapid eye movement sleep

A case of chronic painful nocturnal penile erection is described. Repeated awakenings led to a degree of REM sleep deprivation. Treatment with propanolol was initially successful in alleviating the symptoms, but tolerance to the drug developed rapidly.     

Fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder

Fragmentary myoclonus is a result of muscle activity consisting of brief potentials in surface electromyography during polysomnography. Excessive fragmentary myoclonus is defined by increased intensity of the potentials. A few studies report excessive fragmentary myoclonus occurrence in neurodegenerative diseases. Because idiopathic rapid eye movement sleep behaviour disorder is considered as an early stage of neurodegeneration with involvement of the brainstem, we charted the prevalence and quantified the intensity of excessive fragmentary myoclonus in idiopathic rapid eye movement sleep behaviour disorder. Twenty‐nine patients (one woman, 28 men, mean age 68 years, SD 6.2) and 29 controls (two women, 27 men, mean age 65.6 years, SD 8.6) underwent polysomnography. Fragmentary myoclonus potentials were identified and counted according to internationally used criteria. Fragmentary myoclonus intensity was quantified by the fragmentary myoclonus index. Excessive fragmentary myoclonus was diagnosed in 75.9% (22 subjects) in idiopathic rapid eye movement sleep behaviour disorder, while in 34.5% (10 subjects) among the controls (p = 0.003). Quantitative analysis showed a wide‐range fragmentary myoclonus index in idiopathic rapid eye movement sleep behaviour disorder (4.0–632.4; median 60.7) and in the controls (0.8–938.1; median 34.3). The overall difference in fragmentary myoclonus index was not significant between the groups; however, patients with idiopathic rapid eye movement sleep behaviour disorder showed trends for higher fragmentary myoclonus index scores in wakefulness (p = 0.027), N1 (p = 0.032), N3 (p = 0.046) and R (p = 0.007). Fragmentary myoclonus index does not correlate with age, idiopathic rapid eye movement sleep behaviour disorder duration or R stage atonia deficiency. The prevalence of excessive fragmentary myoclonus is higher in idiopathic rapid eye movement sleep behaviour disorder compared with the controls, so fragmentary myoclonus should be taken into account in future research of rapid eye movement sleep behaviour disorder and motor control in sleep.     

Cardiorespiratory response to spontaneous cortical arousals during stage 2 and rapid eye movement sleep in healthy children

Arousal from sleep is associated with transient and abrupt cardiorespiratory changes, and elevated arousals associated with sleep disorders may trigger adverse cardiovascular sequela. In this paper, we provide the first data in children on cardiorespiratory responses to cortical arousal. Heart rate and ventilatory responses to arousal from stage 2 and rapid eye movement (REM) sleep were investigated in 40 normal, healthy Caucasian children (age: 7.7 ± 2.6 years; body mass index z‐score: 0.30 ± 0.8). All children underwent overnight polysomnography studies. Cortical arousals were scored according to standard criteria. Heart rate changes were assessed over 30 s, starting 15 s prior to cortical arousal onset. Breathing rates were quantified three breaths before and after arousal onset. Arousals from stage 2 as well as REM sleep resulted in an R–R interval shortening of about 15%, independent of age and gender. The R–R interval shortening initiated at least 3 s before the cortical arousal onset. The breathing interval immediately after cortical arousal onset was significantly shortened (P < 0.001). In conclusion, cortical arousals in children are associated with an increase in breathing rate and significant heart rate accelerations, which typically precede the cortical arousal onset.     

Phasic activities of rapid eye movement sleep in vegetative state patients

STUDY OBJECTIVES: To assess the phasic components of rapid eye movement (REM) sleep in patients in vegetative state and to evaluate the possible relationship of these activities to patient outcome. SETTING: Sleep disorders unit at a major rehabilitation hospital. DESIGN: Comparative control study. PATIENTS: Eleven patients in vegetative state (10 males and 1 female) aged 17-53 years. INTERVENTIONS: Continuous 24-hour polysomnographic recording. MEASUREMENTS AND RESULTS: All the patients had REM sleep periods during the 24-hr recording session. Mean total REM sleep time for the whole session was 66.5 +/- 34.9 min, and for the nocturnal hours only, 37.3 +/- 19.7 min. Comparison with the control group (79.2 +/- 11.5 min) yielded a significant difference only for nocturnal REM sleep time (p<0.0003). The duration of the REM sleep periods was significantly shorter in the patients than the controls for the whole 24-hr session (10.9 +/- 6.0 vs.19.6 +/- 4.9 min, p<0.008), but not for the nocturnal period alone. Compared to controls, the density of rapid eye movements (REMs) (p=0.001), chin twitches (p=0.002), and leg muscle twitches (p=0.023) was significantly lower in the patient group. The density of the sawtooth waves was also lower in the patients, but the difference did not reach significance (p=0.069). Similar results were obtained when the comparison was done only for the nocturnal period. There was no significant difference for any of the REM sleep characteristics or REM sleep phasic activities (24-hr, nocturnal and diurnal periods) between the patients who recovered consciousness and those who did not. CONCLUSIONS: The present study shows that patients in vegetative state have a significant reduction in the phasic activities of REM sleep. However, the amount of these activities is unrelated to recovery from the clinical condition. These findings may reflect possible damage to the pedunculopontine tegmentum cholinergic mechanisms in vegetative state.     

特发性和继发性快速眼动睡眠行为障碍的睡眠结构研究

目的：探讨快速眼动睡眠行为障碍（REM sleep behavior disorder,RBD）患者的睡眠结构改变。方法：纳入的22例患者符合国际睡眠障碍协会（第2版）的RBD诊断标准,16例患者符合RBD主要诊断标准以及英国脑库的PD、2005年国际路易体痴呆协作组或者2008年多系统萎缩第2版的诊断标准。同时纳入年龄、性别匹配的健康对照19例。利用日本光电32信道9200K脑电图机,所有患者均完成多项睡眠图监测（PSG）,记录脑电图、眼球运动、下颌和肢体肌电活动、心电图、经鼻气流、胸腹部呼吸运动、血氧、鼾声等多个项目,并录像监测患者的行为。使用Polysmith软件和视觉评估分析睡眠结构、呼吸、运动等相关指标。结果：RBD患者展现了典型临床表现和电生理改变。特发性RBD组（72．7％）较继发性RBD组（43．8％）显示有更多的夜间活动和言语,差异有统计学意义（P=0．071）。特发性RBD在睡眠结构并未发生明显改变,仅有周期性腿动（PLM）指数增高。继发性RBD与特发性RBD和健康对照相比,总体睡眠时间缩短、睡眠效率减低、睡眠潜伏期和REM潜伏期延迟、Ⅱ期和REM睡眠减少、Ⅰ期睡眠增加、低通气指数增高、PLM指数增高。结论：特发性RBD患者具有更多的夜间行为异常,而睡眠结构无改变,仅有PLM指数增加;而继发性RBD出现明显的睡眠结构紊乱、呼吸紊乱以及PLM异常。     

Consolidation of strictly episodic memories mainly requires rapid eye movement sleep

STUDY OBJECTIVES: The aim of this study is to examine the effects of sleep deprivation during the first or second half of the night on episodic memory consolidation. Episodic memory is defined as memory for events located in time and space. It is also characterized by autonoetic consciousness, which gives a subject the conscious sensation of traveling back in time to relive the original event and forward into the future. DESIGN: Consolidation of episodic information was tested after 4-hour retention intervals, which followed learning and occurred during either the early or late half night, respectively dominated by slow wave sleep (SWS) or rapid eye movement (REM) sleep, or corresponding periods of wakefulness. SETTING: Data collection occurred in the sleep laboratory. PARTICIPANTS: Forty-three young healthy subjects: 9 men and 34 women, age ranging from 18 to 26 years (mean 20.18 +/- 1.94 years) were included in this study. INTERVENTIONS: Waking after a 4-hour retention interval filled with early or late sleep, or 4-hour sleep deprivation, during early or late period of night. MEASUREMENTS AND RESULTS: The cognitive task, named the What-Where-When test, was specially designed to assess factual, spatial, and temporal components of episodic memory. This task was associated with the Remember/Know paradigm to assess autonoetic consciousness. We measured performance on immediate free recall, delayed free recall (after a 4-hour interval of wakefulness or sleep), and delayed recognition. We also calculated a forgetting rate for each feature (factual, spatial, and temporal) and, for the recognition task, scores of autonoetic consciousness (R responses). REM-sleep deprivation was associated with significantly lower recall of spatial information compared to SWS deprivation (P < .01) or late sleep (P < .05) conditions. REM-sleep deprivation was also associated with a higher forgetting rate of temporal information as compared to the early sleep condition (P< .01). Finally, REM-sleep deprivation led subjects to give significantly fewer R responses, indicative of true memories, as compared to SWS deprivation (P < .05). CONCLUSIONS: These results suggest that consolidation of truly episodic memories mainly involves REM sleep.     

Hypocapnia decreases the amount of rapid eye movement sleep in cats

CONTEXT: Sleep is disturbed at high altitudes. Low PO2 levels at high altitude cause hyperventilation, which results in secondary hypocapnia (low PaCO2 levels). Thus, although sleep disruption at high altitudes is generally assumed to be caused by hypoxia, it may instead be the result of hypocapnia. OBJECTIVE: To determine whether hypocapnia disrupts sleep. METHODS: Four cats were studied for a total of 345 hours of sleep recordings. Two methods were used to test this idea. First we studied their sleep when the cats breathed oxygen concentrations (15% and 10%) equivalent to those at approximately 12,000 feet and 21,000 feet. Then we studied their sleep again in response to the same hypoxic stimuli but with CO2 added to the inspirate to maintain normal CO2 levels. Second, we used mechanical hyperventilation to vary the levels of CO2 while maintaining normal O2 levels. RESULTS: Hypoxia (10% O2) decreased the amount of rapid eye movement sleep to about 20% of normal, and adding back CO2 restored rapid eye movement sleep to approximately 70% of normal. Periodic breathing and apneas were not observed during hypoxia in sleep. When mechanical hyperventilation lowered the CO2 to 85%, 75%, and 65% of normal, rapid eye movement sleep decreased progressively from a control level of 17% of total recording time to 12%, 7%, and 4%, respectively. CONCLUSION: We conclude that hypocapnia rather than hypoxia may account for most of the sleep disturbance at high altitudes.     

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.     

Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep

The obstructive sleep apnea syndrome is characterized by the occurrence of cyclic snoring and frequent apneic episodes during sleep, with consequent hypoxia and hypercapnia. Obstructive sleep apnea syndrome is associated with excess daytime sleepiness, depression, and an increased incidence of ischemic cardiopathy, cardiac arrhythmias, systemic hypertension and brain infarction. Hypoglossal motoneurons, which innervate extrinsic and intrinsic muscles of the tongue, play a key role in maintaining the patency of the upper airway and in the pathophysiology of obstructive sleep apnea syndrome. Based on data obtained by using extracellular recording techniques, there is a consensus that hypoglossal motoneurons cease to discharge during rapid eye movement sleep, because they are disfacilitated. Since other somatic motoneurons are known to be postsynaptically inhibited during rapid eye movement sleep, we sought to determine, by the use of intracellular recording techniques during cholinergically induced rapid eye movement sleep, whether postsynaptic inhibitory mechanisms act on hypoglossal motoneurons. We found that, during this state, a powerful glycinergic premotor inhibitory system acts to suppress hypoglossal motoneurons. This finding opens new avenues for the treatment of obstructive sleep apnea syndrome, and provides a foundation to explore the neural and pharmacological control of respiration-related motoneurons during rapid eye movement sleep.     

The pretectum mediates rapid eye movement sleep regulation by light.

A variety of sensory stimuli (e.g., visual, auditory, and thermal) are known to induce rapid eye movement (REM) sleep in mammals. Studies have examined the induction of REM sleep in albino rats by light-to-dark transitions, a phenomenon referred to as REM sleep triggering. Recent research has demonstrated that aspiration lesions of the superior colliculus (SC) and pretectal area attenuated REM sleep triggering. To define more specifically the area or areas involved in mediating REM sleep responses to changes in illumination, fiber-sparing neurotoxic lesions were made to the pretectum (PT) or the SC. Lesions of the PT attenuated REM sleep triggering, whereas lesions of the SC did not. Thus, the role of the PT may be expanded to include the regulation of REM sleep in response to photic stimulation in albino rats. These findings provide a paradigm in which to study mechanisms of REM sleep generation and the effects of light on behavioral state.     

Increased apoptosis in rat brain after rapid eye movement sleep loss

Rapid eye movement (REM) sleep loss impairs several physiological, behavioral and cellular processes; however, the mechanism of action was unknown. To understand the effects of REM sleep deprivation on neuronal damage and apoptosis, studies were conducted using multiple apoptosis markers in control and experimental rat brain neurons located in areas either related to or unrelated to REM sleep regulation. Furthermore, the effects of REM sleep deprivation were also studied on neuronal cytoskeletal proteins, actin and tubulin. It was observed that after REM sleep deprivation a significantly increased number of neurons in the rat brain were positive to apoptotic markers, which however, tended to recover after the rats were allowed to undergo REM sleep; the control rats were not affected. Further, it was also observed that REM sleep deprivation decreased amounts of actin and tubulin in neurons confirming our previous reports of changes in neuronal size and shape after such deprivation. These findings suggest that one of the possible functions of REM sleep is to protect neurons from damage and apoptosis.