REM Sleep, sleep fuctions and sleep quality: Comparison
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Please note this is a comparison between Version 1 by Giuseppe Barbato and Version 2 by Rita Xu.

The correct phase relationship of the sleep period with the circadian pacemaker is an important factor to guarantee adequate restorative sleep duration and sleep continuity, thus providing the necessary background for a good night’s sleep. Due to the fact that REM sleep is controlled by the circadian clock, it can provide a window-like mechanism that defines the termination of the sleep period when there is still the necessity to complete the sleep processes  and to meet the circadian end of sleep timing. An adequate amount of REM sleep appears necessary to guarantee sleep continuity, while periodically activating the brain and preparing it for the return to consciousness.

  • sleep quality
  • REM sleep
  • awakening

1. REM Sleep

Despite its pioneering role in the scientific approach to sleep and its fascinating nature due to the link with dream activity, REM sleep is not generally considered to have a fundamental sleep function, especially when looking at homeostasis and wake performance. Studies with antidepressant drugs that significantly reduce REM sleep [1] have also shown no significant impairment in cognitive abilities; instead, according to Vogel et al. [2], suppression of REM sleep is considered a possible mechanism for antidepressant activity. On the other hand, Leary et al. [3] have recently shown that a decreased percentage of REM sleep is associated with a greater risk of all-cause, cardiovascular and other noncancer-related mortality in middle-aged and older adults.Motomura et al. [4] reported that reduced connectivity between the medial prefrontal cortex and amygdala, which is involved in mood deterioration under sleep deprivation, correlated with REM reduction, suggesting that adequate REM sleep may be important for mental health maintenance.
Among the different PSG variables suggested as objective indicators of sleep quality, short total duration of sleep and decreased sleep efficiency appear to be those more consistently reported as indicators of low sleep quality. Considering that a short sleep duration implicates a significant reduction in REM sleep, since REM sleep mostly occurs during the second half of the night, this sleep component can be critical in determining sleep quality; alteration of the systems controlling REM sleep can also produce sleep fragmentation, contributing to decreased sleep efficiency. Furthermore, the use of artificial light during the evening and early nighttime hours can delay and disturb circadian rhythms, especially affecting REM sleep. Chang et al. [5] found that, compared with reading a printed book in reflected light, reading an LE eBook in the hours before bedtime delayed the phase of the endogenous circadian pacemaker that drives the timing of the daily rhythms of melatonin secretion, sleep propensity and REM sleep propensity and impaired morning alertness. Subjects in the LE eBook condition had significantly less REM sleep and were sleepier in the morning. The phase delay of the circadian rhythm reduces the length of the sleep period, thus limiting the occurrence of REM sleep, which is normally concentrated in the last part of the sleep period.
In the seminal work of Webb and Agnew [6] that sought to define natural sleep duration, long sleepers compared to short sleepers showed more REM sleep with no evidence of increased SWS; short sleepers, however, showed a higher percentage of SWS, suggesting that the longer sleep period was achieved by increasing the REM duration. Similarly, Aeschbach et al. [7] reported equal amounts of slow-wave sleep in short and long sleepers, with a higher percentage of SWS in short sleepers, whereas, in long sleepers, REM was both increased in duration and higher in percentage.
An increased duration of REM sleep has been also reported together with an increased duration of total sleep in extended sleep during an LD (light/dark) 10:14 photoperiod study [8][9]; furthermore, compared to the habitual LD 16:8 (light/dark) condition, subjects in this “winter” photoperiod reported increased vigor and a diminished level of fatigue, according to their Profile of Mood States and 100 mm line rating scale [8]. Akerstedt et al. [10] have reported in a large population study that sleep efficiency, NREM stage 1 and stage 2, REM duration and REM % increased with increased total sleep duration; long sleep periods were also perceived to be of better quality. As occurred for sleep continuity, REM sleep duration strongly increased with sleep duration. Although longer REM sleep may simply reflect the longer duration of the sleep period, in the Akerstedt et al. [10] study, also the relative amount of REM (%) increased with increasing sleep duration, suggesting, as stated by the authors, that “may also reflect a sensitivity of REM % to poor sleep continuity as REM % is reduced in insomniacs”.
Riemann et al. [11] have proposed that, in insomnia, “instability” of REM sleep contributes to the experience of disrupted and non-restorative sleep, providing a possible explanation for the discrepancy between minor objective alterations in standard parameters of sleep continuity and the profound subjective impairments in these patients.
Della Monica et al. [12] have shown that self-reported sleep quality is positively associated with the duration of REM sleep, with no significant association with slow-wave sleep. Furthermore, an analysis of performance measures assessed with the goal neglect task showed that fewer awakenings and more REM sleep were associated with better executive function. A significant effect of REM sleep on wake abilities has been previously reported by Feinberg et al. [13], who found a positive association between REM measures (REM duration and REM activity) and cognitive performance as assessed by the Wechsler Adult Intelligence Scale and the Wechsler Memory Scale. REM sleep was also shown to be associated with less cognitive decline in longitudinal studies conducted in elderly subjects. Using data from the (MrOS) Study, Song et al. [14] found that, after adjusting for 15 potentially confounding variables (e.g., age, depression, hypertension), men with the lowest quartile of REM sleep (<15%) and the highest quartile of N1 sleep (≥8.52%) showed an accelerated rate of cognitive decline, as assessed by the Trails B Test and a Modified Mini-Mental State Examination. Pase et al. [15] showed that more REM sleep, but not SWS, was protective against the emergence of dementia.
The fundamental role of REM sleep in the memory process has been further highlighted by experimental models in animals; using a combination of electro-physiological recording and optogenetic techniques, Boyce et al. [16] have demonstrated that neural activity occurring specifically during REM sleep is required for spatial and contextual memory consolidation.
Physiological consequences of REM loss have also been reported, including inflammation and interleukin-17 elevation [17], alteration of the immune system [18] and increased sensitivity to pain [19]. All of these can significantly contribute to impaired sleep quality.
REM density, the frequency of eye movements during a REM period, is another REM measure that can have predictive value regarding sleep quality. REM density appears to be regulated by different mechanisms to those that control the duration of REM sleep. Feinberg et al. [20] proposed that REM density may be related to the level of arousal, with REM density being lower when sleep is deeper. They observed that sleep deprivation increased the level of slow-wave activity, which is an indicator of sleep pressure, and reduced REM density in recovery sleep. REM density typically increases across the night as sleep pressure progressively diminishes. Barbato et al. [21] reported that the propensity to wake from sleep is higher in the REM sleep period with a high density of REM than from the NREM sleep period, possibly reflecting an increased level of the brain arousal process associated with REM sleep. Increased REM density has been reported in depression [22] and post-traumatic stress disorder [23], both conditions characterized by hyperarousal. Recent findings have identified “restless REM”, a condition of fragmented REM sleep with a high frequency of eye movements, as an important marker of insomnia [24]; furthermore, in this patient group, higher REM density together with REM arousal was strongly associated with the slow dissolution of emotional distress.
Aserinsky [25] found that, in extended sleep, REM density increased with each successive REM episode, approaching a maximum value after 7.5–10 h of sleep; thereafter, periods of wakefulness alternated with periods of sleep, with no further changes in REM density levels. According to Aserinsky [25], the levelling-off of REM density as the night proceeds could reflect the satisfaction of a sleep need, or the build-up of a pressure to awaken, and thus may serve as an index of sleep satiety. As elegantly suggested by Dijk and von Schantz [26], “during a nocturnal sleep episode, the sleep-dependent dissipation of sleep propensity is counteracted by a circadian increase in sleep propensity, thereby facilitating sleep consolidation until the very end of the habitual sleep episode. Subsequently, a gate to wakefulness is created by the combined circadian and sleep-dependent promotion of REM sleep and REM density at the appropriate time”.
Alteration of the frequency of REM has been reported in relation to cognitive performance. Feinberg et al. [13] first showed that low REM activity in healthy older adults was associated with lower performance on psychometric tests. Spiegel et al. [27] reported that low REM density predicted the level of cognitive decline in older subjects. In the already cited work of Akerstedt et al. [10], who reported a positive association between sleep quality and total sleep duration, REM intensity (the amplitude of rapid eye movements) decreased markedly with increased TST, further suggesting that REM measurement can provide an index of sleep quality.

2. Why REM Sleep Could Be a Sensitive Indicator of Sleep Quality 

The prevailing assumption that slow-wave sleep is the core sleep component has probably contributed to the notion that REM sleep has a secondary but not essential role; however, as occurs for habitual sleep, which might not be of sufficient duration, healthy individuals can also be REM-sleep-deprived. Scorucak et al. [28] have shown that seven days of sleep restriction (6 h time in bed) resulted primarily in a reduction in REM sleep; interestingly, during the following sleep extension, the REM sleep duration increased. As stated by Scorucack et al., “in the search for the mechanisms underlying the negative consequences of insufficient sleep, the implication of a REM sleep deficit should be considered”. Klerman et al. [29] have recently reported a striking increase in REM sleep during sleep extension over baseline, suggesting a rebound phenomenon from a possible REM deprivation that occurs in a habitual sleep opportunity. A rebound in REM sleep has been also observed after a space shuttle mission, during which sleep duration was approximately 6.5 h [30]. Singh et al. [31] reported the occurrence of SOREMP (short REM latency period), an index of increased REM pressure, in a population sample of 333 adults. Of the variables assessed (MSLT, Epworth Sleepiness Scale and total sleep time from nocturnal polysomnography), objective sleepiness, as determined by the MSLT, was the only measure significantly associated with two or more SOREMPs.
Whereas slow-wave sleep might serve a need created by waking, the functional significance of REM sleep is less clear. Benington and Heller [32] have suggested a homeostatic relationship between NREM sleep and REM sleep, where REM serves a need created during NREM sleep. Data in animals [32][33] and in humans [9] have shown that the REM intervals are regulated by homeostatic rules. REM pressure accumulates during the NREM episodes and is dissipated during the successive REM episode. A longer REM episode causes stronger dissipation of this pressure and thus requires a longer interval to accumulate pressure before the next REM episode can occur. Disruption of REM sleep, by interrupting the pressure dissipation, can impair the quality and continuity of NREM sleep, since, due to REM’s homeostatic mechanism, interruption of REM discharge results in more frequent attempts to enter REM, causing the fragmentation of NREM sleep [34].
Most hypotheses concerning REM sleep have focused on the similarity between neurophysiological events occurring in REM sleep and wakefulness [35]. Broughton [36] reported that the visual evoked potentials of subjects after a forced arousal from REM sleep were similar to those of wakefulness, whereas, after a forced arousal from stage 4 (SWS), subjects showed slower visual evoked potentials. Langford et al. [37] showed that spontaneous arousal from sleep was more likely to occur in REM sleep than in other sleep stages. Lavie et al. [38] found that subjects instructed to wake at a specified time during the night, with no aid of an external alarm clock, mainly awakened from REM sleep. As originally hypothesized by Moruzzi [39], a continuum of increasing arousal levels exists throughout NREM sleep, REM sleep and waking.
A possible REM sleep function is to provide the periodic activation of the brain during sleep, without inducing wakefulness or disturbing the continuity of sleep [40]. Klemm [41] has proposed that the brain uses REM to help wake itself up after it has had a sufficient amount of sleep. Similarly, Horne [42] has suggested that REM seems more likely to prepare for ensuing wakefulness than providing recovery from prior wakefulness, as happens with “deeper” NREM.
The correct phase relationship of the sleep period with the circadian pacemaker is also an important factor to guarantee adequate restorative sleep duration and sleep continuity, thus providing the necessary background for a good night’s sleep. Due to the fact that REM sleep is controlled by the circadian clock [43], it can provide a window-like mechanism that defines the termination of the sleep period when there is still the necessity to complete the sleep process (not only wake-related homeostasis), and to meet the circadian end of sleep timing. Furthermore, the cyclic occurrence of REM sleep could contribute to sleep continuity, while periodically activating the brain and preparing it for the return to consciousness.
Mechanisms that underlie REM occurrence during the night appear thus functional to guarantee sleep continuity and duration.
Arousal processes “monitored” by the frequency of REM can finally further delineate the end of sleep and the awakening, consistently with the reported evidence that awakenings occur much more likely out of a REM period characterized by a high frequency of REM [44][45]. REM sleep can thus be necessary to guarantee sleep continuity, prepare the brain for the wake period and define the natural end of the sleep process.

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