Slow-wave sleep

Slow-wave sleep (SWS), often referred to as deep sleep, is the third stage of non-rapid eye movement sleep (NREM), where electroencephalography activity is characterised by slow delta waves.^[2]

Slow-wave sleep usually lasts between 70 and 90 minutes, taking place during the first hours of the night.^[3] SWS is characterised by moderate muscle tone, slow or absent eye movement, and lack of genital activity. Slow-wave sleep is considered important for memory consolidation, declarative memory, and the recovery of the brain from daily activities.

Prior to 2007, the term SWS referred to both the third and fourth stages of NREM. However, after both stages were combined into stage three, SWS refers only to the third stage.^[4]: 291

Overview

Terminology

This period of sleep is called slow-wave sleep because the EEG activity is synchronized, and characterised by slow waves with a frequency range of 0.5–4.5 Hz and a relatively high amplitude power with peak-to-peak amplitude greater than 75µV. The first section of the wave signifies a "down state", an inhibition or hyperpolarizing phase in which the neurons in the neocortex are silent. This is the period when the neocortical neurons are able to rest. The second section of the wave signifies an "up state", an excitation or depolarizing phase in which the neurons fire briefly at a high rate. The principal characteristics during slow-wave sleep that contrast with REM sleep are moderate muscle tone, slow or absent eye movement, and lack of genital activity.^{[4]: 291, 293}

Prior to 2007, the American Academy of Sleep Medicine (AASM) divided slow-wave sleep into stages 3 and 4.^[5][6][7] The two stages are now combined as Stage three or N3. An epoch (30 seconds of sleep) which consists of 20% or more slow-wave (delta) sleep is now considered to be in slow-wave sleep.

Importance

Slow-wave sleep is considered important for

Large 75-microvolt (0.5–2.0 Hz)

Longer periods of SWS occur in the first part of the night, primarily in the first two sleep cycles (roughly three hours). Children and young adults will have more total SWS in a night than older adults. The elderly may not go into SWS at all during many nights of sleep.^[citation needed]

NREM sleep, as observed on the electroencephalogram (EEG), is distinguished by certain characteristic features.

Slow-wave sleep is an active phenomenon probably brought about by the activation of serotonergic neurons of the raphe system.^[23]

The slow-wave seen in the cortical EEG is generated through recurrent connections within the cerebral cortex, where cortical pyramidal cells excite one another in a positive feedback loop. This recurrent excitation is balanced by inhibition, resulting in the active state of the slow oscillation of slow wave sleep. Failure of this mechanism results in a silencing of activity for a brief period of time. The recurrence of active and silent periods occurs at a rate of 0.5–4 Hz, giving rise to the slow waves of the EEG seen during slow wave sleep.^[24]

Functions

Hemispheric asymmetries in the human sleep

Slow-wave sleep is necessary for survival. Some animals, such as dolphins and birds, have the ability to sleep with only one hemisphere of the brain, leaving the other hemisphere awake to carry out normal functions and to remain alert. This kind of sleep is called unihemispheric slow-wave sleep, and is also partially observable in human beings. Indeed, a study reported a unilateral activation of the somatosensorial cortex when a vibrating stimulus was put on the hand of human subjects. The recordings show an important inter-hemispheric change during the first hour of non-REM sleep and consequently the presence of a local and use-dependent aspect of sleep.^[25] Another experiment detected a greater number of delta waves in the frontal and central regions of the right hemisphere.^[26]

Considering that SWS is the only sleep stage that reports human deep sleep as well as being used in studies with mammals and birds, it is also adopted in experiments revealing the role of

The left hemisphere is shown to be more sensitive to deviant stimuli during the first night—compared to the following nights of an experiment. This asymmetry explains further the reduced sleep of half the brain during SWS. Indeed, in comparison to the right one, the left hemisphere plays a vigilant role during SWS.[27]

Furthermore, a faster behavioral reactivity is detected in the left hemisphere during SWS of the first night. The rapid awakening is correlated to the regional asymmetry in the activities of SWS. These findings show that the hemispheric asymmetry in SWS plays a role as a protective mechanism. SWS is therefore sensitive to danger and non-familiar environment, creating a need for vigilance and reactivity during sleep.^[27]

Neural control of slow-wave sleep

Several neurotransmitters are involved in sleep and waking patterns: acetylcholine, norepinephrine, serotonin, histamine, and orexin.^{[4]: 305–307} Neocortical neurons fire spontaneously during slow-wave sleep, thus they seem to play a role during this period of sleep. Also, these neurons appear to have some sort of internal dialogue, which accounts for the mental activity during this state where there is no information from external signals (because of the synaptic inhibition at the thalamic level). The rate of recall of dreams during this state of sleep is relatively high compared to the other levels of the sleep cycle. This indicates that mental activity is closer to real life events.^[14]

Physical healing and growth

Slow-wave sleep is the constructive phase of sleep for recuperation of the mind-body system in which it rebuilds itself after each day. Substances that have been ingested into the body while an organism is awake are synthesized into complex proteins of living tissue. Growth hormone is also secreted during this stage, which leads some scientists to hypothesize that a function of slow wave sleep is to facilitate the healing of muscles as well as repair damage to tissues.

Learning and memory formation occurs during wakefulness by the process of long-term potentiation; SWS is associated with the regulation of synapses thus potentiated. SWS has been found to be involved in the downscaling of synapses, in which strongly stimulated or potentiated synapses are kept while weakly potentiated synapses either diminish or are removed.^[31] This may be helpful for recalibrating synapses for the next potentiation during wakefulness and for maintaining synaptic plasticity. Notably, new evidence is showing that reactivation and rescaling may be co-occurring during sleep.^[32]

Problems associated with slow-wave sleep

Results from a number of research have shown how sleep affects Aβ dynamics.[34] A good candidate for slow wave activity (SWA), which occurs during deep non-REM sleep, is amyloid-b modulation. The researchers also highlighted a strong relationship between amyloid-b and SWA, pointing out that increased disruption in SWA is correlated with elevated levels of amyloid-b.^[35] Hence, Slow waves of non-rapid eye movement sleep, or NREM sleep, are disrupted or decrease when amyloid beta (Aβ) builds up in the prefrontal cortex. As a result, this may hinder older people' capacity for memory consolidation.^[36]

Moreover, the onset of

Though SWS is fairly consistent within the individual, it can vary across individuals.[39] To some degree, individual variations seem to be influenced by demographic factors such as gender and age.^[21] Age and sex have been noted as two of the biggest factors that affect this period of sleep.^[39]

Slow-wave sleep (SWS) and slow-wave activity (SWA) undergo significant transformations throughout one's lifespan, with aging serving as a particularly influential factor in predicting individual variations.^[21][40] Aging is inversely proportional to the amount of SWS beginning by midlife, so SWS declines with age.^[39] Moreover, recent findings indicate that older individuals exhibit a decreased inclination for daytime sleep compared to younger counterparts, and this decline persists even when accounting for variations in habitual sleep duration. This age-related decrease in daytime sleep propensity is evident in middle-aged individuals and coincides with statistically significant reductions in total sleep time, slow-wave sleep (SWS), and slow-wave activity (SWA).^[21]

Sex differences have also been found, such that females tend to have higher levels of SWS compared to males, at least up until menopause.^[39] Older individuals exhibit gender-based variations in non-rapid eye movement (NREM) sleep, where women demonstrate increased slow-wave sleep (SWS) during both regular and recuperative sleep, along with higher occurrences of stage 3 and 4 which are considered as NREM sleep.^[21] There have also been studies that have shown differences between races. The results showed that there was a lower percentage of SWS in African Americans compared to Caucasians, but since there are many influencing factors (e.g., body mass index, sleep-disordered breathing, obesity, diabetes, and hypertension), this potential difference must be investigated further.^[39]

Mental disorders play a role in individual differences in the quality and quantity of SWS: subjects with depression show a lower amplitude of slow-wave activity (SWA) compared to healthy participants. Sex differences also persist in the former group: depressed men present significantly lower SWA amplitude. This sex divergence is twice as large as the one observed in healthy subjects. However, no age-related difference concerning SWS can be observed in the depressed group.^[41]

Brain regions

This list is incomplete; you can help by adding missing items. (February 2018)

During sleep, the distribution of slow-wave activity (SWA) typically exhibits a prevalence in the

• the parafacial zone (GABAergic neurons),^[43][44][45] located within the medulla oblongata
• the
  D2-type dopamine receptors and adenosine A_2A receptors),^[46][47][48] located within the striatum
• the
  ventrolateral preoptic area (GABAergic neurons),^[44][45][49] located within the hypothalamus
• the lateral hypothalamus (melanin-concentrating hormone-releasing neurons),^{[44][45][50][51]} located within the hypothalamus

Drugs

Some drugs influence sleep architecture by encroaching upon or prolonging deep sleep.^[52] Many drugs known to increase deep sleep in humans are of the GABAergic, dopaminergic, and anti-serotonergic classes.^[53]

The administration of the GABA_a agonist gabaxadol enhances both deep sleep while also positively impacting various indicators of insomnia.^[52]

Levodopa is a drug commonly used to treat Parkinson's disease which acts to increases the brain's dopamine availability. Nocturnal single doses of levodopa have been shown to increase SWS by 10.6% in elderly.^[59]

Antagonists of certain

References