Slow-wave sleep

Last updated
Ostriches sleeping, with REM and slow-wave sleep phases [1]

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]

Contents

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 memory consolidation. [8] This is sometimes referred to as "sleep-dependent memory processing". [9] Impaired memory consolidation has been seen in individuals with primary insomnia, who thus do not perform as well as those who are healthy in memory tasks following a period of sleep. [10] [11] Furthermore, slow-wave sleep improves declarative memory (which includes semantic and episodic memory). A central model has been hypothesized that the long-term memory storage is facilitated by an interaction between the hippocampal and neocortical networks. [10] In several studies, after the subjects have had training to learn a declarative memory task, the density of human sleep spindles present was significantly higher than the signals observed during the control tasks, which involved similar visual stimulation and cognitively-demanding tasks but did not require learning. [12] [13] This associated with the spontaneously occurring wave oscillations that account for the intracellular recordings from thalamic and cortical neurons. [14]

Specifically, SWS presents a role in spatial declarative memory. Reactivation of the hippocampus during SWS is detected after the spatial learning task. [15] In addition, a correlation can be observed between the amplitude of hippocampal activity during SWS and the improvement in spatial memory performance, such as route retrieval, on the following day. [16] Additionally, studies have found that when odour cues are given to subjects during sleep, this stage of sleep excluslvely allows contextual cues to be reactivated after sleep, favoring their consolidation. [15] A separate study found that when subjects hear sounds associated with previously shown pictures of locations, the reactivation of individual memory representations was significantly higher during SWS as compared to other sleep stages. [17]

Affective representations are generally better remembered during sleep compared to neutral ones. Emotions with negative salience presented as a cue during SWS show better reactivation, and therefore an enhanced consolidation in comparison to neutral memories. The former was predicted by sleep spindles over SWS, which discriminates the memory processes during sleep as well as facilitating emotional memory consolidation. [17] Acetylcholine plays an essential role in hippocampus-dependent memory consolidation. An increased level of cholinergic activity during SWS is known to be disruptive for memory processing. Considering that acetylcholine is a neurotransmitter that modulates the direction of information flow between the hippocampus and neocortex during sleep, its suppression is necessary during SWS in order to consolidate sleep-related declarative memory. [18]

Sleep deprivation studies with humans suggest that the primary function of slow-wave sleep may be to allow the brain to recover from its daily activities. Glucose metabolism in the brain increases as a result of tasks that demand mental activity. [4] Another function affected by slow-wave sleep is the secretion of growth hormone, which is always greatest during this stage. [19] It is also thought to be responsible for a decrease in sympathetic and increase in parasympathetic neural activity. [19]

Electroencephalographic characteristics

Polysomnogram demonstrating SWS, stage four. High amplitude EEG is highlighted in red. Sleep EEG Stage 4.jpg
Polysomnogram demonstrating SWS, stage four.
High amplitude EEG is highlighted in red.

Large 75-microvolt (0.5–2.0 Hz) delta waves predominate the electroencephalogram (EEG). Stage N3 is defined by the presence of 20% delta waves in any given 30-second epoch of the EEG during sleep, by the current 2007 AASM guidelines. [7] [20]

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. Sleep spindles, marked by spindle-like changes in the amplitude of 12–14 Hz oscillations, K complexes lasting at least 0.5 seconds, consisting of a distinct negative sharp wave followed by a positive component, and slow waves or delta waves characterized by slow frequency (< 2 Hz) and high amplitude (> 75 µV) are key indicators. [21] The presence and distribution of sleep spindle activity and slow waves vary across NREM sleep, leading to its subdivision into stages 1–4. While slow waves and sleep spindles are present in stages 2, 3, and 4, stage 2 sleep is characterized by a higher prevalence of spindles, while slow waves dominate the EEG during stages 3 and 4. [22] [21]

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 hemispheric asymmetries during sleep. A predominance of the left hemisphere in the neural activity can be observed in the default-mode network during SWS. This asymmetry is correlated with the sleep onset latency, which is a sensitive parameter of the so-called first night effect—the reduced quality of sleep during the first session in the laboratory. [27]

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. [28] [29] Lastly, glial cells within the brain are restored with sugars to provide energy for the brain. [30]

Learning and synaptic homeostasis

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

Bedwetting, night terrors, and sleepwalking are all common behaviors that can occur during stage three of sleep. These occur most frequently amongst children, who then generally outgrow them. [4] : 297–8  Another problem that may arise is sleep-related eating disorder. An individual will sleep-walk leaving his or her bed in the middle of the night seeking out food, and will eat not having any memory of the event in the morning. [4] Over half of individuals with this disorder become overweight. [4] : 298  Sleep-related eating disorder can usually be treated with dopaminergic agonists, or topiramate, which is an anti-seizure medication. This nocturnal eating throughout a family suggests that heredity may be a potential cause of this disorder. [4]

Effects of sleep deprivation

J. A. Horne (1978) reviewed several experiments with humans and concluded that sleep deprivation has no effects on people's physiological stress response or ability to perform physical exercise. It did, however, have an effect on cognitive functions. Some people reported distorted perceptions or hallucinations and lack of concentration on mental tasks. Thus, the major role of sleep does not appear to be rest for the body, but rest for the brain.

When sleep-deprived humans sleep normally again, the recovery percentage for each stage of sleep is not the same. Only seven percent of stages one and two are regained, but 68 percent of stage-four slow-wave sleep and 53 percent of REM sleep are regained. This suggests that stage-four sleep (known today as the deepest part of stage-three sleep) is more important than the other stages.

During slow-wave sleep, there is a significant decline in cerebral metabolic rate and cerebral blood flow. The activity falls to about 75 percent of the normal wakefulness level. The regions of the brain that are most active when awake have the highest level of delta waves during slow-wave sleep. This indicates that rest is geographical. The "shutting down" of the brain accounts for the grogginess and confusion if someone is awakened during deep sleep, since it takes the cerebral cortex time to resume its normal functions.

According to J. Siegel (2005), sleep deprivation results in the build-up of free radicals and superoxides in the brain. Free radicals are oxidizing agents that have one unpaired electron, making them highly reactive. These free radicals interact with electrons of biomolecules and damage cells. In slow-wave sleep, the decreased rate of metabolism reduces the creation of oxygen byproducts, thereby allowing the existing radical species to clear. This is a means of preventing damage to the brain. [33]

Amyloid beta pathology

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 Alzheimer's disease (AD) is marked by the deposition of amyloid beta (Aβ) in the brain. [34] AD is distinguished by the presence of amyloid-beta plaques and neurofibrillary tangles. These structural anomalies are linked to disruptions in the sleep-wake cycle, particularly in non-rapid eye movement (NREM), slow wave sleep (SWS). [37] Thus, individuals diagnosed with Alzheimer's often experience disturbances in sleep, resulting in diminished levels of non-rapid eye movement (NREM) sleep and reduced slow wave activity (SWA), that is a prominent brain rhythm during NREM sleep. [38] Similarly, even cognitively healthy individuals with detectable amyloid beta exhibit sleep disturbances, characterized by compromised sleep quality and an increased frequency of daytime napping. [35]

Individual differences

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

During sleep, the distribution of slow-wave activity (SWA) typically exhibits a prevalence in the frontal region of the brain. [42] In the subsequent recovery sleep after experiencing sleep deprivation, the frontal cortex exhibits the most significant rise in slow-wave activity (SWA) compared to the central region, parietal region, and occipital region. [21] [42] The notable increase in SWA following sleep deprivation in the frontal areas, coupled with the prevailing presence of SWA in the frontal regions even during baseline sleep, has been construed as evidence supporting the involvement of slow-wave sleep (SWS) in functions typically linked to the frontal cortices. Thus, the prevalence of slow-wave sleep (SWS) in the frontal regions, particularly those linked to advanced cognitive functions or cognitive regions highly active during wakefulness, underscores the considerable importance of SWS. [21]

Some of the brain regions implicated in the induction of slow-wave sleep include:

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]

Gamma-hydroxybutyrate (GHB) is synthesized in the central nervous system (CNS) from gamma-aminobutyric acid (GABA). [52] Oral administration of GHB has been shown to enhance SWS without suppressing REM sleep. [54] [55] [56] In the United States, GHB is a prescription drug under the brand name Xyrem. It has been shown to reduce cataplexy attacks and excessive daytime sleepiness in patients with narcolepsy.

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

Tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor, demonstrated to shown to improve sleep maintenance and to significantly increase SWS in healthy elderly subjects and adult patients with primary insomnia. [57] [58]

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 serotonergic receptors (namely 5-HT2A and 5-HT2C) have also been demonstrated to enhance SWS sleep, although they do not consistently bring about improvements in overall sleep duration or symptoms associated with insomnia. [52] Trazodone, an atypical antidepressant, increases the duration of SWS; it is suspected that trazodone's antagonistic action at the 5-HT2A receptor may contribute to this effect. [60] A variety of drugs that antagonise the on 5-HT2A and 5-HT2C receptors exhibit SWS-enhancing effects in humans. [61] [62]

See also

Related Research Articles

Multiple hypotheses explain the possible connections between sleep and learning in humans. Research indicates that sleep does more than allow the brain to rest; it may also aid the consolidation of long-term memories.

<span class="mw-page-title-main">Sleep</span> Naturally recurring resting state of mind and body

Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with the surrounding environment. While sleep differs from wakefulness in terms of the ability to react to stimuli, it still involves active brain patterns, making it more reactive than a coma or disorders of consciousness.

<span class="mw-page-title-main">Rapid eye movement sleep</span> Phase of sleep characterized by random & rapid eye movements

Rapid eye movement sleep is a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream vividly.

<span class="mw-page-title-main">Delta wave</span> High amplitude low frequency brain wave

Delta waves are high amplitude neural oscillations with a frequency between 0.5 and 4 hertz. Delta waves, like other brain waves, can be recorded with electroencephalography (EEG) and are usually associated with the deep stage 3 of NREM sleep, also known as slow-wave sleep (SWS), and aid in characterizing the depth of sleep. Suppression of delta waves leads to inability of body rejuvenation, brain revitalization and poor sleep.

Non-rapid eye movement sleep (NREM), also known as quiescent sleep, is, collectively, sleep stages 1–3, previously known as stages 1–4. Rapid eye movement sleep (REM) is not included. There are distinct electroencephalographic and other characteristics seen in each stage. Unlike REM sleep, there is usually little or no eye movement during these stages. Dreaming occurs during both sleep states, and muscles are not paralyzed as in REM sleep. People who do not go through the sleeping stages properly get stuck in NREM sleep, and because muscles are not paralyzed a person may be able to sleepwalk. According to studies, the mental activity that takes place during NREM sleep is believed to be thought-like, whereas REM sleep includes hallucinatory and bizarre content. NREM sleep is characteristic of dreamer-initiated friendliness, compared to REM sleep where it is more aggressive, implying that NREM is in charge of simulating friendly interactions. The mental activity that occurs in NREM and REM sleep is a result of two different mind generators, which also explains the difference in mental activity. In addition, there is a parasympathetic dominance during NREM. The reported differences between the REM and NREM activity are believed to arise from differences in the memory stages that occur during the two types of sleep.

Sexsomnia, also known as sleep sex, is a distinct form of parasomnia, or an abnormal activity that occurs while an individual is asleep. Sexsomnia is characterized by an individual engaging in sexual acts while in non-rapid eye movement (NREM) sleep. Sexual behaviors that result from sexsomnia are not to be mistaken with normal nocturnal sexual behaviors, which do not occur during NREM sleep. Sexual behaviors that are viewed as normal during sleep and are accompanied by extensive research and documentation include nocturnal emissions, nocturnal erections, and sleep orgasms.

<span class="mw-page-title-main">K-complex</span>

A K-complex is a waveform that may be seen on an electroencephalogram (EEG). It occurs during stage 2 NREM sleep. It is the "largest event in healthy human EEG". They are more frequent in the first sleep cycles.

Sleep spindles are bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz with a duration of 0.5 seconds or greater. After generation as an interaction of the TRN neurons and thalamocortical cells, spindles are sustained and relayed to the cortex by thalamo-thalamic and thalamo-cortical feedback loops regulated by both GABAergic and NMDA-receptor mediated glutamatergic neurotransmission. Sleep spindles have been reported for all tested mammalian species. Considering animals in which sleep-spindles were studied extensively, they appear to have a conserved main frequency of roughly 9–16 Hz. Only in humans, rats and dogs is a difference in the intrinsic frequency of frontal and posterior spindles confirmed, however.

<span class="mw-page-title-main">Ventrolateral preoptic nucleus</span> Nucleus of the anterior hypothalamus

The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain of humans and other animals. The brain's sleep-promoting nuclei, together with the ascending arousal system which includes components in the brainstem, hypothalamus and basal forebrain, are the interconnected neural systems which control states of arousal, sleep, and transitions between these two states. The VLPO is active during sleep, particularly during non-rapid eye movement sleep, and releases inhibitory neurotransmitters, mainly GABA and galanin, which inhibit neurons of the ascending arousal system that are involved in wakefulness and arousal. The VLPO is in turn innervated by neurons from several components of the ascending arousal system. The VLPO is activated by the endogenous sleep-promoting substances adenosine and prostaglandin D2. The VLPO is inhibited during wakefulness by the arousal-inducing neurotransmitters norepinephrine and acetylcholine. The role of the VLPO in sleep and wakefulness, and its association with sleep disorders – particularly insomnia and narcolepsy – is a growing area of neuroscience research.

<span class="mw-page-title-main">Unihemispheric slow-wave sleep</span>

Unihemispheric slow-wave sleep (USWS) is sleep where one half of the brain rests while the other half remains alert. This is in contrast to normal sleep where both eyes are shut and both halves of the brain show unconsciousness. In USWS, also known as asymmetric slow-wave sleep, one half of the brain is in deep sleep, a form of non-rapid eye movement sleep and the eye corresponding to this half is closed while the other eye remains open. When examined by electroencephalography (EEG), the characteristic slow-wave sleep tracings are seen from one side while the other side shows a characteristic tracing of wakefulness. The phenomenon has been observed in a number of terrestrial, aquatic and avian species.

Recurrent thalamo-cortical resonance or Thalamocortical oscillation is an observed phenomenon of oscillatory neural activity between the thalamus and various cortical regions of the brain. It is proposed by Rodolfo Llinas and others as a theory for the integration of sensory information into the whole of perception in the brain. Thalamocortical oscillation is proposed to be a mechanism of synchronization between different cortical regions of the brain, a process known as temporal binding. This is possible through the existence of thalamocortical networks, groupings of thalamic and cortical cells that exhibit oscillatory properties.

<span class="mw-page-title-main">Sleep in animals</span>

Sleep in animals refers to a behavioral and physiological state characterized by altered consciousness, reduced responsiveness to external stimuli, and homeostatic regulation observed in various animals. Sleep has been observed in mammals, birds, reptiles, amphibians, and some fish, and, in some form, in insects and even in simpler animals such as nematodes. The internal circadian clock promotes sleep at night for diurnal organisms and in the day for nocturnal organisms. Sleep patterns vary widely among species. It appears to be a requirement for all mammals and most other animals.

Ponto-geniculo-occipital waves or PGO waves are distinctive wave forms of propagating activity between three key brain regions: the pons, lateral geniculate nucleus, and occipital lobe; specifically, they are phasic field potentials. These waves can be recorded from any of these three structures during and immediately before REM sleep. The waves begin as electrical pulses from the pons, then move to the lateral geniculate nucleus residing in the thalamus, and end in the primary visual cortex of the occipital lobe. The appearances of these waves are most prominent in the period right before REM sleep, albeit they have been recorded during wakefulness as well. They are theorized to be intricately involved with eye movement of both wake and sleep cycles in many different animals.

Sleep onset is the transition from wakefulness into sleep. Sleep onset usually transmits into non-rapid eye movement sleep but under certain circumstances it is possible to transit from wakefulness directly into rapid eye movement sleep.

<span class="mw-page-title-main">Sleep and memory</span> Relationship between sleep and memory

The relationship between sleep and memory has been studied since at least the early 19th century. Memory, the cognitive process of storing and retrieving past experiences, learning and recognition, is a product of brain plasticity, the structural changes within synapses that create associations between stimuli. Stimuli are encoded within milliseconds; however, the long-term maintenance of memories can take additional minutes, days, or even years to fully consolidate and become a stable memory that is accessible. Therefore, the formation of a specific memory occurs rapidly, but the evolution of a memory is often an ongoing process.

The activation-synthesis hypothesis, proposed by Harvard University psychiatrists John Allan Hobson and Robert McCarley, is a neurobiological theory of dreams first published in the American Journal of Psychiatry in December 1977. The differences in neuronal activity of the brainstem during waking and REM sleep were observed, and the hypothesis proposes that dreams result from brain activation during REM sleep. Since then, the hypothesis has undergone an evolution as technology and experimental equipment has become more precise. Currently, a three-dimensional model called AIM Model, described below, is used to determine the different states of the brain over the course of the day and night. The AIM Model introduces a new hypothesis that primary consciousness is an important building block on which secondary consciousness is constructed.

<span class="mw-page-title-main">Hypnogram</span> Graph of a persons sleep

A hypnogram is a form of polysomnography; it is a graph that represents the stages of sleep as a function of time. It was developed as an easy way to present the recordings of the brain wave activity from an electroencephalogram (EEG) during a period of sleep. It allows the different stages of sleep: rapid eye movement sleep (REM) and non-rapid eye movement sleep (NREM) to be identified during the sleep cycle. NREM sleep can be further classified into NREM stage 1, 2 and 3. The previously considered 4th stage of NREM sleep has been included within stage 3; this stage is also called slow wave sleep (SWS) and is the deepest stage of sleep.

<span class="mw-page-title-main">Neuroscience of sleep</span> Study of the neuroscientific and physiological basis of the nature of sleep

The neuroscience of sleep is the study of the neuroscientific and physiological basis of the nature of sleep and its functions. Traditionally, sleep has been studied as part of psychology and medicine. The study of sleep from a neuroscience perspective grew to prominence with advances in technology and the proliferation of neuroscience research from the second half of the twentieth century.

Sharp waves and ripples (SWRs) are oscillatory patterns produced by extremely synchronised activity of neurons in the mammalian hippocampus and neighbouring regions which occur spontaneously in idle waking states or during NREM sleep. They can be observed with a variety of imaging methods, such as EEG. They are composed of large amplitude sharp waves in local field potential and produced by tens of thousands of neurons firing together within 30–100 ms window. They are some of the most synchronous oscillations patterns in the brain, making them susceptible to pathological patterns such as epilepsy.They have been extensively characterised and described by György Buzsáki and have been shown to be involved in memory consolidation in NREM sleep and the replay of memories acquired during wakefulness.

The parafacial zone (PZ) is a brain structure located in the brainstem within the medulla oblongata believed to be heavily responsible for non-rapid eye movement (non-REM) sleep regulation, specifically for inducing slow-wave sleep.

References

  1. ↑ Lesku JA, Meyer LC, Fuller A, Maloney SK, Dell'Omo G, Vyssotski AL, Rattenborg NC (2011). Balaban E (ed.). "Ostriches sleep like platypuses". PLOS ONE. 6 (8): e23203. Bibcode:2011PLoSO...623203L. doi: 10.1371/journal.pone.0023203 . PMC   3160860 . PMID   21887239.
  2. ↑ Rechtschaffen A, Kales A (1968). A Manual of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. US Dept of Health, Education, and Welfare; National Institutes of Health.
  3. ↑ Reinoso Suárez, F. (1999). "[The neurobiology of slow-wave sleep]". Anales de la Real Academia Nacional de Medicina. 116 (1): 209–224, discussion 224–226. ISSN   0034-0634. PMID   10554397.
  4. 1 2 3 4 5 6 7 8 Carlson NR (2013). Physiology of behavior (Eleventh ed.). Boston. ISBN   978-0-205-23939-9.{{cite book}}: CS1 maint: location missing publisher (link)
  5. ↑ Schulz H (April 2008). "Rethinking sleep analysis". Journal of Clinical Sleep Medicine. 4 (2): 99–103. doi:10.5664/jcsm.27124. PMC   2335403 . PMID   18468306. Although the sequence of non-REM (NREM) sleep stages one to four (R&K classification) or N1 to N3 (AASM classification) fulfills the criteria...
  6. ↑ "Glossary. A resource from the Division of Sleep Medicine at Harvard Medical School, in partnership with WG Education Foundation". Harvard University. 2008. Archived from the original on 2018-10-04. Retrieved 2009-03-11. The 1968 categorization of the combined Sleep Stages 3 – 4 was reclassified in 2007 as Stage N3.
  7. 1 2 Iber, C; Ancoli-Israel, S; Chesson, A; Quan, SF. for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Westchester: American Academy of Sleep Medicine; 2007.
  8. ↑ Carey, Benedict (2013-01-27). "Aging in Brain Found to Hurt Sleep Needed for Memory". The New York Times. Archived from the original on 2017-03-17. Retrieved 2017-04-17.
  9. ↑ Walker MP (1 January 2008). "Sleep-dependent memory processing". Harvard Review of Psychiatry. 16 (5): 287–98. doi:10.1080/10673220802432517. PMID   18803104.
  10. 1 2 Walker, Matthew P. "The Role of Slow Wave Sleep in Memory Processing" (PDF). Journal of Clinical Sleep Medicine. Supplement to Vol.5, No. 2, 2009. Archived (PDF) from the original on 2013-05-09. Retrieved 2014-05-06.
  11. ↑ Walker MP (April 2009). "The role of slow wave sleep in memory processing". Journal of Clinical Sleep Medicine. 5 (2 Suppl): S20-6. doi:10.5664/jcsm.5.2S.S20. PMC   2824214 . PMID   19998871.
  12. ↑ Steriade M (1 January 2006). "Grouping of brain rhythms in corticothalamic systems" (PDF). Neuroscience. 137 (4): 1087–106. doi:10.1016/j.neuroscience.2005.10.029. PMID   16343791. S2CID   15470045. Archived from the original (PDF) on 18 April 2017.
  13. ↑ Gais S, Mölle M, Helms K, Born J (August 2002). "Learning-dependent increases in sleep spindle density". The Journal of Neuroscience. 22 (15): 6830–4. doi: 10.1523/JNEUROSCI.22-15-06830.2002 . PMC   6758170 . PMID   12151563.
  14. 1 2 Steriade, M. (2004). "Slow-wave sleep: serotonin, neuronal plasticity, and seizures". Archives Italienne de Biologie. 142 (4): 359–367. PMID   15493541. Archived from the original on 2014-05-06. Retrieved 2014-05-06.
  15. 1 2 Rasch B, Büchel C, Gais S, Born J (March 2007). "Odor cues during slow-wave sleep prompt declarative memory consolidation". Science. 315 (5817): 1426–9. Bibcode:2007Sci...315.1426R. doi:10.1126/science.1138581. PMID   17347444. S2CID   19788434.
  16. ↑ Peigneux P, Laureys S, Fuchs S, Collette F, Perrin F, Reggers J, et al. (October 2004). "Are spatial memories strengthened in the human hippocampus during slow wave sleep?". Neuron. 44 (3): 535–45. doi:10.1016/j.neuron.2004.10.007. hdl: 2268/21205 . PMID   15504332. S2CID   1424898.
  17. 1 2 Cairney SA, Durrant SJ, Hulleman J, Lewis PA (April 2014). "Targeted memory reactivation during slow wave sleep facilitates emotional memory consolidation". Sleep. 37 (4): 701–7, 707A. doi:10.5665/sleep.3572. PMC   3954173 . PMID   24688163.
  18. ↑ Gais S, Born J (February 2004). "Low acetylcholine during slow-wave sleep is critical for declarative memory consolidation". Proceedings of the National Academy of Sciences of the United States of America. 101 (7): 2140–4. Bibcode:2004PNAS..101.2140G. doi: 10.1073/pnas.0305404101 . PMC   357065 . PMID   14766981.
  19. 1 2 Slow-Wave Sleep: Beyond Insomnia. Wolters Kluwer Pharma Solutions. ISBN   978-0-9561387-1-2.
  20. ↑ Brancaccio A, Tabarelli D, Bigica M, Baldauf D (April 2020). "Cortical source localization of sleep-stage specific oscillatory activity". Scientific Reports. 10 (1): 6976. Bibcode:2020NatSR..10.6976B. doi:10.1038/s41598-020-63933-5. PMC   7181624 . PMID   32332806.
  21. 1 2 3 4 5 6 7 8 Dijk, Derk-Jan (2009). "Regulation and Functional Correlates of Slow Wave Sleep". J Clin Sleep Med. 5 (2 Suppl): 6–15. doi:10.5664/jcsm.5.2S.S6. PMC   2824213 . PMID   19998869.
  22. ↑ Dijk, D. J.; Hayes, B.; Czeisler, C. A. (1993). "Dynamics of electroencephalographic sleep spindles and slow wave activity in men: effect of sleep deprivation". Brain Res. 626 (1–2): 190–9. doi:10.1016/0006-8993(93)90579-c. PMID   8281430. S2CID   42683788.
  23. ↑ Jones BE (May 2003). "Arousal systems". Frontiers in Bioscience. 8 (6): s438-51. doi: 10.2741/1074 . PMID   12700104.
  24. ↑ Sanchez-Vives, MV; McCormick, DA (2000). "Cellular and network mechanisms of rhythmic recurrent activity in neocortex". Nat Neuroscience. 3 (10): 1027–1034. doi:10.1038/79848. PMID   11017176. S2CID   509469.
  25. ↑ Kattler H, Dijk DJ, Borbély AA (September 1994). "Effect of unilateral somatosensory stimulation prior to sleep on the sleep EEG in humans". Journal of Sleep Research. 3 (3): 159–164. doi: 10.1111/j.1365-2869.1994.tb00123.x . PMID   10607121. S2CID   26078900.
  26. ↑ Sekimoto M, Kato M, Kajimura N, Watanabe T, Takahashi K, Okuma T (May 2000). "Asymmetric interhemispheric delta waves during all-night sleep in humans". Clinical Neurophysiology. 111 (5): 924–8. doi:10.1016/S1388-2457(00)00258-3. PMID   10802465. S2CID   44808363.
  27. 1 2 3 Tamaki M, Bang JW, Watanabe T, Sasaki Y (May 2016). "Night Watch in One Brain Hemisphere during Sleep Associated with the First-Night Effect in Humans". Current Biology. 26 (9): 1190–4. Bibcode:2016CBio...26.1190T. doi:10.1016/j.cub.2016.02.063. PMC   4864126 . PMID   27112296.
  28. ↑ "What Happens When You Sleep: The Science of Sleep". Sleep Foundation. 2009-12-22. Archived from the original on 2021-06-21. Retrieved 2021-06-25.
  29. ↑ Payne JD, Walker WP (June 2008). "Review article: Does delta sleep matter?". INSOM: INSomnia and Its Optimized Management (10): 3–6. CiteSeerX   10.1.1.723.1235 . Archived from the original on 2021-06-25. Retrieved 2021-06-25– via CiteSeerX.
  30. ↑ "The importance of sleep & why we need it". Human Givens Institute. 2015-10-23. Archived from the original on July 11, 2019.
  31. ↑ Tononi G, Cirelli C (February 2006). "Sleep function and synaptic homeostasis". Sleep Medicine Reviews. 10 (1): 49–62. doi:10.1016/j.smrv.2005.05.002. PMID   16376591. S2CID   16129740.
  32. ↑ Gulati T, Guo L, Ramanathan DS, Bodepudi A, Ganguly K (September 2017). "Neural reactivations during sleep determine network credit assignment". Nature Neuroscience. 20 (9): 1277–1284. doi:10.1038/nn.4601. PMC   5808917 . PMID   28692062.
  33. ↑ Carlson, Neil R. (2012). Physiology of Behavior. Pearson. p. 299-300. ISBN   0205239390.
  34. 1 2 Varga, Andrew W.; Wohlleber, Margaret E.; Giménez, Sandra; Romero, Sergio; Alonso, Joan F.; Ducca, Emma L.; Kam, Korey; Lewis, Clifton; Tanzi, Emily B.; Tweardy, Samuel; Kishi, Akifumi; Parekh, Ankit; Fischer, Esther; Gumb, Tyler; Alcolea, Daniel; Fortea, Juan; Lleó, Alberto; Blennow, Kaj; Zetterberg, Henrik; Mosconi, Lisa; Glodzik, Lidia; Pirraglia, Elizabeth; Burschtin, Omar; Leon, Mony J.; Rapoport, David M.; Lu, Shou-en Lu; Ayappa, Indu; Osorio, Ricardo S. (2016). "Reduced Slow-Wave Sleep Is Associated with High Cerebrospinal Fluid Aβ42 Levels in Cognitively Normal Elderly". Sleep. 39 (11): 2041–2048. doi:10.5665/sleep.6240. PMC   5070758 . PMID   27568802.
  35. 1 2 Ju, Yo-El; Ooms, Sharon J.; Sutphen, Courtney; Macauley, Shannon L.; Zangrilli, Margaret A.; Jerome, Gina; Fagan, Anne M.; Mignot, Emmanuel; Zempel, John M.; Claassen, Jurgen A.; Holtzman, David (2017). "Slow wave sleep disruption increases cerebrospinal fluid amyloid-β levels". Brain. 140 (8): 2104–2111. doi:10.1093/brain/awx148. PMC   5790144 . PMID   28899014.
  36. ↑ Mander BA, Marks SM, Vogel JW, Rao V, Lu B, Saletin JM, et al. (July 2015). "β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation". Nature Neuroscience. 18 (7): 1051–7. doi:10.1038/nn.4035. PMC   4482795 . PMID   26030850.
  37. ↑ Lee, Lee Fun; Gerashchenko, Dmitry; Timofeev, Igor; Bacskai, Brian J.; Kastanenka, Ksenia V. (2020). "Slow Wave Sleep Is a Promising Intervention Target for Alzheimer's Disease". Front. Neurosci. 14: 705. doi: 10.3389/fnins.2020.00705 . PMC   7340158 . PMID   32714142.
  38. ↑ Moran, Maria; Lynch, C. A.; Walsh, C.; Coen, R.; Coakley, D.; Lawlor, B. A. (2005). "Sleep disturbance in mild to moderate Alzheimer's disease". Sleep Med. 6 (4): 347–52. doi:10.1016/j.sleep.2004.12.005. PMID   15978517.
  39. 1 2 3 4 5 Mokhlesi B, Pannain S, Ghods F, Knutson KL (April 2012). "Predictors of slow-wave sleep in a clinic-based sample". Journal of Sleep Research. 21 (2): 170–5. doi:10.1111/j.1365-2869.2011.00959.x. PMC   3321544 . PMID   21955220.
  40. ↑ Dijk, Derk-Jan; Groeger, John A.; Stanley, Neil; Deacon, Stephen (2010). "Age-related reduction in daytime sleep propensity and nocturnal slow wave sleep". Sleep. 33 (2): 211–23. doi:10.1093/sleep/33.2.211. PMC   2817908 . PMID   20175405.
  41. ↑ Armitage R, Hoffmann R, Trivedi M, Rush AJ (September 2000). "Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls" (PDF). Psychiatry Research. 95 (3): 201–13. doi:10.1016/S0165-1781(00)00178-5. PMID   10974359. S2CID   1903649.
  42. 1 2 Finelli, L.A.; Borbély, A.A.; Achermann, P. (2001). "Functional topography of the human nonREM sleep electroencephalogram". Eur J Neurosci. 13 (12): 2282–90. doi:10.1046/j.0953-816x.2001.01597.x. PMID   11454032. S2CID   206682.
  43. ↑ Anaclet C, Ferrari L, Arrigoni E, Bass CE, Saper CB, Lu J, Fuller PM (September 2014). "The GABAergic parafacial zone is a medullary slow wave sleep-promoting center" (PDF). Nat. Neurosci. 17 (9): 1217–1224. doi:10.1038/nn.3789. PMC   4214681 . PMID   25129078. Archived (PDF) from the original on 2018-11-04. Retrieved 2018-11-04. In the present study we show, for the first time, that activation of a delimited node of GABAergic neurons located in the medullary PZ can potently initiate SWS and cortical SWA in behaving animals. ... For now however it remains unclear if the PZ is interconnected with other sleep– and wake–promoting nodes beyond the wake–promoting PB. ... The intensity of cortical slow–wave–activity (SWA: 0.5–4Hz) during SWS is also widely accepted as a reliable indicator of sleep need ... In conclusion, in the present study we demonstrated that all polygraphic and neurobehavioral manifestation of SWS, including SWA, can be initiated in behaving animals by the selective activation of a delimited node of GABAergic medullary neurons.
  44. 1 2 3 Schwartz MD, Kilduff TS (December 2015). "The Neurobiology of Sleep and Wakefulness". The Psychiatric Clinics of North America. 38 (4): 615–644. doi:10.1016/j.psc.2015.07.002. PMC   4660253 . PMID   26600100. More recently, the medullary parafacial zone (PZ) adjacent to the facial nerve was identified as a sleep-promoting center on the basis of anatomical, electrophysiological and chemo- and optogenetic studies.23, 24 GABAergic PZ neurons inhibit glutamatergic parabrachial (PB) neurons that project to the BF,25 thereby promoting NREM sleep at the expense of wakefulness and REM sleep. ... Sleep is regulated by GABAergic populations in both the preoptic area and the brainstem; increasing evidence suggests a role for the melanin-concentrating hormone cells of the lateral hypothalamus and the parafacial zone of the brainstem
  45. 1 2 3 Brown RE, McKenna JT (June 2015). "Turning a Negative into a Positive: Ascending GABAergic Control of Cortical Activation and Arousal". Front. Neurol. 6: 135. doi: 10.3389/fneur.2015.00135 . PMC   4463930 . PMID   26124745. The sleep-promoting action of GABAergic neurons located in the preoptic hypothalamus (6–8) is now well-known and accepted (9). More recently, other groups of sleep-promoting GABAergic neurons in the lateral hypothalamus (melanin-concentrating hormone neurons) and brainstem [parafacial zone; (10)] have been identified.
  46. ↑ Valencia Garcia S, Fort P (December 2017). "Nucleus Accumbens, a new sleep-regulating area through the integration of motivational stimuli". Acta Pharmacologica Sinica. 39 (2): 165–166. doi:10.1038/aps.2017.168. PMC   5800466 . PMID   29283174. The nucleus accumbens comprises a contingent of neurons specifically expressing the post-synaptic A2A-receptor (A2AR) subtype making them excitable by adenosine, its natural agonist endowed with powerful sleep-promoting properties[4]. ... In both cases, large activation of A2AR-expressing neurons in NAc promotes slow wave sleep (SWS) by increasing the number and duration of episodes. ... After optogenetic activation of the core, a similar promotion of SWS was observed, whereas no significant effects were induced when activating A2AR-expressing neurons within the shell.
  47. ↑ Oishi Y, Xu Q, Wang L, Zhang BJ, Takahashi K, Takata Y, Luo YJ, Cherasse Y, Schiffmann SN, de Kerchove d'Exaerde A, Urade Y, Qu WM, Huang ZL, Lazarus M (September 2017). "Slow-wave sleep is controlled by a subset of nucleus accumbens core neurons in mice". Nature Communications. 8 (1): 734. Bibcode:2017NatCo...8..734O. doi:10.1038/s41467-017-00781-4. PMC   5622037 . PMID   28963505. Here, we show that chemogenetic or optogenetic activation of excitatory adenosine A2A receptor-expressing indirect pathway neurons in the core region of the NAc strongly induces slow-wave sleep. Chemogenetic inhibition of the NAc indirect pathway neurons prevents the sleep induction, but does not affect the homoeostatic sleep rebound.
  48. ↑ Yuan XS, Wang L, Dong H, Qu WM, Yang SR, Cherasse Y, Lazarus M, Schiffmann SN, d'Exaerde AK, Li RX, Huang ZL (October 2017). "Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus". eLife. 6: e29055. doi: 10.7554/eLife.29055 . PMC   5655138 . PMID   29022877.
  49. ↑ Varin C, Rancillac A, Geoffroy H, Arthaud S, Fort P, Gallopin T (2015). "Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism". The Journal of Neuroscience. 35 (27): 9900–11. doi:10.1523/JNEUROSCI.0609-15.2015. PMC   6605416 . PMID   26156991.
  50. ↑ Monti JM, Torterolo P, Lagos P (2013). "Melanin-concentrating hormone control of sleep-wake behavior". Sleep Medicine Reviews. 17 (4): 293–8. doi:10.1016/j.smrv.2012.10.002. PMID   23477948. MCHergic neurons are silent during wakefulness (W), increase their firing during slow wave sleep (SWS) and still more during REM sleep (REMS). Studies in knockout mice for MCH (MCH(-/-)) have shown a reduction in SWS and an increase of W during the light and the dark phase of the light-dark cycle.
  51. ↑ Torterolo P, Lagos P, Monti JM (2011). "Melanin-concentrating hormone: a new sleep factor?". Frontiers in Neurology. 2: 14. doi: 10.3389/fneur.2011.00014 . PMC   3080035 . PMID   21516258. Neurons containing the neuropeptide melanin-concentrating hormone (MCH) are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. ... Intraventricular microinjection of MCH increases both slow wave sleep (SWS) and REM sleep; however, the increment in REM sleep is more pronounced. ... Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.
  52. ↑ Walsh, James K. (2009). "Enhancement of Slow Wave Sleep: Implications for Insomnia". J Clin Sleep Med. 5 (2 Suppl): 27–32. doi:10.5664/jcsm.5.2S.S27. PMC   2824211 . PMID   19998872.
  53. ↑ Mamelak, M.; Escriu, J. M.; Stokan, O. (April 1977). "The effects of gamma-hydroxybutyrate on sleep". Biological Psychiatry. 12 (2): 273–288. ISSN   0006-3223. PMID   192353.
  54. ↑ Roehrs T, Roth T (December 2010). "Drug-related Sleep Stage Changes: Functional Significance and Clinical Relevance". Sleep Medicine Clinics. 5 (4): 559–570. doi:10.1016/j.jsmc.2010.08.002. PMC   3041980 . PMID   21344068.
  55. ↑ "Xyrem - European Drugs Reference Encyclopedia". Archived from the original on 2013-08-21. Retrieved 2013-07-16.
  56. ↑ Walsh, James K.; Zammit, Gary; Schweitzer, Paula K.; Ondrasik., John; Roth, Thomas (2005). "Tiagabine enhances slow wave sleep and sleep maintenance in primary insomnia". Sleep Med. 7 (2): 155–61. doi:10.1016/j.sleep.2005.05.004. PMID   16260179.
  57. ↑ Walsh, James K.; Perlis, Michael; Rosenthal, Murray; Krystal, Andrew; Jiang, John; Roth, Thomas (2006). "Tiagabine increases slow-wave sleep in a dose-dependent fashion without affecting traditional efficacy measures in adults with primary insomnia". J Clin Sleep Med. 15 (2(1)): 35–41. doi:10.5664/jcsm.26433. PMID   17557435.
  58. ↑ Isotalus, Hanna K.; Carr, Will J.; Blackman, Jonathan; Averill, George G.; Radtke, Oliver; Selwood, James; Williams, Rachel; Ford, Elizabeth; McCullagh, Liz; McErlane, James; O'Donnell, Cian; Durant, Claire; Bartsch, Ullrich; Jones, Matt W.; Muñoz-Neira, Carlos (2023). "L-DOPA increases slow-wave sleep duration and selectively modulates memory persistence in older adults". Frontiers in Behavioral Neuroscience. 17: 1096720. doi: 10.3389/fnbeh.2023.1096720 . ISSN   1662-5153. PMC   10113484 . PMID   37091594.
  59. ↑ Suzuki, H; Yamadera, H; Nakamura, S; Endo, S (August 2002). "Effects of trazodone and imipramine on the biological rhythm: an analysis of sleep EEG and body core temperature". Journal of Nippon Medical School. 69 (4): 333–41. doi: 10.1272/jnms.69.333 . PMID   12187365.
  60. ↑ Sharpley, AL; Elliott, JM; Attenburrow, MJ; Cowen, PJ (March 1994). "Slow wave sleep in humans: role of 5-HT2A and 5-HT2C receptors". Neuropharmacology. 33 (3–4): 467–71. doi:10.1016/0028-3908(94)90077-9. PMID   7984285. S2CID   46587971.
  61. ↑ Dijk, DJ (June 2010). "Slow-wave sleep deficiency and enhancement: implications for insomnia and its management". The World Journal of Biological Psychiatry. 11 (Suppl 1): 22–8. doi:10.3109/15622971003637645. PMID   20509829. S2CID   37749231.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.