Slow-wave sleep

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 75 μV. 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 can 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. The two stages are now combined as Stage Three or N3. An epoch (30 seconds of sleep) that consists of 20% or more slow-wave (delta) sleep is now considered slow-wave sleep. Importance Slow-wave sleep is considered important for memory consolidation. This is sometimes referred to as "sleep-dependent memory processing". 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. Furthermore, slow-wave sleep improves declarative memory (which includes semantic and episodic memory). A central model has been hypothesized that long-term memory storage is facilitated by an interaction between the hippocampal and neocortical networks. This associated with the spontaneously occurring wave oscillations that account for the intracellular recordings from thalamic and cortical neurons. Specifically, SWS presents a role in spatial declarative memory. Reactivation of the hippocampus during SWS is detected after the spatial learning task. 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. Additionally, studies have found that when odour cues are given to subjects during sleep, this stage of sleep exclusively allows contextual cues to be reactivated after sleep, favoring their consolidation. 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. 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. It is also thought to be responsible for a decrease in sympathetic and increase in parasympathetic neural activity. ==Electroencephalographic characteristics==

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. 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. 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 ( 75 μV) are key indicators. The presence and distribution of sleep spindle activity and slow waves vary across NREM sleep, leading to its subdivision into stages 1–3. While slow waves and sleep spindles are present in stages 2 and 3, stage 2 sleep is characterized by a higher prevalence of spindles, while slow waves dominate the EEG during stage 3. 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. 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. ==Functions==

Neural control of slow-wave sleep Several neurotransmitters are involved in sleep and waking patterns: acetylcholine, norepinephrine, serotonin, histamine, and orexin. Lastly, glial cells within the brain are restored with sugars to provide energy for the brain. Learning and synaptic homeostasis Learning and memory formation occur during wakefulness by the process of long-term potentiation; SWS is associated with the regulation of synapses thus potentiated. SWS is involved in the downscaling of synapses, in which strongly stimulated or potentiated synapses are kept while weakly potentiated synapses either diminish or are removed. 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. ==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 generally outgrow them. Amyloid beta pathology A number of research studies have shown that sleep affects amyloid beta (Aβ) dynamics. A good candidate for slow wave activity (SWA), which occurs during deep non-REM sleep, is Aβ modulation. The researchers also highlighted a strong relationship between Aβ and SWA, pointing out that increased disruption in SWA is correlated with elevated levels of Aβ. Hence, Slow waves of non-rapid eye movement sleep are disrupted or decrease when Aβ builds up in the prefrontal cortex. As a result, this may hinder older people's capacity for memory consolidation. Moreover, the onset of Alzheimer's disease is marked by the deposition of amyloid beta (Aβ) in the brain. Thus, individuals diagnosed with Alzheimer's often experience disturbances in sleep, resulting in diminished levels of non-rapid eye movement sleep and reduced slow wave activity, which is a prominent brain rhythm during deep non-REM sleep. Similarly, even cognitively healthy individuals with detectable Aβ exhibit sleep disturbances, characterized by compromised sleep quality and an increased frequency of daytime napping. ==Individual differences==

Though slow-wave sleep is fairly consistent within the individual, it can vary across individuals. Individual variations seem to be influenced by demographic factors such as gender and age. Aging is inversely proportional to the amount of SWS beginning by midlife, so slow-wave sleep declines with age. ==Brain regions==

During sleep, the distribution of slow-wave activity (SWA) typically exhibits a prevalence in the frontal region of the brain. 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 temporal region, parietal region, and occipital region. located within the medulla oblongata • the nucleus accumbens core (GABAergic medium spiny neurons; specifically, the subset of these neurons that expresses both D2-type dopamine receptors and adenosine A2A receptors), located within the striatum • the ventrolateral preoptic area (GABAergic neurons), located within the hypothalamus • The lateral hypothalamus (melanin-concentrating hormone-releasing neurons), located within the hypothalamus ==Drugs==

Some drugs influence sleep architecture by encroaching upon or prolonging deep sleep. Many drugs known to increase deep sleep in humans are of the GABAergic, dopaminergic, and anti-serotonergic classes. Gamma-hydroxybutyrate is synthesized in the central nervous system from gamma-aminobutyric acid (GABA). In the United States, it is sold as 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 and also positively impacts various indicators of insomnia. 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 increase slow-wave sleep by 10.6% in the elderly. Antagonists of certain serotonergic receptors (namely 5-HT2A and 5-HT2C) have also been demonstrated to enhance slow-wave sleep, although they do not consistently bring about improvements in overall sleep duration or symptoms associated with insomnia. A variety of drugs that antagonise the on 5-HT2A and 5-HT2C receptors exhibit SWS-enhancing effects in humans. N-type calcium channel modulating gabapentinoids such as pregabalin are also known to increase slow-wave sleep in patients with fibromyalgia, restless leg syndrome, and partial seizures. Moreover, the results of a small double-blind randomized controlled trial suggests the enhancement of slow-wave sleep by pregabalin seems to carry on to healthy individuals as well. ==See also==