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For other uses, see Sleep (disambiguation).

Sleep is the regular state of natural rest observed in all mammals, birds and fish. Sleep is not actually "unconsciousness," but rather, it is a natural state of rest characterized by a reduction in voluntary body movement and decreased awareness of the surroundings. Therefore, since consciousness is literally the awareness of the surroundings, being asleep is just an altered state of consciousness, as opposed to being unconscious. It is heavily influenced by circadian rhythms, and by hormonal and environmental factors as well. Sleep appears to perform a restorative function for the brain and body, as evidenced by the myriad symptoms of metabolic dysfunction that result when animals are deprived of sleep (Gottlieb et al., 2005).

The function of sleep in health and in disease is being increasingly studied in specialized sleep laboratories throughout the world, especially in developed countries such as Japan and the United States where such funding is available. Not only insomnia, but more recently elucidated sleep disorders such as sleep apnea and narcolepsy are evaluated in such facilities. The increasing prevalence of sleep disorders is likely to be a function both of more sophisticated diagnostic tests and the disruption of the normal day-night cycle in modern societies.

Sleep physiology

Methodology

Before advances in the fields of neurology, neuroscience, electronics and genetics were made, scientists studied the behavioral characteristics of sleep, such as its pattern, depth, and varying frequency. In more recent times, the electrical impulses generated by the brain are recorded using a device called an electroencephalograph (EEG), and individual genes relating to sleep-related brain function, such as the circadian rhythm, have been isolated. Molecular biology, medical science and epidemiology all play an important role in modern studies of sleep.

Sleep is often defined using specific criteria relating to EEG data. All mammals and birds fulfill the criteria for sleep based on EEG recordings. In animals where EEG data is not readily available, or their small size precludes recording an EEG, behavioral and gene specific data are utilized for sleep studies.

Sleep regulation

The cycle of sleep and wakefulness is regulated by the brain stem, thalamus, external stimuli, and various hormones produced by the hypothalamus. Some neurohormones and neurotransmitters are highly correlated with sleep and wake states. For example, melatonin levels are highest during the night, and this hormone appears to promote sleep. Adenosine, a nucleoside involved in generating energy for biochemical processes, gradually accumulates in the human brain during wakefulness but decreases during sleep. Researchers believe that its accumulation during the day encourages sleep. The stimulant properties of caffeine are attributed to its negating the effects of adenosine.

The suprachiasmatic nucleus (SCN) of the hypothalamus plays an important role in the regulation of circadian rhythms. The SCN is influenced by external light and also generates its own rhythm in isolation. In the presence of light it sends messages to the pineal gland that instruct it to cease secreting melatonin.

Thus, three processes, each influenced by hormonal, neurological, and environmental factors, underlie sleep regulation:

• A homeostatic process determined by prior sleep and wakefulness, determining "sleep need".
• A circadian process determining periods of high and low sleep propensity, and high and low rapid eye movement (REM) sleep propensity.
• An ultradian process

The interrelationships and relative importance of each process and system remain uncertain.

Stages of sleep

Studies of human sleep have established five well-defined stages, according to electroencephalographic (EEG) recordings and polysomnography:

• Non-REM sleep (NREM), accounts for 75-80% of total sleep time:
  • Stage 1, with near-disappearance of the alpha waves seen in awake states, and appearance for the first time of theta waves. The stage is sometimes referred to as somnolence, or "drowsy sleep". It appears at sleep onset (as it is mostly a transition state into Stage 2), and can be associated with so-called hypnagogic hallucinations. In this period, the subject loses some muscle tone, and conscious awareness of the external environment: Stage 1 can be thought of as a gateway state between wake and sleep.
  • Stage 2, with "sleep spindles" (12–16 Hz) and "K-complexes". The EMG lowers, and conscious awareness of the external environment all but disappears. This occupies 45-55% of total sleep.
  • Stage 3, with delta waves, also called delta rhythms (1–2 Hz), is considered part of SWS and functions primarily as a transition into stage four. Overall it occupies 3-8% of total sleep time.
  • Stage 4 is true delta sleep. It predominates the first third of the night and accounts for 10-15% of total sleep time. This is often described as the deepest stage of sleep; it is exceedingly difficult to wake a subject in this state. This is the stage in which night terrors and sleepwalking occur.

• Stage 5, or Rapid eye movement (REM) sleep, associated with dreaming, especially bizarre, visual, and seemingly random dreams. REM sleep is predominant in the final third of a sleep period, its timing linked to circadian rhythm and body temperature. The EEG in this period is aroused and looks similar to stage 1, and sometimes includes beta waves.

Sleep proceeds in cycles of NREM and REM phases. In humans, the cycle of REM and NREM is approximately 90 minutes. Each stage may have a distinct physiological function. Drugs such as alcohol and sleeping pills can suppress certain stages of sleep (see sleep deprivation below). This can result in a sleep that exhibits loss of consciousness but does not fulfill its physiological functions.

Each sleep stage is not necessarily uniform. Within a given stage, a cyclical alternating pattern may be observed.

Theories regarding the function of sleep

Restorative theories of sleep describe sleep as a dynamic time of healing and growth for organisms. For example, during stages 3 and 4, or slow-wave sleep, growth hormone levels increase, and changes in immune function occur. The myriad illnesses associated with sleep deprivation testify to its restorative function.

According to the ontogenetic hypothesis of REM sleep, the activity occurring during neonatal REM sleep (or active sleep) seems to be particularly important to the developing organism (Marks et al., 1995). Studies investigating the effects of deprivation of active sleep have shown that deprivation early in life can result in behavioral problems, permanent sleep disruption, decreased brain mass (Mirmiran et al. 1983), and an abnormal amount of neuronal cell death (Morrissey, Duntley & Anch, 2004). Given sleep's heterogeneous nature, however, no single theory predominates, as it is difficult to describe one single "function" of sleep.

One process known to be highly dependent on sleep is memory. REM sleep appears to help with the consolidation of spatial and procedural memory, while slow-wave sleep helps with the consolidation of declarative memories. When experimental subjects are given academic material to learn, especially if it involves organized, systematic thought, their retention is markedly increased after a night's sleep. Mere rote memorization is retained similarly well with or without an intervening period of sleep.

Non-REM sleep is an anabolic state marked by physiological processes of growth and rejuvenation of the organism's immune, nervous, muscular, and skeletal systems. Sleep also restores neurons and increases production of brain proteins and certain hormones. Wakefulness may perhaps be viewed as a cyclical, temporary, hyperactive catabolic state during which the organism acquires nourishment and procreates. Asking the question "Why do we awaken?" instead of "Why do we sleep?" yields a different perspective toward understanding how sleep and its stages contribute to a healthy organism.

One view, Preservation and Protection, is that sleep serves an adaptive function. It protects the individual during that portion of the 24-hour day in which being awake, and hence roaming around, would place the individual at greatest risk. Organisms don't require 24 hours to feed themselves and meet other necessities. From this perspective of adaptation, organisms are safer by staying out of harm's way where potentially they could be prey to other stronger organisms. They sleep at times that maximizes their safety, given their physical capacities and their habitats. (Allison & Cicchetti, 1976; Webb, 1982).

Another view is that the function of sleep is for memory processing. This theory argues that saving memory directly into the long-term memory is a slow and error prone process, and, thus, proposes that the memory formed during waking time is not saved directly into the long-term memory; instead it is saved into a temporary memory store first. The function of sleep is to process, encode and transfer the data from the temporary memory store to the long-term memory store. (Zhang, 2004).

Dreaming

Main article: Dream

The demonstrably necessary phenomenon of dreaming would suffice to prove the importance of sleep to humans, and perhaps to other animals as well. Dreaming involves an involuntary conjuring up of images in a sequence in which the sleeper/dreamer is usually more a participant than an observer. Most scientists agree that dreaming is stimulated by the pons and occurs during the REM phase of sleep.

Many functions have been hypothesized for dreaming. Freud postulated that dreams are the symbolic expression of frustrated desires that had been relegated to the subconscious, and used dream interpretation in the form of psychoanalysis he pioneered. Scientists today have become more skeptical about details of Freudian interpretation, and place more emphasis on dreaming as a requirement for organization and consolidation of recent memory and experience. Another theory is that dreaming allows an animal to play out scenarios that may help the animal avoid dangers when awake. For example, a rabbit might dream about being cornered by a fox and may play out different scenarios that might increase chances of survival should he come across a fox in reality.

Sleep deprivation

Main article: Sleep deprivation

A common misperception is that everyone needs eight hours of sleep. The amount of sleep needed is different for each person. This amount needed is individually and biologically determined. Some can do with six hours of sleep, others need nine. However, as a general rule, eight hours is recommended. Sleep experts state that you cannot "store" sleep by sleeping more on the weekends in preparation for the normal work week. Just how much sleep deprivation leads to death in humans is unknown.[1]

Another commonly held view is that the amount of sleep one requires decreases as one ages, but this is not necessarily the case. The ability to sleep, rather than the need for sleep, appears to decrease when people get older. [2]

Failure to sleep results in progressively severe psychological and physical distress. In 1965, California teenager Randy Gardner attempted to resist sleep in an uncontrolled "experiment". As his ordeal progressed he fell into a silent stupor, bringing into doubt whether he was actually awake in any practical sense.

A 1999 University of Chicago team led by Eve Van Cauter limited a group of lean young men to four hours of sleep per night for 16 days. The subjects showed decreased levels of leptin and increased levels of cortisol. The subjects also increased their daily caloric intake by 1,000 calories. The team discovered that the subjects' insulin and blood sugar levels resembled the impaired glucose tolerance of prediabetics, an indication that they were no longer properly processing carbohydrates. Studies have also linked sleep deprivation to an increased incidence of obesity.

At Harvard Medical School, researchers have identified associations between sleep deprivation and illnesses ranging from hypertension and heart attacks to cancer. Poor sleepers generate increased levels of stress hormones and show more inflammatory changes in the walls of their small blood vessels, both of which contribute to elevated blood pressure. Because of their exposure to light at night, night-shift workers produce less melatonin, a hormone which not only promotes sleep but has been shown to have cancer-prevention benefits as well.

Experiments with rats have measured the effects of long-term sleep deprivation. In one experiment, a pair of rats were placed on a circular rotating platform and separated by a wall. Both were instrumented with electroencephalograms. Whenever the "subject" rat began to show signs of sleep, the platform rotated, forcing both rats to either walk in the direction opposite to the rotation or be forced off the platform into shallow water. The "control" rat was allowed to sleep while the "subject" rat was awakened. After approximately 3 weeks the "subject" rat became unable to regulate body temperature; even if allowed to sleep at this point, it died shortly afterward from septic shock.

In sleep-deprived states less extreme than that suffered by Randy Gardner, humans display irritability, impaired cognitive function, and poor judgment. Experiments on sleep-deprived medical trainees, for example, have shown them less able to interpret EKGs and x-rays than their well rested peers. As late as the early 21st century people thought that too little sleep could be negated by "paying back the sleep debt". However, recent studies have shown this to be false.

Sleep disorders

Main article: Sleep disorder

Disorders of sleep are broadly classified into three groups. Dyssomnias are characterized by difficulty getting to sleep, as in primary insomnia, narcolepsy, and restless legs syndrome. Obstructive sleep apnea, a condition that is being diagnosed with increased frequency, may be classified either as a dyssomnia or as an example of a parasomnia. The latter conditions involve bothersome awakenings during sleep, and also include bruxism and sleepwalking. The third group includes sleep disorders resulting from a number of psychiatric problems, such as bipolar disorder, depression, or schizophrenia.

Many sleep disorders result from errors in synchronization of sleep with the body clock. Other sleep problems are organic and cannot be resolved with chronotherapy. One often effective solution to some kinds of insomnia involves free-running sleep. Free-running sleep entails ignoring alarm clocks and schedules in order to sleep when, and only when, tired. Free-running sleep can resolve the majority of synchronization-dependent sleep disorders, but is difficult to sustain due to the resulting loss of synchronization of sleep with the outside world (including the day-night cycle).

Animal sleep

Animals vary widely in their amounts of sleep, from 2 hours a day for giraffes to 20 hours for bats. Generally, required sleeping time decreases as body size increases. Cats are one of the few animals that do not have most of their sleep consolidated into one session, preferring instead to spread their sleep fairly evenly throughout the day.

Water mammals "sleep" with alternate hemispheres of their brains asleep and the other awake. They need to do this so they can breathe above water while sleeping. Migratory birds also seem to sleep this way.

Even fish and fruit flies appear to have a "sleeplike" state. This alternation of the sleeplike state and its absence is referred to as a "Basic Rest and Activity Cycle", or BRAC. Since the modern definition of sleep is defined using EEG criteria, and such tiny brains preclude the recording of EEG's, this may not technically be described as sleep. However, if fruit flies are repeatedly disturbed so that they can not rest, they have what is referred to as a "rest rebound". This behavior is strikingly similar to that exhibited by mammals and birds in similar conditions. As research equipment improves, the definition of sleep may soon be revised.

Many animals hibernate in a deep sleeplike state during winter to conserve body heat and energy. Estivation is a similar state in which other animals hibernate to escape the heat of summer.

Cattle, horses, and sheep are unique in that they can sleep while standing, though for cattle and sheep, REM sleep will not occur in such a position. For REM sleep to take place, the animals must lie down. Sleeping while standing is thus only partial sleep. However, birds may have periods of REM sleep while perched.

Approaches to sleeping better

Many non-pharmacological approaches exist to improve falling asleep and staying asleep. Doctors and health professionals may suggest any of the following, depending on the type of sleep disruption, the person's situation, and their specific sleep needs.

• Decrease the light level in the sleeping environment. Studies have indicated that the brain has a separate neural pathway to the optical nerve, separate from the visual path, to detect whether it's day or night. This detection system could have a direct effect on successful sleep inducement. Moreover, other studies have shown sleep inducement is dramatically increased by reductions in light level, in the sleeping environment. Use appropriate curtains and shading to keep light out or at minimal levels.
• Set a quiet time approximately 30 minutes before bedtime: no computer, television, unrelaxing music, video games, office work, housework, or other stressful, dutiful, or mentally stimulating activities—to slow down the metabolic rate.
• Reading calming material or other light mental activity at bedtime.
• Consuming any source of the amino acid tryptophan, which may help relax the nervous system and induce drowsiness. This may explain the theory of warm milk, likely rooted in a folk remedy, though scientific evidence ^{[citation needed]} suggests that simply drinking milk may or may not help.
• Get up to do some quiet activity or slowly walk around until feeling tired, if one does not fall asleep in bed after 20 to 30 minutes. Paradoxically, this may increase restlessness in some people. Intense exercise will impair the ability to sleep for most people, short of utter exhaustion, and should be avoided.
• Make sure one's sleeping position or posture is comfortable and provides enough support, especially for the lower back.
• Quiet, slow-paced, simplistic music can also help sleep inducement. Audio music products are available on the market that are designed to help fulfill this function.
• Avoid using the bed for activities other than sleep, to maintain an association between getting into bed and sleeping.
• Engaging in sexual activity ending in orgasm, including masturbation, is anecdotally known to make it easier to fall asleep and improve the quality of sleep.
• Avoid certain chemicals (e.g., caffeine, cocaine and Ritalin), which are stimulants and can adversely affect sleep. Many non-stimulant medications, including glucocorticoids, may also cause sleeping problems.
• Avoid coffee, tea, soft drinks and beverages containing sugars or caffeine^[3]. (Some claim green tea is an exception that calms nerves to induce sleep despite its caffeine.)
• Decrease in body temperature can also help. Studies have shown sleep inducement is increased when body temperature is lowered beyond normal heat.
• For those with difficulty digesting, avoid a large evening meal, especially if consumed within four hours of bedtime. Bulky meals may lead to abdominal discomfort, nausea, or heartburn which disrupt sleep.
• Avoid excessive stress and worrying, especially in the hours just before bedtime.
• Controlled crying is used as a method of increasing the length of time babies or young children will sleep.

Drugs and sleep

Sleep aiding

The pharmacological approach to facilitating sleep involves the use of depressant drugs, with the goal of inducing sleep without producing excessive drowsiness the following morning. [4]. Until the 1970s, barbiturates were commonly prescribed for sleep, but today benzodiazepines and other newer families of drugs with less potential for abuse and overdose are more commonly used. Non-prescription antihistamines also have a sedative effect, and are commonly marketed as sleep aids.

Sleeping pills are best prescribed only on a short-term basis and only if symptoms of insomnia are marked enough to interfere with a patient's life. Habitual consumption of any depressant drug to aid sleep may result in psychological and/or physical drug dependence. Drug tolerance may also develop, in which increasingly higher doses are required to produce the desired effect. Physical addiction to benzodiazepines may lead to a withdrawal syndrome involving insomnia and anxiety, and in some cases more severe problems, including seizures. Chronic use can also cause "paradoxical insomnia," where the drug produces the opposite of the intended effect.

Stimulant drugs

Conversely, drugs may also be used to dissuade or delay sleep. The stimulant modafinil reduces drowsiness and is prescribed to treat narcolepsy. It allows the user to cope with shorter sleep periods while producing only minimal euphoric effects. The amphetamine family of stimulants by comparison would help to keep people awake longer but preclude the opportunity for a given person to obtain "recovery sleep" for a longer time. Modafinil, while maintaining a longer elimination half-life, does seem to allow sleep earlier than amphetamines. Simply put, modafinil removes the urge to fall asleep, rather than encouraging wakefulness. Modafinil also appears to reduce, but not elimate, the need for recovery sleep, compared to amphetamine and placebo PMID 10607162.

See also

• Circadian rhythm
• Co-sleeping
• Jet lag
• Myoclonic twitch
• Microsleep
• Mucopurulent discharge, white substance found in corner of eye, also known as "sleep"
• Seasonal affective disorder
• Segmented sleep
• Sleep hygiene
• Sleep inertia
• Polyphasic sleep
• Hibernation
• Meditation
• Yoga Nidra

References

• Gottlieb, D. J., Punjabi, N. M., Newman, A. B., Resnick, H. E., Redline, S., Baldwin, C. M., et al. (2005). Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med, 165(8), 863-867.
• Morrissey, M. J., Duntley, S. P., Anch, A. M., & Nonneman, R. (2004). Active sleep and its role in the prevention of apoptosis in the developing brain. Medical Hypotheses, 62(6), 876-879.
• Marks, G. A., Shaffery, J. P., Oksenberg, A., Speciale, S. G., & Roffwarg, H. P. (1995). A functional role for rem sleep in brain maturation. Behav Brain Res, 69(1-2), 1-11.
• Mirmiran, M., Scholtens, J., van de Poll, N. E., Uylings, H. B., van der Gugten, J., & Boer, G. J. (1983). Effects of experimental suppression of active (rem) sleep during early development upon adult brain and behavior in the rat. Brain Res, 283(2-3), 277-286.
• Zhang, J. (2004). Memory process and the function of sleep. Journal of Theoretics.Vol 6-6.

External links

• National Sleep Foundation
• National Center on Sleep Disorders Research
• Everything you wanted to know about sleep and sleep disorders
• American Academy of Sleep Medicine
• Find an accredited sleep center
• Sleep Research Society
• How to Get Great Sleep
• Down for the Count
• Tips for Sleeping
• Sleep primer from the journal Nature
• Sleep Apnea, Isomina, Narcolepsy Foundational Resources
• Sleep News
• TalkAboutSleep.com Provides information and resources on all 80+ sleep disorders including: Sleep Apnea, Insomnia, Narcolepsy, Fibromyalgia, etc.
• The Basics of Sleep Behavior
• Getting the Sleep You Need: Sleep Stages, Sleep Tips and Aids
• Sleep: Understanding its importance (article from thedoctorslounge.net)
• Going without sleep Scientific American response to question from the public
• Sleep and Obesity
• Neurobehavioral Consequenses of Sleep Dysfunction
• Determinants of Obesity and Metabolic Dysfunction in Adolescents
• Metabolic Dysfunction Associated with Sleep-disordered Breathing Increases the Risk of Cardiovascular Morbidity and Mortality
• Improvement of Metabolic Function in Sleep Apnea

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