Normal Sleep, Sleep Physiology, and Sleep Deprivation

Updated: Nov 05, 2019
  • Author: Pradeep C Bollu, MD; Chief Editor: Selim R Benbadis, MD  more...
  • Print

Normal Sleep in Adults, Infants, and the Elderly

Normal sleep is divided into non–rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is further divided into progressively deeper stages of sleep: stage N1 (NREM 1), stage N2 (NREM 2), and stage N3 (NREM 3). [1]  As NREM stages progress, stronger stimuli are required to result in an awakening. Stage R sleep (REM sleep) is characterized by decreased EEG amplitude, muscle atonia, autonomic variability, and episodic rapid eye movement. REM sleep has tonic and phasic components. The phasic component is a sympathetically driven state with rapid eye movements, distal muscle twitches, cardiorespiratory variability, and middle ear muscle activity. Tonic REM is a parasympathetically driven state with no eye movements, decreased EEG amplitude, and atonia. [2]  The REM period length and density of eye movements increase throughout the sleep cycle.

Waking usually transitions into light NREM sleep. NREM sleep typically begins in the lighter stages (N1 and N2) and progressively deepens to slow-wave sleep as evidenced by higher-voltage delta waves. When delta waves account for more than 20% of the sleep EEG, the sleep stage is considered to be stage N3. [1]  REM sleep follows NREM sleep and occurs 4–5 times during a normal 8-hour sleep period. The REM period becomes progressively longer through the night where the first REM period of the night may be less than 10 minutes in duration, while the last may exceed 60 minutes. The NREM–REM cycles vary in length from 70 to 100 minutes initially to 90 to120 minutes later in the night. [2]

Typically, N3 sleep is present more in the first third of the night, whereas REM sleep predominates in the last third of the night. NREM parasomnias such as sleep walking typically occur in the first third of the night with the presence of N3 sleep. This contrasts with REM sleep behavior disorder (RBD), which typically occurs in the last half of the night.

Sleep in adults

Stage N1 is considered a transition between wake and sleep. It occurs upon falling asleep and during brief arousal periods within sleep and usually accounts for 2–5% of total sleep time. Stage N2 occurs throughout the sleep period and represents 45–55% of total sleep time. Stage N3 (slow-wave sleep) occurs mostly in the first third of the night and constitutes 10–20% of total sleep time. REM represents 20–25% of total sleep time and occurs in 4–5 episodes throughout the night. [2]

Sleep in infants

Infants have an overall greater total sleep time than any other age group; their sleep time can be divided into multiple periods.

In newborns, the total sleep duration in a day can be 16 to 18 hours and NREM–REM sleep cycle every 45–60 minutes. REM sleep comprises 50% of the sleep in newborns. Until age 3 months, newborns transition from wake into REM sleep. Thereafter, wake begins to transition directly into NREM. [3]

Over the first several months of life, sleep time decreases; by age 5–6 months, sleep consolidates into an overnight period with at least 1 nap during the day. REM sleep in infants represents a larger percentage of the total sleep at the expense of stage N3. 

Overall, electrocortical recorded voltage remains high during sleep, as it does during periods of wakefulness. Sleep spindles begin appearing in the second month of life with a density greater than that seen in adults (see Sleep Physiology). After the first year, the spindles begin decreasing in density and progress toward adult patterns. K complexes develop by the sixth month of life. [3]

Sleep in the elderly

In elderly persons, the time spent in stage N3 sleep decreases, and the time in stage N2 compensatorily increases. Latency to fall asleep and the number and duration of overnight arousal periods increase. This often causes total time in bed to increase, which can lead to complaints of insomnia. Sleep fragmentation results from the increase in overnight arousals and may be exacerbated by the increasing number of geriatric medical conditions, including sleep apnea, musculoskeletal disorders, and cardiopulmonary disease. [4]  Older individuals are also more sensitive to auditory stimuli leading to frequent arousals from sleep. [5] Percentage of REM sleep is well preserved into healthy elderly populations. [2]


Sleep Physiology

Sleep is a state of unconsciousness in which the brain is relatively more responsive to internal than external stimuli. The predictable cycling of sleep and the reversal of relative external unresponsiveness are features that assist in distinguishing sleep from other states of unconsciousness. The brain gradually becomes less responsive to visual, auditory, somatosensory, and other environmental stimuli during the transition from wake to sleep, which is considered by some to be stage I of sleep. [6, 7]

Historically, sleep was thought to be a passive state that was initiated through the withdrawal of sensory input. Currently, withdrawal of sensory awareness is believed to be a factor in sleep, but an active initiation mechanism that facilitates brain withdrawal is also recognized. [8] Both homeostatic factors (factor S) and circadian factors (factor C) interact to determine the timing and quality of sleep.

The "switch" for sleep is considered to be the ventrolateral preoptic nucleus (VLPO) of the anterior hypothalamus. This area becomes active during sleep and uses the inhibitory neurotransmitters GABA and galanin to initiate sleep by inhibiting the arousal regions of the brain. The VLPO innervates and can inhibit the wake-promoting regions of the brain including the tuberomammillary nucleus, lateral hypothalamus, locus coeruleus, dorsal raphe, laterodorsal tegmental nucleus, and pedunculopontine tegmental nucleus. The hypocretin (orexin) neurons in the lateral hypothalamus help stabilize this switch and the loss of these neurons results in narcolepsy. [9]

The tuberoinfundibular region projects rostrally to the intralaminar nuclei of the thalamus and to the cerebral cortex. Inhibition of the tuberoinfundibular region is a critical step toward falling asleep because it results in a functional disconnection between the brain stem and the more rostral thalamus and cortex. A decrease in ascending thalamic cholinergic transmissions occurs in association with decreasing cortical responsiveness. In addition to inhibiting higher cortical consciousness, the tuberoinfundibular tract projects caudally into the pontine reticular system and inhibits afferent transmissions from ascending cholinergic tracts. [10]

NREM is an active state that is maintained partly through oscillations between the thalamus and the cortex. The 3 major oscillation systems are sleep spindles, delta oscillations, and slow cortical oscillations. [7]  Sleep spindles, a hallmark of stage N2 sleep, are generated by bursts of hyperpolarizing GABAnergic neurons in the reticular nucleus of the thalamus. These bursts inhibit thalamocortical projection neurons. As deafferentation spreads, corticothalamic projections back to the thalamus synchronize. As hyperpolarization of the thalamic reticular neurons progresses, delta waves are produced by interactions from both thalamic reticular and cortical pyramidal sources. Slow cortical oscillations are produced in neocortical networks by cyclic hyperpolarizations and depolarizations. [7]

Although the functions of NREM sleep remain speculative, several theories have been put forth. One theory proposes that decreased metabolic demand facilitates the replenishment of glycogen stores. Another theory, which utilizes neuronal plasticity, suggests that the oscillating depolarizations and hyperpolarizations consolidate memory and remove redundant or excess synapses. [11]

REM sleep is generated by the cholinergic mediated "REM-on neurons" in the mesencephalic and pontine cholinergic neurons. [7]  The pedunculopontine tegmental nucleus (PPT) and the lateral dorsal tegmental (LDT) neurons use acetylcholine to trigger cortical desynchrony via the thalamus. Cortical desynchrony (also described as low voltage mixed frequency) is the EEG hallmark of REM sleep. An additional EEG hallmark of REM sleep is "sawtooth waves." A pharmacologic offshoot of the cholinergic mediation of REM sleep is stage R increasing with cholinergic agonists and decreasing with anticholinergics.

"REM-off neurons" are the noradrenergic locus coeruleus and serotonergic raphe neurons. The REM-off neurons use norepinephrine, serotonin, and histamine to inhibit the REM-on cholinergic cells and stop REM sleep. These REM-off neurons become inactive during REM sleep. Medications, such as antidepressants, that increase the amount of norepinephrine or serotonin can cause a pharmacologic suppression of REM sleep. [10, 12]

REM sleep (stage R) is characterized by muscle atonia, cortical activation, low-voltage desynchronization of the EEG, and rapid eye movements. [13] REM sleep has a parasympathetically medicated tonic component and a sympathetically mediated phasic component. The phasic portion of REM sleep is characterized by skeletal muscle twitches, increased heart rate variability, pupillary dilation, and increased respiratory rate. [14]

Muscle atonia is present throughout REM sleep, except for phasic muscle twitches. It results from inhibition of alpha motor neurons by clusters of peri–locus coeruleus neurons, which are referred to collectively as the dorsolateral small cell reticular group. [7]

Projection of the presumed cholinergic, dorsolateral, small-cell, reticular group is through the medullary reticular formation, which projects through the ventrolateral reticulospinal tract to inhibitory spinal and bulbar interneurons. Glycinergic interneurons produce postsynaptic inhibition and hyperpolarization of the spinal alpha motor neurons. Tonic cortical activation with EEG desynchronization is promoted by projections from cholinergic lateral dorsal tegmental and pedunculopontine tegmental neurons to the thalamic nuclei. Other projections through brainstem reticular formation neurons are likely to be involved as well. [7]

Phasic rapid eye movements are composed of lateral saccades generated in the paramedian pontine reticular formation and vertical saccades thought to be generated in the mesencephalic reticular formation. [7]  REM density is a term used to describe the frequency per minute of the eye movement bursts.

Phasic pontine-geniculate-occipital (PGO) spikes are another neurophysiological feature of REM sleep seen in animals, but not humans. These spikes appear to be generated by lateral dorsal tegmental and pedunculopontine tegmental neuronal bursts. They are projected to the lateral geniculate and other thalamic nuclei, and then to the occipital cortex. PGO bursts precede rapid eye movements by several seconds. Increases in PGO bursts are seen after REM sleep deprivation.65 In humans, intracerebral recordings, noninvasive PET, fMRI, and magnetoencephalography scanning in healthy volunteers indicate that the rapid eye movements observed during REM sleep are generated by mechanisms similar or identical to PGO waves in animals. [2]

During NREM sleep, the metabolic demand of the brain decreases. This is supported by oxygen positron emission tomography (PET) studies, which show that, during NREM sleep, the blood flow throughout the entire brain progressively decreases. PET studies also show that, during REM sleep, blood flow increases in the thalamus and the primary visual, motor, and sensory cortices, while remaining comparatively decreased in the prefrontal and parietal associational regions. The increase in blood flow to the primary visual regions of the cortex may explain the vivid nature of REM dreaming, while the continued decrease in blood flow to the prefrontal cortex may explain the unquestioning acceptance of even the most bizarre dream content. [15, 16]


Circadian Rhythms That Influence Sleep

Circadian sleep rhythm is one of the several intrinsic body rhythms modulated by the hypothalamus. [17] The suprachiasmatic nucleus in the anterior hypothalamus sets the body clock to approximately 24.2 hours, with both light exposure and schedule clues entraining to the 24.2-hour cycle. [18] The retinohypothalamic tract allows light cues to directly influence the suprachiasmatic nucleus. Light is called a zeitgeber, a German word meaning time-giver because it sets the suprachiasmatic clock. Examples of other external zeitgebers are exercise, social activities, and mealtimes. [19]  A practical purpose has been proposed for the circadian rhythm, using the analogy of the brain functioning somewhat like a battery charging during sleep and discharging during the wake period.

The nadir of this rhythm is in the early morning. The downswing in circadian rhythm prior to the nadir is thought to assist the brain to remain asleep overnight for full restoration by preventing premature awakening. The morning upswing then facilitates awakening and through the day acts as a counterbalance to the progressive discharge of wake neuronal activity. After the circadian apex in the early evening, the downswing aids sleep initiation. This model explains the relatively steady cognitive function throughout wakefulness. [20, 7]

Body temperature cycles are also under hypothalamic control. An increase in body temperature is seen during the course of the day and a decrease is observed during the night. The temperature peaks and troughs are thought to mirror the sleep rhythm. People who are alert late in the evening (ie, evening types) have body temperature peaks late in the evening, while those who find themselves most alert early in the morning (ie, morning types) have body temperature peaks early in the evening. [21, 7]

Melatonin has been implicated as a modulator of light entrainment. It is secreted maximally during the night by the pineal gland. Prolactin, testosterone, parathyroid hormone, and growth hormone also demonstrate circadian rhythms, with maximal secretion during the night. [22, 2]

For excellent reviews of clinically applicable information on circadian rhythm disorders, please refer to Sack, 2007. [23, 24]


Effects of Sleep Deprivation

As the full function of sleep has not been fully determined, the absolute number of hours necessary to fulfill its function is still unknown. Some individuals claim full effectiveness with only 3–5 hours of sleep per night, while most admit needing at least 8 hours or more of sleep per night to perform effectively. The inability to meet this biological requirement is what constitutes sleep deprivation and this loss of sleep can be total or partial or selective sleep deprivation or chronic sleep deprivation. Total sleep deprivation results from the elimination of sleep for at least one night to significantly prolong wakefulness. Partial sleep deprivation results from reducing the amount of nighttime sleep preventing the individuals from obtaining their usual sleep time. When this partial sleep deprivation happens over extended periods of time, it results in a state of chronic sleep deprivation. Selective sleep deprivation is achieved by depriving subjects of a specific stage of sleep.

With decreased sleep, higher-order cognitive tasks are affected early and disproportionately. Tests requiring both speed and accuracy demonstrate considerably slowed speed before accuracy begins to fail. Total sleep duration of 7 hours per night over 1 week has resulted in decreased speed in tasks of both simple reaction time and more demanding computer-generated mathematical problem-solving. Total sleep duration of 5 hours per night over 1 week shows both reduction in speed and the beginning of the failure of accuracy. [25]

Total sleep duration of 7 hours per night over a 1-week period leads to impairment of cognitive work requiring a simultaneous focus on several tasks. In driving simulations, for example, accidents increase progressively as total sleep duration is decreased to 7, 5, and 3 hours per night over 1 week. In the same simulations, 3 hours total sleep duration was associated with loss of ability to simultaneously appreciate peripheral and centrally presented visual stimuli, which could be termed as a form of visual simultanagnosia and peripheral visual neglect. [26, 27, 28]

In tasks requiring judgment, increasingly risky behaviors emerge as the total sleep duration is limited to 5 hours per night. The high cost of action seemingly is ignored as the sleep-deprived individual focuses on limited benefit. [26]

One explanation for decreasing performance in sleep deprivation is the occurrence of microsleep. Microsleep is defined as a brief (several seconds) runs of theta or delta activities that break through the otherwise beta or alpha EEG of waking. It has been seen to increase with sleep deprivation. In studies in which polysomnography is recorded simultaneously, microsleep impairs continuity of cognitive function and occurs prior to performance failure. However, the occurrence of microsleep has not been shown in most instances of polysomnographic correlated performance failure. Other explanations for performance impairments include sensory-perceptual impairments such as the development of visual neglect phenomena. [29]

These experimental findings can be explained by FDG glucose-PET studies, which show that individuals deprived of sleep for 24 hours have a decrease in metabolism in the prefrontal and parietal associational areas. The areas most important for judgment, impulse control, attention, and visual association are disproportionately hypometabolic compared to the primary sensory and motor areas necessary for receiving and acting upon the environmental inputs. This finding leads to the hypothesis that the areas of the brain most responsible for higher-order cognition are to some degree less functional during sleep-deprived wakefulness. [16, 30]

Sleep deprivation is a relative concept. Small amounts of sleep loss (eg, 1 hour per night over many nights) have subtle cognitive costs, which appear to go unrecognized by the individual experiencing the sleep loss. More severe restriction of sleep for a week leads to profound cognitive deficits similar to those seen in some stroke patients, which also appear to go unrecognized by the individual. The lack of recognition of the effects of sleep deprivation appears to be a constant feature, one which, it is hoped, will be overcome by further research and education. [26, 31]

Short-term sleep deprivation has been implicated in contributing to obesity as well as glycemic dysregulation contributing to poor control of type II diabetes. [32, 33, 34, 35]  In chronically sleep-deprived individuals, sleep extension to more than 6 hours per night showed improvement in glucose metabolism. [36]  Exposure to bright light during the early night, as seen in many adolescents with the use of electronic device screens, leads to insufficient sleep and irregular sleep pattern. Sleep deprivation and irregular sleep are implicated in metabolic dysfunction, obesity, and excessive caffeine intake among school-age children. [37]  Sleep deprivation is also shown to affect the normal physiological profiles of various hormones including TSH, cortisol, [38]  and growth hormone. [39, 40]

Sleep deprivation is a risk factor for cardiovascular and cerebrovascular disease. Part of the risk is attributed to the wide range of metabolic abnormalities and increased prevalence of obesity, diabetes, dyslipidemia, and hypertension in the sleep-deprived population. [41]  However, sleep loss constitutes an independent risk factor for stroke in the setting of sleep deprivation with alterations in immune response and heightened sympathetic drive possibly contributing to this independent link between sleep deprivation and cerebrovascular disease. [42, 40]

Sleep deprivation also affects many neurological and psychiatric disorders. Sleep deprivation is a well-known trigger for seizure precipitation in patients with epilepsy. [43]  Chronic headaches, including migraines and tension headaches, are more common in sleep-deprived individuals. [44, 45] Shift work that increases sleep deprivation can be a risk factor for multiple sclerosis. [46, 40]