Various stages of sleep are described based on their different electroencephalographic (EEG) features.
The first scoring manual (1968) with standardized criteria for sleep staging included five stages of sleep. This scoring method remained in effect until 2007, when the American Academy of Sleep Medicine (AASM) further revised the scoring of sleep stages. The AASM scoring manual divided sleep into four stages.
A clear appreciation of the normal sleep patterns provides the background for understanding clinical conditions in which normal characteristics are altered, as well as for predicting certain consequences of sleep disorders by their differences from the normative pattern.
Normal human sleep comprises two types of sleep that alternate cyclically across a sleep episode—rapid eye movement (REM) and non–REM (NREM) sleep.
Stages of sleep are well defined:
1. Non-rem (NREM) sleep or deep sleep
- accounts for approximately 75–80% of total sleep time and is characterized by persistent motor activity with a relatively inactive brain.
- is conventionally subdivided into 4 stages defined along one measurement axis, the electroencephalogram (EEG).
- The EEG pattern in NREM sleep is described as synchronous, with such characteristic waveforms as sleep spindles, K-complexes, and high-voltage slow waves associated with low muscle tonus and minimal or fragmentary psychological activity;
- The 4 NREM stages (stages 1, 2, 3, and 4) roughly parallel a depth-of-sleep continuum. The arousal thresholds are generally lowest in stage 1 and highest in stage 4 sleep (deep sleep).
- K-complexes during Stage 2 sleep can occur in response to an environmental stimulus. Legend has it that the ‘K’ stands for ‘Knock,’ from the observation that some K- complexes can be induced by knocking sounds. It is well known that not all knocks produce K-complexes. Some of them yield more prolonged microarousals, whereas others yield none at all, or may be associated with entrained sleep spindles.
2. REM sleep
- is usually 20% to 25% of sleep, occurring in four to six discrete episodes.
- is characterized by relative loss of motor activity with a more active brain
- The EEG is desynchronized and very different from that seen during other stages of sleep; It is characterized by a slow, high-voltage pattern.
- muscles are atonic
- mental activity is associated with dreaming, based on dream recall reported after approximately 80% of arousals from this state of sleep.
REM sleep can be subdivided into tonic and phasic REM sleep. These types are distinguished for certain research purposes.
Tonic REM is represented by the desynchronized EEG and muscle atonia.
Phasic REM briefly interrupts tonic REM with bursts of rapid eyes movements, muscle twitches including the facial, limb, middle ear, and tongue muscles, and irregularities of respiration, heart rate, and blood pressure. Phasic REM occurs in clusters separated by episodes of relative quiescence.
Rapid, symmetrical REM periods, shorter earlier in the night, are separated from the previous by approximately 90–100 min. Simultaneous recording of the electroencephalogram (EEG) reveal a low-voltage, mixed-frequency pattern very similar to that recorded during wakefulness. This EEG pattern during these periods of REM sleep indicate that brain neuronal activity increases to a level similar to that of wakefulness.
REM sleep is also called paradoxical sleep due to the presence of rapid eyes movements and an EEG pattern resembling wakefulness.
There are some physiological changes that are unique to REM sleep. In comparison with non-REM sleep, REM is a metabolically active stage of sleep. Thermoregulation ceases during REM sleep and the body temperature tends to approach the environmental temperature.
During periods of REM sleep, heart and respiratory rates are more variable and are usually increased. Combined with the activated EEG pattern, this phase of sleep might be associated with emotional disturbances caused by dreaming.
Increased cortical activity is also associated with increased cerebral blood flow and metabolism. Parasympathetic activity is decreased during tonic REM sleep, compared with increases in sympathetic activity that occurs during phasic REM sleep.
REM sleep has also been theorized to play a role in memory consolidation, in particular procedural memory (not declarative memory).
A common sleep-onset experience is hypnic myoclonia. It is experienced as a general or localized muscle contraction very often associated with vivid visual imagery. Hypnic myoclonias are not pathologic events, although they tend to occur more often in association with stress or with unusual or irregular sleep schedules.
The precise mechanism of hypnic myoclonias is not clearly understood. According to one hypothesis, the onset of sleep is marked by a dissociation of REM sleep components, wherein a breakthrough of the imagery component of REM sleep (hypnagogic hallucination) occurs in the absence of the REM motor inhibitory component. A response by the individual to the image, therefore, results in a movement or jerk.
The increased frequency of these events in association with irregular sleep schedules is consistent with the increased probability of REM sleep occurring at the wake-to-sleep transition under such conditions. Although the usual transition in adult human beings is to NREM sleep, the REM portal into sleep, can become partially opened under unusual circumstances.
Sleep Facts – Memory Near Sleep Onset
The transition from wake to sleep produces a memory impairment. It is thought that sleep inactivates the transfer of storage from short- to long-term memory. Encoding of the material before sleep onset is of insufficient strength to allow recall.
One may infer that memory is lost for the few minutes before sleep. A few examples of this phenomenon are:
- the inability to grasp the instant of sleep onset in your memory.
- forgetting a telephone call that had come in the middle of the nigh
- the inability to remember the news you were told when awakened in the night.
- not remembering the ringing of the alarm clock.
Patients with syndromes of excessive sleepiness can experience similar memory problems in the daytime if sleep becomes intrusive.
Stages of Sleep Across the Night
Normal sleep cycle
There is a typical and predictable progression during the night through the different stages of non-REM and REM sleep.
Sleep is divided into 90–110 min cycles alternating between NREM and REM sleep. Four to six such cycles may be observed during the night.
Sleep begins in NREM and progresses through deeper NREM stages (stages 2, 3, and 4).
The first episode of REM sleep is slightly shorter than the subsequent ones, lasting approximately 30 min and generally occurs 90–110 min after sleep onset
Thereafter, NREM sleep and REM sleep cycle with a period of approximately 90 minutes. NREM stages 3 and 4 concentrate in the early NREM cycles, and REM sleep episodes usually become longer across the night. With each sleep cycle, the amount of REM sleep increases, with more REM sleep occurring in the last third of the sleep period.
First Sleep Cycle
The first cycle of sleep in the normal adult begins with stage 1 sleep which is characterized by a reduction of the rhythmic alpha EEG activity that is seen in wakefulness. It is a very light stage of sleep, often perceived as drowsiness in individuals and usually persists for only a few (1 to 7) minutes at the onset of sleep. It is associated with a low arousal threshold and generally constitutes approximately 2% to 5% of sleep.
Stage 1 sleep also occurs as a transitional stage throughout the night. A common sign of severely disrupted sleep is an increase in the amount and percentage of stage 1 sleep.
Stage 2 NREM usually follows stage 1 sleep and continues for approximately 10 to 25 minutes. It generally constitutes approximately 45% to 55% of sleep and comprises sleep spindles or K-complexes in the EEG. In stage 2 sleep, a more intense stimulus is required to produce arousal. The same stimulus that produced arousal from stage 1 sleep often results in an evoked K-complex but no awakening in stage 2 sleep.
As stage 2 sleep progresses, high-voltage slow-wave activity gradually appears in the EEG. The criteria for stage 3 NREM sleep is high-voltage (at least 75 μV) slow-wave activity accounting for more than 20% but less than 50% of the EEG activity. Stage 3 sleep generally constitutes approximately 3% to 8% of sleep. It usually lasts only a few minutes in the first cycle and is transitional to stage 4 as more and more high-voltage slow-wave activity occurs.
Stage 4 NREM sleep is identified when the high-voltage slow-wave activity comprises more than 50% of the record. It usually lasts approximately 20 to 40 minutes in the first cycle and generally constitutes approximately 10% to 15% of sleep.
The combined stages 3 and 4 sleep are also called slow-wave sleep [SWS], delta sleep, or deep sleep.
Stages 3 and 4 sleep occupy less time in the second cycle and might disappear altogether from later cycles, as stage 2 sleep expands to occupy the NREM portion of the cycle.
A larger stimulus is usually required to produce an arousal from stage 3 or 4 sleep than from stage 1 or 2 sleep.
A series of body movements usually signals an “ascent” to lighter NREM sleep stages. A brief (1- or 2-minute) episode of stage 3 sleep might occur, followed by perhaps 5 to 10 minutes of stage 2 sleep interrupted by body movements preceding the initial REM episode.
Distribution of Sleep Stages across the Night
SWS dominates the NREM portion of the sleep cycle toward the beginning of the night (the first one third). This preferential distribution of SWS toward the beginning of a sleep episode reflects the homeostatic sleep system, highest at sleep onset and diminishing across the night as sleep pressure wanes.
REM sleep episodes are longest in the last one third of the night and this is thought to be linked to the circadian rhythm of body temperature.
Brief episodes of wakefulness tend to intrude later in the night, near REM sleep transitions, and they usually do not last long enough to be remembered in the morning. Wakefulness in sleep usually accounts for less than 5% of the night.
Sleep Rhythm and its Regulation
Sleep is regulated by two processes, the homeostatic drive and the circadian rhythm. These processes work in conjunction with each other to determine the sleep–wake cycle.
The homeostatic drive refers to one’s need for sleep which increases as wakefulness is prolonged. Time spent asleep reduces the sleep load and the desire to sleep.
The homeostatic drive can be reduced by taking naps during the day and this can lead to difficulties falling asleep at night.
Circadian rhythms are cycles of behaviors and physiological processes in the body. The sleep–wake cycle is only one of the body’s circadian rhythms. The main control center for the sleep–wake cycle is the suprachiasmatic nucleus of the anterior hypothalamus and is endogenously regulated by genes and melatonin.
Alterations of the circadian rhythm can lead to significant derangement with ensuing abnormal sleep. Aging is strongly related to a multitude of sleep disturbances in which the circadian rhythm may play a crucial role.
- newborns (0–2 months) sleep for 16–18 h per day
- infant (3–11 months) need 14–15 h per day.
- toddlers (1–3 years) should average 12–14 h of TST, which includes 1–2 naps throughout the day.
- preschoolers (3–5 years) require 11–13 h of sleep and may or may not nap during the day to achieve their TST.
- school age children (5–10 years) need 10–11 h per night
- teenagers (11–17 years) require 8.5–9.5 h of sleep.
- adult requires approximately 7–9 h of sleep to feel well rested.
- elderly adults require the same amount of sleep as other adults; to achieve the recommended sleep time they often take one or more naps throughout the day
There are small percentages of the adult population that require more or less sleep than average. They are described as long sleepers (10–12 h per night) and short sleepers (less than 5 h per night) These individuals have had similar, age-adjusted sleep requirements in their whole lives, beginning in childhood, unrelated to any medical condition.
Factors that modify the distribution of sleep stages
Arousals during sleep become more prevalent in later life: extended wake episodes of which the individual is aware and can report, as well as brief and probably unremembered arousals which may occur often associated with other sleep disturbances, such as periodic limb movements (PLMS) and sleep-related respiratory irregularities
By age 60 years, SWS might no longer be present, particularly in men. Women usually maintain SWS later into life.
2. Prior Sleep History
A person who has lost sleep for a long period of time shows a sleep pattern that favors SWS during recovery. Recovery sleep is also prolonged and deeper than basal sleep. It is associated with a high arousal threshold.
REM sleep tends to show a rebound on the subsequent recovery nights after an episode of sleep loss. Therefore, SWS tends to be preferentially recovered compared with REM sleep, which tends to recover only after the recuperation of SWS.
Cases in which a person is differentially deprived of REM or SWS show a preferential rebound of that stage of sleep when natural sleep is resumed (sleep-onset REM periods as a result of a REM sleep rebound).
Chronic sleep deprivation or frequent disturbance of nocturnal sleep and also an irregular sleep schedule, can cause a peculiar distribution of sleep states, characterized by premature REM sleep. Such episodes can be associated with hypnagogic hallucinations, sleep paralysis, or an increased incidence of hypnic myoclonia in persons with no organic sleep disorder.
3. Circadian Rhythms
The circadian phase at which sleep occurs affects the distribution of sleep stages.
REM sleep occurs with a circadian distribution that peaks in the morning hours coincident with the trough of the core body temperature rhythm. Thus, REM sleep tends to predominate and can even occur at the onset of sleep if sleep onset is delayed until the peak REM phase of the circadian rhythm which is in the early morning. This reversal of the normal sleep-onset pattern is commonly seen in a normal person who undergoes a phase shift (as a result of a work shift change or from jet travel across a number of time zones).
The timing of sleep onset and the length of sleep occur as a function of circadian phase.
Extremes of temperature in the sleeping environment tend to disrupt sleep. REM sleep is more sensitive to temperature-related disruption than NREM sleep.
Human beings have only minimal ability to thermoregulate during REM sleep. This affects the response to temperature extremes. Such conditions are less of a problem early during a night than late, when REM sleep tends to predominate. Responses as sweating or shivering during sleep under ambient temperature extremes occur in NREM sleep and are limited in REM sleep.
5. Drug Ingestion
The distribution of sleep stages is affected by many common drugs, including those typically prescribed as sleeping pills.
Actually is unknown if changes in sleep stage distribution have any relevance to health, illness, or psychological well-being.
- Benzodiazepines suppress SWS and have no consistent effect on REM sleep.
- Tricyclic antidepressants, monoamine oxidase inhibitors, and certain selective serotonin reuptake inhibitors suppress REM sleep. Some of these compounds can also produce an increased level of motor activity during sleep, leading to a pattern of REM sleep without motor inhibition or an increased incidence of periodic limb movements of sleep. Fluoxetine is associated with rapid eye movements across all sleep stages (“Prozac eyes”).
- Withdrawal from drugs that selectively suppress a stage of sleep tends to be associated with a rebound of that sleep stage. Thus, acute withdrawal from a benzodiazepine is likely to produce an increase of SWS; acute withdrawal from a tricyclic antidepressant or monoamine oxidase inhibitor is likely to produce an increase of REM sleep.
- Acute presleep alcohol intake can produce an increase in SWS and suppress REM sleep early in the night, which can be followed by REM sleep rebound in the latter portion of the night as the alcohol is metabolized. Low doses of alcohol have minimal effects on sleep stages, but they can increase sleepiness late at night.
- Acute effects of marijuana (tetrahydrocannabinol [THC]) include a slight reduction of REM sleep. Chronic ingestion of THC produces a long-term suppression of SWS.
6. Pathology and sleep fragmentation
Sleep disorders, as well as other non-sleep problems, have an impact on the structure and distribution of sleep. A number of common sleep-stage anomalies are commonly associated with sleep disorders.
Sleep disturbance can be caused by mood disorders including depression. Abnormalities in sleep architecture have been revealed by polysomnographic studies of depressed patients which include: decreased time in slow-wave sleep, reduced latency to rapid eye movement (REM) sleep onset, and disrupted sleep continuity.
Fragmentation of sleep and increased frequency of arousals occur in association with sleep disorders as well as with medical disorders involving physical pain, sleep apnea syndromes, periodic limb movements of sleep, chronic fibrositis. Brief arousals occur as a symptom of allergic rhinitis, Parkinson’s disease and juvenile rheumatoid arthritis. In upper airway resistance syndrome the most important markers are EEG arousals because the respiratory signs of this syndrome are less obvious than in frank obstructive sleep apnea syndrome, and only subtle indicators may be available.
Transient changes of blood pressure can signify arousals and they are highly correlated with the extent of EEG arousals.
Older persons, particularly men have less slow-wave sleep (stages 3 and 4).
Certain patients have sleep complaints (insomnia, hypersomnia) that result from attempts to sleep or be awake at times not in synchrony with their circadian phase.
Patients who wake up early in the night might have a disorder affecting NREM sleep and those who wake with events late in the night may have a disorder affecting REM sleep.
When using sleep restriction to build sleep pressure, treatment will be more effective if sleep is scheduled at the correct circadian phase.
The problem of napping in patients with insomnia is that naps diminish the homeostatic drive to sleep.
Normal sleep-wake cycle
Daytime alertness and timing of sleep vary in a circadian fashion. They are determined primarily by the body’s internal clock.
The suprachiasmatic nucleus is the anatomical location of the master pacemaker for the circadian timing system. The rhythm of the suprachiasmatic nucleus is entrained to the environment by outside light. The retinohypothalamic tract conveys light from the retina to the suprachiasmatic nucleus.
Consequently, changes in ambient light intensity and color are important for synchronizing the internal sleep–wake cycle with that of the environmental day–night cycle.
The suprachiasmatic nucleus regulates daily rhythms of nearly all physiological and behavioral processes (for example sleep/wake, drinking, body temperature, and hormonal rhythms).
Pacemaker activity in the suprachiasmatic nucleus is regulated at the molecular level by circadian clock genes in transcription–translation-based autoregulatory feedback loops, generating a near 24-h rhythm that is synchronized to the environmental light/dark cycle by light and other stimuli such as rest/activity state, feeding, and melatonin.
More than 25 neurochemicals of endogenous and exogenous origin have been identified in the suprachiasmatic nucleus. The most prevalent neurotransmitter in the suprachiasmatic nucleus is gamma- aminobutyric acid (GABA).
Light synchronizes the circadian system. A direct photic pathway from the retina to the suprachiasmatic nucleus uses glutamate as a neurotransmitter.
The most important photoreceptors for the circadian system are the melanopsin. They are most sensitive to short wavelength (blue light, in the range of 446–477 nm).
The suprachiasmatic nucleus receives nonphotic information via serotonin from the raphe nuclei and melatonin provided by the pineal gland.
As a result of suprachiasmatic nucleus stimulation, physiology and behavior is regulated, including sleep and wakefulness, thermoregulation, metabolism, autonomic function, cognition, and pineal melatonin secretion.
In addition to the sleep–wake cycle, circadian rhythms also exist for:
- hormones, such as melatonin and growth hormone ;
- hemodynamic characteristics: blood pressure and urine output;
The circadian cycle (the suprachiasmatic nucleus) has a rhythm that is longer than 24 h (approximately 24.5–25 h), whereas the day–night cycle is exactly 24 h. If individuals are allowed to exhibit their natural sleep–wake cycle, in the absence of environmental cues of light and dark, they will demonstrate an endogenous sleep–wake cycle that is longer than 24 h.
The result of having a slightly longer internal biological clock is the tendency to retire to bed later with each passing night.
Appropriate exposure to light or other stimuli such as meals, exercise, and work schedule that influence the circadian rhythm can shift the circadian clock.
Exposure to light in the morning can advance the biological clock and cause an individual to wake up earlier the following morning. Conversely, exposure to light in the evening can delay the biological clock and cause an individual to fall asleep later and wake up later the following morning.
Sleep and wakefulness are regulated by a homeostatic process and a circadian process. Homeostasis is a process by which the pressure to sleep increases in proportion to the duration of wakefulness. Superimposed on homeostasis is the circadian process, which is regulated by the hypothalamus and reflects the brain’s intrinsic sleep–wake cycle.
Circadian rhythm disturbances occur when the biological clock does not meet the demands of the external environment. Specifically, there is a mismatch between the sleep–wake cycle and the light–dark cycle or social demands and this can lead to insomnia, hypersomnia, and fatigue. Examples of circadian rhythm disturbances include delayed sleep phase syndrome (DSPS), advanced sleep phase syndrome (ASPS), shift work, and jet lag.
Individuals with delayed sleep phase syndrome prefer sleeping late at night and waking up late the next day. Their sleep architecture is normal but they are difficult to awaken early in the morning.
Individuals with advanced sleep phase syndrome enjoy going to bed early and waking up early the following morning. The elderly population typically exhibits an advanced sleep–wake cycle.
Shift work problems arise when there is a mismatch between the sleep–wake cycle and the shift work schedule.
Jet lag occurs when an individual travels across several time zones. Traveling west delays the sleep cycle, whereas traveling east advances the sleep cycle. It is usually easier to adjust to travel in the east-to-west direction.