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Parents rely on bedtime stories, soothing songs, and white noise to help calm their children before sleep. But while we understand the calming effect these rituals have on children, we often forget that adults, too, benefit immensely from ambient sounds to help them relax and fall asleep.
The human body cycles through two phases of sleep, (1) rapid eye movement (REM) and (2) non-rapid eye movement (NREM) sleep, which is further divided into three stages, N1-N3. Each phase and stage of sleep includes variations in muscle tone, brain wave patterns, and eye movements. The body cycles through all of these stages approximately 4 to 6 times each night, averaging 90 minutes for each cycle.[1] This article will discuss the progression of the sleep stages and the unique features associated with each.
Sleep quality and time spent in each sleep stage may become altered by depression, aging, traumatic brain injuries, medications, and circadian rhythm disorders. The pathophysiology associated with each will be discussed later in detail.
GABA is the primary inhibitory neurotransmitter of the central nervous system (CNS), and it has been well established that activation of GABA-a receptors favors sleep.[2] Sleep-promoting neurons in the anterior hypothalamus release GABA, which inhibits wake-promoting regions in the hypothalamus and brainstem.[3] Adenosine also promotes sleep by inhibiting wakefulness-promoting neurons localized to the basal forebrain, lateral hypothalamus, and tuberomammillary nucleus.[4]
Neurochemicals such as acetylcholine (ACh), dopamine (DA), norepinephrine (NE), serotonin (5-HT), histamine (HA), and the peptide hypocretin maintain the waking state.[3] Cortical ACh release is greatest during waking and REM sleep and lowest during NREM sleep.[5] 5-HT is released from serotonin-containing neurons of the dorsal raphe nucleus. NE is released from norepinephrine-containing neurons of the locus coeruleus (LC). The noradrenergic cells of the LC inhibit REM sleep, promote wakefulness, and project to various other arousal-regulating brain regions, including the thalamus, hypothalamus, basal forebrain, and cortex. HA is released from histamine-containing neurons of the tuberomammillary nucleus of the posterior thalamus. The cell bodies of hypocretin-producing neurons are localized to the dorsolateral hypothalamus and send projections to all the major brain regions that regulate arousal.[4]
Sleep timing in newborns is distributed evenly across day and night for the first few weeks of life, with no regular rhythm or concentration of sleeping and waking. Newborns sleep approximately 16-18 hours per day discontinuously, with the longest continuous sleep episode typically lasting 2.5 to 4 hours. Newborns have three different types of sleep: quiet sleep (similar to NREM), active sleep (similar to REM), and indeterminate sleep. In contrast to children and adults, newborn sleep onset occurs through REM, not NREM, with each sleep episode consisting of only one or two cycles. These differences in sleep and sleep stages occur as circadian rhythms have not fully been determined.
Circadian rhythms begin to develop around two to three months of age, with greater durations of waking hours during the day and longer periods of sleep at night. At two months of age, the progression of nocturnal sleeping begins. Three months of age is when the cycling of melatonin and cortisol in a circadian rhythm occurs and when sleep onset begins with NREM. At this time, REM sleep decreases and shifts to the later part of the sleep cycle. The total NREM and REM sleep cycle is typically 50 minutes instead of the adult 90-minute cycle. At six months of age, the longest continuous sleep episode lengthens to six hours. At 12 months of age, infants typically sleep 14-15 hours per day, with most sleep now occurring in the evening with only one to two naps needed during the day.[6]
Around the ages of two to five, the total sleep time needed each day decreases by two hours, from 13 to 11 hours. By six years old, children will manifest circadian sleep phase preferences and tend toward being a night owl or an early riser. One study found that children appear to have longer REM sleep latencies than adolescents and thus spend more time in stage N3.[7]
The total sleep time required for adolescents is 9-10 hours each night. Due to various pubertal and hormonal changes that accompany the onset of puberty, slow-wave-sleep and sleep latency time declines, and time in stage N2 increases. Around mid puberty, greater daytime sleepiness occurs than is seen at earlier stages of puberty.[8]
Adults tend to demonstrate earlier sleep time, wake time, and reduced sleep consolidation. Older adults (65+) have been shown to awaken approximately 1.5 hours earlier and sleep one hour earlier than younger adults (20 to 30).[9]
Men tend to spend a greater time in stage N1 sleep and experience more nighttime awakenings, causing them to be more likely to complain of daytime sleepiness. Women maintain slow-wave sleep longer than men and tend to complain more often of difficulty falling asleep. Additionally, daytime sleepiness increases during pregnancy and the first few months postpartum.[10]
The sleep cycle is regulated by the circadian rhythm, which is driven by the suprachiasmatic nucleus (SCN) of the hypothalamus. GABAergic sleep-promoting nuclei are found in the brainstem, lateral hypothalamus, and preoptic area.[11]
As previously stated, the sleep cycle is regulated by the circadian rhythm, which is driven by the SCN. The circadian rhythm also controls the nocturnal release of adrenocorticotropic hormone (ACTH), prolactin, melatonin, and norepinephrine (NE).[12]
Although it is apparent that humans need sleep, the current understanding of precisely why sleep is an essential part of life is still yet to be determined. We might suggest that the primary value of sleep is to restore natural balances among neuronal centers, which is necessary for overall health. However, the specific physiological functions of sleep remain a mystery and are the subject of much research. The current hypotheses as to the function of sleep include:
Sleep occurs in five stages: wake, N1, N2, N3, and REM. Stages N1 to N3 are considered non-rapid eye movement (NREM) sleep, with each stage a progressively deeper sleep. Approximately 75% of sleep is spent in the NREM stages, with the majority spent in the N2 stage.[14] A typical night's sleep consists of 4 to 5 sleep cycles, with the progression of sleep stages in the following order: N1, N2, N3, N2, REM.[15] A complete sleep cycle takes roughly 90 to 110 minutes. The first REM period is short, and, as the night progresses, longer periods of REM and decreased time in deep sleep (NREM) occur.
This is the lightest stage of sleep and begins when more than 50% of the alpha waves are replaced with low-amplitude mixed-frequency (LAMF) activity. Muscle tone is present in the skeletal muscle, and breathing tends to occur at a regular rate. This stage lasts around 1 to 5 minutes, consisting of 5% of total sleep time.
This stage represents deeper sleep as your heart rate and body temperate drop. It is characterized by the presence of sleep spindles, K-complexes, or both. Sleep spindles are brief, powerful bursts of neuronal firing in the superior temporal gyri, anterior cingulate, insular cortices, and thalamus, inducing calcium influx into cortical pyramidal cells. This mechanism is believed to be integral to synaptic plasticity. Numerous studies suggest that sleep spindles play an important role in memory consolidation, specifically procedural and declarative memory.[17]
K-complexes are long delta waves that last for approximately one second and are known to be the longest and most distinct of all brain waves. K-complexes have been shown to function in maintaining sleep and memory consolidation.[18] Stage 2 sleep lasts around 25 minutes in the first cycle and lengthens with each successive cycle, eventually consisting of about 45% of total sleep. This stage of sleep is when bruxism (teeth grinding) occurs.
N3 is also known as slow-wave sleep (SWS). This is considered the deepest stage of sleep and is characterized by signals with much lower frequencies and higher amplitudes, known as delta waves. This stage is the most difficult to awaken from, and, for some people, even loud noises (> 100 decibels) will not awaken them. As people age, they tend to spend less time in this slow, delta wave sleep and more time in stage N2 sleep. Although this stage has the greatest arousal threshold, if someone is awoken during this stage, they will have a transient phase of mental fogginess, known as sleep inertia. Cognitive testing shows that individuals awakened during this stage tend to have moderately impaired mental performance for 30 minutes to an hour.[19] This is the stage when the body repairs and regrows tissues, builds bone and muscle and strengthens the immune system. This is also the stage when sleepwalking, night terrors, and bedwetting occurs.[20]
REM is associated with dreaming and is not considered a restful sleep stage. While the EEG is similar to an awake individual, the skeletal muscles are atonic and without movement, except for the eyes and diaphragmatic breathing muscles, which remain active. However, the breathing rate becomes more erratic and irregular. This stage usually starts 90 minutes after you fall asleep, with each of your REM cycles getting longer throughout the night. The first period typically lasts 10 minutes, with the final one lasting up to an hour.[21] REM is when dreaming, nightmares, and penile/clitoral tumescence occur.
The clinical evaluation of sleep is performed using a polysomnogram, a procedure that utilizes an electroencephalogram (EEG), electrooculogram, electromyogram, electrocardiogram, pulse oximetry, airflow, and respiratory effort. These tests are performed overnight and usually require a minimum of 6 hours of monitoring. Specifically, an EEG records brain wave patterns via small electrodes placed on the scalp. A polysomnogram is the gold standard test for diagnosing sleep-related breathing disorders such as obstructive sleep apnea, central sleep apnea, and sleep-related hypoventilation/hypoxia. A polysomnogram may also be used to evaluate nocturnal seizures, periodic limb movement disorder, narcolepsy, and REM sleep behavior disorder.[23]
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