Sleep: Physiology, Sleep Stages

Sly Saint · Jul 28, 2023

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Introduction
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.

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Issues of Concern
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.

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Cellular Level
Sleep-promoting

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]

Wakefulness-promoting

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]

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Development
The time spent in each sleep stage develops and changes as we age, with the consistent trend being that amounts of sleep decrease as individuals age.

Newborns & infants (birth-1 year)

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]

Toddlers (age 1 to 3) and children (age 3 to 9)

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]

Adolescents (age 10 to 18)

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 (age 18+)

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]

Gender Differences

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]

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Organ Systems Involved
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]

Transitions between sleep and wake states are orchestrated by multiple brain structures, which include:

Hypothalamus: controls onset of sleep

Hippocampus: memory region active during dreaming

Amygdala: emotion center active during dreaming

Thalamus: prevents sensory signals from reaching the cortex

Reticular formation: regulates the transition between sleep and wakefulness

Pons: helps initiate REM sleep. The extraocular movements that occur during REM are due to the activity of PPRF (paramedian pontine reticular formation/conjugate gaze center).

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Function
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:

Neural maturation

Facilitation of learning or memory

Targeted erasure of synapses to "forget" unimportant information that might clutter the synaptic network

Cognition

Clearance of metabolic waste products generated by neural activity in the awake brain

Conservation of metabolic energy[13]

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full article
https://www.ncbi.nlm.nih.gov/books/NBK526132/

Creekside · Jul 28, 2023

I'm all too aware of the 90-minute cycle, since I now generally fully wake up at the end of each cycle. Consuming CLAs (conjugated linoleic acids) can help me sleep through one or two of those cycles each night.

I wonder whether anyone has done a proper study of the sleep cycles in PWME, with the duration and strength of the brainwaves, blood flows, and whatever else could be measured.

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Sleep: Physiology, Sleep Stages

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