The neuroscience of sleep is the study of the
neuroscientific and
physiological
Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...
basis of the nature of
sleep
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a de ...
and its functions. Traditionally, sleep has been studied as part of
psychology
Psychology is the scientific study of mind and behavior. Psychology includes the study of conscious and unconscious phenomena, including feelings and thoughts. It is an academic discipline of immense scope, crossing the boundaries betwe ...
and
medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
. The study of sleep from a neuroscience perspective grew to prominence with advances in technology and proliferation of neuroscience research from the second half of the twentieth century.
The importance of sleep is demonstrated by the fact that organisms daily spend hours of their time in sleep, and that
sleep deprivation
Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
can have disastrous effects ultimately leading to death in animals.
For a phenomenon so important, the purposes and mechanisms of sleep are only partially understood, so much so that as recently as the late 1990s it was quipped: "The only known function of sleep is to cure sleepiness". However, the development of improved imaging techniques like
EEG
Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
,
PET
A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...
and
fMRI
Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
, along with high computational power have led to an increasingly greater understanding of the mechanisms underlying sleep.
The fundamental questions in the neuroscientific study of sleep are:
# What are the correlates of sleep i.e. what are the minimal set of events that could confirm that the organism is sleeping?
# How is sleep triggered and regulated by the
brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
and the
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
?
# What happens in the brain during sleep?
# How can we understand sleep function based on physiological changes in the brain?
# What causes various
sleep disorders
A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are test ...
and how can they be treated?
Other areas of modern neuroscience sleep research include the
evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
of sleep, sleep during
development
Development or developing may refer to:
Arts
*Development hell, when a project is stuck in development
*Filmmaking, development phase, including finance and budgeting
*Development (music), the process thematic material is reshaped
* Photograph ...
and
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
,
animal sleep, mechanism of effects of drugs on sleep, dreams and nightmares, and stages of
arousal
Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, th ...
between sleep and wakefulness.
__TOC__
Introduction
Rapid eye movement sleep
Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream viv ...
(REM),
non-rapid eye movement sleep
Non-rapid eye movement sleep (NREM), also known as quiescent sleep, is, collectively, sleep stages 1–3, previously known as stages 1–4. Rapid eye movement sleep (REM) is not included. There are distinct electroencephalographic and other char ...
(NREM or non-REM), and waking represent the three major modes of consciousness, neural activity, and physiological regulation.
[J. Alan Hobson, Edward F. Pace-Scott, & Robert Stickgold (2000), "Dreaming and the brain: Toward a cognitive neuroscience of conscious states", ''Behavioral and Brain Sciences'' 23.] NREM sleep itself is divided into multiple stages – N1, N2 and N3. Sleep proceeds in 90-minute cycles of REM and NREM, the order normally being N1 → N2 → N3 → N2 → REM. As humans fall asleep, body activity slows down. Body temperature, heart rate, breathing rate, and energy use all decrease. Brain waves get slower and bigger. The excitatory neurotransmitter
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
becomes less available in the brain. Humans often maneuver to create a thermally friendly environment—for example, by curling up into a ball if cold. Reflexes remain fairly active.
REM sleep is considered closer to wakefulness and is characterized by rapid eye movement and muscle atonia. NREM is considered to be deep sleep (the deepest part of NREM is called
slow wave sleep
Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both St ...
), and is characterized by lack of prominent eye movement or muscle paralysis. Especially during non-REM sleep, the brain uses significantly less energy during sleep than it does in waking. In areas with reduced activity, the brain restores its supply of
adenosine triphosphate
Adenosine triphosphate (ATP) is an organic compound that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, condensate dissolution, and chemical synthesis. Found in all known forms of ...
(ATP), the molecule used for short-term storage and transport of energy. (Since in quiet waking the brain is responsible for 20% of the body's energy use, this reduction has an independently noticeable impact on overall energy consumption.)
During slow-wave sleep, humans secrete bursts of
growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
. All sleep, even during the day, is associated with secretion of
prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
.
[Eve Van Cauter & Karine Spiegel (1999). "Circadian and Sleep Control of Hormonal Secretions", in Turek & Zee (eds.), ''Regulation of Sleep and Circadian Rhythms'', pp. 397–425.]
According to the Hobson & McCarley
activation-synthesis hypothesis
The activation-synthesis hypothesis, proposed by Harvard University psychiatrists John Allan Hobson and Robert McCarley, is a neurobiological theory of dreams first published in the American Journal of Psychiatry in December 1977. The differences ...
, proposed in 1975–1977, the alternation between REM and non-REM can be explained in terms of cycling, reciprocally influential neurotransmitter systems.
Sleep timing is controlled by the
circadian clock
A circadian clock, or circadian oscillator, is a biochemical oscillator that cycles with a stable phase (waves), phase and is synchronized with solar time.
Such a clock's ''in vivo'' period is necessarily almost exactly 24 hours (the earth's curre ...
, and in humans, to some extent by willed behavior. The term circadian comes from the Latin ''circa'', meaning "around" (or "approximately"), and ''diem'' or dies, meaning "day". The circadian clock refers to a biological mechanism that governs multiple biological processes causing them to display an endogenous, entrainable oscillation of about 24 hours. These rhythms have been widely observed in plants, animals, fungi and cyanobacteria.
Correlates of sleep
One of the important questions in sleep research is clearly defining the sleep state. This problem arises because sleep was traditionally defined as a state of
consciousness
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
and not as a physiological state, thus there was no clear definition of what minimum set of events constitute sleep and distinguish it from other states of partial or no consciousness. The problem of making such a definition is complicated because it needs to include a variety of modes of sleep found across different species.
At a symptomatic level, sleep is characterized by lack of reactivity to
sensory inputs, low
motor
An engine or motor is a machine designed to convert one or more forms of energy into mechanical energy.
Available energy sources include potential energy (e.g. energy of the Earth's gravitational field as exploited in hydroelectric power gen ...
output, diminished conscious
awareness
Awareness is the state of being conscious of something. More specifically, it is the ability to directly know and perceive, to feel, or to be cognizant of events. Another definition describes it as a state wherein a subject is aware of some inform ...
and rapid reversibility to
wakefulness
Wakefulness is a daily recurring Human brain, brain state and state of consciousness in which an individual is conscious and engages in coherent cognition, cognitive and behavioral responses to the external world.
Being awake is the opposite of ...
. However, to translate these into a biological definition is difficult because no single pathway in the brain is responsible for the generation and regulation of sleep. One of the earliest proposals was to define sleep as the deactivation of the
cerebral cortex
The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...
and the
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
because of near lack of response to sensory inputs during sleep. However, this was invalidated because both regions are active in some phases of sleep. In fact, it appears that the thalamus is only deactivated in the sense of transmitting sensory information to the cortex.
Some of the other observations about sleep included decrease of
sympathetic activity and increase of
parasympathetic activity in non-REM sleep, and increase of heart rate and blood pressure accompanied by decrease in
homeostatic response and
muscle tone
In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial muscle contraction, contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sull ...
during
REM sleep
Rapid eye movement sleep (REM sleep or REMS) is a unique phase of sleep in mammals and birds, characterized by random rapid movement of the eyes, accompanied by low muscle tone throughout the body, and the propensity of the sleeper to dream viv ...
. However, these symptoms are not limited to sleep situations and do not map to specific physiological definitions.
More recently, the problem of definition has been addressed by observing overall brain activity in the form of characteristic EEG patterns.
Each
stage of sleep and wakefulness has a characteristic pattern of
EEG
Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
which can be used to identify the stage of sleep. Waking is usually characterized by
beta
Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...
(12–30 Hz) and
gamma
Gamma (uppercase , lowercase ; ''gámma'') is the third letter of the Greek alphabet. In the system of Greek numerals it has a value of 3. In Ancient Greek, the letter gamma represented a voiced velar stop . In Modern Greek, this letter re ...
(25–100 Hz) depending on whether there was a peaceful or stressful activity. The onset of sleep involves slowing down of this frequency to the drowsiness of
alpha
Alpha (uppercase , lowercase ; grc, ἄλφα, ''álpha'', or ell, άλφα, álfa) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter aleph , whic ...
(8–12 Hz) and finally to
theta
Theta (, ; uppercase: Θ or ; lowercase: θ or ; grc, ''thē̂ta'' ; Modern: ''thī́ta'' ) is the eighth letter of the Greek alphabet, derived from the Phoenician letter Teth . In the system of Greek numerals, it has a value of 9.
Gr ...
(4–10 Hz) of Stage 1 NREM sleep. This frequency further decreases progressively through the higher stages of NREM and REM sleep. On the other hand, the amplitude of sleep waves is lowest during wakefulness (10–30μV) and shows a progressive increase through the various stages of sleep. Stage 2 is characterized by
sleep spindles
Sleep spindles are bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz (usually 12–14 Hz) ...
(intermittent clusters of waves at sigma frequency i.e. 12–14 Hz) and
K complexes
A K-complex is a waveform that may be seen on an electroencephalogram (EEG). It occurs during stage 2 of NREM sleep. It is the "largest event in healthy human EEG". They are more frequent in the first sleep cycles.
K-complexes have two proposed ...
(sharp upward deflection followed by slower downward deflection). Stage 3 sleep has more sleep spindles.
Stages 3 and 4 have very high amplitude
delta waves
Delta waves are high amplitude neural oscillations with a frequency between 0.5 and 4 hertz. Delta waves, like other brain waves, can be recorded with electroencephalography (EEG) and are usually associated with the deep stage 3 of NREM sleep, ...
(0–4 Hz) and are known as slow wave sleep. REM sleep is characterized by low amplitude, mixed frequency waves. A sawtooth wave pattern is often present.
Ontogeny and phylogeny of sleep
![Sleep Tiger](https://upload.wikimedia.org/wikipedia/commons/a/ad/Sleep_Tiger.jpg)
The questions of how sleep evolved in the animal kingdom and how it developed in humans are especially important because they might provide a clue to the functions and mechanisms of sleep respectively.
Sleep evolution
The evolution of different types of sleep patterns is influenced by a number of
selective pressures, including body size, relative metabolic rate, predation, type and location of food sources, and immune function.
[McNamara, P., R. A. Barton, and C. L. Nunn. 2010, Evolution of sleep: Phylogenetic and functional perspectives. Cambridge University Press, Cambridge.] Sleep (especially deep
SWS and
REM) is tricky behavior because it steeply increases
predation
Predation is a biological interaction where one organism, the predator, kills and eats another organism, its prey. It is one of a family of common feeding behaviours that includes parasitism and micropredation (which usually do not kill the ...
risk. This means that, for sleep to have evolved, the functions of sleep should have provided a substantial advantage over the risk it entails. In fact, studying sleep in different organisms shows how they have balanced this risk by evolving partial sleep mechanisms or by having protective habitats. Thus, studying the evolution of sleep might give a clue not only to the developmental aspects and mechanisms, but also to an
adaptive
Adaptation, in biology, is the process or trait by which organisms or population better match their environment
Adaptation may also refer to:
Arts
* Adaptation (arts), a transfer of a work of art from one medium to another
** Film adaptation, a ...
justification for sleep.
One challenge studying sleep evolution is that adequate sleep information is known only for two phyla of animals-
chordata
A chordate () is an animal of the phylum Chordata (). All chordates possess, at some point during their larval or adult stages, five synapomorphies, or primary physical characteristics, that distinguish them from all the other taxa. These fiv ...
and
arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
a.
With the available data, comparative studies have been used to determine how sleep might have evolved. One question that scientists try to answer through these studies is whether sleep evolved only once or multiple times. To understand this, they look at sleep patterns in different classes of animals whose evolutionary histories are fairly well-known and study their similarities and differences.
Humans possess both slow wave and REM sleep, in both phases both eyes are closed and both
hemispheres of the brain involved. Sleep has also been recorded in
mammals
Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fur or ...
other than humans. One study showed that
echidna
Echidnas (), sometimes known as spiny anteaters, are quill-covered monotremes (egg-laying mammals) belonging to the family Tachyglossidae . The four extant species of echidnas and the platypus are the only living mammals that lay eggs and the ...
s possess only slow wave sleep (non-REM). This seems to indicate that REM sleep appeared in evolution only after
therians
Theria (; Greek: , wild beast) is a subclass of mammals amongst the Theriiformes. Theria includes the eutherians (including the placental mammals) and the metatherians (including the marsupials) but excludes the egg-laying monotremes.
C ...
. But this has later been contested by studies that claim that sleep in echidna combines both modes into a single sleeping state. Other studies have shown a peculiar form of sleep in
odontocetes
The toothed whales (also called odontocetes, systematic name Odontoceti) are a parvorder of cetaceans that includes dolphins, porpoises, and all other whales possessing teeth, such as the beaked whales and sperm whales. Seventy-three species of t ...
(like
dolphins
A dolphin is an aquatic mammal within the infraorder Cetacea. Dolphin species belong to the families Delphinidae (the oceanic dolphins), Platanistidae (the Indian river dolphins), Iniidae (the New World river dolphins), Pontoporiidae (t ...
and
porpoises
Porpoises are a group of fully aquatic marine mammals, all of which are classified under the family Phocoenidae, parvorder Odontoceti (toothed whales). Although similar in appearance to dolphins, they are more closely related to narwhals an ...
). This is called the
unihemispherical slow wave sleep (USWS). At any time during this sleep mode, the EEG of one brain hemisphere indicates sleep while that of the other is equivalent to wakefulness. In some cases, the corresponding eye is open. This might allow the animal to reduce predator risk and sleep while swimming in water, though the animal may also be capable of sleeping at rest.
The correlates of sleep found for mammals are valid for
birds
Birds are a group of warm-blooded vertebrates constituting the class Aves (), characterised by feathers, toothless beaked jaws, the laying of hard-shelled eggs, a high metabolic rate, a four-chambered heart, and a strong yet lightweigh ...
as well i.e. bird sleep is very similar to mammals and involves both SWS and REM sleep with similar features, including closure of both eyes, lowered muscle tone, etc. However, the proportion of REM sleep in birds is much lower. Also, some birds can sleep with one eye open if there is high predation risk in the environment.
This gives rise to the possibility of sleep in flight; considering that sleep is very important and some bird species can fly for weeks continuously, this seems to be the obvious result. However, sleep in flight has not been recorded, and is so far unsupported by EEG data. Further research may explain whether birds sleep during flight or if there are other mechanisms which ensure their remaining healthy during long flights in the absence of sleep.
Unlike in birds, very few consistent features of sleep have been found among
reptile
Reptiles, as most commonly defined are the animals in the class Reptilia ( ), a paraphyletic grouping comprising all sauropsids except birds. Living reptiles comprise turtles, crocodilians, squamates (lizards and snakes) and rhynchocephalians ( ...
species. The only common observation is that reptiles do not have REM sleep.
Sleep in some
invertebrates
Invertebrates are a paraphyletic group of animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), derived from the notochord. This is a grouping including all animals apart from the chordate ...
has also been extensively studied, e.g., sleep in
fruitflies (Drosophila) and
honeybees
A honey bee (also spelled honeybee) is a eusocial flying insect within the genus ''Apis'' of the bee clade, all native to Afro-Eurasia. After bees spread naturally throughout Africa and Eurasia, humans became responsible for the current cosmo ...
. Some of the mechanisms of sleep in these animals have been discovered while others remain quite obscure. The features defining sleep have been identified for the most part, and like mammals, this includes reduced reaction to sensory input, lack of motor response in the form of
antennal immobility, etc.
The fact that both the forms of sleep are found in mammals and birds, but not in reptiles (which are considered to be an intermediate stage) indicates that sleep might have evolved separately in both. Substantiating this might be followed by further research on whether the EEG correlates of sleep are involved in its functions or if they are merely a feature. This might further help in understanding the role of sleep in long term plasticity.
According to Tsoukalas (2012), REM sleep is an evolutionary transformation of a well-known defensive mechanism, the
tonic immobility
Apparent death, colloquially known as playing dead, feigning death, or playing possum, is a behavior in which animals take on the appearance of being dead. It is an immobile state most often triggered by a predatory attack and can be found in a ...
reflex. This reflex, also known as animal hypnosis or death feigning, functions as the last line of defense against an attacking predator and consists of the total immobilization of the animal: the animal appears dead (cf. "playing possum"). The neurophysiology and phenomenology of this reaction show striking similarities to REM sleep, a fact which betrays a deep evolutionary kinship. For example, both reactions exhibit brainstem control, paralysis, sympathetic activation, and thermoregulatory changes. This theory integrates many earlier findings into a unified, and evolutionary well informed, framework.
Sleep development and aging
The ontogeny of sleep is the study of sleep across different age groups of a species, particularly during
development
Development or developing may refer to:
Arts
*Development hell, when a project is stuck in development
*Filmmaking, development phase, including finance and budgeting
*Development (music), the process thematic material is reshaped
* Photograph ...
and
aging
Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...
. Among mammals, infants sleep the longest. Human babies have 8 hours of REM sleep and 8 hours of NREM sleep on an average. The percentage of time spent on each mode of sleep varies greatly in the first few weeks of development and some studies have correlated this to the degree of precociality of the child.
Within a few months of postnatal development, there is a marked reduction in percentage of hours spent in REM sleep. By the time the child becomes an adult, he spends about 6–7 hours in NREM sleep and only about an hour in REM sleep.
This is true not only of humans, but of many animals dependent on their parents for food. The observation that the percentage of REM sleep is very high in the first stages of development has led to the hypothesis that REM sleep might facilitate early brain development.
However, this theory has been contested by other studies.
Sleep behavior undergoes substantial changes during
adolescence
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
. Some of these changes may be societal in humans, but other changes are hormonal. Another important change is the decrease in the number of hours of sleep, as compared to childhood, which gradually becomes identical to an adult. It is also being speculated that
homeostatic regulation mechanisms may be altered during adolescence. Apart from this, the effect of changing routines of adolescents on other behavior such as cognition and attention is yet to be studied.
Ohayon et al, for example, have stated that the decline in total sleep time from childhood to adolescence seems to be more associated with environmental factors rather than biological feature.
In adulthood, the sleep architecture has been showing that the sleep latency and the time spent in NREM stages 1 and 2 may increase with aging, while the time spent in REM and SWS sleep seem to decrease.
These changes have been frequently associated with brain atrophy, cognitive impairment and neurodegenerative disorders in old age.
[Mander, B., Rao, V., Lu, B., Saletin, J., Lindquist, J., Ancoli-Israel, S., . . . Walker, M. (2013). Prefrontal atrophy, disrupted NREM slow waves and impaired hippocampal-dependent memory in aging. 357 - 364.] For instance, Backhaus et al have pointed out that a decline in declarative memory consolidation in midlife (in their experiment: 48 to 55 years old) is due to a lower amount of SWS, which might already start to decrease around age of 30 years old.
According to Mander et al, atrophy in the medial prefrontal cortex (mPFC) gray matter is a predictor of disruption in slow activity during NREM sleep that may impair memory consolidation in older adults.
And sleep disturbances, such as excessive daytime sleepiness and nighttime
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
, have been often referred as factor risk of progressive functional impairment in
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD) or
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD).
Therefore, sleep in aging is another equally important area of research. A common observation is that many older adults spend time awake in bed after sleep onset in an inability to fall asleep and experience marked decrease in sleep efficiency. There may also be some changes in
circadian rhythm
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogeno ...
s.
Studies are ongoing about what causes these changes and how they may be reduced to ensure comfortable sleep of old adults.
Brain activity during sleep
![Sleep Hypnogram](https://upload.wikimedia.org/wikipedia/commons/3/3e/Sleep_Hypnogram.svg)
Understanding the activity of different parts of the brain during sleep can give a clue to the functions of sleep. It has been observed that mental activity is present during all stages of sleep, though from different regions in the brain. So, contrary to popular understanding, the brain never completely shuts down during sleep. Also, sleep intensity of a particular region is
homeostatically related to the corresponding amount of activity before sleeping. The use of imaging modalities like PET, fMRI and MEG, combined with EEG recordings, gives a clue to which brain regions participate in creating the characteristic wave signals and what their functions might be.
Historical development of the stages model
The stages of sleep were first described in 1937 by
Alfred Lee Loomis
Alfred Lee Loomis (November 4, 1887 – August 11, 1975) was an American attorney, investment banker, philanthropist, scientist, physicist, inventor of the LORAN Long Range Navigation System and a lifelong patron of scientific research. He estab ...
and his coworkers, who separated the different
electroencephalography
Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...
(EEG) features of sleep into five levels (A to E), representing the spectrum from wakefulness to deep sleep. In 1953, REM sleep was discovered as distinct, and thus
William C. Dement
William Charles Dement (July 29, 1928 – June 17, 2020) was an American sleep researcher and founder of the Sleep Research Center at Stanford University. He was a leading authority on sleep, sleep deprivation and the diagnosis and treatment of s ...
and
Nathaniel Kleitman reclassified sleep into four NREM stages and REM.
The staging criteria were standardized in 1968 by
Allan Rechtschaffen
Allan Rechtschaffen (December 8, 1927 – November 29, 2021) was a noted pioneer in the field of sleep research whose work includes some of the first laboratory studies of insomnia, narcolepsy, sleep apnea, and napping. He received his PhD from Nor ...
and Anthony Kales in the "R&K sleep scoring manual."
In the R&K standard, NREM sleep was divided into four stages, with slow-wave sleep comprising stages 3 and 4. In stage 3, delta waves made up less than 50% of the total wave patterns, while they made up more than 50% in stage 4. Furthermore, REM sleep was sometimes referred to as stage 5. In 2004, the AASM commissioned the AASM Visual Scoring Task Force to review the R&K scoring system. The review resulted in several changes, the most significant being the combination of stages 3 and 4 into Stage N3. The revised scoring was published in 2007 as ''The AASM Manual for the Scoring of Sleep and Associated Events''. Arousals, respiratory, cardiac, and movement events were also added.
NREM sleep activity
NREM sleep
Non-rapid eye movement sleep (NREM), also known as quiescent sleep, is, collectively, sleep stages 1–3, previously known as stages 1–4. Rapid eye movement sleep (REM) is not included. There are distinct electroencephalographic and other char ...
is characterized by decreased global and regional
cerebral blood flow
Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. Arterie ...
. It constitutes ~80% of all sleep in adult humans. Initially, it was expected that the
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is cont ...
, which was implicated in arousal would be inactive, but this was later on found to have been due to low resolution of PET studies and it was shown that there is some slow wave activity in the brainstem as well. However, other parts of the brain, including the
precuneus
In neuroanatomy, the precuneus is the portion of the superior parietal lobule on the medial surface of each brain hemisphere. It is located in front of the cuneus (the upper portion of the occipital lobe). The precuneus is bounded in front by th ...
,
basal forebrain
Part of the human brain, the basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia (including nucleus accumbens and ventral pallidum), nucleus basalis, diagonal band ...
and
basal ganglia
The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...
are deactivated during sleep. Many areas of the cortex are also inactive, but to different levels. For example, the
ventromedial prefrontal cortex
The ventromedial prefrontal cortex (vmPFC) is a part of the prefrontal cortex
in the mammalian brain. The ventral medial prefrontal is located in the frontal lobe at the bottom of the cerebral hemispheres and is implicated in the processing of r ...
is considered the least active area while the
primary cortex, the least deactivated.
NREM sleep is characterized by slow oscillations,
spindles and
delta waves
Delta waves are high amplitude neural oscillations with a frequency between 0.5 and 4 hertz. Delta waves, like other brain waves, can be recorded with electroencephalography (EEG) and are usually associated with the deep stage 3 of NREM sleep, ...
. The slow oscillations have been shown to be from the cortex, as lesions in other parts of the brain do not affect them, but lesions in the cortex do.
The delta waves have been shown to be generated by reciprocally connected thalamic and cortical neural circuits. During sleep, the thalamus stops relaying sensory information to the brain, however it continues to produce signals that are sent to its cortical projections. These waves are generated in the thalamus even in the absence of the cortex, but the cortical output seems to play a role in the simultaneous firing by large groups of neurons. The
thalamic reticular nucleus
The thalamic reticular nucleus is part of the ventral thalamus that forms a capsule around the thalamus laterally. However, recent evidence from mice and fish question this statement and define it as a dorsal thalamic structure. It is separated fro ...
is considered to be the pacemaker of the sleep spindles. This has been further substantiated by the fact that rhythmic stimulation of the thalamus leads to increased secondary
depolarization
In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is esse ...
in cortical neurons, which further results in the increased amplitude of firing, causing self-sustained activity. The sleep spindles have been predicted to play a role in disconnecting the cortex from sensory input and allowing entry of calcium ions into cells, thus potentially playing a role in
Plasticity
Plasticity may refer to:
Science
* Plasticity (physics), in engineering and physics, the propensity of a solid material to undergo permanent deformation under load
* Neuroplasticity, in neuroscience, how entire brain structures, and the brain it ...
.
NREM 1
NREM Stage 1 (N1 – light sleep,
somnolence
Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
, drowsy sleep – 5–10% of total sleep in adults): This is a stage of sleep that usually occurs between sleep and wakefulness, and sometimes occurs between periods of deeper sleep and periods of REM. The muscles are active, and the eyes roll slowly, opening and closing moderately. The brain transitions from
alpha waves having a frequency of 8–13
Hz (common in the awake state) to
theta wave
Theta waves generate the theta rhythm, a neural oscillation in the brain that underlies various aspects of cognition and behavior, including learning, memory, and spatial navigation in many animals. It can be recorded using various electrophysio ...
s having a frequency of 4–7 Hz. Sudden twitches and
hypnic jerk
A hypnic jerk, hypnagogic jerk, sleep start, sleep twitch, myoclonic jerk, or night start is a brief and sudden involuntary contraction of the muscles of the body which occurs when a person is beginning to fall asleep, often causing the person t ...
s, also known as positive
myoclonus
Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus (myo "muscle", clonic "jerk") describes a medical sign and, generally, is ...
, may be associated with the onset of sleep during N1. Some people may also experience
hypnagogic hallucination
Hypnagogia is the experience of the transitional state from wakefulness to sleep: the ''hypnagogic'' state of consciousness, during the onset of sleep. Its opposite state is described as the transitional state from sleep into wakefulness. Mental ...
s during this stage. During Non-REM1, humans lose some
muscle tone
In physiology, medicine, and anatomy, muscle tone (residual muscle tension or tonus) is the continuous and passive partial muscle contraction, contraction of the muscles, or the muscle's resistance to passive stretch during resting state.O’Sull ...
and most conscious awareness of the external environment.
NREM 2
NREM Stage 2 (N2 – 45–55% of total sleep in adults
): In this stage,
theta activity is observed and sleepers become gradually harder to awaken; the
alpha wave
Alpha waves, or the alpha rhythm, are neural oscillations in the frequency range of 8–12 Hz likely originating from the synchronous and coherent (in phase or constructive) electrical activity of thalamic pacemaker cells in humans. Historica ...
s of the previous stage are interrupted by abrupt activity called
sleep spindle
Sleep spindles are bursts of neural oscillatory activity that are generated by interplay of the thalamic reticular nucleus (TRN) and other thalamic nuclei during stage 2 NREM sleep in a frequency range of ~11 to 16 Hz (usually 12–14 Hz) ...
s (or thalamocortical spindles) and
K-complex
A K-complex is a waveform that may be seen on an electroencephalogram (EEG). It occurs during stage 2 of NREM sleep. It is the "largest event in healthy human EEG". They are more frequent in the first sleep cycles.
K-complexes have two proposed ...
es.
Sleep spindles range from 11 to 16 Hz (most commonly 12–14 Hz). During this stage, muscular activity as measured by EMG decreases, and conscious awareness of the external environment disappears.
NREM 3
![Sleep Stage N3](https://upload.wikimedia.org/wikipedia/commons/9/95/Sleep_Stage_N3.png)
NREM Stage 3 (N3 – 15–25% of total sleep in adults): Formerly divided into stages 3 and 4, this stage is called
slow-wave sleep
Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both St ...
(SWS) or deep sleep. SWS is initiated in the
preoptic area
The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region, (medial, median, lateral, and periventricular).
Functions
The preoptic area is responsible for ther ...
and consists of
delta activity, high amplitude waves at less than 3.5 Hz. The sleeper is less responsive to the environment; many environmental stimuli no longer produce any reactions. Slow-wave sleep is thought to be the most restful form of sleep, the phase which most relieves subjective feelings of sleepiness and restores the body.
This stage is characterized by the presence of a minimum of 20%
delta wave
Delta waves are high amplitude neural oscillations with a frequency between 0.5 and 4 hertz. Delta waves, like other brain waves, can be recorded with electroencephalography (EEG) and are usually associated with the deep stage 3 of NREM sleep, ...
s ranging from 0.5–2 Hz and having a peak-to-peak amplitude >75 μV. (EEG standards define delta waves to be from 0 to 4 Hz, but sleep standards in both the original R&K model (
Allan Rechtschaffen
Allan Rechtschaffen (December 8, 1927 – November 29, 2021) was a noted pioneer in the field of sleep research whose work includes some of the first laboratory studies of insomnia, narcolepsy, sleep apnea, and napping. He received his PhD from Nor ...
and Anthony Kales in the "R&K sleep scoring manual."),
Brown
Brown is a color. It can be considered a composite color, but it is mainly a darker shade of orange. In the CMYK color model used in printing or painting, brown is usually made by combining the colors orange and black. In the RGB color model used ...
, pp. 1108–1109. as well as the new 2007 AASM guidelines have a range of 0.5–2 Hz.) This is the stage in which parasomnias such as
night terror
Night terror, also called sleep terror, is a sleep disorder causing feelings of panic or dread and typically occurring during the first hours of stage 3–4 non-rapid eye movement (NREM) sleep and lasting for 1 to 10 minutes. It can last long ...
s,
nocturnal enuresis
Nocturnal enuresis, also informally called bedwetting, is urinary incontinence, involuntary urination while sleep, asleep after the age at which bladder control usually begins. Bedwetting in children and adults can result in emotional stress. Com ...
,
sleepwalking
Sleepwalking, also known as somnambulism or noctambulism, is a phenomenon of combined sleep and wakefulness. It is classified as a sleep disorder belonging to the parasomnia family. It occurs during slow wave stage of sleep, in a state of low ...
, and
somniloquy
Somniloquy, commonly referred to as sleep-talking, is a parasomnia in which one speaks aloud while asleep. It can range from simple mumbling sounds to loud shouts or long, frequently inarticulate, speeches. It can occur many times during a sleep c ...
occur. Many illustrations and descriptions still show a stage N3 with 20–50% delta waves and a stage N4 with greater than 50% delta waves; these have been combined as stage N3.
REM sleep activity
![Sleep Stage REM](https://upload.wikimedia.org/wikipedia/commons/4/4d/Sleep_Stage_REM.png)
REM Stage (REM Sleep – 20–25% of total sleep in adults
): REM sleep is where most muscles are paralyzed, and heart rate, breathing and body temperature become unregulated. REM sleep is turned on by
acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
secretion and is inhibited by neurons that secrete monoamines including
serotonin
Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
. REM is also referred to as ''paradoxical sleep'' because the sleeper, although exhibiting high-frequency EEG waves similar to a waking state, is harder to arouse than at any other sleep stage.
[ Vital signs indicate arousal and oxygen consumption by the brain is higher than when the sleeper is awake.] REM sleep is characterized by high global cerebral blood flow, comparable to wakefulness. In fact, many areas in the cortex have been recorded to have more blood flow during REM sleep than even wakefulness- this includes the hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
, temporal-occipital
The occipital bone () is a cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone overlies the occipital lobes of the cereb ...
areas, some parts of the cortex, and basal forebrain
Part of the human brain, the basal forebrain structures are located in the forebrain to the front of and below the striatum. They include the ventral basal ganglia (including nucleus accumbens and ventral pallidum), nucleus basalis, diagonal band ...
. The limbic
The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...
and paralimbic system including the amygdala
The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...
are other active regions during REM sleep. Though the brain activity during REM sleep appears very similar to wakefulness, the main difference between REM and wakefulness is that, arousal
Arousal is the physiological and psychological state of being awoken or of sense organs stimulated to a point of perception. It involves activation of the ascending reticular activating system (ARAS) in the brain, which mediates wakefulness, th ...
in REM is more effectively inhibited. This, along with the virtual silence of monoaminergic
Monoaminergic means "working on monoamine neurotransmitters", which include serotonin, dopamine, norepinephrine, epinephrine, and histamine.
A monoaminergic, or monoaminergic drug, is a chemical, which functions to directly modulate the serotoni ...
neurons in the brain, may be said to characterize REM.
A newborn baby spends 8 to 9 hours a day just in REM sleep. By the age of five or so, only slightly over two hours is spent in REM. The function of REM sleep is uncertain but a lack of it impairs the ability to learn complex tasks. Functional paralysis from muscular atonia
This glossary of medical terms is a list of definitions about medicine, its sub-disciplines, and related fields.
A
* Aarskog–Scott syndrome – (AAS) A rare, inherited (X-linked) disease characterized by short stature, facial abnormalities ...
in REM may be necessary to protect organisms from self-damage through physically acting out scenes from the often-vivid dreams that occur during this stage.
In EEG recordings, REM sleep is characterized by high frequency, low amplitude activity and spontaneous occurrence of beta
Beta (, ; uppercase , lowercase , or cursive ; grc, βῆτα, bē̂ta or ell, βήτα, víta) is the second letter of the Greek alphabet. In the system of Greek numerals, it has a value of 2. In Modern Greek, it represents the voiced labiod ...
and gamma waves
A gamma wave or gamma Rhythm is a pattern of neural oscillation in humans with a frequency between 25 and 140 Hertz, Hz, the 40-Hertz, Hz point being of particular interest. Gamma rhythms are correlated with Large scale brain networks, large scal ...
. The best candidates for generation of these fast frequency waves are fast rhythmic bursting neurons in corticothalamic circuits. Unlike in slow wave sleep, the fast frequency rhythms are synchronized over restricted areas in specific local circuits between thalamocortical and neocortical areas. These are said to be generated by cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
processes from brainstem structures.
Apart from this, the amygdala plays a role in REM sleep modulation, supporting the hypothesis that REM sleep allows internal information processing. The high amygdalar activity may also cause the emotional responses during dreams. Similarly, the bizarreness of dreams may be due to the decreased activity of prefrontal regions, which are involved in integrating information as well as episodic memory
Episodic memory is the memory of everyday events (such as times, location geography, associated emotions, and other contextual information) that can be explicitly stated or conjured. It is the collection of past personal experiences that occurred ...
.
Ponto-geniculo-occipital waves
REM sleep is also related to the firing of ponto-geniculo-occipital waves (also called phasic activity or PGO waves) and activity in the cholinergic ascending arousal system. PGO waves have been recorded in the lateral geniculate nucleus
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral projec ...
and occipital cortex
The occipital lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The name derives from its position at the back of the head, from the Latin ''ob'', "behind", and ''caput'', "head".
The occipital lobe is the vi ...
during the pre-REM period and are thought to represent dream content. The greater signal-to-noise ratio in the LG cortical channel suggests that visual imagery in dreams may appear before full development of REM sleep, but this has not yet been confirmed. PGO waves may also play a role in development and structural maturation of brain, as well as long term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...
in immature animals, based on the fact that there is high PGO activity during sleep in the developmental brain.
Network reactivation
The other form of activity during sleep is reactivation. Some electrophysiological studies have shown that neuronal activity patterns found during a learning task before sleep are reactivated in the brain during sleep. This, along with the coincidence of active areas with areas responsible for memory have led to the theory that sleep might have some memory consolidation functions. In this relation, some studies have shown that after a sequential motor task, the pre-motor and visual cortex
The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...
areas involved are most active during REM sleep, but not during NREM. Similarly, the hippocampal
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...
areas involved in spatial learning tasks are reactivated in NREM sleep, but not in REM. Such studies suggest a role of sleep in consolidation of specific memory types. It is, however, still unclear whether other types of memory are also consolidated by these mechanisms.
Hippocampal neocortical dialog
The hippocampal neocortical dialog refers to the very structured interactions during SWS between groups of neurons called ensembles in the hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
and neocortex
The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, sp ...
. Sharp wave patterns (SPW) dominate the hippocampus during SWS and neuron populations in the hippocampus participate in organized bursts during this phase. This is done in synchrony with state changes in the cortex (DOWN/UP state) and coordinated by the slow oscillations in cortex. These observations, coupled with the knowledge that the hippocampus plays a role in short to medium term memory whereas the cortex plays a role in long term memory, have led to the hypothesis that the hippocampal neocortical dialog might be a mechanism through which the hippocampus transfers information to the cortex. Thus, the hippocampal neocortical dialog is said to play a role in memory consolidation.
Sleep regulation
Sleep regulation
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
refers to the control of when an organism transitions between sleep and wakefulness. The key questions here are to identify which parts of the brain are involved in sleep onset and what their mechanisms of action are. In humans and most animals sleep and wakefulness seems to follow an electronic flip-flop model i.e. both states are stable, but the intermediate states are not. Of course, unlike in the flip-flop, in the case of sleep, there seems to be a timer ticking away from the minute of waking so that after a certain period one must sleep, and in such a case even waking becomes an unstable state. The reverse may also be true to a lesser extent.
Sleep onset
Some light was thrown on the mechanisms on sleep onset by the discovery that lesions in the preoptic area
The preoptic area is a region of the hypothalamus. MeSH classifies it as part of the anterior hypothalamus. TA lists four nuclei in this region, (medial, median, lateral, and periventricular).
Functions
The preoptic area is responsible for ther ...
and anterior hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
lead to insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
while those in the posterior hypothalamus lead to sleepiness. This was further narrowed down to show that the central midbrain tegmentum is the region that plays a role in cortical activation. Thus, sleep onset seems to arise from activation of the anterior hypothalamus along with inhibition of the posterior regions and the central midbrain tegmentum. Further research has shown that the hypothalamic region called ventrolateral preoptic nucleus
The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain ...
produces the inhibitory neurotransmitter GABA that inhibits the arousal system during sleep onset.
Models of sleep regulation
Sleep is regulated by two parallel mechanisms, homeostatic regulation and circadian regulation, controlled by the hypothalamus and the suprachiasmatic nucleus (SCN), respectively. Although the exact nature of sleep drive is unknown, homeostatic pressure builds up during wakefulness and this continues until the person goes to sleep. Adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
is thought to play a critical role in this and many people have proposed that the pressure build-up is partially due to adenosine accumulation. However, some researchers have shown that accumulation alone does not explain this phenomenon completely. The circadian rhythm is a 24-hour cycle in the body, which has been shown to continue even in the absence of environmental cues. This is caused by projections from the SCN to the brain stem.
This two process model was first proposed in 1982 by Borbely, who called them Process S (homeostatic) and Process C (Circadian) respectively. He showed how the slow wave density increases through the night and then drops off at the beginning of the day while the circadian rhythm is like a sinusoid. He proposed that the pressure to sleep was the maximum when the difference between the two was highest.
In 1993, a different model called the opponent process model was proposed. This model explained that these two processes opposed each other to produce sleep, as against Borbely's model. According to this model, the SCN, which is involved in the circadian rhythm, enhances wakefulness and opposes the homeostatic rhythm. In opposition is the homeostatic rhythm, regulated via a complex multisynaptic pathway in the hypothalamus that acts like a switch and shuts off the arousal system. Both effects together produce a see-saw like effect of sleep and wakefulness. More recently, it has been proposed that both models have some validity to them, while new theories hold that inhibition of NREM sleep by REM could also play a role. In any case, the two process mechanism adds flexibility to the simple circadian rhythm and could have evolved as an adaptive measure.
Thalamic regulation
Much of the brain activity in sleep has been attributed to the thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and it appears that the thalamus may play a critical role in SWS. The two primary oscillations in slow wave sleep
Slow-wave sleep (SWS), often referred to as deep sleep, consists of stage three of non-rapid eye movement sleep. It usually lasts between 70 and 90 minutes and takes place during the first hours of the night. Initially, SWS consisted of both St ...
, delta and the slow oscillation, can be generated by both the thalamus and the cortex. However, sleep spindles can only be generated by the thalamus, making its role very important. The thalamic pacemaker hypothesis holds that these oscillations are generated by the thalamus but the synchronization of several groups of thalamic neurons firing simultaneously depends on the thalamic interaction with the cortex. The thalamus also plays a critical role in sleep onset when it changes from tonic to phasic mode, thus acting like a mirror for both central and decentral elements and linking distant parts of the cortex to co-ordinate their activity.
Ascending reticular activating system
The ascending reticular activating system
The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. It is not anatomically well defined, because it includes neurons located in different parts of the brain. The neurons of the reticular formatio ...
consists of a set of neural subsystems that project from various thalamic nuclei and a number of dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...
, noradrenergic
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
, serotonergic
Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...
, histaminergic
Histaminergic means "working on the histamine system", and histaminic means "related to histamine".
A histaminergic agent (or drug) is a chemical which functions to directly modulate the histamine system in the body or brain. Examples include his ...
, cholinergic
Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation. F ...
, and glutamatergic
Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/ aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...
brain nuclei. When awake, it receives all kinds of non-specific sensory information and relays them to the cortex. It also modulates fight or flight responses and is hence linked to the motor system. During sleep onset, it acts via two pathways: a cholinergic pathway that projects to the cortex via the thalamus and a set of monoaminergic pathways that projects to the cortex via the hypothalamus. During NREM sleep this system is inhibited by GABAergic neurons in the ventrolateral preoptic area
The ventrolateral preoptic nucleus (VLPO), also known as the intermediate nucleus of the preoptic area (IPA), is a small cluster of neurons situated in the anterior hypothalamus, sitting just above and to the side of the optic chiasm in the brain ...
and parafacial zone
The parafacial zone (PZ) is a brain structure located in the brainstem within the medulla oblongata believed to be heavily responsible for Non-rapid eye movement sleep, non-rapid eye movement (non-REM) sleep regulation, specifically for inducing s ...
, as well as other sleep-promoting neurons in distinct brain regions.
Sleep function
The need and function of sleep are among the least clearly understood areas in sleep research. When asked, after 50 years of research, what he knew about the reason people sleep, William C. Dement
William Charles Dement (July 29, 1928 – June 17, 2020) was an American sleep researcher and founder of the Sleep Research Center at Stanford University. He was a leading authority on sleep, sleep deprivation and the diagnosis and treatment of s ...
, founder of Stanford University
Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...
's Sleep Research Center, answered, "As far as I know, the only reason we need to sleep that is really, really solid is because we get sleepy." It is likely that sleep evolved to fulfill some primeval function and took on multiple functions over time (analogous to the larynx
The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...
, which controls the passage of food and air, but descended over time to develop speech capabilities).
The multiple hypotheses proposed to explain the function of sleep reflect the incomplete understanding of the subject. While some functions of sleep are known, others have been proposed but not completely substantiated or understood. Some of the early ideas about sleep function were based on the fact that most (if not all) external activity is stopped during sleep. Initially, it was thought that sleep was simply a mechanism for the body to "take a break" and reduce wear. Later observations of the low metabolic
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
rates in the brain during sleep seemed to indicate some metabolic functions of sleep. This theory is not fully adequate as sleep only decreases metabolism by about 5–10%.["Function of Sleep."](_blank)
Scribd.com. Retrieved on 1 December 2011. With the development of EEG, it was found that the brain has almost continuous internal activity during sleep, leading to the idea that the function could be that of reorganization or specification of neuronal circuits or strengthening of connections. These hypotheses are still being explored. Other proposed functions of sleep include- maintaining hormonal balance, temperature regulation and maintaining heart rate.
According to a recent sleep disruption and insomnia review study, there are short-term and long-term negative consequences on healthy individuals. The short term consequences include increased stress responsivity and psychosocial issues such as impaired cognitive or academic performance and depression. Experiments indicated that, in healthy children and adults, episodes of fragmented sleep or insomnia increased sympathetic activation, which can disrupt mood and cognition. The long term consequences include metabolic issues such as glucose homeostasis disruption and even tumor formation and increased risks of cancer.
Preservation
The "Preservation and Protection" theory holds that sleep serves an adaptive function. It protects the animal during that portion of the 24-hour day in which being awake, and hence roaming around, would place the individual at greatest risk.[Choi, Charles Q. (25 August 2009]
LiveScience.com. Organisms do not 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 maximize their safety, given their physical capacities and their habitats.
This theory fails to explain why the brain disengages from the external environment during normal sleep. However, the brain consumes a large proportion of the body's energy at any one time and preservation of energy could only occur by limiting its sensory inputs. Another argument against the theory is that sleep is not simply a passive consequence of removing the animal from the environment, but is a "drive"; animals alter their behaviors in order to obtain sleep.
Therefore, circadian regulation is more than sufficient to explain periods of activity and quiescence
Quiescence (/kwiˈɛsəns/) is a state of quietness or inactivity. It may refer to:
* Quiescence search, in game tree searching (adversarial search) in artificial intelligence, a quiescent state is one in which a game is considered stable and unl ...
that are adaptive to an organism, but the more peculiar specializations of sleep probably serve different and unknown functions. Moreover, the preservation theory needs to explain why carnivores like lions, which are on top of the food chain
A food chain is a linear network of links in a food web starting from producer organisms (such as grass or algae which produce their own food via photosynthesis) and ending at an apex predator species (like grizzly bears or killer whales), det ...
and thus have little to fear, sleep the most. It has been suggested that they need to minimize energy expenditure when not hunting.
Waste clearance from the brain
During sleep, metabolic waste
Metabolic wastes or excrements are substances left over from metabolic processes (such as cellular respiration) which cannot be used by the organism (they are surplus or toxic), and must therefore be excreted. This includes nitrogen compounds, ...
products, such as immunoglobulins
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
, protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
fragments or intact proteins like beta-amyloid
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which i ...
, may be cleared from the interstitium
The interstitium is a contiguous fluid-filled space existing between a structural barrier, such as a cell membrane or the skin, and internal structures, such as organs, including muscles and the circulatory system. The fluid in this space is cal ...
via a glymphatic system
The glymphatic system (or glymphatic clearance pathway, or paravascular system) was described and named in 2013 as a system for waste clearance in the central nervous system (CNS) of vertebrates. According to this model, cerebrospinal fluid (CSF) ...
of lymph
Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...
-like channels coursing along perivascular space
A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role fo ...
s and the astrocyte
Astrocytes (from Ancient Greek , , "star" + , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of endo ...
network of the brain. According to this model, hollow tubes between the blood vessels and astrocytes act like a spillway
A spillway is a structure used to provide the controlled release of water downstream from a dam or levee, typically into the riverbed of the dammed river itself. In the United Kingdom, they may be known as overflow channels. Spillways ensure tha ...
allowing drainage of cerebrospinal fluid
Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates.
CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...
carrying wastes out of the brain into systemic blood.[ Such mechanisms, which remain under preliminary research as of 2017, indicate potential ways in which sleep is a regulated maintenance period for brain ]immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
functions and clearance of beta-amyloid, a risk factor
In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection.
Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
for Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
.[
]
Restoration
Wound healing
Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue.
In undamaged skin, the epidermis (surface, epithelial layer) and dermis (deeper, connective layer) form a protective barrier again ...
has been shown to be affected by sleep.
It has been shown that sleep deprivation affects the immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
. It is now possible to state that "sleep loss impairs immune function and immune challenge alters sleep," and it has been suggested that sleep increases white blood cell counts. A 2014 study found that depriving mice of sleep increased cancer growth and dampened the immune system's ability to control cancers.
The effect of sleep duration on somatic
Somatic may refer to:
* Somatic (biology), referring to the cells of the body in contrast to the germ line cells
** Somatic cell, a non-gametic cell in a multicellular organism
* Somatic nervous system, the portion of the vertebrate nervous sys ...
growth is not completely known. One study recorded growth, height, and weight, as correlated to parent-reported time in bed in 305 children over a period of nine years (age 1–10). It was found that "the variation of sleep duration among children does not seem to have an effect on growth." It is well established that slow-wave sleep affects growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
levels in adult men. During eight hours' sleep, Van Cauter, Leproult, and Plat found that the men with a high percentage of SWS (average 24%) also had high growth hormone secretion, while subjects with a low percentage of SWS (average 9%) had low growth hormone secretion.
There is some supporting evidence of the restorative function of sleep. The sleeping brain has been shown to remove metabolic waste products at a faster rate than during an awake state. While awake, metabolism generates reactive oxygen species, which are damaging to cells. In sleep, metabolic rates decrease and reactive oxygen species generation is reduced allowing restorative processes to take over. It is theorized that sleep helps facilitate the synthesis of molecules that help repair and protect the brain from these harmful elements generated during waking. The metabolic phase during sleep is anabolic; anabolic hormones such as growth hormones (as mentioned above) are secreted preferentially during sleep.
Energy conservation could as well have been accomplished by resting quiescent without shutting off the organism from the environment, potentially a dangerous situation. A sedentary nonsleeping animal is more likely to survive predators, while still preserving energy. Sleep, therefore, seems to serve another purpose, or other purposes, than simply conserving energy. Another potential purpose for sleep could be to restore signal strength in synapses that are activated while awake to a "baseline" level, weakening unnecessary connections that to better facilitate learning and memory functions again the next day; this means the brain is forgetting some of the things we learn each day.
Endocrine function
The secretion of many hormones
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and beh ...
is affected by sleep-wake cycles. For example, melatonin
Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates ...
, a hormonal timekeeper, is considered a strongly circadian
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
hormone, whose secretion increases at dim light and peaks during nocturnal sleep, diminishing with bright light to the eyes. In some organisms melatonin secretion depends on sleep, but in humans it is independent of sleep and depends only on light level. Of course, in humans as well as other animals, such a hormone may facilitate coordination of sleep onset. Similarly, cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
and thyroid stimulating hormone (TSH) are strongly circadian and diurnal hormones, mostly independent of sleep. In contrast, other hormones like growth hormone (GH) & prolactin
Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...
are critically sleep-dependent, and are suppressed in the absence of sleep. GH has maximum increase during SWS while prolactin is secreted early after sleep onset and rises through the night. In some hormones whose secretion is controlled by light level, sleep seems to increase secretion. Almost in all cases, sleep deprivation has detrimental effects. For example, cortisol, which is essential for metabolism (it is so important that animals can die within a week of its deficiency) and affects the ability to withstand noxious stimuli, is increased by waking and during REM sleep. Similarly, TSH increases during nocturnal sleep and decreases with prolonged periods of reduced sleep, but increases during total acute sleep deprivation.
Because hormones play a major role in energy balance and metabolism, and sleep plays a critical role in the timing and amplitude of their secretion, sleep has a sizable effect on metabolism. This could explain some of the early theories of sleep function that predicted that sleep has a metabolic regulation role.
Memory processing
According to Plihal & Born, sleep generally increases recalling of previous learning and experiences, and its benefit depends on the phase of sleep and the type of memory. For example, studies based on declarative and procedural memory tasks applied over early and late nocturnal sleep, as well as wakefulness controlled conditions, have been shown that declarative memory improves more during early sleep (dominated by SWS) while procedural memory during late sleep (dominated by REM sleep).
Regarding to declarative memory, the functional role of SWS has been associated with hippocampal replays of previously encoded neural patterns that seem to facilitate long-term memories consolidation. This assumption is based on the active system consolidation hypothesis, which states that repeated reactivations of newly encoded information in hippocampus during slow oscillations in NREM sleep mediate the stabilization and gradually integration of declarative memory with pre-existing knowledge networks on the cortical level. It assumes the hippocampus might hold information only temporarily and in fast-learning rate, whereas the neocortex is related to long-term storage and slow-learning rate. This dialogue between hippocampus and neocortex occurs in parallel with hippocampal sharp-wave ripples and thalamo-cortical spindles, synchrony that drives the formation of spindle-ripple event which seems to be a prerequisite for the formation of long-term memories.
Reactivation of memory also occurs during wakefulness and its function is associated with serving to update the reactivated memory with new encoded information, whereas reactivations during SWS are presented as crucial for memory stabilization. Based on targeted memory reactivation (TMR) experiments that use associated memory cues to triggering memory traces during sleep, several studies have been reassuring the importance of nocturnal reactivations for the formation of persistent memories in neocortical networks, as well as highlighting the possibility of increasing people’s memory performance at declarative recalls.
Furthermore, nocturnal reactivation seems to share the same neural oscillatory patterns as reactivation during wakefulness, processes which might be coordinated by theta activity. During wakefulness, theta oscillations have been often related to successful performance in memory tasks, and cued memory reactivations during sleep have been showing that theta activity is significantly stronger in subsequent recognition of cued stimuli as compared to uncued ones, possibly indicating a strengthening of memory traces and lexical integration by cuing during sleep. However, the beneficial effect of TMR for memory consolidation seems to occur only if the cued memories can be related to prior knowledge.
Other studies have been also looking at the specific effects of different stages of sleep on different types of memory. For example, it has been found that sleep deprivation does not significantly affect recognition of faces, but can produce a significant impairment of temporal memory (discriminating which face belonged to which set shown). Sleep deprivation was also found to increase beliefs of being correct, especially if they were wrong. Another study reported that the performance on free recall of a list of nouns is significantly worse when sleep deprived (an average of 2.8 ± 2 words) compared to having a normal night of sleep (4.7 ± 4 words). These results reinforce the role of sleep on declarative memory
Explicit memory (or declarative memory) is one of the two main types of long-term human memory, the other of which is implicit memory. Explicit memory is the conscious, intentional recollection of factual information, previous experiences, and con ...
formation. This has been further confirmed by observations of low metabolic activity in the prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, ...
and temporal and parietal lobes
The parietal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus.
The parietal lobe integrates sensory informa ...
for the temporal learning and verbal learning tasks respectively. Data analysis has also shown that the neural assemblies during SWS correlated significantly more with templates than during waking hours or REM sleep. Also, post-learning, post-SWS reverberations lasted 48 hours, much longer than the duration of novel object learning (1 hour), indicating long term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...
.
Moreover, observations include the importance of nap
A nap is a short period of sleep, typically taken during daytime hours as an adjunct to the usual nocturnal sleep period. Naps are most often taken as a response to drowsiness during waking hours. A nap is a form of biphasic or polyphasic sl ...
ping: improved performance in some kinds of tasks after a 1-hour afternoon nap; studies of performance of shift workers, showing that an equal number of hours of sleep in the day is not the same as in the night. Current research studies look at the molecular and physiological basis of memory consolidation
Memory consolidation is a category of processes that stabilize a memory trace after its initial acquisition. A memory trace is a change in the nervous system caused by memorizing something. Consolidation is distinguished into two specific processe ...
during sleep. These, along with studies of genes that may play a role in this phenomenon, together promise to give a more complete picture of the role of sleep in memory.
Renormalizing the synaptic strength
Sleep can also serve to weaken synaptic connections that were acquired over the course of the day but which are not essential to optimal functioning. In doing so, the resource demands can be lessened, since the upkeep and strengthening of synaptic connections constitutes a large portion of energy consumption by the brain and tax other cellular mechanisms such as protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
for new channels. Without a mechanism like this taking place during sleep, the metabolic needs of the brain would increase over repeated exposure to daily synaptic strengthening, up to a point where the strains become excessive or untenable.
Behavior change with sleep deprivation
One approach to understanding the role of sleep is to study the deprivation of it. Sleep deprivation
Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
is common and sometimes even necessary in modern societies because of occupational and domestic reasons like round-the-clock service, security or media coverage, cross-time-zone projects etc. This makes understanding the effects of sleep deprivation very important.
Many studies have been done from the early 1900s to document the effect of sleep deprivation. The study of REM deprivation began with William C. Dement
William Charles Dement (July 29, 1928 – June 17, 2020) was an American sleep researcher and founder of the Sleep Research Center at Stanford University. He was a leading authority on sleep, sleep deprivation and the diagnosis and treatment of s ...
around 1960. He conducted a sleep and dream research project on eight subjects, all male. For a span of up to 7 days, he deprived the participants of REM sleep by waking them each time they started to enter the stage. He monitored this with small electrodes attached to their scalp and temples. As the study went on, he noticed that the more he deprived the men of REM sleep, the more often he had to wake them. Afterwards, they showed more REM sleep than usual, later named REM rebound.
The neurobehavioral basis for these has been studied only recently. Sleep deprivation has been strongly correlated with increased probability of accidents and industrial errors. Many studies have shown the slowing of metabolic activity in the brain with many hours of sleep debt
Sleep debt or sleep deficit is the cumulative effect of not getting enough sleep. A large sleep debt may lead to mental or physical fatigue, and can adversely affect one's mood, energy and ability to think clearly.
There are two kinds of sleep ...
. Some studies have also shown that the attention
Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Atte ...
network in the brain is particularly affected by lack of sleep, and though some of the effects on attention may be masked by alternate activities (like standing or walking) or caffeine consumption, attention deficit cannot be completely avoided.
Sleep deprivation has been shown to have a detrimental effect on cognitive tasks, especially involving divergent functions or multitasking. It also has effects on mood and emotion, and there have been multiple reports of increased tendency for rage, fear or depression with sleep debt. However, some of the higher cognitive functions seem to remain unaffected albeit slower. Many of these effects vary from person to person i.e. while some individuals have high degrees of cognitive impairment with lack of sleep, in others, it has minimal effects. The exact mechanisms for the above are still unknown and the exact neural pathways and cellular mechanisms of sleep debt are still being researched.
Sleep disorders
A sleep disorder, or somnipathy, is a medical disorder of the sleep patterns of a person or animal. Polysomnography
Polysomnography (PSG), a type of sleep study, is a multi-parameter study of sleep and a diagnostic tool in sleep medicine. The test result is called a polysomnogram, also abbreviated PSG. The name is derived from Greek and Latin roots: the Gree ...
is a test commonly used for diagnosing some sleep disorders. Sleep disorders are broadly classified into dyssomnias
Dyssomnias are a broad classification of sleeping disorders involving difficulty getting to sleep, remaining asleep, or of excessive sleepiness.
Dyssomnias are primary disorders of initiating or maintaining sleep or of excessive sleepiness and ar ...
, parasomnias
Parasomnias are a category of sleep disorders that involve abnormal movements, behaviors, emotions, perceptions, and dreams that occur while falling asleep, sleeping, between sleep stages, or during arousal from sleep. Parasomnias are dissociate ...
, circadian rhythm sleep disorders(CRSD), and other disorders including ones caused by medical or psychological conditions and sleeping sickness
African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...
. Some common sleep disorders include insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
(chronic inability to sleep), sleep apnea
Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times ...
(abnormally low breathing during sleep), narcolepsy
Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affec ...
(excessive sleepiness at inappropriate times), cataplexy
Cataplexy is a sudden and transient episode of muscle weakness accompanied by full conscious awareness, typically triggered by emotions such as laughing, crying, or terror. Cataplexy affects approximately 70% of people who have narcolepsy, and is ...
(sudden and transient loss of muscle tone), and sleeping sickness (disruption of sleep cycle due to infection). Other disorders that are being studied include sleepwalking
Sleepwalking, also known as somnambulism or noctambulism, is a phenomenon of combined sleep and wakefulness. It is classified as a sleep disorder belonging to the parasomnia family. It occurs during slow wave stage of sleep, in a state of low ...
, sleep terror
Night terror, also called sleep terror, is a sleep disorder
A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social a ...
and bed wetting
Nocturnal enuresis, also informally called bedwetting, is urinary incontinence, involuntary urination while sleep, asleep after the age at which bladder control usually begins. Bedwetting in children and adults can result in emotional stress. Com ...
.
Studying sleep disorders is particularly useful as it gives some clues as to which parts of the brain may be involved in the modified function. This is done by comparing the imaging and histological patterns in normal and affected subjects. Treatment of sleep disorders typically involves behavioral and psychotherapeutic
Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome prob ...
methods though other techniques may also be used. The choice of treatment methodology for a specific patient depends on the patient's diagnosis, medical and psychiatric history, and preferences, as well as the expertise of the treating clinician. Often, behavioral or psychotherapeutic and pharmacological
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
approaches are compatible and can effectively be combined to maximize therapeutic benefits.
Frequently, sleep disorders have been also associated with neurodegenerative diseases, mainly when they are characterized by abnormal accumulation of alpha-synuclein
Alpha-synuclein is a protein that, in humans, is encoded by the ''SNCA'' gene. Alpha-synuclein is a neuronal protein that regulates synaptic vesicle trafficking and subsequent neurotransmitter release.
It is abundant in the brain, while smaller a ...
, such as multiple system atrophy
Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by autonomic dysfunction, tremors, slow movement, muscle rigidity, and postural instability (collectively known as parkinsonism) and ataxia. This is caused by progr ...
(MSA), Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
(PD) and Lewy body disease
Lewy body dementias are two similar and common subtypes of dementia—dementia with Lewy bodies (DLB) and
Parkinson's disease dementia (PDD). Both are characterized by changes in thinking, movement, behavior, and mood. The two conditions have sim ...
(LBD). For instance, people diagnosed with PD have often presented different kinds of sleep concerns, commonly regard to insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
(around 70% of the PD population), hypersomnia
Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
(more than 50% of the PD population), and REM sleep behavior disorder
Rapid eye movement sleep behavior disorder or REM behavior disorder (RBD) is a sleep disorder in which people act out their dreams. It involves abnormal behavior during the sleep phase with rapid eye movement (REM) sleep. The major feature of ...
(RBD) - that may affect around 40% of the PD population and it is associated with increased motor symptoms. Furthermore, RBD has been also highlighted as a strong precursor of future development of those neurodegenerative diseases over several years in prior, which seems to be a great opportunity for improving treatments.
Sleep disturbances have been also observed in Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
(AD), affecting about 45% of its population. Moreover, when it is based on caregiver reports this percentage is even higher, about 70%.[Dick-Muehlke, C. (2015). Psychosocial studies of the individual's changing perspectives in Alzheimer's disease (Premier Reference Source). Hershey, PA: Medical Information Science Reference.] As well as in PD population, insomnia
Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
and hypersomnia
Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes (such as seasonal affective disorder) and can cause distress and problems with functioning. In the fifth edition ...
are frequently recognized in AD patients, which are associated with accumulation of Beta-amyloid
Amyloid beta (Aβ or Abeta) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid precursor protein (APP), which i ...
, circadian rhythm sleep disorders (CRSD) and melatonin
Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle.
In vertebrates ...
alteration. Additionally, changes in sleep architecture
Sleep is a sedentary state of mind and body. It is characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and reduced interactions with surroundings. It is distinguished from wakefulness by a d ...
are observed in AD too. Even though with ageing the sleep architecture seems to change naturally, in AD patients it is aggravated. SWS is potentially decreased (sometimes totally absent), spindles and the time spent in REM sleep are also reduced, while its latency is increased. The poorly sleep onset in AD has been also associated with dream-related hallucination, increased restlessness, wandering and agitation, that seem to be related with sundowning - a typical chronobiological phenomenon presented in the disease.
The neurodegenerative conditions are commonly related to brain structures impairments, which might disrupt the states of sleep and wakefulness, circadian rhythm, motor or non motor functioning. On the other hand, sleep disturbances are also frequently related to worsening patient's cognitive functioning, emotional state and quality of life. Furthermore, these abnormal behavioural symptoms negatively contribute to overwhelming their relatives and caregivers. Therefore, a deeper understanding of the relationship between sleep disorders and neurodegenerative diseases seems to be extremely important, mainly considering the limited research related to it and the increasing expectancy of life.
A related field is that of sleep medicine
Sleep medicine is a medical specialty or subspecialty devoted to the diagnosis and therapy of sleep disturbances and sleep disorder, disorders. From the middle of the 20th century, research has provided increasing knowledge and answered many ...
which involves the diagnosis and therapy of sleep disorders and sleep deprivation, which is a major cause of accidents. This involves a variety of diagnostic methods including polysomnography, sleep diary
A sleep diary is a record of an individual's sleeping and waking times with related information, usually over a period of several weeks. It is self-reported or can be recorded by a care-giver.
The sleep diary, or sleep log, is a tool used by docto ...
, multiple sleep latency test, etc. Similarly, treatment may be behavioral such as cognitive behavioral therapy
Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
or may include pharmacological medication or bright light therapy
Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circadi ...
.
Dreaming
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep (mainly the REM stage). The content and purpose of dreams are not yet clearly understood though various theories have been proposed. The scientific study of dreams is called oneirology
Oneirology (; from Greek ''ὄνειρον'', ''oneiron'', "dream"; and -''λογία'', -''logia'', "the study of") is the scientific study of dreams. Current research seeks correlations between dreaming and current knowledge about the func ...
.
There are many theories about the neurological basis of dreaming. This includes the activation synthesis theory
The activation-synthesis hypothesis, proposed by Harvard University psychiatrists John Allan Hobson and Robert McCarley, is a neurobiological theory of dreams first published in the American Journal of Psychiatry in December 1977. The differences ...
—the theory that dreams result from brain stem activation during REM sleep; the continual activation theory—the theory that dreaming is a result of activation and synthesis but dreams and REM sleep are controlled by different structures in the brain; and dreams as excitations of long term memory—a theory which claims that long term memory excitations are prevalent during waking hours as well but are usually controlled and become apparent only during sleep.
There are multiple theories about dream function as well. Some studies claim that dreams strengthen semantic memories. This is based on the role of hippocampal neocortical dialog and general connections between sleep and memory. One study surmises that dreams erase junk data in the brain. Emotional adaptation and mood regulation are other proposed functions of dreaming.
From an evolution
Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...
ary standpoint, dreams might simulate and rehearse threatening events, that were common in the organism's ancestral environment, hence increasing a persons ability to tackle everyday problems and challenges in the present. For this reason these threatening events may have been passed on in the form of genetic memories. This theory accords well with the claim that REM sleep is an evolutionary transformation of a well-known defensive mechanism, the tonic immobility reflex.[
Most theories of dream function appear to be conflicting, but it is possible that many short-term dream functions could act together to achieve a bigger long-term function.] It may be noted that evidence for none of these theories is entirely conclusive.
The incorporation of waking memory events into dreams is another area of active research and some researchers have tried to link it to the declarative memory consolidation functions of dreaming.
A related area of research is the neuroscience basis of nightmares
A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of d ...
. Many studies have confirmed a high prevalence of nightmares and some have correlated them with high stress
Stress may refer to:
Science and medicine
* Stress (biology), an organism's response to a stressor such as an environmental condition
* Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
levels. Multiple models of nightmare production have been proposed including neo-Freudian
Sigmund Freud ( , ; born Sigismund Schlomo Freud; 6 May 1856 – 23 September 1939) was an Austrian neurologist and the founder of psychoanalysis, a clinical method for evaluating and treating pathologies explained as originating in conflicts i ...
models as well as other models such as image contextualization model, boundary thickness model, threat simulation model etc. Neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neuro ...
imbalance has been proposed as a cause of nightmares, as also affective network dysfunction- a model which claims that nightmare is a product of dysfunction of circuitry normally involved in dreaming. As with dreaming, none of the models have yielded conclusive results and studies continue about these questions.
See also
* NPSR mutations
References
{{reflist, 32em
Neurophysiology
Sleep