Sleep is a universal necessity of humans, and approximately one-third of the human life is spent in the sleep state. Deprivation or disruption of sleep consistently results in adverse physiologic effects.
Despite large amounts of research into the true definition of sleep, the complete purpose for sleep is not fully understood. It is known, though, that adequate sleep is needed to heal the body, maintain alertness, and assist with learning and memory. However, the complexity and study of sleep requires a comprehensive understanding of the physiology, neurochemistry, neuroanatomy and associated mechanisms by which these areas interact.
Normal sleep can be viewed from two aspects:
(1) The actual distribution of sleep cycles relative to nonrapid eye movement (NREM) and rapid eye movement (REM)
(2) The neurotransmitters that affect regulation of the sleep-wake cycle. Each of these areas changes as the human progresses from infancy to elderly.
NREM AND REM SLEEP
Structural characteristics of normal sleep can be referred to as sleep architecture, which comprises two distinct states: NREM, which is subdivided into Stages 1-4 ; and REM .
NREM and REM sleep occur in varying proportions during a sleep period, and they also alternate in cyclical fashion with each other throughout sleep. Also, their proportional distribution during sleep changes with age.
The typical pattern in normal sleep is for the individual to progress from wakefulness to the NREM sleep state, followed by the REM sleep state, and then cyclically alternating between REM and NREM stages. Typically, a night of sleep comprises about 75-80% of NREM sleep and 20-25% of REM sleep. When this cycling becomes irregular and / or there is a deficiency of NREM sleep stages, such as what occurs with narcolepsy, sleep disorders can develop.
Muscle activity during sleep also varies depending on REM or NREM sleep. In REM sleep, there appears to be an increase in activity in the motor centers of the brain, but there is active inhibition of these motor neurons.
In NREM sleep, muscle activity is decreased with the maximum effect during the more restorative stages 3 and 4.
NREM sleep has historically been subdivided into four distinct stages on the basis of characteristic brain wave and physiologic activities ever since it was initially observed and measured through electroencephalography (EEG): NREM Stage 1, NREM stage 2, NREM Stage 3, and NREM Stage 4.
These four stages of NREM sleep are typically defined as follows:
Stage 1: This stage indicates a change in brain wave activity from rhythmic alpha waves to mixed frequency- waves as the individual passes from wakefulness to the initiation of sleep. NREM Stage 1 comprises about 2-5 % of the total sleep time, and it is considered to be a light sleep / drowsy stage from which one can usually be easily awakened. Sudden muscle contractions can occur in this stage, and the individual may also experience a sensation of falling.
Stage 2 : Although this begins to be a deeper stage of sleep with a reduction in heart rate and body temperature, it is still regarded to be light with mixed-frequency EEG activity. One can again be easily awakened, although an additional amount of stimulus is needed as compared to NREM Stage 1.
This stage comprises about 45-55% of the total sleep time. Unique and significant features in the EEG activity of this stage are the presence of K-complex and sleep spindles, the latter of which has been postulated to being associated with memory consolidation.
Stages3 and 4: These two NREM stages have their own unique and individually recognized brain waveforms, but they are usually viewed as one stage of sleep, being referred to as slow-wave sleep, deep sleep, or restorative sleep. Because of their unique EEG waveform, they are also known as delta sleep. Together, they comprise about 13-23% of the total sleep time. NREM Stage 4 reflects the highest threshold for awakening from sleep relative to the other NREM stages.
REM sleep is also referred to as dream sleep. Although it comprises about 20-25% of the total sleep time, this state recurs several times throughout the overall cyclical activity of NREM and REM states during a sleep period. In normal sleep, each subsequent recurring REM period is longer than the prior REM period.
EEG activity is increased with a characteristic “sawtooth” waveform and can also appear similar to wakefulness relative to mixed frequency. There is an accompanying increase in heart rate, respiration, blood pressure, and jerky eye movements. During this state of increased cerebral activity, there may be an immobility or paralysis of the muscles in the limbs, which has been thought to be a preventative mechanism of the individual to not physically act out their dreams during sleep. REM sleep may also be contributory to memory consolidation.
REM sleep may be further regarded as two phases: tonic and phasic. Although, a typical sleep study report will not make a distinction between these two phases.
Tonic REM is a unique phase by virtue of the following characteristics:
- Atonia (loss of muscle tone) of the skeletal muscles that appears near paralysis;
- Desynchronized EEG activity with widespread neural activation or wake-like EEG activity.
Phasic REM is also unique because it occurs intermittently instead of continuously, and it reflects the following characteristics:
- Bursts of REMs in all directions
- Transient swings in blood pressure and heart rate along with tongue movement and irregular respiration;
- Myoclonus (muscular jerks), twitching of the chin, and limb movements
Alternative sleep scoring/staging
In 2007, a new method of scoring sleep studies led to a revision in sleep staging, and sleep study reports may increasingly refer to this nomenclature as opposed to the staging that has been historically utilized in the past:
- Stage W (Wakefulness)
- Stage N1 (NREM 1)
- Stage N2 (NREM2 )
- Stage N3 (NREM 3; this replaces NREM stages 3 and 4)
- Stage R (REM)
Cycles and hours of sleep
Sleep patterns change for individuals throughout life. From infancy to elderly, these changes are dynamic and distinct, relative to sleep initiation, sleep maintenance and the amount of time for each sleep stage.
During normal sleep, the human typically cycles through the NREM and REM sleep stages four to six times per sleep period. In the adult, regardless of the age, these stages occur at about 90-minute intervals. In children, these stages are shorter and occur at about 50-60 minute intervals. Also, children have different proportions of REM and NREM sleep as well as different numbers of hours of sleep. A newborn typically sleeps 16-18 hours , and 50% of this sleep time is REM sleep. Slow wave sleep (NREM Stages 3 and 4 ) is at its maximum in young children since this is when growth hormone is secreted.
As we age, slow wave sleep decreases, which appears to begin after adolescence. After the age of 70, slow -wave sleep is minimal or, in some cases, nonexistent. Lastly, the elderly spend more time in bed and less time actively sleeping.
As people become elderly, they often begin to adjust the time that they go to bed to an earlier hour. The result is that they have the increased potential to wake up earlier in the morning, which is called advanced sleep phase syndrome. In this syndrome, the individual is purposely adjusting the sleep – wake schedule by attempting to initiate sleep in advance of the circadian rhythm. The intentional adjustment is not coordinated with this internal biological rhythm.
With the aging process, the typical sleep cycle becomes more fragmented with increased awakenings or arousals during the sleep period and people tend to subsequently have an increased risk for sleep disorders, including sleep-related breathing disorders (SRBD) and insomnia. With SRBD, the muscle tissue that supports the airway becomes more relaxed during sleep. This lends itself to increased collapsibility. Consequently, as one’s age increases, the potential risk for SRBD is increased. The role of the dentist is significant for the recognition of obstructive sleep apnea (OSA) and for the management of this sleep disorder with custom oral appliance therapy.
Neurotransmitters of wakefulness and sleep
The role of neurotransmitters in both the sleep and awake state is a multifaceted topic. Because of their interactions and varying levels throughout the 24-hour period that impacts their function, many of the neurotransmitters might appear to have contradictory functions by impacting sleep as well as wakefulness.
The interaction of these various substances (neuromodulators, neurohormones, and neurotransmitters) is responsible for maintaining wakefulness and initiating sleep. No one substance acts alone. Instead, a complex interaction of these is responsible to maintain the two states of wakefulness and sleep.
Neurotransmitters of wakefulness
The basic neurotransmitters affecting the awake state are the biogenic amines (also known as monoamines). They have the role of either initiating sleep or maintaining wakefulness.
This neurotransmitter is predominately for vigilance and cortical activation. It is found at the neuromuscular junctions in the sympathetic, parasympathetic, and central nervous systems. It is considered to have excitatory properties, and it also plays a role in the formation of REM sleep, especially the phasic state. In addition, Acetylcholine is critical for memory function.
Catecholamines are found to be necessary for arousal and wakefulness, and each has unique properties.
Dopamine maintains the wakefulness and can impact one’s behavior. A degradation of dopamine production is frequently associated with movement disorders.
Noriepinephrine maintains EEG activity.
Epinephrine is unique because it is blood-borne. Plus, it is only found to be at low levels in the brain. It is released from the adrenal medulla and is not known to impact the sleep – wake cycle through autonomic and neuroendocrine regulation.
The neurotransmitter is recognized for a wide variety of functions that are associated with mood, depression, headache, pain and sleep. It is found to be excitatory and can impact the awake state. Though, the main role is to promote deep sleep.
The main function of histamine is to maintain quiet wakefulness. The role of histamine was not known until it was documented that antihistamine-containing medications could produce sleepiness. Furthermore, investigation led to the discovery of the role of histamine in the promotion of wakefulness and vigilance. Histamine functions in a fashion similar to norepinephrine by promoting cortical activation during wakefulness.
The role of orexin (hypocretin) has also been uncovered as a neurochemical that preserves wakefulness.
Cortisol is a hormone that is present to maintain wakefulness. This chemical substance is released by the adrenal glands and is often time associated with stress. It plays a role in maintaining alertness and may be increased in the early morning hours to promote wakefulness. Cortisol will be increased with stress, it can also be associated with depression and insomnia.
Glutamate is a fairly significant excitatory neurotransmitter in the brain that is associated with normal brain function. Glutamat has a basic role in the activity of the waking brain. It is present mostly during wakefulness when the largest amounts can be found.
Neurotransmitters and sleep
There are a number of neurotransmitters that promote sleep, including the following.
Gaba-aminobutyric acid or y-aminobutyric acid (GABA) is the main neurotransmitter of sleep. It is released from the hypothalamus. With its greatest influence at the posterior hypothalamus, GABA inhibits the activating systems, hence promoting sleep. Sleep medications such as Ambien, Lunesta, and Sonata, work by causing the release of GABA. Benzodiazepine-type medications are also known to increase GABA. This explains their sedating effects. GABA is synthesized from glutamate.
Adenosine is not a classic neurotransmitter. Associated with ongoing activity, it may accumulate over time as a by-product of degradation from ATP. The concentration of adenosine increases with prolonged wakefulness and decreases during sleep. Adenosine is purported to be a key neurotransmitter in the homeostatic regulation of sleep. Adenosine seems to have an inhibitory affect in the central nervous system on acetylcholine and glutamate. Plus, it has the role of facilitating sleep along with GABA, which is demonstrated by the fact that caffeine (methylxanthine) blocks adenosine receptors, thus explaining the role of caffeine as a stimulant.
Serotonin plays a role in the control of many different functions. It is made from tryptophan in the pineal gland of the brain, where serotonin is further affected by norepinephrine, which in turn leads to the production of melatonin. The role of serotonin in sleep is, therefore, directly linked to the release of melatonin. About 90% of serotonin is actually produced in the intestine, and the remaining 10% is found in the brain and the platelets.
Other sleep inducing factors
Melatonin is a hormone that is released by the pineal gland in the brain and its major impact is on the circadian rhythm. As a result, there is an association of light with the release of melatonin. Light that penetrates the eye terminates the release of melatonin. As darkness approaches, the stimulus to release melatonin increases, which promotes the sleep state.
The neurologic pathway related to the release of melatonin is not a direct one. The release of melatonin is initiated by the absence of light penetrating the eye, which then triggers neural activity that proceeds from the suprachiasmatic nucleus in the brain stem to the hypothalamus. The signal then travels into the superior cervical nucleus of the spinal column and subsequently to the pineal gland.
Insulin is known to have slow-wave (NREM Stage 3 and 4) sleep inducing properties. Insulin receptors have been found in the brain, which accounts for insulin’s role in promoting sleep. One research study has proposed a type of insulin dependence associated with the brain that has been termed diabetes type 3. The findings are preliminary and appear to offer evidence of a relationship between sleep deprivation and Alzheimer’s disease.
These peptides originate in the gut, and they appear to have the ability to promote sleep by stimulating the production of interleukins that are known to promote slow-wave deep sleep.
ANATOMY AND FUNCTION OF THE AIRWAY
The anatomy of the airway from the dentist’s perspective is mainly focused on the upper airway, especially the musculature that directly controls airway function. These muscle groups have been categorized by anatomical location, and these same muscles are employed in the function of speaking and swallowing.
The palatoglossus and palatopharyngeus muscles are included with the soft palate because their origin is from the palatine aponeurosis. The control of these muscles is the same as the musculus uvulae and levator veli palatini.
The posterior portions of the airway and the tongue comprise the muscles of the oropharynx. The tongue muscles are further divided into two groups: extrinsic and intrinsic.
The hyoid is an integral osseus structure that supports the suprahyoid and infrahyoid muscles. The position of the hyoid relative to the mandibular plane is of importance as a reliable predictor of OSA when viewed on a cephalometric radiograph. The muscles associated with the positioning of the hyoid are divided into two groups: the suprahyoids and the infrahyoids.
The pharynx is the portion of the airway that runs from the base of the tongue down to the larynx and the epiglottis. Because the pharynx is unsupported, it is subject to narrowing or collapse with SRBD. The pharyngeal constrictor muscles function mainly during swallowing.
Other airway muscle considerations
Other muscles associated with mandibular function and the cervical spine play a role in positioning the mandible and head as well as maintaining the airway both in the awake and sleep states. The muscles include the temporalis, masseter, pterygoids (lateral and medial), and the anterior and posterior cervical groups.
The two main muscles of the neck that are considered as accessory to respiration are the same sternocleidomastoid (SCM) and the scalene. The SCM’S primary purpose is to rotate, tilt, and flex the head. They also act as accessory muscles of respiration by elevating the sternum. The scalene group causes lateral flexion of the neck, and the anterior scalene specifically elevated the first rib as well as stabilizes the upper ribs with respiration.
The primary muscles of respiration during inspiration, are the diaphragm and the external intercostals. During expiration, the abdominal muscles and the internal intercostals are active.
If the airway becomes compromised during inspiration, inspiratory pressures will elevate, which will result in and increased negative pressure in the airway that further compromised and possibly even collapses the airway. Many times, the muscles that are intended to support the airway as well as tongue position can no longer maintain the airway, and further collapse is inevitable. This airway collapse occurs because the musculature relaxes during sleep, thereby further complicating the compromised airway.
BASICS OF AIRWAY DYNAMICS
The Venturi effect and the Bernoulli’s principle are two basic principles of airway dynamics. According to the Venturi effect, if the diameter of a tube (e.g.,the airway) is decreased, then for a given volume of fluid to pass through the tube, the velocity has to increase. This concept applies to the airway relative to snoring. The Bernoulli’s principle states that as a fluid flows through a tube and with an increase in the flow of that substance there is an increase in negative pressure at the periphery. The result is an increasing potential for airway collapse
Under normal circumstances, respiration is considered to be involuntary. It is primarily under the control of the diaphragm, which is innervated by the phrenic nerve that arises from the cervical nerves C3 to C5. It is primarily due to the muscle fibers that cause contraction of the diaphragm. During passive breathing, the diaphragm contracts and moves downward, causing an increase in the negative pressure within the lung and the alveoli. This negative pressure causes air to flow into the lungs to fill them. In addition, this action may be impacted by the intercostal muscles and the scalenes. Expiration during quiet breathing is passive and there is no active muscle activity. The process is related to the elastic recoil of the lungs and the rib cage.
Forced inspiration and expiration are different. With forced inspiration, the scalene and the SCM muscles are active. They impact the first and second ribs as well as the sternum, and this causes elevation of the bony cage.
Forced expiration is primarily an action of the intercostal muscles that pull the thoracic cage inward and force out air of the lungs. They prevent the increased intrathoracic pressure from causing any bulging at the intercostal spaces.
Understanding sleep and the processes related to it is important because it helps on understanding the dynamics of sleep disorders. The dentist does not have to understand the complex neurologic and neurochemical relationships that exist with sleep. It is sensible to have an understanding of the basics, the knowledge of the relevant aspects of sleep, and the ability to recognize how normal sleep may become altered. This understanding allows the dentist to have a foundational knowledge to explain certain aspects of sleep to patients who wish to have a better appreciation of their sleep and why disruption of it is occurring.
Furthermore, understanding sleep and sleep disorders will enable the dentist to better communicate with physicians regarding a patient who may have sleep disorder. For the benefit of the patient, the dentist should have an ever-increasing awareness of medical issues relative to their patients.
Humans spend nearly a fourth to a third of their lives sleeping. It is important to understand this process and much as the other physical conditions. The time that is spent sleeping has an important role in maintaining health, improving memory, enabling, humans to learn, and maintaining alertness and vigilance while awake. Without quality sleep, the awake time, moos ad ability to function may be significantly impaired.