Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Normal Sleep, Sleep Physiology, and Sleep Deprivation 

  • Author: M Suzanne Stevens, MD, MS, D-ABSM; Chief Editor: Selim R Benbadis, MD  more...
 
Updated: Dec 03, 2015
 

Normal Sleep in Adults, Infants, and the Elderly

Normal sleep is divided into non–rapid eye movement (NREM) and rapid eye movement (REM) sleep. NREM sleep is further divided into progressively deeper stages of sleep: stage N1, stage N2, and stage N3 (deep or delta-wave sleep). As NREM stages progress, stronger stimuli are required to result in an awakening. Stage R sleep (REM sleep) has tonic and phasic components. The phasic component is a sympathetically driven state characterized by rapid eye movements, muscle twitches, and respiratory variability. Tonic REM is a parasympathetically driven state with no eye movements. The REM period length and density of eye movements increases throughout the sleep cycle.[1]

Waking usually transitions into light NREM sleep. NREM sleep typically begins in the lighter stages N1 and N2, and progressively deepens to slow wave sleep as evidenced by higher-voltage delta waves. N3 (slow wave sleep) is present when delta waves account for more than 20% of the sleep EEG. REM sleep follows NREM sleep and occurs 4-5 times during a normal 8-hour sleep period. The first REM period of the night may be less than 10 minutes in duration, while the last may exceed 60 minutes. The NREM-REM cycles vary in length from 70-100 minutes initially to 90-120 minutes later in the night.

Typically, N3 sleep is present more in the first third of the night, whereas REM sleep predominates in the last third of the night. This can be helpful clinically as NREM parasomnias such as sleep walking typically occur in the first third of the night with the presence of N3 sleep. This contrasts with REM sleep behavior disorder (RBD), which typically occurs in the last half of the night.

Sleep in adults

Stage N1 is considered a transition between wake and sleep. It occurs upon falling asleep and during brief arousal periods within sleep and usually accounts for 2-5% of total sleep time. Stage N2 occurs throughout the sleep period and represents 45-55% of total sleep time. Stage N3 (delta or slow wave sleep) occurs mostly in the first third of the night and constitutes 5-15% of total sleep time. REM represents 20-25% of total sleep time and occurs in 4-5 episodes throughout the night.[2]

Sleep in infants

Infants have an overall greater total sleep time than any other age group; their sleep time can be divided into multiple periods. In newborns, the total sleep duration in a day can be 14-16 hours.

Over the first several months of life, sleep time decreases; by age 5-6 months, sleep consolidates into an overnight period with at least 1 nap during the day. REM sleep in infants represents a larger percentage of the total sleep at the expense of stage N3. Until age 3-4 months, newborns transition from wake into REM sleep. Thereafter, wake begins to transition directly into NREM.

Overall, electrocortical recorded voltage remains high during sleep, as it does during periods of wakefulness. Sleep spindles begin appearing in the second month of life with a density greater than that seen in adults (see Sleep Physiology). After the first year, the spindles begin decreasing in density and progress toward adult patterns. K complexes develop by the sixth month of life.

Sleep in the elderly

In elderly persons, the time spent in stage N3 sleep decreases, and the time in stage N2 compensatorily increases. Latency to fall asleep and the number and duration of overnight arousal periods increase. This often causes total time in bed to increase which can lead to complaints of insomnia. Sleep fragmentation results from the increase in overnight arousals and may be exacerbated by the increasing number of geriatric medical conditions, including sleep apnea, musculoskeletal disorders, and cardiopulmonary disease.[3]

Next

Sleep Physiology

Sleep is a state of unconsciousness in which the brain is relatively more responsive to internal than external stimuli. The predictable cycling of sleep and the reversal of relative external unresponsiveness are features that assist in distinguishing sleep from other states of unconsciousness. The brain gradually becomes less responsive to visual, auditory, and other environmental stimuli during the transition from wake to sleep, which is considered by some to be stage I of sleep.

Historically, sleep was thought to be a passive state that was initiated through withdrawal of sensory input. Currently, withdrawal of sensory awareness is believed to be a factor in sleep, but an active initiation mechanism that facilitates brain withdrawal is also recognized.[4] Both homeostatic factors (factor S) and circadian factors (factor C) interact to determine the timing and quality of sleep.

The "switch" for sleep is considered to be the ventrolateral preoptic nucleus (VLPO) of the anterior hypothalamus. This area becomes active during sleep and uses the inhibitory neurotransmitters GABA and galanin to initiate sleep by inhibiting the arousal regions of the brain. The VLPO innervates and can inhibit the wake-promoting regions of the brain including the tuberomammillary nucleus, lateral hypothalamus, locus coeruleus, dorsal raphe, laterodorsal tegmental nucleus, and pedunculopontine tegmental nucleus. The hypocretin (orexin) neurons in the lateral hypothalamus helps stabilize this switch. When the hypocretin neurons are lost, narcolepsy can result.[5]

The tuberoinfundibular region projects rostrally to the intralaminar nuclei of the thalamus and to the cerebral cortex. Inhibition of the tuberoinfundibular region is a critical step toward falling asleep because it results in functional disconnection between the brain stem and the more rostral thalamus and cortex. A decrease in ascending thalamic cholinergic transmissions occurs in association with decreasing cortical responsiveness. In addition to inhibiting higher cortical consciousness, the tuberoinfundibular tract projects caudally into the pontine reticular system and inhibits afferent transmissions from ascending cholinergic tracts.[6]

NREM is an active state that is maintained partly through oscillations between the thalamus and the cortex. The 3 major oscillation systems are sleep spindles, delta oscillations, and slow cortical oscillations. Sleep spindles, a hallmark of stage N2 sleep, are generated by bursts of hyperpolarizing GABAnergic neurons in the reticular nucleus of the thalamus. These bursts inhibit thalamocortical projection neurons. As deafferentation spreads, corticothalamic projections back to the thalamus synchronize. As hyperpolarization of the thalamic reticular neurons progresses, delta waves are produced by interactions from both thalamic reticular and cortical pyramidal sources. Slow cortical oscillations are produced in neocortical networks by cyclic hyperpolarizations and depolarizations.

Although the functions of NREM sleep remain speculative, several theories have been put forth. One theory proposes that decreased metabolic demand facilitates replenishment of glycogen stores. Another theory, which utilizes neuronal plasticity, suggests that the oscillating depolarizations and hyperpolarizations consolidate memory and remove redundant or excess synapses.[7]

REM sleep is generated by the cholinergic mediated "REM-on neurons" in the mesencephalic and pontine cholinergic neurons. The pedunculopontine tegmental nucleus (PPT) and the lateral dorsal tegmental (LDT) neurons use acetylcholine to trigger cortical desynchrony via the thalamus. Cortical desynchrony (also described as low voltage mixed frequency) is the EEG hallmark of REM sleep. An additional EEG hallmark of REM sleep is "sawtooth waves." A pharmacologic offshoot of the cholinergic mediation of REM sleep is stage R increasing with cholinergic agonists and decreasing with anticholinergics.

"REM-off neurons" are the monoadrenergic locus ceruleus and serotonergic raphe neurons. The REM-off neurons use norepinephrine, serotonin, and histamine to inhibit the REM-on cholinergic cells and stop REM sleep. These REM-off neurons become inactive during REM sleep. Medications, such as antidepressants, that increase the amount of norepinephrine or serotonin can cause a pharmacologic suppression of REM sleep.[6, 8]

REM sleep (stage R) is characterized by muscle atonia, cortical activation, low-voltage desynchronization of the EEG, and rapid eye movements.[9] REM sleep has a parasympathetically medicated tonic component and sympathetically mediated phasic component. The phasic portion of REM sleep is characterized by skeletal muscle twitches, increased heart rate variability, pupil dilation, and increased respiratory rate.[10]

Muscle atonia is present throughout REM sleep, except for phasic muscle twitches. It results from inhibition of alpha motor neurons by clusters of peri–locus ceruleus neurons, which are referred to collectively as the dorsolateral small cell reticular group.

Projection of the presumed cholinergic, dorsolateral, small-cell, reticular group is through the medullary reticular formation, which projects through the ventrolateral reticulospinal tract to inhibitory spinal and bulbar interneurons. Glycinergic interneurons produce postsynaptic inhibition and hyperpolarization of the spinal alpha motor neurons. Tonic cortical activation with EEG desynchronization is promoted by projections from cholinergic lateral dorsal tegmental and pedunculopontine tegmental neurons to the thalamic nuclei. Other projections through brainstem reticular formation neurons are likely to be involved as well.

Phasic rapid eye movements are composed of lateral saccades generated in the paramedian pontine reticular formation and vertical saccades thought to be generated in the mesencephalic reticular formation. REM density is a term used to describe the frequency per minute of the eye movement bursts.

Phasic pontine-geniculate-occipital (PGO) spikes are another neurophysiological feature of REM sleep seen in animals, but not humans. These spikes appear to be generated by lateral dorsal tegmental and pedunculopontine tegmental neuronal bursts. They are projected to the lateral geniculate and other thalamic nuclei, and then to the occipital cortex. PGO bursts precede rapid eye movements by several seconds. Increases in PGO bursts are seen after REM sleep deprivation.

During NREM sleep, the metabolic demand of the brain decreases. This is supported by oxygen positron emission tomography (PET) studies, which show that, during NREM sleep, the blood flow throughout the entire brain progressively decreases. PET studies also show that, during REM sleep, blood flow increases in the thalamus and the primary visual, motor, and sensory cortices, while remaining comparatively decreased in the prefrontal and parietal associational regions. The increase in blood flow to the primary visual regions of the cortex may explain the vivid nature of REM dreaming, while the continued decrease in blood flow to the prefrontal cortex may explain the unquestioning acceptance of even the most bizarre dream content.[11, 12]

Previous
Next

Circadian Rhythms That Influence Sleep

Circadian sleep rhythm is one of the several intrinsic body rhythms modulated by the hypothalamus.[13] The suprachiasmatic nucleus sets the body clock to approximately 24.2 hours, with both light exposure and schedule clues entraining to the 24.2-hour cycle.[14] The retinohypothalamic tract allows light cues to directly influence the suprachiasmatic nucleus. Light is called a zeitgeber, a German word meaning time-giver, because it sets the suprachiasmatic clock. A practical purpose has been proposed for the circadian rhythm, using the analogy of the brain being somewhat like a battery charging during sleep and discharging during the wake period.

The nadir of the rhythm is in the early morning. The downswing in circadian rhythm prior to the nadir is thought to assist the brain to remain asleep overnight for full restoration by preventing premature awakening. The morning upswing then facilitates awakening and through the day acts as a counterbalance to the progressive discharge of wake neuronal activity. After the circadian apex in the early evening, the downswing aids sleep initiation. This model explains the relatively steady cognitive function throughout wakefulness.

Body temperature cycles are also under hypothalamic control. An increase in body temperature is seen during the course of the day and a decrease is observed during the night. The temperature peaks and troughs are thought to mirror the sleep rhythm. People who are alert late in the evening (ie, evening types) have body temperature peaks late in the evening, while those who find themselves most alert early in the morning (ie, morning types) have body temperature peaks early in the evening.

Melatonin has been implicated as a modulator of light entrainment. It is secreted maximally during the night by the pineal gland. Prolactin, testosterone, and growth hormone also demonstrate circadian rhythms, with maximal secretion during the night.[15]

For excellent reviews of clinically applicable information on circadian rhythm disorders, please refer to Sack, 2007.[16, 17]

Previous
Next

Effects of Sleep Deprivation

Glucose-PET studies in individuals deprived of sleep have shown that after 24 hours of sustained wakefulness, the metabolic activity of the brain decreases significantly (up to 6% for the whole brain and up to 11% for specific cortical and basal ganglionic areas). In humans, sleep deprivation also results in a decrease in core body temperature, a decrease in immune system function as measured by white cell count and activity, and a decrease in the release of growth hormone. Sleep deprivation has also been implicated as a cause of increased heart rate variability.[18, 19, 20]

As the function of sleep has not been fully determined, the absolute number of hours necessary to fulfill its function is still unknown. Some individuals claim full effectiveness with only 3-5 hours of sleep per night, while some admit needing at least 8 hours of sleep per night (or more) to perform effectively. Sleep deprivation is best defined at this point by group means and in terms of the tasks impaired.

With decreased sleep, higher-order cognitive tasks are affected early and disproportionately. Tests requiring both speed and accuracy demonstrate considerably slowed speed before accuracy begins to fail. Total sleep duration of 7 hours per night over 1 week has resulted in decreased speed in tasks of both simple reaction time and more demanding computer-generated mathematical problem solving. Total sleep duration of 5 hours per night over 1 week shows both decrease in speed and the beginning of accuracy failure.[21]

Total sleep duration of 7 hours per night over 1 week leads to impairment of cognitive work requiring simultaneous focus on several tasks. In driving simulations, for example, accidents increase progressively as total sleep duration is decreased to 7, 5, and 3 hours per night over 1 week. In the same simulations, 3 hours total sleep duration was associated with loss of ability to simultaneously appreciate peripheral and centrally presented visual stimuli, which could be termed as a form of visual simultanagnosia and peripheral visual neglect.[22] }[23, 24]

In tasks requiring judgment, increasingly risky behaviors emerge as the total sleep duration is limited to 5 hours per night. The high cost of an action seemingly is ignored as the sleep-deprived individual focuses on limited benefit.[22]

One explanation for decreasing performance in sleep deprivation is the occurrence of microsleep. Microsleep is defined as brief (several seconds) runs of theta or delta activities that break through the otherwise beta or alpha EEG of waking. It has been seen to increase with sleep deprivation. In studies in which polysomnography is recorded simultaneously, microsleep impairs continuity of cognitive function and occurs prior to performance failure. However, the occurrence of microsleep has not been shown in most instances of polysomnographic correlated performance failure. Other explanations for performance impairments include sensory perceptual impairments such as the development of visual neglect phenomena.[25]

These experimental findings can be explained by glucose-PET studies, which show that individuals deprived of sleep for 24 hours have a decrease in metabolism in the prefrontal and parietal associational areas. The areas most important for judgment, impulse control, attention, and visual association are disproportionately hypometabolic compared to the primary sensory and motor areas necessary for receiving and acting upon the environmental inputs. This finding leads to the hypothesis that the areas of the brain most responsible for higher-order cognition are to some degree less functional during sleep-deprived waking activity.[12, 26]

Sleep deprivation is a relative concept. Small amounts of sleep loss (eg, 1 hour per night over many nights) have subtle cognitive costs, which appear to go unrecognized by the individual experiencing the sleep loss. More severe restriction of sleep for a week leads to profound cognitive deficits similar to those seen in some stroke patients, which also appear to go unrecognized by the individual. The lack of recognition of the effects of sleep deprivation appears to be a constant feature, one which, it is hoped, will be overcome by further research and education.[22, 27]

Short-term sleep deprivation has been implicated in contributing to obesity as well as glycemia dysregulation contributing to poor control of type II diabetes.[28, 29, 30, 31]

Previous
 
Contributor Information and Disclosures
Author

M Suzanne Stevens, MD, MS, D-ABSM Assistant Clinical Professor, Director of Sleep Medicine Clinic, Department of Neurology, University of Kansas School of Medicine; Consulting Staff, Sleep Disorders Institute; Medical Director, Sleep Resolutions

M Suzanne Stevens, MD, MS, D-ABSM is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS Professor with Tenure, Departments of Neurology, Pharmacology, and Physiology, Assistant Dean for the MD/PhD Program, Program Director of the Clinical Neurophysiology Fellowship, University of Texas School of Medicine at San Antonio; Co-Director, South Texas Comprehensive Epilepsy Center, University Hospital System; Director, San Antonio Veterans Affairs Epilepsy Center of Excellence and Neurodiagnostic Centers, Audie L Murphy Veterans Affairs Medical Center

Jose E Cavazos, MD, PhD, FAAN, FANA, FACNS is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Neurological Association, Society for Neuroscience, American Epilepsy Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Brain Sentinel, consultant.<br/>Stakeholder (<5%), Co-founder for: Brain Sentinel.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cyberonics; Eisai; Lundbeck; Sunovion; UCB; Upsher-Smith<br/>Serve(d) as a speaker or a member of a speakers bureau for: Cyberonics (Livanova); Eisai; Lundbeck; Sunovion; UCB<br/>Received research grant from: Cyberonics (Livanova); GW, Lundbeck; Sunovion; UCB; Upsher-Smith.

Additional Contributors

Carmel Armon, MD, MSc, MHS Chair, Department of Neurology, Assaf Harofeh Medical Center, Tel Aviv University Sackler Faculty of Medicine, Israel

Carmel Armon, MD, MSc, MHS is a member of the following medical societies: American Academy of Neurology, Massachusetts Medical Society, American Academy of Sleep Medicine, American Stroke Association, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American College of Physicians, American Epilepsy Society, American Medical Association, American Neurological Association, Sigma Xi

Disclosure: Received research grant from: Neuronix Ltd, Yoqnea'm, Israel.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Michael B Russo, MD to the development and writing of this article.

References
  1. Iber C, Ancoli-Israel S, Chesson AL, Quan SF. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Westchester, IL: American Academy of Sleep Medicine; 2007.

  2. Kryger MH, Roth T, Dement WC, eds. Principals and Practice of Sleep Medicine. Philadelphia, Pa: Saunders; 2005.

  3. Zdanys KF, Steffens DC. Sleep Disturbances in the Elderly. Psychiatr Clin North Am. 2015 Dec. 38 (4):723-41. [Medline].

  4. Siegel JM. Clues to the functions of mammalian sleep. Nature. October 2005. 437(7063):1264-1271. [Medline].

  5. Siegal JM, Moore R, Thannickal T, et al. A Brief History of Hypocretin/Orexin and Narcolepsy. Neuropsychopharmacology. 2001. 25:S14-S20. [Full Text].

  6. Espana, Rodrigo A, Scammell, Thomas E. Sleep Neurobiology for the Clinician. Sleep. 2004. 27:811-820.

  7. Chokroverty S. Physiologic changes in sleep. Sleep Disorders Medicine. Boston: Butterworth-Heinemann; 1999. 95-126.

  8. Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature. 2005 Oct 27. 437(7063):1257-63. [Medline].

  9. Morrison AR. Coming to grips with a "new" state of consciousness: the study of rapid-eye-movement sleep in the 1960s. J Hist Neurosci. 2013. 22(4):392-407. [Medline].

  10. Tobaldini E, Nobili L, Strada S, Casali KR, Braghiroli A, Montano N. Heart rate variability in normal and pathological sleep. Front Physiol. 2013 Oct 16. 4:294. [Medline].

  11. Braun AR, Balkin TJ, Wesenten NJ, et al. Regional cerebral blood flow throughout the sleep-wake cycle. An H2(15)O PET study. Brain. 1997 Jul. 120 ( Pt 7):1173-97. [Medline]. [Full Text].

  12. Desseilles M, Dang-Vu T, Schabus M, Sterpenich V, Maquet P, Schwartz S. Nueroimaging insights into the pathophysiology of sleep disorders. Sleep. June 2008. 31(6):777-94. [Medline].

  13. Anderson KN, Catt M, Collerton J, Davies K, von Zglinicki T, Kirkwood TB, et al. Assessment of sleep and circadian rhythm disorders in the very old: the Newcastle 85+ Cohort Study. Age Ageing. 2013 Oct 11. [Medline].

  14. Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science. 1999 Jun 25. 284(5423):2177-81. [Medline].

  15. Tosini G, Pozdeyev N, Sakamoto K, et al. The circadian clock system in the mammalian retina. Bioessays. 2008 Jul. 30(7):624-33. [Medline]. [Full Text].

  16. Sack RL, Auckley D, Auger R, Carskadon MA, Wright KP, Vitello MV, et al. Circadian Rhythm Disorders: Part 1, Basic Principles, Shift Work and Jet Lab Disorders. Sleep. November 2007. 30(11):1460-83. [Medline]. [Full Text].

  17. Sack RL, Auckley D, Auger RR, et al. Circadian rhythm sleep disorders: Part II, advanced sleep phase disorder, delayed sleep phase disorder, free-running disorder and irregular sleep-wake rhythtm. Sleep. November 2007. 30(11):1484-501. [Medline]. [Full Text].

  18. Banks S, Dinger DF. Behavioral and Physiological Consequences of Sleep Restriction. Jounal of Clinical Sleep Medicine. August 2007. 3(5):519-528. [Medline]. [Full Text].

  19. Bonnet MH, Arand DL. We are chronically sleep deprived. Sleep. 1995 Dec. 18(10):908-11. [Medline].

  20. Moldofsky H. Sleep and the immune system. Int J Immunopharmacol. 1995 Aug. 17(8):649-54. [Medline].

  21. Gomes AA, Tavares J, de Azevedo MH. Sleep and Academic Performance in Undergraduates: A Multi-measure, Multi-predictor Approach. Chronobiol Int. 2011 Nov. 28(9):786-801. [Medline].

  22. Thorne D, Thomas M, Russo M, et al. Performance on a driving-simulator divided attention task during one week of restricted nightly sleep. Sleep. 1999. 22(Suppl 1):301.

  23. Boto LR, Crispim JN, de Melo IS, Juvandes C, Rodrigues T, Azeredo P, et al. Sleep deprivation and accidental fall risk in children. Sleep Med. 2011 Nov 4. [Medline].

  24. Howard ME, Jackson ML, Berlowitz D, O'Donoghue F, Swann P, Westlake J, et al. Specific sleepiness symptoms are indicators of performance impairment during sleep deprivation. Accid Anal Prev. 2013 Sep 13. 62C:1-8. [Medline].

  25. Veauthier C. Younger age, female sex, and high number of awakenings and arousals predict fatigue in patients with sleep disorders: a retrospective polysomnographic observational study. Neuropsychiatr Dis Treat. 2013. 9:1483-94. [Medline]. [Full Text].

  26. Baird AL, Coogan AN, Siddiqui A, Donev RM, Thome J. Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Mol Psychiatry. 2011 Nov 22. [Medline].

  27. Thorne D, Thomas M, Sing H, et al. Driving-simulator accident rates before, during, and after one week of restricted night sleep. Sleep. 1998. 21(Suppl 3):235.

  28. Knutson KL, Ryden AM, Mander BA, Van Cauter E. Role of sleep duration and quality in tihe risk and severity of type 2 diabetes mellitus. Archives of Internal Medicine. 18 Sep 2006. 166(16):1768-1774.

  29. Knutson KL, Spiegel K, Penev P, VanCauter E. The Metabolic Consequence of Sleep Deprivation. Sleep Med Review. June 2007. 11(3):163-178. [Medline]. [Full Text].

  30. Knutson, Kristen L.; Spiegel, Karine; Penev, Plamen; Van Cauter, Eve. The Metabolic Consequences of Sleep Deprivation. Sleep Medicine Review. 2007. 11:163-178. [Full Text].

  31. Hanlon EC, Tasali E, Leproult R, Stuhr KL, Doncheck E, de Wit H, et al. Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-arachidonoylglycerol. Sleep. 2015 Nov 19. [Medline].

  32. Dinges DF, Douglas SD, Hamarman S, et al. Sleep deprivation and human immune function. Adv Neuroimmunol. 1995. 5(2):97-110. [Medline].

  33. Miller JD, Morin LP, Schwartz WJ, Moore RY. New insights into the mammalian circadian clock. Sleep. 1996 Oct. 19(8):641-67. [Medline].

  34. Stern J. Eye activity measures of fatigue, and napping as a countermeasure. [USDOT Technical Report] FHWA-MC-99-028. January 1999. 26.

  35. Thomas M, Sing H, Belenky G. Neural basis of alertness and cognitive performance impairments during sleepiness. II. Effects of 48-72 hours of sleep deprivation on waking human regional brain activity. Thalamus Relat Syst. 2003. 2:199-229.

  36. Thomas M, Sing H, Belenky G, et al. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. J Sleep Res. 2000 Dec. 9(4):335-52. [Medline].

  37. Welsh A, Thomas M, Thorne D, et al. Effect of 64 hours of sleep deprivation on accidents and sleep events during a driving simulator. Sleep. 1998. 21(Suppl 3):234.

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.