March 18, 2024	PSY 340 Brain and Behavior Class 22: Stages of Sleep & Brain Mechanisms

A. Sleep and Other Levels of Consciousness

There are multiple levels of consciousness that humans may experience from (1) being completely awake, alert, and aware to (2) a deep level of coma. The diagram on the right shows the varying levels of consciousness that neuropsychologists generally discuss. Note that these different levels of consciousness are modeled using two axes: (1) the horizontal axis considers the level of "wakefulness, eye opening, and arousal" running from none/minimal to moderate/high while( 2) the vertical axis is concerned with the content of consciousness, that is, how aware the individual is of the external environment (from none/minimal to moderate/high). 

For the purposes of this course, consider the following five brain states:

• Sleep: "[S]leep is an actively induced, highly organized brain state" marked by these four qualities --

   

  1. Reduced motor activity

  2. Lowered response to sensory stimulation

  3. Adoption of stereotypical postures such as lying down with the eyes closed, and

  4. Easy reversibility (compared to coma, stupor, hibernation, etc.) [Rechtschaffen & Siegel, 2000]

• Vegetative State: alternation between sleep and moderate arousal without awareness of surroundings. No clear sign of purposeful activity though there may be some cognitive activity. The term 'vegetative" -- while widely used over the decades -- has been challenged as both imprecise and pejorative. Laureys et al (2010) now prefers "Unresponsive Wakefulness Syndrome" while NYU neuroscientist, Joseph LeDoux, has recently (2023) proposed "Persistent Visceral State."
  

• Minimally Conscious State: Brief periods of purposeful activity and some speech comprehension (but no speech production). Some patients with this condition do improve over a period of time with greater levels of activity and awareness. Rarely do they completely recover to the point that they can live independently or without significant assistance (Maiese, 2022).
   
  
• Coma: unconsciousness due to head trauma, disease, or stroke in which an individual cannot be awakened or brought to consciousness.

• Brain Death: no sign of brain activity and no response to stimuli (for 24 hours). These criteria include (1) a total unawareness to externally applied stimuli, (2) no movements or breathing, (3) no reflexes [e.g., pupils fixed and dilated], and a flat EEG. The tests for 1 through 4 must be repeated 24 hours later with no change.
  
• Originally proposed by the Ad Hoc Committee of the Harvard Medical School to Examine the Definition Brain Death in 1968
  
• The brain cannot itself sustain the body without significant life support.
  
• "The term brain death is defined as "irreversible unconsciousness with complete loss of brain function," including the brain stem, although the heartbeat may continue." (Encyclopedia of Death & Dying)
• Note, though, that there has been continuing controversy over these criteria.
  

Image from Laureys, S. (2005). Death, unconsciousness and the brain. Nature Reviews Neuroscience, 6, 899-909, fig. 2.

B. The Stages of Sleep

• The overall patterns of electrical activity of the brain can be measured by a recording device attached to the head called an electroencephalograph (EEG).

• The EEG has allowed us to understand better the activity of the brain in both the awake and sleep states.
    
• When we are awake ("Stage W" in AASM 2007 system) we are in one of two different states according to the EEG, that is,

• a relaxed mental state (alpha waves) or
  
• an alert mental state (beta waves).
  

    

• When we are asleep, we enter into several different states including theta & delta waves which are much slower than those in the awake state.

•  A polysomnograph combines the EEG, heart beat, breathing rate, oxygen (O2) level, & eye movement detector (electrooculograph EOG). For more details see: Polysomnography {Wikipedia}
  

The chart above is a revision based on the AASM Sleep Scoring Manual (Iber et al., 2007; see also Schartzmiller et al., 2010).
It replaces the information in our text.

 

Non-REM Sleep includes Stages N1 to N3 Stage N1: Mixed frequencies esp. theta waves Stage N2: Sleep spindles and K-complex waves Stage N3: Slow waves (delta) > 20% ("deep sleep")    May involve dreaming, but these dreams tend to be less intense than in REM sleep. Constitutes about 75-80% of total sleep time in adults (Porter et al., 2018)	Stage R (REM ("Rapid Eye Movement") Sleep) (= "paradoxical" sleep in animals who do not move eyes) Brain waves somewhat similar to awake state or Stage N1 sleep (low-voltage, mixed/fast waves) Rapid eye movements Almost complete loss of muscle control ("atonia") Often, penile erection (males) & vaginal moistening (females) Easy to awaken Usually a time of more intensive, vivid dreams
Sleep Cycle Movement from Stage N1 to Stage N3 and back to Stage N1 Stage R (REM Sleep) substitutes for Stage N1 sleep during cycle Between 90-110 minutes to move through an entire cycle Each night = 3 to 5 complete cycles Toward the end of sleeping, individual often does not reach Stage N3

Note that the Sleep Cycle chart above is idealized and somewhat unrealistic. An example of someone who is having trouble sleeping might look like this:

C. Brain Mechanisms of Wakefulness & Arousal
 

D. Sleep and the Inhibition of Brain Activity

• Sleep requires a lowering of sensory input to the cortex. There is an overall decrease of activity in the thalamus where the neurons become hyperpolarized in sleep.
  
• The role of GABA (see figure above) is to inhibit signaling between neurons in localized areas of the cerebral cortex.
• Similarly, during REM sleep, the pons & medulla send signals to the spinal neurons controlling large muscles (legs, arms) to inhibit their movement. Occasionally, the signals from the pons/medulla doesn't shut off when people awaken and they experience sleep paralysis: they are aware but cannot move their muscles.
  
• Sleepwalking (somnambulism) ==> much of the brain is asleep, but the motor and a few other areas are not.
  

E. Brain Function in REM Sleep: PGO Waves

• Activity in the pons triggers REM sleep which is associated with a distinctive pattern: PGO waves (see figure on right)
• The pons also sends instructions to spinal cord to inhibit motor neurons associated with large muscles
• Activity decreases in prefrontal cortex, primary visual cortex, & motor cortex, but increases in temporal & parietal cortex
• Acetylcholine (ACh) moves sleeper into REM
• Carbachol (which stimulates ACh synapses) quickly moves sleeper into REM
• Serotonin & norepinepherine interrupt or shorten REM

F. Sleep Disorders (Parasomnias)  [Overview at the Cleveland Clinic]

These are often called parasomnias ("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" Wikipedia, 20170317)

1. Insomnia

= not sleeping enough due to (1) difficulty falling asleep (onset insomnia), (2) frequent awakening during sleep (maintenance insomnia), or (3) waking up too early (termination insomnia)

• About 50% of adults report insomnia at some point in their lives (WHO, 2009)
  
• Can be caused by noise, temperature, stress, diet, medications, and some psychiatric or neurological disorders (e.g., epilepsy, Parkinson's, depression, anxiety)
• Insomnia is related to a 3+ greater risk of anxiety and 2.5-2.8 greater risk for major depression, and a somewhat smaller risk of alcohol abuse in adults (Baglioni et al., 2011,  Hertenstein et al. 2019)
• Recent GWAS studies in Europe/U.K. suggest that there may be a genetic link between some forms of insomnia and major psychological disorders (such as depression), cardiovascular problems, and metabolic disorders [Type II diabetes] (Makin, 2019)
• May be caused by prolonged use of sleeping pills!
• Often associated with poor sleep hygiene, e.g., use of caffeine or alcohol in the evening, exercise before bedtime, bright lights.
• May be related to shifts in circadian rhythms

2. Sleep Apnea (in Greek, a = not; pneuma = breath) = intermittent stopping of breathing during sleep due to obstruction of the airway or central nervous system problems

• Sleep apnea occurs in about 25% of men and nearly 10% of women
  
• Often caused by obesity, hormonal imbalances, genetics, or even deterioration of brain mechanisms in old age.
• Requires a polysomnograph sleep test for diagnosis
• Treated by various devices such as a "continuous positive airway pressure" (CPAP) device
• If left untreated, sleep apnea can result in a number of health problems including hypertension, stroke, arrhythmias, cardiomyopathy (enlargement of the muscle tissue of the heart), heart failure, diabetes, obesity and heart attacks. [Cleveland Clinic]
  

3. Narcolepsy = frequent, unexpected periods of sleep or sleepiness during the day.

Includes one or more of these symptoms:

1. Gradual/sudden onset of sleepiness
2. Cataplexy: muscle weakness while remaining awake. Often triggered by strong emotions. Occurs occasionally.
3. Sleep paralysis: inability to move when falling asleep or waking up
4. Hypnagogic hallucinations: dreamlike experiences at the beginning of sleep.

Equivalent to REM-like sleep intruding into the awake state

• Axons using the neurotransmitter orexin (= hypocretin) in the hypothalamus connect to areas which increase arousal & wakefulness. Humans with narcolepsy do not have these cells in the hypothalamus (perhaps due to an autoimmune disorder).

• "Degeneration of [hypocretin] neurons or genetic mutations that prevent the normal synthesis of [hypocretin] or of its receptors causes human and animal narcolepsy. Narcolepsy is characterized by an impaired ability to maintain alertness for long periods and by sudden losses of muscle tone (cataplexy). Administration of [hypocretin] can reverse symptoms of narcolepsy in animals, may be effective in treating human narcolepsy, and may affect a broad range of motivated behaviors" (Siegel, 2004, Abstract)

Treated with stimulants, e.g., Ritalin or Cylert

4. Periodic Limb Movement Disorder

 = during NREM sleep individual moves legs and sometimes arms every 20-30 seconds for minutes or hours.

• Treated with tranquilizers. This is NOT "restless leg syndrome" which is less common.

5. REM Behavior Disorder

= during REM sleep individual moves vigorously or violently (kick, punch, etc.); dreams of violent nature

• occurs mostly in older men (> 60 years old) with brain diseases, esp. Parkinson's disease.

6. Night Terrors

 = an experience intense anxiety involving crying and screaming, but often not actually awakening.

• Occurs during NREM sleep, often earlier in the sleep cycle
• Most frequently seen in children
• "Sleep terrors are most likely to happen during the first third of the night when child is in a deep sleep. They are not awake during these episodes. Sleep terrors usually last five to 10 minutes and can be very alarming. Your child may shout, scream, kick and flail, sit up suddenly and appear terrified. Despite the intensity of sleep terrors, children don’t remember it happening in the morning, unlike a nightmare." [Cleveland Clinic]
  

7. Sleep Talking

• We all do it.

8. Sleepwalking

• usually seen in children 2-12 years old
• generally harmless; occasionally individuals have suffered accidents during sleepwalking.
• cause(s) is/are unknown. Possibly related to genetics.
  
• no danger to wake the sleepwalking person up
• no treatment other than making sure that the person's environment is safe.

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References

Ad Hoc Committee of the Harvard Medical School (1968). A definition of irreversible coma: Report of the ad hoc committee of the Harvard Medical School to examine the definition of brain death. Journal of the American Medical Association 205, 337–340. https://doi.org/10.1001/jama.1968.03140320031009

Baglioni et al. (2011) Insomnia as a predictor of depression - A meta-analytic evaluation of longitudinal epidemiological studies. Journal of Affective Disorders, 135, 10-19. https://doi.org/10.1016/j.jad.2011.01.011

Gosseries, O., Vanhaudenhuyse, A., Bruno, M.-A., et al. (2011). Disorders of consciousness: Coma, vegetative and minimally conscious states. In D. Cvetkovic & I. Cosic (Eds.), States of Consciousness (pp. 29-55). Springer-Verlag. https://doi.org/10.1007/978-3-642-18047-7_2

Hertenstein et al. (2019) Insomnia as a predictor of mental disorders - A systematic review and meta-analysis. Sleep Medicine Reviews, 43, 96-105. https://doi.org/10.1016/j.smrv.2018.10.006

Iber, C., Ancoli-Israel, S., Chesson, A., & Quan, S. F. (2007). The AASM manual for the scoring of sleep and associated events. Westchester, IL: American Academy of Sleep Medicine. Available at https://www.sleep.pitt.edu/wp-content/uploads/2020/03/The-AASM-Manual-for-Scoring-of-Sleep-and-Associated-Events-2007-.pdf

Laureys, S. (2005) Science and society: Death, unconsciousness and the brain. Nature Reviews Neuroscience, 6(11), 899-909. https://doi.org/10.1038/nrn1789

Laureys, S., Celesia, G. G., Cohadon, F., Lavrijsen, J., León-Carrión, J., Sannita, W. G., ... & European Task Force on Disorders of Consciousness. (2010). Unresponsive wakefulness syndrome: A new name for the vegetative state or apallic syndrome. BMC Medicine, 8, 1-4. http://www.biomedcentral.com/1741-7015/8/68

LeDoux, J. E. (2023). The four realms of existence: A new theory of being human. Cambridge, MA: Harvard University Press.

Maiese, K. (2022, Sept.). Minimally conscious state. Merck Manual Consumer Version [Online]. https://www.merckmanuals.com/home/brain,-spinal-cord,-and-nerve-disorders/coma-and-impaired-consciousness/minimally-conscious-state

Makin, S. (2019, March 12). A genetics basis for insomnia emerges from the twilight. Scientific American [online]. Retrieved from https://www.scientificamerican.com/article/a-genetic-basis-for-insomnia-emerges-from-the-twilight/

Porter, R. S.,Kaplan, J. L, Lynn, R. B., & Reddy, M. T. (Eds.). (2018).  The Merck manual of diagnosis and therapy (20th ed). Kenilworth, NJ: Merck Sharpe & Dohme Corp.

Rechtschaffen, A. & Kales, A. (1968). A manual of standardized terminology, techniques, and scoring system for sleep stages of human subjects. National Institutes of Health Publication No. 204. Washington, DC: U.S. Government Printing Office. Available at https://archive.org/details/RKManual/page/n7/mode/2up

Rechtschaffen, A., & Siegel, J. M. (2000). Sleep and dreaming. In E. R. Kandell, J. H. Schwartz, & T. M. Jessel (Eds.), Principles of neuroscience (4th ed.; pp. 936-947). New York: McGraw-Hill. Available at https://www.semel.ucla.edu/sites/default/files/publications/sleep-and-dreaming.pdf

Shatzmiller, R. A., Gonzalez A. A., Ko, D. Y., & Zeidler, M. R. (2010). Sleep stage scoring. WebMD: eMedicine Neurology. http://emedicine.medscape.com/article/1188142-overview

Siegel, J. M. (2004). Hypocretin (Orexin): Role in normal behavior and neuropathology. Annual Review of Psychology, 55, 125-148. https://10.1146/annurev.psych.55.090902.141545

World Health Organization (WHO). (2009). Pharmacological Treatment of Mental Disorders in Primary Health Care. Geneva, Switzerland. Available at https://www.who.int/publications/i/item/9789241547697

The first version of this page was posted on March 6, 2005.