1. IzBen C. Williams, MD, MPH Instructor

2. Lecture 9 NORMAL SLEEP AND SLEEP-WAKE DISORDERS

3. DRIVES Sleep should be considered in the context of biological “drives” DRIVES are innate biological forces, which are manifested in all forms of animal life. Some others are Hunger, thirst, pain, temperature, sex, Sleep has many of the attributes of a drive The only way to overcome that drive is to sleep

4. DRIVES Sleep deprivation leads to increased urge to sleep and to extended periods of sleep immediately following the deprivation After several days of sleep deprivation, a confusional state may occur with Disordered attention, emotional lability Reduced memory, Delusions Hallucinations (occasionally)

5. DRIVES The physiologic function of sleep is unclear Our current understanding suggests that people follow the urge to sleep in order to avoid the consequences of sleep deprivation Freud’s explanation was that sleep provided a time for dreaming and discharging unconscious wishes, and for expressing unconscious fantasies which are unacceptable to conscious thought and expression

6. Sleep Physiology Most animals experience a daily cycle of changes in levels of arousal as well as sleep and waking Normal sleep is an active process that requires activity of neurons in the brainstem Neurophysiologic studies demonstrate that nerve cells in the pontine reticular formation begin to discharge minutes prior to the onset of certain stages of sleep

7. Sleep Physiology Our awake state is characterized by two associated EEG patterns Alpha waves: over the occipital and parietal lobes are seen when a person relaxes with eyes closed Beta waves: over the frontal lobes are seen with active concentration Sleep latency (time between going to bed and falling asleep) is usually less than 20 minutes

8. Normal Sleep Physiology During sleep, we usually pass through five Stages Stages 1, 2, 3, and 4 also called non-rapid eye movement sleep) or slow wave sleep, and Stage 5 - Rapid Eye Movement (REM) sleep These phases progress in a cycle from the waking state, then the cycle restarts The time required to pass through the complete sequence of sleep stages is about 90 minutes, and the cycle is repeated some three to five times each night

9. Normal EEG

10. Normal Sleep Architecture Sleep architecture: The characteristic map of EEG tracings reflecting the various stages of sleep Sleep architecture: Changes with age….the elderly have: reduced REM sleep reduced delta sleep (stage 3-4, or slow wave) reduced total sleep time Increased night-time wakenings

11. Sleep Architecture

12. Normal Sleep Architecture Sleep architecture: Sedative agents (eg. alcohol, barbiturates and benzodiazepines) are also associated with reduced REM sleep and delta sleep Most delta sleep occurs during first half of sleep cycle The longest REM periods occur during the second half of the sleep cycle

14. Normal Sleep Architecture During REM sleep high levels of brain activity occur: Average time between first REM period and falling asleep (Rem latency) is 90 minutes REM periods lasting aprox. 10-40 minutes each occur about every 90 minutes throughout the night REM rebound: making up for lost REM sleep with subsequent increased REM sleep Extended REM deprivation or total sleep deprivation may result in transient psychiatric symptomatology, usually anxiety or psychosis

15. Hypnogram

16. Neurotransmitters and Sleep Neurotransmitters control many aspects of sleep. Falling asleep Staying asleep Getting deep sleep (REM) The waking process

17. Neurotransmitters and Sleep Neurotransmitters may play either an excitatory role or an inhibitory role in sleep: Excitatory: energizing, motivating, provide focus, revving up the system Inhibitory: calming, relaxing, sleep inducing, slowing down the system

18. Neurotransmitters and Sleep Elevated levels of excitatory neurotransmitters can lead to decrease in total sleep time and REM sleep Excitatory neurotransmitters related to sleep: Epinephrine (adrenalin) Norepinephrine (noradrenalin) Phenylethylamine (PEA) Glutamate Histamine

19. Neurotransmitters and Sleep Acetyl Choline: Increased levels of Acetyl Choline in the reticular formation, both increase sleep time and REM sleep. Acetyl choline levels, total sleep time, and REM sleep decrease in normal aging as well as in Alzheimer’s disease

20. Neurotransmitters and Sleep Increased levels of inhibitory neurotransmitters can increase both sleep time and delta sleep. Inhibitory neurotransmitters related to sleep: Serotonin, GABA, Taurine, Glycine Damage to the dorsal raphe nuclei, which produce serotonin, decrease both these measures Treatment with antidepressants, which increase serotonin availability, can improve sleep in depressed patients

21. Neurotransmitters and Sleep Dopamine: Increased levels of Dopamine decrease total sleep time. Treatment with antipsychotics, which block dopamine receptors, may improve sleep in patients with psychotic symptoms

22. Neurotransmitters and Sleep During the day, excitatory neurotransmitter levels are high, providing the energy and motivation necessary to carry out normal functions. During the evening, excitatory levels drop and inhibitory transmitter levels rise, preparing the body for rest.

23. Neurotransmitters and Sleep Around bed time, the drop in excitatory neurotransmitter levels and rise in inhibitory levels signal the production of melatonin. During the night, low levels of excitatory transmitters and increased levels of inhibitory transmitters and melatonin are what the body needs for deep, restful sleep.

24. Hormones and sleep Melatonin: Known as the “sleep hormone”, and is responsible for inducing sleep in humans. Melatonin is made from serotonin in the body. Low levels of serotonin could lead to low levels of melatonin.

25. Hormones and sleep Cortisol, the “stress hormone” is produced by the adrenal gland. People experiencing high amounts of stress may have elevated cortisol levels. High night time cortisol levels can cause sleep disturbances.

26. Sleep-Wake Disorders Classification of Sleep Disorders Classification of Sleep Disorders A. A. Dyssomnias: Characterized by problems in the timing, quality or amount of sleep. They include: Insomnia Hypersomnia Narcolepsy, Kleine-Levin Syndrome (primary hypersomnias ) Sleep Apnea (breathing related sleep disorder) as well as: Circadian rhythm sleep disorder, Nocturnal myoclonus (restless leg syndrome)

27. Sleep-Wake Disorders Classification of Sleep Disorders Classification of Sleep Disorders B. B. Parasomnias: characterized by abnormalities in physiology or in the behavior associated with sleep. They include: Bruxism Sleepwalking Sleep terror REM sleep behavior Nightmare disorders

28. Sleep-Wake Disorders Insomnia: Insomnia: Difficulty falling asleep or staying asleep that occurs…….. Three times a week for at least one month Leads to sleepiness during the day, or Causes problems fulfilling social or occupational obligations. It is present in at least 30% of the population

29. Sleep-Wake Disorders Factors contributing to Insomnia: Factors contributing to Insomnia: Situational problems Medical disorders Aging Drug-related episodes Psychological conditions (affective, anxiety, psychotic)

30. Sleep-Wake Disorders Hypersomnia Hypersomnia 1) Narcolepsy: (usually occurs before age 40, and includes one or more of the following conditions) i. Sleep attacks: sudden, reversible, short, occurs during any type of activity; direct progression to REM sleep; awakes refreshed; refractory period of 1-5 hrs before another attack ii. Cataplexy: sudden loss of muscle tone; small group to general; slumping to ground; often initiated by emotional outburst; lasts seconds to 30 minutes

31. Sleep-Wake Disorders Hypersomnia Hypersomnia 1) Narcolepsy: (cont’d) iii. Sleep paralysis: flaccid muscle tone with full consciousness, either during awakening or while falling asleep; there’s usually intense fear, occasionally followed by auditory hallucinations iv. Hallucinations (hypnagogic or hypnopompic) The occurrence of symptoms of the narcoleptic triad are: 1) sleep attacks almost 100%; sleep attacks and cataplexy ~70%; sleep paralysis alone ~5%

32. Sleep-Wake Disorders Hypersomnia Hypersomnia 2) Kleine-Levin syndrome: Hypersomnic attacks may last up to 20 hrs, 3-4 times a year, followed by confusion upon awakening. This syndrome is a separate entity from narcolepsy

33. Sleep-Wake Disorders Hypersomnia Hypersomnia 3) Sleep apnea: Apneic episodes occur in both REM and NREM sleep; noisy, stertorous snoring and hypersomnolence the next day, are common; i. Central apnea: cessation of respiratory movement with loss of air flow ii. Obstructive apnea: persistent respiratory effort but upper airway blockage

34. Sleep-Wake Disorders Stage 4 Sleep Disorders Stage 4 Sleep Disorders Enuresis: seen with variable nightly occurrence in children; usually stage four Somnambulism: mostly in children, usually in stage 3 and 4 (amnesia for episode) Pavor nocturnus: (night terrors) usually in children, predominantly in stage 4 (amnesia for episode)