“There was this constant, overwhelming exhaustion. It didn't matter how much I slept.” – Scott

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Normal Sleep-Wake States

Optimal health and cognitive function require the coordinated timing and appropriate duration of three distinct states: wakefulness, non-REM sleep, and REM sleep.1-5

Wakefulness, normally promoted during the biologic day,7 is characterized by high muscle tone, fast-frequency neuronal activity, and is necessary for alertness and higher-order neurocognitive functioning.3,5,7

Non-REM sleep is a state with slower-frequency neuronal activity and light to deep stages of sleep; skeletal muscle tone is lower than during wakefulness.3,5 Nighttime sleep normally begins with an episode of non-REM sleep.3

During REM sleep, which is associated with dreaming and skeletal muscle atonia, neuronal activity is faster and desynchronized, with distinct wave patterns (e.g., sawtooth waves) on electroencephalogram (EEG).3,5,8 Episodes of REM sleep typically occur after non-REM sleep and become longer over the course of the night.3

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How does the brain regulate the timing and stability of sleep and wakefulness?

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How does narcolepsy affect sleep and wakefulness?

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  1. España RA, Scammell TE. Sleep neurobiology from a clinical perspective. Sleep. 2011;34(7):845-858.
  2. Scammell TE. The neurobiology, diagnosis, and treatment of narcolepsy. Ann Neurol. 2003;53(2):154-166.
  3. Scammell TE, Arrigoni E, Lipton JO. Neural circuitry of wakefulness and sleep. Neuron. 2017;93(4):747-765.
  4. Schwartz JR, Roth T. Neurophysiology of sleep and wakefulness: basic science and clinical implications. Curr Neuropharmacol. 2008;6(4):367-378.
  5. Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. Control of sleep and wakefulness. Physiol Rev. 2012;92(3):1087-1187.
  6. Broughton R, Valley V, Aguirre M, Roberts J, Suwalski W, Dunham W. Excessive daytime sleepiness and the pathophysiology of narcolepsy-cataplexy: a laboratory perspective. Sleep. 1986;9:205-215.
  7. Morris CJ, Yang JN, Scheer FA. The impact of the circadian timing system on cardiovascular and metabolic function. Prog Brain Res. 2012;199:337-358.
  8. Pearl PL, LaFleur BJ, Reigle SC, et al. Sawtooth wave density analysis during REM sleep in normal volunteers. Sleep Med. 2002;3(3):255-258.

Performance of routine tasks without awareness.

Sudden and brief loss of muscle strength or tone, often triggered by strong emotions. Narcolepsy with cataplexy is known as type 1 narcolepsy.

Complete collapse to the ground; all skeletal muscles are involved.

Only certain muscle groups are involved.

Biological clock mechanism that regulates the 24-hour cycle in the physiological processes of living beings. It is controlled in part by the SCN in the hypothalamus and is affected by the daily light-dark cycle.

Frequent inappropriate transitions between states of sleep and wakefulness.

The inability to stay awake and alert during the day.

A neurotransmitter that supports wakefulness. The TMN is the only source of histamine in the brain.

Vivid, realistic, and frightening dream-like events that occur when falling asleep.

A neuropeptide that supports wakefulness and helps control non-REM sleep and REM sleep.

Primary brain region for regulating the timing of sleep-wake states.

Unintentionally falling asleep due to excessive daytime sleepiness.

Brief, unintentional lapses into sleep or loss of awareness.

A validated objective measure of the tendency to fall asleep in quiet situations.

A state of sleep when muscle tone is decreased. Deep stages help to restore the body.

Overnight study used to diagnose sleep disorders by monitoring sleep stages and cycles to detect disruptions of a normal sleep pattern.

Normally occurs at night and includes vivid dreams. Also known as “paradoxical sleep.”

Daytime and evening habits and routines to help improve nighttime sleep.

Brief loss of control of voluntary muscles with retained awareness.

Sleep-onset REM period.

People with type 1 narcolepsy have low levels of hypocretin.

Narcolepsy without cataplexy; the cause of type 2 narcolepsy is unknown.