87. Circadian Rhythm + Sleep

Question 1

What are the 5 stages of sleep and signs on EEG?

What centers control Wake, NREM, and REM?

Answer 1

1. Awake - alpha waves (low amp, high freq)
2. N1 - light sleep - theta waves (higher amp, lower freq)
3. N2 - sleep spindles (fast bursts) and K complex (huge slow wave)
4. N3 - deep sleep, delta waves (HIGH amp, SLOW freq)
5. REM - b/w awake and N1 - muscle tone paralysis and rapid eye movement

Wake: ARAS and monoaminergic receptors - redundant NT modulators to keep us awake

NREM: VLPO (ventrolateral preoptic nucleus) - inhibits wake centers; orexigenic nucleus in lateral hypothalamus promotes wakefulness and inhibits VLPO to stay awake

REM: upward projections from spinal interneurons, ventrolateral medulla, ACh (downward projections for muscle atonia)

Question 2

Describe the molecular switch for wake and sleep.

Outline the two process model for sleep

Answer 2

Wake: OREX = LC, TMN, Raphe Nucleus, ARAS = Awake and inhibit VLPO

Asleep: VLPO inhibits OREX and LC, TMN, Raphe Nuclei, ARAS = sleep

1. Sleep - the longer awake, the greater need for sleep
2. Circadian - cyclical with light
   high diff. b/w sleep need and circadian rhythm creates DRIVE to sleep

Question 3

How is the circadian rhythm controlled? What genes?How can the circadian rhythm be modified with different substances?

Answer 3

Suprachiasmatic nucleus - controls circadian rhythm, centers for melanopsin-containing RGC tracts to adjust 24+ hr clock with daylight (in hypothalamus above optic tract)

CLOCK + BMAL1: synthesize, dimerize, induce expression of PER + CRY
PER + CRY: dimerize and feedback to inhibit CLOCK + BMAL1 expression
CKI-delta enzyme regulates speed of feedback loop cycle (clock)

Light stim: early sleep = phase delay; late sleep = phase advance

Melatonin: -3hrs bedtime = phase advance; past bedtime = no change or phase delay (BAD)

Question 4

Advanced Sleep Wake Phase Disorder

• describe
• cause
• tx

Answer 4

Advance in phase (5pm-2am) - wakes up early and can’t fall asleep
Normal quality/duration when pt controls schedule
Cause: genetic mutations in CKI-delta - cycle less regulated

Tx: planned sleep schedules, timed evening light exposure and morning melatonin (theoretical)

Question 5

Irregular Sleep Wake Disorder

• describe
• cause
• tx

Answer 5

Chronic insomnia/excessive sleepiness
Multiple irregular sleep bouts during 24hrs (total sleep time over 24 hrs is normal)
Cause: poor sleep hygeine, neuro impairment (in developmentally delayed children, adults with dementia)

Tx: mixed modality - timed light exposure and melatonin use

Question 6

Delayed Sleep Wake Phase Disorder

• describe
• tx

Answer 6

Delay in phase (6am - 1pm); normal sleep/quality when pt chooses schedule
tx: planned sleep schedules, timed light (2hrs before wake), timed melatonin (5hr before bed)

Question 7

Non-24hr Sleep Wake Disorder

• describe
• cause
• tx

Answer 7

Abnormal Synchronization b/w 24hr light-dark cycle and endogenous circadian rhythm - fall asleep later every night because circadian rhythm not modulated by light
Cause: blindness (lose light stim) or multifactorial
Tx: timed melatonin (1hr before bed), strict sleep schedule, timed light exposure (on awakening)

Question 8

Shift Work Sleep Disorder

• describe
• tx

Answer 8

Work schedule overlaps with usual sleep time - disturbed circadian/sleep time misalignment
tx: compromise b/w work and off days - light stim at work/on awakening - adjust sleep schedule on last work day

Question 9

Jet Lag Sleep Disorder

• describe
• tx

Answer 9

travel across at least 2 time zones
impairment of daytime fx, general malaise, GI disturbance
Tx: evening light exposure if traveling west, evening melatonin and morning light exposure if traveling east (before actual travel)