92b - Circadian Rhythms and Sleep

Question 1

What EEG pattern will you see if a patient is in Stage N1 sleep?

Answer 1

Theta waves

In general, the waves are slowing down

N1 = “light sleep”

Question 2

Where is the primary circaidan pacemaker located?

From where does it receive input?

Answer 2

Suprachiasmatic nucleus in the hypothalamus

Receives photic input from the retinohypothalamic tract

Question 3

What EEG pattern will you see if a patient is in Stage N3 sleep?

Answer 3

Larger slower waves at delta frequency (5-6 Hz)

Question 4

What is the FDA-approved medication for the treatment of non-24h sleep wake disorder?

Answer 4

Hetlioz (tasimelteon)

Question 5

In general, what is the treatment for circaidan rhythm sleep disorders?

Answer 5

Timed light and/or melatonin exposure

Planned sleep schedules

Hypnotics are not recommended; they can help with sleep, but will not re-set the circadian rhythm

Question 6

Describe the molecular clock and associated feedback loop

Answer 6

The following process takes ~24h, thus providing the basis for our intrinsic circadian rhythm

• CLOCK and BMAL1 are synthesized
• They exit the nucleus and dimerize
• CLOCK/BMAL1 dimer acts as a transcription factor that promotes the transcription of PER and CRY
• They exit the nucelus and dimerize
• They are phosphorylated by CK1ε/δ​
  
  • This is the rate limiting step
• Phosphorylated PER/CRY dimer acts as a transcription factor that inhibits its own transcription
• When enough Phosphorylated PER/CRY gets into the nucleus transcription of PER and CRY stops, thus allowing it to start being transcribec again
  *

Question 7

The VLPO [activates/inhibits] orexinergic nuclei

This stabilizes [wakefulness/sleep]

Answer 7

The VLPO inhibits orexinergic nuclei

This stabilizes sleep

Question 8

The [ARAS/VLPO] dominates when we are asleep, while the [ARAS/VLPO] dominates when we are awake

Answer 8

The VLPO dominates when we are asleep, while the ARAS ​dominates when we are awake

Question 9

When does the “biological morning” start?

Answer 9

After the core body temperature minimum (which is usually ~2h before wake)

Question 10

Which neuromodulator stabilizes the “awake” state?

Answer 10

Orexin (aka hypocretin)

@scientists y tho ¯_(-_-)

Question 11

Inhibiting the VLPO results in [sleep/wakefulness]

Answer 11

Inhibiting the VLPO results in wakefulenss

• The VLPO usually inhibits wake-promoting nuclei

Question 12

Orexinergic nuclei stabilize the [ARAS/VLPO]

This results in [wakefulness/sleep]

Answer 12

Orexinergic nuclei stabilize the ARAS

This results in wakefulness

• The VLPO inhibits orexinergic nuclei, resulting in sleep

Question 13

When do you give melatonin to treat:

• Delayed sleep/wake disorder:
• Non-24h sleep/wake disorder:

Answer 13

• Delayed sleep/wake disorder:
  
  • Give melatonin ~5h before bedtime
• Non-24h sleep/wake disorder:
  
  • Give melatonin ~1h before bedtime

Question 14

What EEG pattern will you see if a patient is in REM sleep?

Answer 14

Theta waves (just like Stage N1 sleep), may also see beta waves (like awake state)

But also:

• Atonia
• Rapid eye movements behind closed eyelids

Question 15

Which neurotransmitters are most active in wakefulness?

Answer 15

ACh

Monoamines (NE, Serotonin, Dopamine)

Orexin

Question 16

What EEG pattern will you see if a patient is in Stage N2 sleep?

Answer 16

Sleep spindles

K complexes

Theta waves will still be present

Question 17

Describe the two process model that controls sleep

Answer 17

Process S (sleep) and Process C (circadian) work together

• Process S
  
  • Homeostatic sleep need
  • The longer we are awake, the more we need to sleep
• Proces C
  
  • Helps us stay awake in the afternoon when our sleep drive is high, but we’re supposed to be awake
  • Falls at night, allowing process S to knock us out

Question 18

Which system modulates arousal?

Answer 18

Ascending reticular activating system

• Nuclei of monoamines
• Inhibits the VLPO

Question 19

Traveling from Hawaii to Chicago will result in jet lag, with symptoms similar to which circadian rhythm sleep disorder?

How would you minimize these symtoms?

Answer 19

Similar to delayed sleep/wake disorder

• Light in the biological morning when you arrive in Chicago
  
  • After the core body temp minimum, usually about 2h before wake time
• Melatonin ~5h before bedtime

Question 20

Which neurotransmitters are most active in NREM sleep?

Answer 20

VLPO

Some monoamines (Serotonin, NE, Dopamine)

Question 21

Which neurotransmitters are most active in REM sleep?

Answer 21

ACh

MCH

VLPO

Question 22

Light exposure at night and melatonin in the morning [advance/delay] the circadian clock

Answer 22

Light exposure at night and melatonin in the morning delay the circadian clock

Note: to treat advanced sleep/wake disorder, planned sleep schedule + light exposure in the evening. Usually don’t give melatoin in the morning

Question 23

Light exposure in the biological morning and melatonin at night [advance/delay] the circadian clock

Answer 23

Light exposure in the biological morning and melatonin at night advance the circadian clock

Question 24

ACh is active in [Wakefulness/NREM sleep/REM sleep]

Answer 24

ACh is active in wakefulnes and REM sleep

Question 25

What EEG pattern will you see if a patient is in “relaxed wakefulness?”

Answer 25

Alpha waves

Question 26

REM sleep occurs when monoamines levels are [low/high] and ACh levels are [low/high]

Answer 26

REM sleep occurs when monoamines levels are low and ACh levels are high

MCH and VLPO activity are also high