Neuroscience Week 7: Sleep Disorders Flashcards
How is sleep regulated at a cellular level
There are sleep-promoting neurons and wake-promoting neurons that inhibit each other
flip-flop switch circuit of sleep
- There are sleep-promoting neurons and wake-promoting neurons that inhibit each other
- notice which segments fire during wakefulness or sleep

sleep pressure
builds throughout the day to make you want to sleep
need more stuff on this!!!
physiological variables and circadian rhythyms
- Core body temperature
- Cortisol
- Urine volume
- thyroid stimulating hormone
- Growth hormone
- Prolactin
- Parathyroid hormone
- Motor activity

Clock genes description and function
at least 10 of them
(e.g Bmal1, Clock, Per, Cry, etc.)
create circadian oscillations generated by negative feedback loops
The main timekeeper of brain
Suprachiasmatic nucleus

Suprachiasmatic nucleus location
above the optic chiasm

Key Zeitgebers
4 listed
- Light
- Feeding schedules
- Melatonin
- Activity
zeitgeber definition
time givers
or
time cues
length of internal clock
24.2-24.9 hours
Neurotransmitter systems active during sleep
Preoptic area (inhibits wakeful ness neurons
SCN uses __________ to help synchronize or reset the clock daily
Zeitgebers
Neurotransmitter systems that promote wakefulness and inhibit the sleep-promoting neuro systems
- Basal Forebrain
- Locus coeruleus
- Tuberomammillary nucleus
Lighten up to stay awake
- sun comes into eyes
- Retinohypothalamic tract
- tells SCN that it is time to be active
- NE to superior cervical ganglion to rest of body

Melatonin is built up by
NE breakdown
Melatonin release is inhibited by?
Light
Process for sleep cycles

What releases melatonin?
Pineal gland
Homeostatic Sleep Drive AKA
Sleep pressure
Sleep pressure _________ the longer we are awake
increases
What comprises sleep pressure?
Adenosine rises as sleep debt builds up (a by-product of ATP)
Adenosine rises as sleep debt builds up and causes
- inhibits body processes of wakefulness
- “Rinsed out” during sleep

What reduces adenosine levels?
sleep

How does coffee work?
caffeine antagonizes adenosine

caffeine antagonizes
adenosine
Polysomnography
- awake eyes and dreaming eyes look very similar
- chin tone: should be really skinny and relaxed ( if movement could be grinding teeth)
- K complexes (stage 2 sleep)
- Spindles (stage 2 sleep)

K complexes are present in this stage
stage 2 sleep
spindles come from this stage of sleep
Stage 2 sleep
Spindles function
thalamus telling brain to ignore sensory signals
packets of info when consolidating memory
K complexes
from cortices telling theyre still busy
alpha is seen when
someone is about to go to sleep
Nasal line flat
no air coming in
trying to breath but no air is coming in

Polysomnographic features of normal REM sleep
5 listed
- Rapid eye movements
- Low chin tone
- EEG dyssynchrony
- Heart rate variability
- Respiratory variability

Question 1

C. 70-120 minutes
In a depressed person? - 30-70 minutes
Treated for depression? - 120-180 minutes
sleep deprived? - 15-30 minutes
Average time % spent in NREM1
5%
Average time % spent in NREM2
45%
Average time % spent in NREM3
25%
Average time % spent in REM
25%
Hardest stages to wake up?
darker colors harder to wake up

stages most asleep?
darker colors

The most common sleep complaint
Insomnia
Types of insomnia
2 listed
- Chronic insomnia disorder
- Short-term insomnia disorder
Insomnia description
complaint of sleep quantity or quality associated with problems falling asleep, staying asleep and or early morning awakenings
Insomnia criteria
3 listed
- causes distress/impairment
- sleep problem occurs at least 3 nights/week
- The sleep problem occurs despite adequate opportunity for sleep
Insomnia Non-pharmacological treatment
- CBT-I - Cognitive behavioral therapy (4-8 weeks)
- Learn healthy sleep habits and develop new sleep behaviors to improve sleep quality and consolidation

Insomnia first-line treatment
CBT-I
Sleep hygiene
11 listed

FDA medications approved for insomnia

FDA medications approved for insomnia: Classes
5 listed
- Benzodiazepine receptor agonists
- Non-Benzodiazepine receptor agonists
- Selective melatonin receptor agonists
- Antidepressant
- Orexin receptor antagonist
Benzodiazepine receptor agonists for insomnia
- Triazolam
- Temazepam
- Estazolam
- Quazepam
- Florazepam
Non-Benzodiazepine receptor agonists for insomnia
3 listed
- Zaleplon
- Zolpidem
- Eszopiclone
Selective melatonin receptor agonist for insomnia
Ramelteon
antidepressant for insomnia
Doxepin
Orexin receptor antagonist for insomnia
Suvorexant
Suvorexant halflife
medium
Doxepin half-life
medium
Ramelteon half-life
short
Eszopiclone half-life
6 hr
zolpidem half-life
3 hr
Zaleplon half-life
1 hr
Florazepam half-life
longest
Quazepam half-life
Longer
Estazolam half-life
long
Temazepam half-life
short
Triazolam half-life
shortest
sleep-related breathing disorders
3 listed
- Obstructive apnea
- Central apnea
- Mixed apnea

We classify sleep apnea in a ______ based upon _________ effort during absent airflow
- PSG
- INSPIRATORY
Obstructive sleep apnea and symptoms
9 listed

Obstructive sleep apnea risk factors
6 listed
- male sex
- older age (40-70)
- Postmenopausal status
- BMI >35
- Hypertension
- Large neck circumference
Obstructive sleep apnea consequences
9 listed
- stroke
- heart failure
- atrial fibrillation
- heart attack
- insulin resistance
- obesity
- sudden death
- mood problems
- memory problems
Treatment for Obstructive sleep apnea
5 listed

Obstructive sleep apnea CPAP
continuous positive air pressure therapy
Obstructive sleep apnea psychiatric
behavioral therapies are often helpful in desensitizing treatment options improving overall sleep hygiene and alleviating underlying causes of anxiety and depression
Obstructive sleep apnea dental devices
small and easy to wear dental devices are an excellent treatment for mild to moderate sleep apnea
Obstructive sleep apnea weight loss
a loss of 10% body weight may be an effective treatment for some sleep apnea cases
Obstructive sleep apnea surgical
New treatments require less recovery time, and some can be performed in an outpatient setting
Before and after PAP

Narcolepsy description
an irresistible need to sleep due to loss of orexin neurons
Narcolepsy symptoms
5 listed

Narcolepsy sleep attacks
irresistible need to sleep
Narcolepsy sleep paralysis
REM atonia when going to sleep or waking
Narcolepsy Hypnagogic hallucinations
dream intrusion into wake
Narcolepsy poor sleep at night
- due to sleep fragmentation
- poor sleep/wake stability
Narcolepsy Cataplexy (Type I)
- sudden loss of voluntary muscle tone
- Reflexes are absent
- in response to strong emotional stimuli
Narcolepsy Treatment

Narcolepsy Treatment: Hypersomnolence
3 listed
- timed SHORT naps during the day
- Stimulant medications (methylphenidate and amphetamines)
- Wakeful promoting agents (Modafinil and Armodafinil)
Narcolepsy Treatment: Cataplexy
- Antidepressants
- decrease REM intrusion
- Sodium Oxybate (only FDA approved RX)
Only approved Rx for Narcolepsy Cataplexy
Sodium Oxybate
Narcolepsy Treatment: Poor sleep at night
2 listed
- Sodium Oxybate
- Timing of naps and stimulant use
Circadian Rhythm Disorders
6 listed
- Delayed sleep-wake phase disorder
- Advanced sleep-wake phase disorder
- Irregular sleep-wake rhythm
- Non-24-hour sleep-wake rhythm disorder
- Shift work disorder
- Jet lag disorder
Delayed Sleep phase syndrome may look like?
Sleep onset insomnia
Delayed Sleep phase syndrome symptoms
4 listed
- Inability to arise in the morning
- normal sleep if initiated at a delayed bedtime
- Bedtime & wake times are later on vacations (4 a.m. - 12p.m.)
- Peak onset at adolescence
Delayed Sleep phase syndrome prevalence
peak onset in adolescence
Delayed Sleep phase syndrome differentials
- sleep-onset insomnia
- bipolar disorder
- inadequate sleep hygeine
NREM Parasomnias description
unwanted nocturnal behaviors
NREM Parasomnias pathogenesis
heritable
NREM Parasomnias occurs when and what sleep stage
- often in the first 3rd of the night
- NREM 3 stage
NREM Parasomnias prevalence
most common in children
NREM Parasomnias increased with?
4 listed
- Sleep deprivation
- sickness
- stress
- side effects to medications
NREM Parasomnias examples
4 listed
- Night terrors
- Confusional arousals
- sleepwalking
- sleep-related eating disorders
Night Terrors characteristics
7 listed
Episodes of abrupt terror
intense fear
autonomic arousal
inconsolable
eyes open
brief to 30+ minutes
not easily remembered in the AM
Confusional arousals characteristics
3 listed
- Mental confusion or confused behavior
- absence of terror or ambulation
- not easily remembered in the AM
Sleepwaking AKA
Somnambulism
Sleep talking AKA
Somniloquy
Bedwetting AKA
Enuresis
Teeth grinding AKA
Bruxism
Sleep-related eating disorders characteristics
eating while asleep
REM Parasomnias examples
3 listed
- REM sleep behavior disorder
- Recurrent isolated sleep paralysis
- Nightmare disorder
Nightmares memory and time of occurence
recall intact upon awakening
second half of the night
Sleep paralysis definition
awake but unable to move
Sleep-related hallucinations subtypes
2 listed
- Hypnogogic (when falling asleep)
- Hypnopompic (when waking up)
REM Behavioral Disorder memory
recall intact upon awakening
REM Behavioral Disorder characteristics
dream enactment (themes of being pursued or fear)
REM Behavioral Disorder associated with?
Neurodegenerative diseases
Predates onset of Alpha-synucleinopathies: REM Behavioral Disorder
3 listed
- Parkinson’s disease
- Multiple system atrophy
- Dementia with Lewy bodies
REM Behavioral Disorder: Lesions affecting the brainstem
3 listed
- Multiple Sclerosis
- Narcolepsy
- Stroke
REM Behavioral Disorder: Medications
Antidepressants
Normal Neurophysiology of REM Sleep

REM sleep without Atonia
ACh from the superior pons starts dreaming but the glycine is not activated to inhibit the anterior spinal horn cells and REM behavioral disorder is caused

Acting out dreams

RBD Treatment
REM Behavioral Disorder
- Ensure safe environment
- Melatonin
- Clonazepam
- Antidepressant change
- Other medications: Selegeline, Donepzil , Barbiturate withdrawal, bisoprolol

Medications linked to RBD
5 listed
- Antidepressants
- Selegiline
- Donepezil
- Barbiturate withdrawal
- bisoprolol
Sleep-related movement disorders examples
4 listed
- Restless leg syndrome
- Periodic limb movement disorder
- Sleep-related leg cramps
- Sleep-related bruxism
Restless leg syndrome
URGES

Restless leg syndrome improvement with
- getting up
- dopaminergic therapy
Restless leg syndrome limb movements in sleep
80%
Restless leg syndrome deficiency
Serum ferritin <50 mg/L
Restless leg syndrome Prevalence
- Family history
- middle to older age
- usually progressive course
Restless leg syndrome vs Periodic limb movement disorder

Restless leg syndrome is bothersome when?
While awake
Restless leg syndrome is associated with?
3 listed
- Iron deficiency
- FHx
- overlap with periodic limb movements disorder 80%
Restless leg syndrome treated with
2 listed
- iron
- dopamine agonists
Periodic Limb Movement Disorder is bothersome when?
during sleep
Periodic Limb Movement Disorder and effect on sleep
movements interrupt/worsen sleep
Periodic Limb Movement Disorder is associated with?
Overlap with Restless Leg Syndrome 20%
Periodic Limb Movement Disorder criteria
2 listed
may not be a disorder if:
- it is not interrupting sleep
- not causing daytime dysfunction
Question 1


Question 2


Question 3


Question 4


Core body temp during sleep
↓

Cortisol during sleep
steady ↑ where it is at its maximum as soon as waking

Urine volume during sleep
remains ↓

TSH during sleep
slow ↓

GH during sleep
↑↑↑

Prolactin during sleep
mild ↑ to plateau

Parathyroid hormone during sleep
initial ↑ and then ↓

Motor activity during sleep
should basically be none

What promotes REM atonia?
Glycine in the spinal cord anterior horn
REM sleep Superior pons
ACh on
REM sleep Locus Coeruleus
Off
REM sleep Raphe Nucleus
5HT off