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• Be familiar with effects of sleep on facial recognition described by Walker.
class data: Ability to remember and sort faces is unaffected by sleep/tiredness
• What were the results of the memory sound experiment described by Walker on pg 119-120
Sounds associated with a pictured-object that played during NREM sleep can trigger selective reactivation of corresponding memories (pictured-objects). The next day, tests will show a significant increase of remembrance for the objects that were activated using sound cues overnight versus those that weren’t
• According to Walker, how can sleep be used to forget?
Sleep helps reduce emotional intensity (amygdala activity) and “wipe away” emotional charge (REM function)
Sleep selectively boosts the retention of important information and actively avoids the strengthening of unimportant memories (NREM sleep spindles perform this)
• Be familiar with the results of Walker’s (and our replication) of the motor memory experiment.
Finger tapping task:
Sleep → 20% faster, 35% more accurate
No sleep → no improvement
Sleep required for performance gains
Results: group 2 performed much better on the latter half of the experiment due to sleep allowing for increased motor memory and performance
• What were the results of our class experiment on sleep and facial recognition and reaction time?
Facial recognition → not affected
Reaction time → faster in morning than evening
• What do cortical slow oscillations, thalamocortical sleep spindles and hippocampal ripples have to do with learning?
They coordinate memory consolidation:
During NREM sleep, neocortical slow oscillations drive the reactivation of hippocampal memory representations during sharp wave ripples in the hippocampus which is coordinated with spindles (blue) in the thalamus. This dialogue between slow oscillations, spindles and hippocampal ripples is thought to mediate the transfer of selected new memories from temporary storage in the hippocampus to longer-term representation in the neocortex.
• What is a nychthemeron?
24-hour period
• What does adenosine have to do with process S and how does adenosine influence the brain’s sleep control centers?
Adenosine builds up → increases sleep pressure
Sleep deprivation → increased adenosine receptor density (upregulation in adenosine receptor expression)
Takeaway: sleep deprivation makes brain more responsive to adenosine
• What happens when a person is exposed to light in the evening before sleeping or in the morning before waking? (phase responsive curve)
Evening light → delays circadian rhythm
Morning light → advances circadian rhythm
middle day: dead zone - light cannot effect CR
• Be familiar with the PSQI, the Stanford Sleepiness scale, the Epworth sleepiness scale and the MSLT.
PSQI, Stanford, Epworth → subjective sleep measures
MSLT → objective physiological measure (nap every 20 mins)
downside: may not be realistic as it is a stimulating environment which may mask sleepiness (not representative of real world)
• Describe the methods for studying sleep deprivation in rats and what happens to them.
Methods:
Disk over water method - disk over water, 2 rats, floor rotates when rat sleeps (causing rat to move and stay awake)
flower pot method
eliminates REM sleep (not total sleep deprivation)
Effects
Much skinnier
Severe lesions on the tail and paws
Increased food intake
Increased energy expenditure
Decrease body temp
Severe weight loss
Death (after 11-32 days)
No significant post-mortem differences in brains or other major organ
death from sleep deprivation linked to gut damage
accumulation of reactive oxygen species leading to oxidative stress in gut
antioxidents allowed these rats to have normal lifespan despite severe sleep deprivation
• Who is Randy Gardner?
Stayed awake 264 hours
science experiment
by end could not count backwards from 100 by 7
would also forget question whilst answering it
couple days in did beat someone in mental game then declined
• Outline the effects of sleep deprivation on body systems.
(immune, metablic, cardiovascular, brain)
Immune: ↓ T cell perforin
Metabolic: ↑ glucose, insulin disruption
Cardiovascular: ↑ hypertension risk
Brain: emotional instability, poor decision making
Hormonal disruption
• What is the SAFTE model and what is it used for?
a method of contextualizing sleep and its effects on performance used by the military, the FAA and other organizations to optimize safety in shift workers.
The sleep reservoir represents a finite capacity to perform. • The sleep reservoir is replenished by sleep that is affected by sleep intensity and quality. • Performance use depletes the reservoir and contributes to inertia (wakefulness) and cognitive effectiveness.
• What is the relationship between sleep deprivation and psychiatric conditions?
“No major psychiatric condition in which sleep is normal”
Linked to:
Depression
Anxiety
PTSD
Bipolar
• What is the relationship between sleep duration and college GPA?
every hour = 0.07 increase in end year GPA
• Be familiar with the history of daylight savings time.
Originally adopted by germans in ww1 to save electricity and fuel - allies quickly followed
Met with resistance - left to state and local governments to decide
Uniform time act (1966) made dst a law
Hawaii and Arizona do not observe daylight saving
70 countries follow dst (25% worlds population)
Equatorial have no need to change time for daylight hours
• Why is the start of daylight savings time so dangerous form a public health perspective? Cite some statistics.
40 min less sleep
24% ↑ heart attacks
spring 21% decrease in heart attacks
6% ↑ mining injuries
67% ↑ workdays lost
$434 million cost
natural killer cells
4 hours sleep for 1 night = 70% drop in killer cell activity
• What were the results of our class’s DST experiment?
Non usual environments = worse sleep
DST sleep score worse than baseline
Sleep duration, light sleep, deep sleep, rem sleep, wake time, nap time
All statistically significant
• What effect does sleep deprivation have on adenosine receptor density? What does this mean?
Upregulation
→ brain becomes more sensitive to sleep pressure
What do brain imaging studies reveal about the effects of sleep deprivation on amygdala activation? What does this have to do with the frontal cortex and decision making?
Amygdala (brains fear center - responds to negative emotions) 60% more active when sleep deprived
Prefrontal cortex: rational thought + decision making (acts as a brake on the amygdala)
prefrontal cortex sleep deprived – amygdala allowed to “over-react” to emotional stimuli)
• What is the function of the nucleus accumbens and how is it affected by sleep deprivation?
Nucleus accumbens: brains pleasure center
Survival (food) and reproduction (sex)
Participants make decision of low risk vs high risk scenarios
High risk scenario activates nucleus acumbens
In sleep deprived subjects: higher risk nucleus accumbens activation was enhanced
Means: anticipated reward overestimated by sleep deprived brain as it lacks rational control
• What is the relationship between intrusive memories, PTSD, the rDLPFC, the hippocampus and sleep deprivation?
Important role in onset and maintenance of anxiety, depression, ptsd
Fmri study: brains of sleep deprived subjects showed reduced engagement of rDLPFC and weaker disengagement of right hippocampus during memory suppression task
Suggests: sleep deprivation disrupts brains ability to keep intrusive memories at bay
• Why is sleep deprivation used as a therapy for depression? How effective is it?
Total sleep deprrivation reduced symptoms in 59% of patients (ONLY 1 NIGHT)
Symptoms return following single night of sleep
Antidepressants reduce REM and prolong latency of first episode of rem
More practical approach:
Use deprivation of second half of night when rem occurs
• Be familiar with some of the research on the relationship between sleep and Alzheimer’s disease.
Poor sleep (beta amyloid build up) - neuron death (synapse loss) - cognitive decline alzheimers
Degenerative neurological disease (destroying the brain)
Primary pathology:
Accumulation of misfolded proteins that form extracellular amyloid plaques in brain (they are toxic to neurons)
Overall - shrinkage of brain tissue, sulci widened, gyri reduced, cortex thinned, ventricles noticeably enlarged
Sleep and alheimers disease
Association: short sleep in 40s and 50s associated with accumulation of toxic alzheimers proteins later in life
Two proteins: amyloid and tau
High accumulations of tau proteins found in wake promoting regions of brain
Poor sleep associated with build up of toxic amyloid protein
Disrupted sleep spindles (shown with early signs of alzheimers)
Sleep eeg being explored as potential tool for diagnosis of alzehimers
• What is the glymphatic system, aquaporins and what does it have to do with sleep and Alzheimer’s disease?
glymphatic system: Brain waste clearance system (More active during sleep)
deep sleep most important role in this
Aquaporins = water channels
glial cells (brain cells that arent neurons) shrink and open aquaporins to allow fluid to flow through extracellular space
these fluids (cerebrospinal fluid) flush the brain - carrying waste (amyloid and tau proteins) to venous system (out of brain)
Clears amyloid → protects against Alzheimer’s
Poor sleep can affect aquaporins (cleansing system) which leads to accumulation of bad proteins (amyloid) which then leads to worse sleep (a bad cycle) (and also contributes to alzheimers)
Solution: Ketogenic diet (high fat/protein and low carb diet) and sleeping on side enhances glyphatic flow
• What does the statement “Neurons that fire together shower together” mean?
Slow wave sleep (pyramidal neurons synchronized firing)
Suggests: deep sleep may be for the brain to cleanse itself
What does the cleansing of the brain have to do with cortical slow oscillations, thalamocortical sleep spindles and hippocampal ripples?
In addition to enhancing memory consolidation - coordination of slow wave electrical activity in cerebral cortex, spindle activity in thalamus and high frequency ripples in hippocampus appear to mediate the flushing of CSF in brain
• What is restless REM and what does it have to do with amygdala activation? What are the implications for PTSD?
Restless REM: frequent awakenings from REM
Suggests: REM sleep helps wipe away days bad experiences
Restless rem and failure of amygdala to adapt may contribute to depression and PTSD
• What happens to a person when deprived of REM sleep? What about slow wave sleep deprivation?
REM:
no major consequences, increased liveliness, appetite, interest in sex, memory impairment
Selective rem deprivation increases propensity of subjective to enter REM
REM pressure: deprived of rem - brain tries to get even more
REM rebound: more than usual amount of time in REM
SWS:
Lethargy
Muscle aches
no major behavioral issues
SWS pressure: deprivation from SWS requires 6x more interruptions vs REM
NREM recovery takes priority over REM recovery
• What is the connection between cortical slow oscillations, thalamocortical sleep spindles, heartrate variability and diabetes? (hrv??)
Coupling of NREM sleep spindles and slow oscillations night before is associated with improved next day glucose control
Suggests: may be sleeping brain body framework of optimal human glucose homeostasis that may be therapeutic approach to treating diabetes
• Why are perforins important for T cell function and what happens to them during sleep deprivation?
They recognize a cell infected with virus - activate sticky proteins (perforins) that attach to virally infected cell and kill it
T cells taken from sleeping volunteers showed much higher levels of perforin activation than T cells taken from wakeful subjects
Sleep enhances efficiency of T cell responses and activation of perforin
What happened in the study that examined melatonin, glucose and insulin blood levels following a night of complete sleep deprivation? What are the implications?
Melatonin unchanged
100 proteins in blood changed due to just one all nighter
Glucose & insulin elevated
→ risk for diabetes/metabolic disease (ex: shift work)
• What is a myclonus and a hypnogogic jerk?
Myoclonus → involuntary muscle jerk (ex: hiccups)
Not a symptom of a disorder
Positive myoclonus: muscle contraction
Negative myoclonus: muscle relaxation
Hypnic jerk → a myoclonus that occurs when falling asleep
associated with heartbeat, quickened breathing, sweat, feeling of shock
• What is the difference between tonic and phasic REM and what is their relationship to the autonomic nervous system?
Phasic REM → bursts of rapid eye movements
sudden increases in sympathetic activity
parasympathetic (calming) activated but slightly less than sympathetic (fight or flight)
Tonic REM → between phasic bursts (eyes moving less)
• What happens to heart rate and blood pressure during sleep?
NREM → decreased HR and BP
Tonic REM → HR and BP about same as NREM
Phasic REM → HR and BP fluctuate wildly
• What effect does sleep deprivation have on cardiovascular health and how is the sympathetic nervous system involved?
regularly varying nightly bed time by over 30 minutes (or less sleep than 6 hours or more than 9 hours) associated with 32% increase in hypertension risk (high BP)
sympathetic nervous system consistently elvated
epinephrine elevated (adrenaline) - stress response (NOT SUSTAINABLE)
body stuck in semi fight or flight response
results in high BP, reduced HRV, increased heart workload,
big issue here is chronic overactivation of sympathetic nervous system (and lack of parasympathetic nervous system)
• What happens to breathing and body temperature during sleep?
Breathing:
NREM → regular (slightly deeper)
15% decrease tidal volume
breathing exlusively under chemical and mechanical feedback control
REM → irregular
low oxygen + high co2 - ventilatory responses decrease
this + atonia can lead to sleep apnea
Temperature:
NREM → regulated lower
REM → not regulated
• What is tumescence?
vascular congestion of the sex organs in both men and women
Strongly associated with REM sleep but not with dream content
• When are growth hormone, cortisol and melatonin released during a typical night of sleep?
Growth hormone → during SWS (by pituitary gland)
Melatonin → night
Cortisol → peaks before waking (so that we wake feeling hungry and alert)
• Be familiar with the hormones listed on slides 15 and 16 from 03-27-26 and how they relate to sleep. (slides)
Hormones released by brain during sleep
Pituatary gland
Growth hormone: essential for growth and tissue repair
Antidiuretic hormone (ADH): prevents the production of urine
Prolactin: involved in over 300 functions including lactation, metabolism, and immune system regulation
Hypothalamus
Involved in childbirth, lactation and social bonding, may influence content of dreams
Hormones released in body that relate to sleep
Ghrelin: released by stomach - stimulates hunger
poor sleep makes you hungry
Insulin: released by pancreas, controls glucose levels and bodys use of carbs
Controlled by sleep so we wake hungry
Cortisol: releaed by adrenal gland, involved in metabolism, immune and stress responses
Aldosterone: released by adrenal cortex, regulates potassium and sodium in the body
Levels high during sleep, preventing urge to urinate
Leptin: released by fat cells, regulates body weight and inhabits hunger
• What drugs are classified as methylxanthines and what effects do they have on the body and on sleep?
Caffeine, theophylline, theobromine
Effects on body:
Block adenosine
sympathetic arrousal (f or f)
reduces fatigue and boredom, improves mood, enhances athletic performance
Smooth muscles (involuntary) relax and striated muscles (voluntary) are strengthened
Dilation of bronchi and peripheral blood vessels (used to treat asthma)
Constriction of blood vessels in brain - used to treat headache caused by high BP (stimulates respiration centers in medulla)
Effects on sleep:
Increases stability of wakefulness - increases the time to sleep and decreases sleeping time
Lowers acoustic arousal threshold
Individual variability due to tolerance levels
Can counteract effects of sedative-hypnotic drugs (sleep pils)
• Explain the biphasic effect of alcohol.
Low dose → stimulant
Higher dose → sedative
• What effect does alcohol have on sleep?
Decreases time to fall asleep
Deep sleep quicker and more deep sleep in first part of night
Suppresses rem in first part of night
Rem rebound: rem deprivation in first part night leads to rebound lengthens rem in second part of night
• What is the definition of insomnia. What are its symptoms?
Persistent difficulty initiating or maintaining sleep
Symptoms
Daytime sleepiness, fatigue, cognitive impairment, decline in work performance, missed work days, depression and anxiety
Occurs in 10-20% of general population, 50% seen in primary care clinics
Most common sleep disorder
• Define sedative and hypnotic and know what happens with increasing doses of a sedative.
Sedative
Drugs should reduce anxiety and exert a calming effect with little or no effect on motor or mental functions
Hyponotic
Drugs should produce drowsiness and encourage the onset and maintenance of a state of sleep as far as possible resembles the natural sleep state
Continuum
Normal - relief from anxiety - dishinibiton - sedation - sleep - anethesia - coma - death
• What are the effects of barbituates and why are they dangerous?
CNS depressants
Short acting barbiturates used as ansthetics - longer acting barbiturates were used as hypnotics
Reasons why no longer used
Narrow therapeutic to toxic range
After affect - hangover, dizzy, drowsiness, amnesia, impaired judgement, disorientation
Suppress rem sleep - rem behavior disorder upon withdrawal
Tolerance develops quickly
High potential for physical dependance and abuse
Liver damage
• How are benzodiazepines similar to and different from barbituates? What is rohypnol?
Benzodiazepines: reduce anxiety, muscle relaxant, induce sleep
many end in pam and lam
Similar: both bind to GabaA receptor and enhancing gaba’s nervous system depressant effects
Different:
Benzos safer
Less REM suppression
less liver damage
less addictive and easier withdrawals (THEY ARE STILL ADDICTIVE)
Rohypnol:
Powerful benzo
Causes amnesia, muscle relaxation, sleep
Used as date rape drug (roofies)
intensifies effects of alcohol
colorless and tasteless when dissolved in drink
not legal in US
• What is so important about the GABA receptor when considering combinations of sedatives?
Main inhibitory neurotransmitter in CNS
Alcohol, benzodiazepines, barbiturates bind to gabaA receptor and enhance gabas nervous system depressant effects
When taken alone drugs cause sedation and enhance sleep onset and maintenance
When taken in combination - drugs have a synergistic effect and can easily lead to overdose
Whitney houston likely died from overdose on valium, xanax, alcohol
• What are the non-benzodiazepine hypnotics and how are they different from benzodiazepines?
Z-drugs
bind to subtypes of gaba receptors that specifically modulate sleep
fewer unwanted side effects
tolerance and abuse much less common
• How does ramelteon work and why is it safer than other hypnotics?
Brand name: Rozerem
Selective agonist at MT1 and MT2 melatonin receptors
FDA approved - non addictive
Associated with headache, dizziness, drowsiness, fatigue, nausea
• How do suvorexant and doxepin work to control and maintain sleep?
Suvorexant → antagonist (blocks) orexin (wake signal)
Doxepin → blocks histamine (H1) (arousal)
• Why are antihistamines a bad choice as a sleep aid?
Little evidence to support use
Caution with PM meds
More than 1 medication in them
Too much tylenol dangerous