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While You Were Sleeping 161) September 4th, 2018 Good sleep 1. Fall asleep easily 2. Sleep through the night 3. Wake up rested Bad events: Exxon Valdez (oil spill) Challenger crash Chernol Nuclear meltdown Lowest attention span am until am Over 40 year period, Americans have reduced avg. total sleep...

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While You Were Sleeping (CAMS-UA 161) September 4th, 2018 Good sleep 1. Fall asleep easily 2. Sleep through the night 3. Wake up rested Bad events: ● Exxon Valdez (oil spill) ● Challenger crash ● Chernobyl Nuclear meltdown ○ Lowest attention span = 1-2 am until 4-5 am ● Over 40 year period, Americans have reduced avg. total sleep time by > 2 hours Sleep metrics ● Behavioural observations ● Neurophysiological definitions ● Objective measures : ○ Polysomnography ○ Actigraphy ● Subjective measures : ○ Surveys ○ Rating scales ○ Self-reports Is someone sleeping? ● Physical quiescence (stillness) ● Posture ● Elevated threshold for arousal/reactivity ● Rapid awakening w/ moderate stimulation ● Rebound recovery (increased sleep following deprivation) *sleep =  reversible behavioural state of perceptual disengagement from, + unresponsiveness to, the environment *EEG = Electroencephalogram; reflects summation of the synchronous activity, neuronal synchrony produces higher amplitude on the EEG Polysomnography ● Video-taped observation ● EEG - brain activity ● EMG (electromyogram) - muscle movement

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EOG (electrooculogram) - eye movement Vital signs

Actigraphy ● Measure of human rest/activity cycles ● Continually records movements ○ E.g: apple watch BEARS  dtime problems ● Be ● Ex cessive daytime sleepiness  akenings during night ● Aw  gularity ● Re  oring ● Sl eep-related breathing problems/S n Dreams ● 3 main features: ○ 1. “Conscious” ○ 2. Accessible to recall ○ 3. Occurs during sleep ● No universal definition Problems w/ Accuracy ● State change ● Time delay ● Visual imagery ● Censorship People who don’t dream: ● May be terrified of revealing themselves ● Sleep too deeply/too groggy to focus ● Sleep deprivation ● Medication/marijuana Assumptions 1. Assume all dreams have meaning (stem from unconscious) 2. Assume they have a unique language 3. You are ultimate authority of the meaning of your dreams 4. Your dreams are about your life + are on your side

September 11th, 2018 Sleep in Antiquity ● References appear in Bible, Veda, Koran ● Opium poppy or belladonna & alcohol known to induce sleep ● Premonitory qualities of dreams ● Early forms of hypnosis and lucid dreaming ● Sleep disturbances described in Egyptian, Greek, & Chinese medicine Early Theories of Sleep ● Alcmaeon ○ 6th century BC, first scientific theory of sleep ○ Sleep secondary to blood drainage from vessels on surface of body ● Aristotle ○ Wrote “On Sleep and Sleeplessness” ○ Vapors from food digesting in stomach rose to heart (brain) to cause sleep ● Galen ○ 2nd century AD ○ Used H  ippocrates 4 Humours Theory ○ Sleep necessary to rebalance the body’s humours: ■ phlegm ■ black bile ■ yellow bile ■ Blood 16th-17th Century ● Age of Discovery ● Descartes ( 1596-1650) ○ Hydraulic Model of Sleep ■ The pineal gland responsible for keeping the cerebral ventricles full to maintain alertness in the waking state 17th Century T  homas Willis ● The London Practice of Physick ○ Four chapters devoted to disorders producing sleepiness & insomnia ○ Coffee could prevent sleep ○ “Sleep”, not a disease but a symptom of underlying causes ○ Animal spirits undergo rest during sleep; those in the cerebellum become active during sleep to maintain control over physiology & cause dreaming ● Restless Legs Syndrome : first described as an escape of these animal humours into the nerves of the limbs ○ Noted treatment was powdered opium Sleep is a Passive State

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Before 1950s sleep was regarded as a passive state 18th century- blood flowing to the head put pressure on the brain which led to sleep 19th century- sleep occurred when brain “shut down” No clear distinction between sleep & other states with reduced awareness of surroundings, such as coma, stupor, intoxication, and hibernation

Popular mid-19th  century theories ● Stimulation ○ Sleep was an inactive state of the brain which occurred because of reduced sensory input (darkness, quiet) ○ Being awake occurred because of being in a loud, bright stimulating environment ● Hypnotoxin ○ Toxins and fatigue products accumulated during the day ultimately causing sleep ○ Toxins gradually eliminated during sleep Vascular Theory ● Sleep was related to the blood vessels caused by either an increase or decrease in brain blood pressure ● Supporting evidence was obtained from pathology and trauma Chemical theories ● Sleep caused by lack of oxygen or an accumulation of toxic substances such as: ○ Cholesterol ○ Carbon dioxide ○ “Urotoxins” ● Toxins built up during day and cause sleep ● As one slept, the toxins slowly drained away Evidence for Hypnotoxins ● 1909- K  uniomi Ishimori hypothesized evidence of “hypnotoxin” ○ (& in 1913 Legendre and Pieron) ● Suggested that hypnotoxin accumulates during wakefulness and dissipates during sleep ● Injected brain and blood extracts from sleep deprived dogs into awake dogs who fell asleep ● Great skepticism until it was replicated in 1960s with rabbits Nathaniel Kleitman ● 1920s- observed that sleep deprived subjects were less impaired and sleepy next morning than in the middle of night ● Kleitman argued that this observation is incompatible with hypnotoxin theory ● Lived for a month with “days” of 28 hours to study circadian rhythms ● In reality there are two systems that contribute to sleep, so they were both right (daily rhythm AND time spent awake)

EEG beginnings ● Richard Carton measures electrical activity in dogs’ brains after removing part of the skull using a g  alvanometer  (1875) ● 1928- German psychiatrist Hans Berger  r ecorded electrical activity of the human brain through the EEG ○ Clear differences when subjects were awake or asleep ○ Recordings of sleep were done for a. few minutes per hour to save paper (no grants) ● He cut out/resected the nervous pathways that bring sensory stimulation to the brain ● This led Frederic Bremer to “isolate” cat brains ○ A. Comatose after the resection of all sensorial info from the body (except olfactory & visual) ○ B. Normal sleep and wake pattern; maintain face sensorial stimulation as resection is below cranial sensory centers (but above spinal centers) ○ Bremer concluded that the sleep is due to lack of stimulation of the cerebral cortex-- “demonstrating” that sleep is a passive phenomenon ■ Correct experiment, wrong conclusion

Encephalitis Lethargica ● 1915-1926- epidemic spread around the world ○ No recurrence has since been reported, though isolated cases continue to occur ● Some patients affected had extreme somnolence, often leading to coma and death ● Others had hypokinetic form presenting with insomnia ● Don’t know what caused it Von Economo ● 1916 Austrian neurologist Konstantin Von Economo ○ Two different cerebral areas affected in the “sleepiness form” and “insomnia agitation” form ○ Excessive sleepiness: in patients with damage in central area of brain (junction of midbrain and posterior hypothalamus) ○ Insomnia: in parents with damage in preoptic area/basal forebrain (behind eyes) and in front of hypothalamus (anterior hypothalamus)

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Diagonal hatching = hypersomnolence ○ Horizontal hatching = insomnia ○ Lesions at the arrow induce narcolepsy ■ These findings suggested that these two areas were the neural circuitry of sleep and wakefulness

Bremer experiment ● Uncovered the existence of an “ascending arousal system” that was disconnected from the brain by upper transection of the cat brain resulting in coma ● Thought that transection A interrupted ascending sensory inputs Ascending Reticular Activating System ● Moruzzi and Magoun demonstrated that they could awaken sleeping cats by stimulating part of their brain ● Called this area the ARAS ● Implanted electrodes into the brains of the cats, anesthetized them, zapped them, leading to a desynchronized EEG (awake state pattern) Psychoanalysis ● Dreams were seen as guardians of sleep and to occur in response to disturbance ● Dreams would keep sleeper asleep ● Freud believed that dreams discharged instinctual drives ○ Dreaming became seen as a safety valve of the mind REM Sleep ● Kleitman and Eugene Aserinsky studying infant sleep noted a rhythm in eye movements ○ Same in adults as well ● Adopted electrooculography (EOG) and discovered periods of R  apid Eye Movement (REM) ● Woke people up during these phases ○ in REM they were reliably dreaming

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○ rarely (and more confusedly) in NREM REM sleep EEG showed pattern close or identical to wakefulness Published in 1953 Sleep is passive no more Came up with 4 sleep stages of NREM + REM

REM Atonia ● Dement noted that when cats started REM sleep their muscle tone disappeared completely ● French researcher Michel Jouvet described the existence of REM in animals and reported that REM was associated with atonia (1959) ● 1960- Dement and Hodes made same observation with humans Medications to improve dream recall (& lucidity) 1. Vitamin B6 (250 mg?) 2. Galantamine (4-8 mg) 3. Choline (250-500mg+?) 4. Silene Capensis/African Dream Root (brewed into a tea) 5. Mugwort (1 ounce dried herb to 1 pint boiling water, 5-10 minutes) 6. Calea Zacatechichi (tea or capsules) Writing Dreams Down ● Carl Jung created concept of “automatic handwriting” ○ Using non-dominant hand to write down dreams (dominant hand intrinsically bound to conscious mind) ● Three Adjective Rule ○ Choose person from your dream & spontaneously identify 3 adjectives to describe that person ■ If a professor you view as harsh, critical, and dismissive shows up in your dream, then perhaps this represents an aspect of your critical character September 18th, 2018 ● Three states of being ○ Awake ○ NREM ○ REM ● Terms ○ Sleep latency  = how long it takes to fall asleep once you are in bed with the intention of going to sleep ○ REM latency = time from sleep onset to first occurrence of REM sleep  how many rapid eye movements you have in 30 seconds ○ REM density = ○ REM rebound  = phenomenon after sleep deprivation where one enters REM sleep more quickly after sleep onset

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Sleep onset REM period  = the actual occurrence of entering REM sleep more quickly after sleep deprivation  aves W

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Gamma ■ Awake and excited Beta ■ Awake or REM sleep ■ Open eyes and/or engaged intellectually Alpha ■ Awake, closed eyes, relaxed Theta ■ Awake or asleep ■ Often seen during light sleep or REM sleep or “trance” like states ■ Awake, N1, and REM Delta ■ Asleep ■ Characteristics of slow wave sleep or deep sleep N3

Scoring EEGs ○ 1. Score sleep stages in 30 second sequential epochs commencing at start of study ○ 2. Assign stage to each epoch ○ 3. If 2 or more stages coexist during a single epoch, assign the stage comprising the greatest portion of the epoch Wakefulness ○ Beta waves dominate ○ Gamma and theta also possible

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○ Alpha waves appear most notably when eyes are shut (drowsy or not) ○ Wakefulness counts for less than 5% of the night in most adults ○ Anterograde amnesia for 1-3 minutes before sleep onset Sleep stages ○ Stage 1 (N1) ■ Low voltage, mixed frequency EEG ■ Defined by exclusion (devoid of sleep spindles and K-complexes, minimal slow wave activity) ■ Cessation of blinking ■ Alpha activity of less than 50% of epoch ■ 4-7 cps, theta waves ■ Slow, pendular eye movements ■ 2-5% of total sleep ■ Perpetual Disengagement ● Experiment by Hoddes et al (1973) ○ Bright strobe lights flashed into eyes of adult volunteers whose eyelids are taped open ○ They are to press a small switch every time they see the light, brain waves are recorded ○ When volunteers entered NREM stage 1 sleep, subjects failed to push the switch and deny seeing flash ○ Stage 2 (N2) ■ Defined by presence of sleep spindles and/or K-complexes ■ Accounts for 45-55% of total adult sleep ● Sleep spindles = EEG waveforms in with a sinusoidal rhythm or 12-14 cps waxes and wanes for 1-2 seconds ○ Occur every 10-30 seconds ○ Occur in NREM stages 2 & 3 but are hard to see in stage 3 (bc of high amplitude slow waves) ● K-complexes  = EEG waveform with a well delineated negative sharp wave followed by a slower positive component ○ Can occur in response to a stimulus (external) but may be spontaneous as well (internal) ○ Stage 3 (N3, slow wave) ■ High amplitude slow waves ■ Sleep spindles and K-complexes may or may not be seen (but often occur) ■ Delta (slow) waves occur at about 2 cps with high voltage peaks (75 microvolts) ■ Accounts for 13-23% of total adult sleep ○ REM sleep ■ Saccadic eye movements ■ Low voltage, mixed frequency EEG

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■ Very low level of below the brain EMG activity ■ Characterized by sawtooth waves Lucid dreaming ○ Dream in which the dreamer is aware he/she is dreaming ○ Term not used until 1913 ■ Dutch psychiatrist Willens Van Eden  published book describing 352 dreams in which he knew he was dreaming ○ References to LD exist as far back as 415, the year in which St Augustine penned a letter recalling a LD experience ○ This phenomenon was subject of many 20th century books ■ Both personal accounts + tools for LD work ○ Stephen LaBerge ■ Brought LD study into scientific reading ○ Scientists still unsure what structure within brain causes LD ○ Tends to occur towards end of night  dreamer thinks he/she is awake but is actually dreaming ○ False awakening =

September 25th, 2018 ● Neurofeedback ○ Musicians and dancers use to attain relaxed theta state-- helps with creativity and performance ○ Binaural beats ● Point of NREM? ○ Sleep spindles ■ Originate in the thalamus ■ Thought to represent periods when the brain is inhibiting processing to keep the sleeper tranquil ○ K-complexes ■ Originate widely in cortex ■ Occur naturally in response to external stimuli ■ Aid in sleep based memory consolidation (usually followed by bursts of sleep spindles) ○ Delta waves ■ Originate in thalamus or cortex ■ Stimulate release of several hormones (GHRH/Prolactin) ■ Inhibit release of TSH ■ Important in declarative memory consolidation ● Point of REM? ○ Important for developing brain, especially during infancy & childhood ■ May provide a “workout” or stimulation for the developing brain, leads to more growth ○ Muscles most relaxed during REM ■ Cell repair

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■ Immune system operations ○ Important for procedural memory NREM physiological changes ○ Autonomic slowing ○ Maintain thermoregulation ○ Episodic, involuntary movements ○ Reduced blood flow ○ Little dreaming REM physiological changes ○ Increased physiological activity ○ Autonomic activation ○ Altered thermoregulation ■ Cells in anterior hypothalamus cease firing, which makes us essentially poikilothermic (cold blooded) ■ REM sleep lost during temperature extremes ○ Partial or full penile erections (significant vaginal lubrication) ○ Skeletal muscle paralysis (muscle atonia) Sleep cycle ○ REM periods every 90-120 minutes ○ First REM is shortest ○ Most sleep occurs during stages 3 & 4 Basic Rest Activity Cycle ( BRAC) ○ For many years been hypothesized to exist ○ Based upon observation that about every 90 minutes while awake (or asleep) our body rhythms cycle ■ Ultradian rhythm of CNS ■ Integrates somatic, visceral, and behavioural functions ● GI activity, sexual fantasies, resting HR, eye movements, EEG frequencies, eating, etc. Synaptic Homeostasis Hypothesis (SHY) ○ Lots of stimulation = creates many pathways among neurons

October 2nd, 2018 ● Sleep across the lifespan ○ I n utero ■ 24 weeks gestation ● EEG activity emerges ■ 28 weeks ● Differentiation into sleep and wakefulness patterns ■ 32 weeks ● REM sleep appears with ○ Body movements ○ Irregular respiratory pattern and irregular heart rate

○ EEG irregular and low voltage 34 weeks ● NREM appears ● Limited body movements ● Regular heart and respiratory rate ● Higher EEG voltage Newborns ■ Active sleep becomes REM sleep ● Uneven respiration ● Muscle atonia, many myoclonic jerks (muscle jerks) ● Continuous EEG activity ● Rapid eye movements ■ Quiet sleep becomes NREM sleep ● Even respiration ● Body is inactive ● Discontinuous EEG (tracé alternant) ○ Different electrical activity ○ Babies’ brains are smaller ● No eye movements ■ Indeterminate sleep ■ 16-18 hours of sleep a day ■ 3-4 hour sleep-wake cycles ■ Shorter sleep cycles (50 min) ■ REM sleep is 50% ■ At 4 weeks, circadian rhythm of core body temperature ■ At 3 months, circadian rhythm of melatonin and cortisol ■ The more immature you are born, the more REM you have ● Baby horse vs. baby kitten Infant sleep consolidation ■ Unpredictability of waking episodes for first 3 months ■ Rhythm with an approx. 25-h period emerges at about 5 weeks ■ Well consolidated pattern at around 15 weeks ■ Sleeping through night achieved at 4-6 months SIDS (Sudden Infant Death Syndrome) ■ Under age 1 ■ Cause unknown but possibly due to: ● Problems with baby’s ability to wake up (sleep arousal) ● Inability for baby’s body to detect a buildup of carbon dioxide in the blood ■ SIDS rates have dropped dramatically since 1992 ■ Still kills about 2500 per year ● 3rd leading cause of death among US infants ■ Peak between 2-4 months ■

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Risk factors: ● Sleeping on the stomach ● Cigarette smoke/illegal drug use ● Elevated room temperature ● Co-sleeping ● Soft bedding in the crib ● Multiple birth babies (being a twin, triplet, etc.) ● Premature birth ● Family history of SIDS ● Short time period between pregnancies ● Late/no prenatal care ● Living in poverty Early childhood ■ 11-12 hours of sleep ■ 20-25% REM sleep ■ Napping generally continues through preschool years but stops once children begin school full-time ■ Dreaming starts…? ■ Highest % of slow wave sleep  (SWS)  with especially high arousal thresholds ■ High incidence of bedwetting, sleepwalking, night terrors Later childhood ■ Proportion of sleep stages (sleep architecture) similar to adults ■ 10-11 hours ■ Less difficulty falling asleep Adolescence ■ Proportion of SWS decreases to adult levels ■ Night owl tendency ■ Adolescents still need around 9 hours ■ Sleep deprived, social jet lag, sleep marathons on weekends Sleep EEGs ■ As more neurons grow and become more synchronized, deep sleep becomes higher voltage ● Higher wave forms bc more nerves are doing the same thing ■ Later see a reduction in deep sleep voltage around teen years as brain prunes Aging ■ SWS decreases during adulthood and may disappear completely by age 60 ■ Men begin losing SWS at 30, women after menopause ■ Amount of REM sleep is preserved in healthy elderly adults, but less rems ■ 6-7 hours

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Unclear whether elderly have a decreased need for sleep or simply a different distribution of sleep ■ Increased fragmentation of sleep ■ Prolonged latency to sleep onset ■ Increased number of arousals ■ More time spent awake ■ Increase of primary sleep disorders ■ Tendency to wake earlier and feel more alert Sleep in women ○ Sexual differences affecting brain and body (different hormonal profile) ○ Childbearing and childrearing/family + social roles ○ Main differences: ■ Duration (sleep longer) ■ Changes with aging ● Sleep better until menopause ● Have more SWS throughout life and less light stage sleep ■ Disorder profiles ● More likely to have insomnia while men more likely to snore/have sleep apnea ■ Distribution of sleep stages ■ More fragmented and disrupted sleep in the perimenopausal period ● Show more Alpha rhythm during sleep, in part secondary to hormonal changes ■ Report more difficulties falling asleep and decreased sleep efficiency ○ 75% report disturbed sleep during pregnancy esp. during 2nd/3rd trimester ○ Estimated that in first year of of a child, parents lose 400-750 hours of sleep ○ Parents of infants and toddlers who have difficulties sleeping are more prone to depression and anxiety Co-sleeping ○ Average US rates on the rise ○ Cultural norm for black children (70%)...