l8 sleep

part 1: biorhythms

• biorhythms
  • a variation in a biological process that repeats or cycles over a period of time (24 hours)
• circadian refers to a day circuit/cycle
• e.g. sleep, prolactin, growth hormone, cortisol, core body temp, urine volume, melatonin
• some are influenced by sleep and aren’t
• can be internal and persist even in absence of cues
  • these are called endogenous/free running rhythms
  • study found leaf movement observed without much light, other examples include activity cycles in animals
• zeitgebers (time givers)
  • cues that modify rhythms
  • we say that a biorhythm has been entrained to that zeitgeber
  • getting the cue at an innapropriate time can disrupt rhythms
  • e.g. our sleep-wake cycle is entrained to light cues
• measuring biorhythms in the lab
  • wheel-running behaviour shows periodic variation in rodents throughout the day, and in nocturnal rodents it is greatest at night
  • biorhythms in the hamster

      * and house sparrow

        * observed in constant light and darkness

• in humans in the absence of external cues, the sleep wake cycle shifts from 24 hours to 25-27 hours
  • light pollution, jet lag, graveyard shift work can disrupt light-regulated biorhythms
  • biorhythms vary in length:
• circadian
  • ~24 hours to repeat, e.g. sleep-wake cycles
• infradian
  • 1 day < infradian biorhythm < 1 year
  • e.g. menstrual cycle, also called circalunar becaue it follows lunar cycle (~28 days)
• ultradian
  • eating behaviour every 90-120 minutes
  • neural basis
• retinal ganglion cells (RGCs) in the eye
  • entrainment begins here
  • 1-3% of them express melanopsin (light-sensitive pigment)
    • sensitive to certain wavelengths of blue light, and doesn’t show much adaptation

• SCN = suprachiasmatic nucleus
  • located in anterior hypothalamus
  • important to biological rhythms, light information affects every other rhythm in the body
  • named for its proximity to the optic chiasm ( where the optic pathway decussates)
  • how do we know it is involved?
    • lesion abolishes many circadian rhythms
    • a SCN lesioned animal can recover if it receives SCN neuron transplant from a healthy animals
    • but the ‘restored rhythm’ in the lesioned animal matches the rhythm of the implanted SCN neurons!
    • SCN neurons have rhythmic activity that is linked to animal’s cycle (more active during the day in diurnal animals
    • SCN neurons maintain rhythm even when deprived of input or removed from brain entirely
    • how do they have independent rhythms?
    • CRY1 gene associated with delayed sleep phase disorder and ADHD accompanied by insomnia
  • pineal gland
• key production site of melatonin
• light inhibits melatonin production
  • paraventricular nucles (PVN)
• key to initiation of cortisol (CORT)
• cortisol levels rise early in the morning, during stress both when you’re unlikely to fall asleep (”cortisol awakening response”)
  • \
• phase shifts
  • earlier exposure to daylight
    • phase advance, tired earlier
  • daylight later
    • phase delay, tired later
  • excercising early
    • phase advance, tired earlier
  • excercising later
    • phase delay, sleep later
  • it’s not just the cue, it is the point in the cycle you recieve the cue
• reticular activating system (RAS)

* sensitive to sensory input
* connected to the basal forebrain, providing cholinergic stimulation to the rest of the brain
* stimulation of the **reticular formation** promotes arousal
* coma can onjur with even minor injury
* evidence for its involvement in sleep:

        * electrical stimulation of the reticular formation wakes a sleeping cat * lesion of it, animal is fine, lesion through it, it is in a coma

  # Part 2: Sleep

• why do we need sleep?

     1. maintenance of the brain (clearance of waste), restoration of injured/damaged tissue 2. ontogenetic development of the brain * the genetic changes of the brain (refer to neurogenesis) mostly occur here 3. maintenance of learning + memory process 4. energetically favourable * argues that sleep is there because there’s nothing we can do at night (dark out can’t see) 5. dreaming

• mean sleap for adults is ~7-8h
  • reccomendations and social perceptions are that thisis the ‘normal’ level, but no magic number as factors such as excercise, stress + genetics all matter
  • preferrably continuous because certain cycles get longer throughout the night, waking up disrupts and restarts them
• DEC2 gene, ADRB1 gene mutations are associated with less sleep in humans and animals
  • more efficient sleep, less sleep still restful
  • putting these genes into mice showed that they need less sleep
• chronotype
  • variations in sleep-wake cycle
  • morning chronotype, evening chronotype
  • affected by many factors; genetics, age, gender
• shifts evident in adolescence, may be exacerbated by increasing use of electronic devices
  • chronotype early when young, shifts later during adolescence, shifts back early when older
• sleeping patterns of adolescents have led to reccomendations about school start times (no eaerlier than 8:30 am)
• morningness associated with better academic performance, even though eveningness is associated with greater cognitive ability
• eveningness assoicated with poorer mental health
• chronotype related to personality
  • morningness: agreeable and conscientousness
  • eveningness: neuroticism in certain cases (females, adolescents), sensation seeking
• sleep has been divided into 4 distinct stages, exemplified by distinct patterns of EEG activity (great temporal resolution, measures electrical activity in specific brain regions), each one potentially serving a dif function
  • 1 stage of rapid eye movement (REM)
  • several stages of non REM sleep (NREM 1-3)
• sleep stages

      * stage NREM1 - light sleep * alpha 7-13hz + theta waves 4-7 hz * slightly lower frequency activity * stage NREM2 * theta waves 4-7 hz * sleep spindles * k - complexes * stage NREM 3/4 - deep or slow wave sleep * delta waves 1-4 hz, some spindles * contributes to feeling of ‘rest’, people who need less sleep show increased time in NREM 3 sleep * REM - dream stage * fast random high frequency activity, similar to eyes open wakefulness * frequency ranges * beta > 13 hz * alpha 7-13 hz * theta 4-7 hz * delta 1-4 hz

• sleep in the elderly
  • greater sleep latency
  • more arousal periods (likely awakenings)
  • less REM, NREM3 (in terms of relative percentage)
  • less overall sleep
• during REM
  • there is atonia, lack of muscle tone

• is REM necessary?
  • with REM deprivation there is REM rebound
    • enter REM stage sooner, spend longer in REM stage
  • lack of REM associated with reduced hippocampal neurogenesis, immune dysfunction and mood disruption
    • but suppression of REM occurs w antidepressant drugs which improve mood
  • REM might be a preparatory stage for wakefulness
    • replacing REM states with wakeful states prevents rebounds
• memory consolidation
  • process by which memory is converted into a long-term form
  • part of the process may involve reaction of the memory trace (L6 replay)
    • replay might occur in waking states as well as REM and NREM states
  • most studies focus on replay in the hippocampus but changes in cortex might also be key
• replay in the hippampus (NREM)
  • after spatial learning, (reflective of declarative memory), cells involved in the task become ‘linked’ (show correalted activity during NREM sleep
• replay in the cortex (REM)
  • in humans, neurons involved in executing an implicit motor task may again become a)ctive during sleep (similar but not identical patterns of brain activity)
• sleep regularity is associated with cognitive performance
  • in a study GPA is positively correlated (0.37) with the sleep regularity index (SRI)
  • GPA also tends to be negatively correlated with dim-light melatonin onset
    • melatonin starts being released earlier, so sleep earlier
  • excercise helps with sleep regularity
• dreams
  • narrative with ‘experiential resemblance to waking life’
  • typically aversive >64%, rarelly happy <18% or sexual <10%
  • increase in complexity with age neurocognitive theory
  • REM dreams ~80% tend to be emotional, illogical, and have sudden plot shifts
  • NREM dreams (~20%) are more thought-like, repetitive, centered around daily tasks
• dream theories
  • dream protection theory
    • Freud
    • sexual + aggressive instincts are transformed into symbols, which represent wish fulfillment
    • interpretation required to understand our desires
  • evolutionary theory
    • dreams about threats to reproductive success, to plan solutions
  • activation-synthesis theory
    • dreams are an attempt by the brain to interpret random activity
    • dreams are not particularly important
• measuring sleep in the lab
  • 2 main approaches, alone or in combination
    • subjective analysis
    • relies upon patient self-report
    • questionnaires on sleep quality are administered to the patient and the patient responds
    • e.g. Athens Insomnia Scale, Pittsburgh Sleep Quality Index, Insomnia Severity Index
    • sleep diaries are used to record the patient’s sleep behaviours
    • benefits
      • cheap, quick, accessible (only need questionnaires and trained professionals)
      • informative of patient attitudes and beliefs, may help in identifying other problems
    • cons
      • doesn’t address physiological function
      • relies upon honest and accurate patient reports
    • objective analysis
    • polysomnography studies
      • incorporates many techniques (EEG, EMG, EOG, ECG, breathing monitors, other devices)

  # Part 3: Sleep Problems

• sleep deprivation
  • has effects on cognitive function, brain structure, health
  • most impacts temporary/reversible
  • some effects of deprivation could last a long time (esp if it occurs during adoelscence)
  • effects of deprivation on relatively greater on PFC structure and function
  • sleeping and the student
    • 50-60% of students report poor sleep, ~10% meet criteria for sleep problem
    • poor sleep linked to less study time, lower GPA
    • moderated by many factors; intrapersonal adjustment, friendship quality, academic stresses **(40%)
• insomnia
  • difficult falling/staying asleep
  • can be acute or chronic (>3-6 mo) may occur in recurring bouts
  • primary insomnia is rare (10%)
  • secondary/comorbid insomnia more common (~90%)
    • heart disease, cancer, high blood pressure, diabetes etc.
    • commonly comorbid with neuropsychiatric disorders (depression and axiety, ~33% insomnia cases linked)
• cataplexy
  • loss of motor control (atonia) without loss of consciousness
    • why?
    • orexin-expressing neurons in the lateral hypothalamus may be involved in the atonia circuit
    • they may inhibit other inhibitory neurons, limiting atonia to appropriate situations
    • loss of orexin neurons (in narcolepsy) disinhibits them, which in turn more strongly inhibits the motor neurons (therefore atonia)
  • triggered by arousing stimuli (laughing, crying, terror etc
  • common in narcolepsy (70% cases)
    • characterized by extreme daytime sleepiness with frequent episoes of dozing
    • rapid descent into REM sleep is common
• REM behavioural disorder
  • loss of atonia during REM, tendency to act out dreams
  • loss of inhibition to spinal motor neurons (poorly understood)
• somnambulism (sleepwalking)
  • person leaves the bed and moves around while still sleep
  • more common in childhood (12 yo) but only ~4% of adults express it
  • been reports of complex, aggressive, illegal behaviours while sleepwalking
  • thought to occur during NREM, not REM