Wakefulness & Sleep
What is sleep?
- An internally/externally generated altered state of consciousness or a behavior?
Brain/Behavior during sleep
To assess:
1)EEG (electroencephalogram)
- records neural activity
-average of population of cells in the area under the electrode.
-signal is amplified and recorded
2)EMG (electromyogram)
-records activity in the muscles.
3) EOG (electro-oculogram)
-records eye movement.
What does the neural activity during stages of waking and sleeping look like?
Awake –beta activity – alert, attentive
Alpha activity – relaxed wakefulness
Stage 1 sleep, theta activity
-transition stage (10 min)
Stage 2 sleep (approx 15 min),
-sleep spindles – decreases brains sensitivity to sensory input
- k-complexes –triggered by noises, helps to keep person asleep
Stage 3 Slow Wave Sleep (SWS), 20-30% delta activity
& Stage 4: SWS – 50% delta activity
-heart/breathing rate slows,
-neuronal activity slows and becomes more synchronized.
REM (rapid eye movement ) 20-30 minutes
-theta and beta activity
-REM (N. Kleitman) in humans / paradoxical (M. Jouvet) in animals
- sleeping, but neural, heart & breathing activity has increased.
- Loss of muscle tone.
- Eye movement (REM) associated with visual imagery.
- Eg Miyauchi, Takino, Azakami (1990).
Typical pattern of stages of sleep: Wake, 1, 2, 3, 4, 3, 2, REM
-cycle approximately every 90 minutes
-SWS occurs during first part of night, REM during latter.
Why do we need to sleep?
Repair and Restoration Theory of Sleep.
brain appears to need to restore itself (ie rebuild proteins, replenish glycogen)
eg.,
increase sleep when
- increase brain temperature
- increase mental activity
eg., groggy, confused if woken from SWS
Infer from sleep deprivation studies
Evidence for:
Humans-report dizziness, impaired concentration, irritability, hand tremors, hallucinations.
Animals:
-difficult to separate out sleep deprivation effects from stress effects
In general results are: weak, uncoordinated, can’t regulate body temperature, appetite increases, metabolism
increases.
1
-eventually immune system fails.
Evidence against:
- variability between people.
- sleep deprivation does not create physiological stress
- never required to regain all sleep lost.
- Not all species require sleep, eg migrating birds
The Evolutionary Theory of Sleep
Evidence for:
-sleep is an adaptive behavior
-sleep conserves energy.
Against:
-if maladaptive would it still have evolved?
Eg Indus dolphins
Why do we dream?
a) How are they formed, and b) what is their function?
a) Freud’s theory from “The interpretation of dreams”, 1899
-dream content represents:
– conflicts between inner desires and society prohibitions against those desires
-unfulfilled wishes = dreams
-manifest content (story line) disguises latent (hidden) content
Activation synthesis or reciprocal interaction hypotheses (Hobson, McCarley, 1977).
- bursts of activity from Pons
REM-on neurons uses ACh triggers arousal in cortex and limbic system
- random internal/external stimuli synthesized into a story by the brain
REM –off cells release NE and 5-HT to counter effects of ACh and stop dreaming
Brain Areas active during REM Sleep
-EEG studies –PGO waves
(Pons, geniculate, occipital)
Neural pathways responsible for muscular paralysis during REM sleep
From Subcoerulear nucleus in Pons, to magnocellular nucleus in Medulla, to Motor neuron in spinal cord to muscle.
But , does this explain all dreams?
We dream during all stages.
REM (78-80% report dreams
storylike
Vivid sensory/motor
Real but bizzare
NREM 15-50% report dreams
Fixed image, tableau
Feelings of dread, anxiety etc
No plot, simple jumbled thoughts
Clinico-anatomical hypothesis
-derived from clinical cases.
Pons not necessary! (Solms, 1997)
Increase DA in ventral medial frontal increases dream activity.
Brain is primed to make up a story from recently activated memory pathways.
If damage
-inferior parietal cortex, can’t integrate body sensation and vision, no dreams
-V2, dream with no visual content
-frontal lobe, don’t dream
Confirmed with functional imaging studies that show dreams -
2
-decreased inferior frontal cortex (affects ability to track time).
-increased auditory/limbic cortex/basal ganglia (explains verbal, emotional, motor component).
-increased activity in extrastriate visual system (not V1) (explains visual imagery)
-Decreased primary Motor/primary Visual cortex (affects movement and visual info)
b) What is the function of REM sleep? or
-what happens during REM sleep deprivation?
-William Dement (1960) showed in general
-deprive subjects of REM sleep
-# of REM periods increase
-get “REM rebound”
-increase irritability
-impaired concentration
-increased appetite/weight gain
i)Vigilance
–sensitive to environmental stimuli.
ii) Learning/memory (hippocampus is active)
- strengthens new procedural skills
- consolidation/integration
- increased studying = increased REM sleep
- decreased intelligence = decreased REM
- emotional information
- creative problem solving
- flushing of clutter or dream to forget
iii)Neural Development
- establishing or modifying neural connections.
iv) shaking eyeballs to get sufficient oxygen to corneas
-but not engaging in REM does not damage corneas
-and fRMI study shows – moving eyeballs does not create activity in visual cortex like scanning an image
does.
Neural Mechanisms of Sleep
-endogenous circadian rhythm
-controlled by a biological clock
-free running rhythm is 24-25 hours
-reset by stimuli/zeitgeber
eg., light, noises, meals etc.
-Difficult to readjust biological clock
eg jet lag
flying east – difficult, phase advance
flying west – easier, phase delay
eg. Daylight saving time
Fall –turn clocks one hour back
Is this equivalent to phase advance or phase delay? Why?
-external stimuli influence “internal clock”.
Where is the biological clock?
Suprachiasmatic nucleus (SCN) in the hypothalamus.
-if damaged disrupts activity patterns, drinking, hormonal secretion, sleeping.
How does the SCN work?
3
i)
Direct neural input from retina.
-retinohypothalamic path from retina (special ganglion cells) to optic nerve to SCN. Cells are special because they
use a photopigment malanopsin & respond to average amount of light in order to gauge time of day
ii)
Feedback from modulators
Eg in fruit flies & mice genes “period”, “timeless” produce proteins “per”, “tim”, “clock”
Increase as day progresses
Their increase shuts genes down
-also give feedback to protein “clock” to induce sleepiness
E.g., hormone melatonin (from pineal gland)
Increases as evening progresses, this induces sleepiness
-feeds back to receptors in SCN.
Brain areas activated during waking/sleeping
a) Reticular Formation (rf)
pontomesencephalon pathway
rf-medial thalamus-basal forebrain-cortex
Neurotransmitter = Acetylcholine, glutamate
-if stimulate, increase wakefulness
-if destroy, decrease arousal, learning attention
b) Raphe nuclei
raphe -thalamus, hypothalamus, basal ganglia, hippocampus
neurotransmitter = serotonin
c) Locus coeruleus (LC)
LC - neocortex, hippocampus, thalamus, cerebellar cortex, pons, medulla.
Neurotransmitter: norepinephrine
d) basal forebrain
i) Wake related cells
-damaged - decreased arousal, impaired learning/attention, and increased time spent in nonREM sleep.
-release Ach
-modulated (inhibited) by adenosine
ii)Sleep related cells
-input from anterior/preoptic lateral hypothalamus
Neurotransmitter = GABA (-)
-if thalamus and cortex inhibited = sleepiness
- if damaged = long periods of wakefulness.
Disorders of Sleep
Insomnia – 20% of population affected
3 types
1)
onset – difficulty falling asleep
2)
maintenance – difficulty staying asleep
3)
termination – wake up early
Produces – grogginess, physical/mental fatigue, anxious, irritable, autonomic hyperactivity
Causes - personal, situational, medical, drugs, psychological, as well as :
-abnormalities in biological rhythms
eg phase delayed or phase advanced body temperature.
-Sleeping medication
- tranquilizers block NE, and histamine
-tolerance develops, drugs ineffective
4
-take more drugs
-pseudoinsomnia
-dreaming that one is awake.
-Sleep Apnea
-inability to breath while asleep
-increased CO2 stimulates person awake
-repeatedly wake up gasping for air
-due to obesity, hypertension, age (> older), sex (m>f), SIDS
-types: neurogenic (rare), obstructive (common), mixed
-causes: alteration to uvula, soft palate, tonsils
Treatment (obstructive): weight loss, CPAP (continuous positive airway pressure) , dental appliance, surgery
-Periodic Limb Movement Disorder
-every 20-30 s movement of legs during NREM sleep
-due to painful sensations in legs
-treatment: tranquilizers.
General management of insomnia:
-Bedroom used for rest/sleep not TV watching etc
-Minimize noise and disruptions
-Regular exercise but not close to bed time
-No caffeine, alcohol close to bed time.
Parasomnias
Sleep Walking:
-blank expression, indifferent to environment, rarely recall event.
expressed during stage 3 and 4 sleep.
-treatment? Protect from injury
Night Terrors:
-experience of intense anxiety
-wake up screaming in terror
-during NREM sleep
-usually in children (1-3%)
-Treatment – drugs to suppress NREM sleep
Nightmares:
-5% of general population
-associated with fears of attack, falling, death, recurring nightly
-during REM sleep
REM sleep Behavioral Disorder:
-REM sleep without atonia (enacting dreams)
-results in violent acts, injuries
-more prevalent with age
Causes of parasomnias:
-genetics, psychological, drug withdrawal.
Narcolepsy
-characterized by excessive daytime sleepiness and irresistible sleep attack:
- frequent unexpected periods of sleepiness during the day.
5
- inappropriate times (precipitated by sedentary, monotonous activity)
-2s-30 minutes in length
- wake up feeling refreshed
-occurs in conjunction with 1 or more of the following:
Cataplexy
-muscle weakness triggered by strong emotions
-similar to massive inhibition of motor neurons during REM
Sleep paralysis
-complete inability to move when falling asleep or waking up.
Hypnagogic hallucinations
-dreamlike experience, difficult to distinguish from reality
-occurs at onset of sleep
Cause – REM sleep mechanisms not working
 genetics
 biochemical abnormalities.
o Acetylcholine, orexin/hypocretin
 Stress
Treatment – stimulants (facilitates NE)
-imipramine (facilitates 5-HT, NE)
Idiopathic hypersomnia
– excessive daytime/night time sleepiness
-constant somnolence (lengthy non refreshing naps)
-difficulty with morning awakening
Causes –genetics, neurochemical abnormalities (eg Dopamine)
Treatment –stimulant medication
6