SLEEP
Defining and describing sleep
Neural mechanisms
Sleep disorders
Functions
SLEEP-WAKE CYCLE
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A circadian rhythm (about 1 day in length).
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ultradian rhythm (>1 per day) e.g. REM sleep.
infradian rhythm (<1 per day) e.g. hibernation.
Rhythms provide temporal organisation
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Anticipating environmental changes
E.g. change from day to night, preparation to feed
etc.
© N. E. Wilson
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Sleep is associated with vertebrates
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A behavioural state of warm-blooded
vertebrates (mammals and birds)
Regarded as evolutionarily recent
Emergent and ‘higher’ brain function.
A behaviour and state of consciousness
Characteristics of sleep
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Recumbent postures (typically closed eyes)
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Raised sensory thresholds
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Reduced motor activity
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Electrographic signs
© N. E. Wilson
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Measuring sleep
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Electroencephalogram (EEG)
Electrooculogram (EOG) - electrical activity of
eye movements.
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Electromyogram (EMG) - muscle activity.
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© N. E. Wilson
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Major EEG patterns
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Synchronised (neurons firing at same time)
Desynchronised (neurons firing at different
times)
Stages of sleep
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5 stages identified by Kleitman and Dement
in the 1950s
Continuous and variable changes in EEG
EEG patterns
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Alpha waves, regular medium frequency of 8-12
Hz during quiet rest
Beta waves, irregular, low amplitude, at 13-30
Hz seen during alert wakefulness and REM sleep
Theta activity (3.5-7.5 Hz) in stage 1 sleep
(transiting from awake to sleep)
Delta waves – high amplitude, low frequency
(<3.5 Hz) pattern seen in stage 3 and 4 sleep
Sleep spindles – short burst of 12-14 Hz activity
during sleep stages 1 – 4
K complexes – sudden sharp waveform only
seen in stage 2 sleep
NREM (non rapid eye movement) sleep
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Stages 1, 2, 3, and 4
A.k.a. synchronised, S or quiet sleep.
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EEG waves grow progressively slower and
larger moving from alpha to delta waves.
Waking threshold increases.
Heart rate and temperature fall. Muscle activity
decreases passively.
Dreams infrequent and of ‘thinking’ type
Slow wave sleep (SWS) used as term for
stages 3 and 4
REM (or emergent stage 1) sleep
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Aserinsky and Kleitman (1953)
EEG irregular, low voltage fast waves (beta
and theta activity), heart rate and breathing
variable, intermittent rapid movement of eyes,
Higher frequency of dreaming than in NREM
sleep (usually involves imagery)
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95% of awakenings from REM report dreams
But REM and dreaming logically distinct (only
correlation as evidence)
Start 60 - 90 mins into sleep. Periods become
more frequent towards morning.
Cycle of sleep
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All mammalian sleep is cyclical with NREM
punctuated by REM sleep.
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Humans have 4 to 5 cycles per night each 90 - 100
mins long and including 20-30 minutes of REM sleep.
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Broader basic rest-activity cycle (Kleitman 1982)
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E.g. eating, drinking, heart rate changes, play behaviour in
kids, day dreaming (Cohen 1979) etc.
Dreaming
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Primarily visual and motor elements
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Lack of coherence consistent with low frontal
lobe activity (reduced executive control)
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In lucid dreaming cortex shows more activity
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PGO (Pons-geniculate-occipital) waves in
REM
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Classic theory: Activation-synthesis
hypothesis (Hobson and McCarley 1977,
McCarley and Hoffman 1981)
Do dreams have meaning?
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For Greeks and Romans had symbolic meanings
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But Greek diviner Artemidorus (AD 120) recognised
that interpreters needed to know about each
dreamer, his/her customs and where he/she lived
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‘the rules of dreaming are not general, and therefore
cannot satisfy all persons, but often, according to times
and persons, they admit of varied interpretations.’
Do dreams have meaning?
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For some, portents of the future
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Compensatory function for Freud and Jung
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Substitute for repressed emotions or unconscious wishes
(Freud)
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An expression of a collective unconscious (Jung)
Do dreams have meaning?
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For biopsychologist Hobson
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‘Meaning’ in creation of story, not expression of
repressed wishes
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Analysis of form rather than content
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E.g. hallucinatory images linked to activation of visual cortex,
emotional salience linked to amygdala etc.
Do dreams have meaning?
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Activation-synthesis theory: Order within dreams is a
function of one’s personal view of the world, current
preoccupations, remote memories, feelings and beliefs
(Hobson 1986) not Freudian disguise and censorship
(similar to Artemidorus?)
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REM sleep as a ‘protoconscious’ state (Hobson 2009)
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Dreaming has features of ‘primary’ consciousness – simple
awareness including perception and emotion
But lacks ‘secondary’ consciousness – self-awareness, abstract
thinking, volition
A ‘protoconsciousness’ – primordial state of brain organisation
that has the building blocks of consciousness
Sleep Disorders
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Narcolepsy (disordered sleep-wake
boundary)
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Peptide hypocretin (orexin) deficiency produces
narcolepsy but mechanism unclear as low activity
of hypocretin is normal during waking and NREM
1 in 2000
Repeated brief (2-30 mins) day time sleep attacks
Sleep Disorders
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Narcoleptic symptoms (not all may be present)
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Sleep attack (intrusion of REM sleep into wakefulness?)
Daytime sleepiness
Microsleeps (continue automatic actions but asleep)
Cataplexy (like REM atonia?)
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Sleep paralysis (like REM inhibition of voluntary movement?)
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inability to move when falling asleep or waking up
Hypnagogic or hypnapompic hallucinations (like REM dreaming?)
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sudden loss of muscle tone that can lead to collapse
triggered by sudden intense emotional stimuli (laughter, anger etc.)
associated with sleep paralysis
dreamlike experiences occurring just as falling asleep (-gogic) or
waking (-pompic) (not unique to narcolepsy)
Treated with stimulants
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modafinil (Provigil)
dexamphetamine (Dexedrine)
Sleep Disorders - parasomnias
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REM sleep behaviour disorder or REM
without atonia
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person acts out dreams
may be associated with impaired inhibition of
motor neurons
Sleep Disorders - parasomnias
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Following all commonest in children and
associated with SWS
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Sleepwalking (somnambulism)
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Night terrors (pavor nocturnus)
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Not acting out of dreams
Can be very complex actions
Experiences of intense anxiety from which person may
awaken screaming
Bedwetting (nocturnal enuresis)
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may be cured with training
Brain mechanisms and sleep
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Consider neural mechanisms in
1. Timing
2. Induction and Inhibition
1. Timing of sleep
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Endogenous circadian rhythms controlled
by internal clocks entrained by external
cues (‘Zeitgebers’)
Free-running rhythms demonstrate intrinsic
activity of clocks
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Isolated cave studies
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(e.g. caver Michel Siffre in 1970s )
25 hr free running period in humans without
external cues (Wever 1979)
Learning unnecessary (Richter 1971)
Endogenous clocks in birds & reptiles
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The pineal gland.
Light sensitive, releases melatonin.
Melatonin regulates circadian rhythms and
seasonal reproductive behaviour
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In humans, no clear evidence that melatonin
promotes sleep, but may affect circadian cycle
(used in jet-lag to promote small phase shifts)
Endogenous clocks in mammals
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The supra-chiasmatic nucleus (SCN) of the
hypothalamus.
10 000 neurons with intrinsic circadian
rhythmic firing.
Connects to eye (retinohypothalamic pathway
independent of vision) and pineal gland.
Evidence that SCN is a clock
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Lesions disrupt rhythms of drinking,
movement and adrenal steroid release
(Stephan and Zucker 1972, Moore and
Eichler 1972))
The SCN controls the length of the sleepwake cycle (Ralph and Menaker 1988, Ralph
et al 1990)
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Transplanted foetal SCN tissue from hamsters
with a 20 hour cycle (tau mutation) into SCN
lesioned normal foetuses (and vice versa).
Donor tissue determined length of cycle
Multiple clocks
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Desynchronisation can occur between free running
sleep and temperature rhythms (Harrington et al
1994)
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Separate clocks for circadian and ultradian rhythms
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Ultradian rhythms occur in animals with no free running
circadian rhythm (Takahashi 1995)
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Destruction of SCN affects circadian rhythms but not
ultradian (these are affected by lesions to other parts of
hypothalamus)
2. Interacting neural mechanisms
(i) The raphé system
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Thin strip of serotonin producing nuclei from
medulla to midbrain.
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Originally suggested that system induces sleep
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Destruction in cats produces complete insomnia for 3 4 days with partial recovery afterwards (<2.5 hours
sleep per day, all SWS) (Jouvet and Renault 1966)
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PCPA injections reduce sleep but recovery occurs
even though serotonin levels stay low (Dement et al
1972)
2. Interacting neural mechanisms
However:
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Serotonin injections don't promote sleep
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PCPA antagonism only disrupts sleep in cats
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Stimulation causes cortical arousal
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Activity of serotonin nuclei is highest during
waking and falls through sleep stages (AstonJones and Bloom 1981)
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Now thought that serotonergic activity promotes
alertness and suppresses REM sleep
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‘REM-off’ cells
(ii) Basal forebrain region and SWS
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In front of hypothalamus
Lesions abolish SWS (Sterman and
Clemente 1962)
Stimulation produces drowsiness and EEG
changes (Sterman and Clemente 1962)
Suppresses histamine mediated alertness
(iii) Locus Coeruleus
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Noradrenergic system in the pons
Active in SWS and inhibits REM
Active during waking when attention to
unusual stimulus is required – role in
vigilance? (Aston-Jones and Bloom 1981)
REM only begins when activity of
serotonergic (raphé system) and adrenergic
systems (LC) reduces
‘REM-off’cells
(iv) Caudal reticular formation REM circuits
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Interacting regions producing atonia, EEG
desynchronisation, REM etc.
Pons crucial
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Lesions abolish REM sleep (Friedman and Jones
1984)
Injections of cholinergic agonists promote REM in
humans, antagonists decrease it (Sitaram et al
1978)
‘REM-on’ cells
(v) The ascending reticular activating
system (ARAS)
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Moruzzi and Magoun 1949
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System of neurons running from the medulla to the forebrain
(near the raphé system) (‘rete’ means net)
‘Active’ vs. passive theory of sleep
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The cerveau isolé (‘isolated forebrain’) lesion produced
prolonged SWS EEG.
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But only if reticular activating system isolated.
The Encéphale isolé (‘isolated brain’) lesion doesn’t disrupt
sleep EEG.
So difference is in ARAS being isolated
Chemical ‘switches’?
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Awake – all brainstem neurons involved,
ACh, dopamine, histamine, noradrenaline,
serotonin
Asleep – balance changes
REM-off cells are aminergic – serotonin
(raphe nuclei) and noradrenaline (LC)
REM-on cells are cholinergic – ACh
Shift from mainly external input to internal
input in dreaming
The ‘off-line’ brain is activated by ACh and
dopamine – the ‘psychosis’ of dreams
So why sleep at all?
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Very strong motivation
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Almost universal - all mammals and birds sleep
(Durie, 1981), reptiles sleep, insects sleep
(Horne, 2006), other organisms ‘rest’, a few
vertebrates never sleep (Kavenau 1998)
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Retained where it would seem maladaptive –
one eyed ducks and dolphins
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Bottlenose dolphin (Mukhametov 1984)
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Blind Indus dolphin (Pilleri 1979)
Sleep deprivation
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Affects cerebral not physical functioning (meta analysis by
Horne 1978)
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Prolonged boring tasks become difficult (e.g. vigilance
task, Gillberg et al 1996)
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Demanding tasks unaffected ( e.g abstract reasoning,
Percival, Horne & Tilley 1983)
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Vision blurs, speech becomes incoherent, mild perceptual
hallucinations, irritability, disorientation
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Most post deprivation recovery is of stage 4 and REM
sleep (common finding).
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Horne (1998) suggests difference between ‘core’ and
optional sleep.
Adaptive or circadian theories
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A behaviour developed through evolution which keeps animal safe
during inactive periods and conserves energy (Meddis 1977)
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REM sleep deprivation leads to loss of homeothermic control
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Size of an animal and danger of being attacked account for 58% of the
differences in length of sleep between species (Allison and Chichetti
1976).
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But bigger animals lose less energy than smaller ones (e.g. humans
vs. mouse) and more advanced animals can adopt ‘relaxed
wakefulness’. Sleep adds little to energy conservation compared to
resting.
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Relaxed wakefulness seems to require a more advanced brain (Horne,
2006).
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A shift of function?
Restoration theories
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Sleep enables ‘repair’ (but of what?)
Fail to account for between species differences in
length of sleep
Effect of exercise
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Sleep deprivation doesn’t affect physical performance
e.g. Takeuchi et al (1985)
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Exercise increases SWS but only if brain temperature
increases (Horne 1988)
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Suggests restoration is ‘cerebral’
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Deprivation affects behaviour and cognitive ability
Cerebral effects
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Horne – with increasing brain complexity and overall size,
sleep becomes less important for energy conservation
through immobilisation and more important for cerebral
recovery.
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Increasing mental activity increases SWS (Horne and Minard, 1985)
suggesting recovery
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Correspondence between task activity and subsequent activity of
related brain areas in sleep (e.g. bird song Dave & Margoliash
2000)
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Ps reducing sleep time lose it from stages 1&2 not 3&4
(Mullaney et al 1977) – increasing sleep efficiency
REM sleep
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Sleep deprived subjects recover mainly REM and
stage 4 sleep.
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Dement (1960) - ‘Pressure’ for REM sleep
increases during REM sleep deprivation.
‘Rebound’ into REM seen in recovery.
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But not essential
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Lavie et al, 1984, report on 33 yr old man injured who
engaged in almost no REM sleep
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Bottlenose dolphins have no REM sleep
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Fur seals have no REM sleep while at sea but regain it
on land (but without recovery of lost periods)
REM sleep and learning
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Various theories involving memory
restructuring
REM sleep increases in animals and
humans learning a task until ‘mastered’ (e.g.
Hennevin et al 1995)
REM deprivation impairs learning
REM sleep and learning
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“Habitual reactions, which are closely linked with
survival, are REM independent; but activities
involving assimilation of unusual information
require REM sleep for optimal consolidation”
(Greenberg and Pearlman 1974 p.516)
Perhaps simpler tasks don’t need REM sleep but
complex ones do or new knowledge do (Pearlman,
1979; Stickgold, 2001)
The developing brain – the
ontogenetic hypothesis
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Infant humans have more REM sleep than
precocial animal infants (Roffwarg, Muzio
and Dement 1966).
50-70% of newborns sleep is REM, 15% in
adult. (1 month premature – 67%, 2 months
80%)
Perhaps active role in brain development is
succeeded by later role in learning.
REM provides necessary stimulation for
development
Integrating SWS and REM
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SWS deprivation affects explicit memories
(consciously recollected) while REM
deprivation affects implicit memories
(performance improvement without
conscious recall) (Plihal and Born 1999)
Distinction may be too simplistic – some
studies (such as the following) suggest
optimal learning needs both types of sleep
Integrating SWS and REM
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Complementary role in learning procedural
task
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First nights sleep after implicit learning of visual
discrimination task is required for improvement
(Stickgold et al 2000)
But optimal performance occurs after both SWS
and REM are experienced (Gais et al 2000).
Dual processes? SWS initiates and is required
for consolidation, REM adds to this process but
isn’t needed.
Is sleep needed for learning?
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Effects are statistically significant but small
Semantic memory not strongly enhanced by
sleep
Selective REM or NREM sleep does not
always affect memory consolidation
REM suppressants like anti-depressant drugs
can enhance learning
So useful but not essential for learning
Integrating theories of sleep
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Adaptive theories better in some key areas
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Relationship between sleep time and vulnerability
Effects of sleep deprivation minor
But adaptive and restorative theories are
complementary
May also be a shifting of function with more
complexity (in evolution)
Waking and REM sleep - dreaming are
distinct states but with relationships affecting
optimal functioning of both
Sleep in Humans
From Hobson, J.A. (2005) ‘Sleep is of the brain, by the brain and for the brain’ Nature 437, 1254 - 1256