SLEEP

Defining and describing sleep

Neural mechanisms

Sleep disorders

Functions

© N. E. Wilson 2

SLEEP-WAKE CYCLE

A circadian rhythm (about 1 day in length). ultradian rhythm (>1 per day) e.g. REM sleep. infradian rhythm (<1 per day) e.g. hibernation.

Rhythms provide temporal organisation Anticipating environmental changes E.g. change from day to night, preparation to feed

etc.

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

Sleep is associated with vertebrates

© N. E. Wilson 4

Characteristics of sleep

Recumbent postures (typically closed eyes)

Raised sensory thresholds

Reduced motor activity Electrographic signs

© N. E. Wilson 5

Measuring sleep

Electroencephalogram (EEG) Electrooculogram (EOG) - electrical activity of

eye movements. Electromyogram (EMG) - muscle activity.

Major EEG patterns

Synchronised (neurons firing at same time) Desynchronised (neurons firing at different

times)

Stages of sleep

5 stages identified by Kleitman and Dement in the 1950s

Continuous and variable changes in EEG

EEG patterns 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 Stages 1, 2, 3, and 4

A.k.a. synchronised, S or quiet sleep. 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 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) 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 All mammalian sleep is cyclical with NREM

punctuated by REM sleep. Humans have 4 to 5 cycles per night each 90 - 100

mins long and including 20-30 minutes of REM sleep. Broader basic rest-activity cycle (Kleitman 1982)

E.g. eating, drinking, heart rate changes, play behaviour in

kids, day dreaming (Cohen 1979) etc.

Dreaming Primarily visual and motor elements Lack of coherence consistent with low frontal

lobe activity (reduced executive control) In lucid dreaming cortex shows more activity PGO (Pons-geniculate-occipital) waves in

REM Classic theory: Activation-synthesis

hypothesis (Hobson and McCarley 1977,

McCarley and Hoffman 1981)

Do dreams have meaning? For Greeks and Romans had symbolic meanings But Greek diviner Artemidorus (AD 120) recognised

that interpreters needed to know about each

dreamer, his/her customs and where he/she lived ‘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?

For some, portents of the future Compensatory function for Freud and Jung

Substitute for repressed emotions or unconscious wishes

(Freud) An expression of a collective unconscious (Jung)

Do dreams have meaning?

For biopsychologist Hobson ‘Meaning’ in creation of story, not expression of

repressed wishes Analysis of form rather than content

E.g. hallucinatory images linked to activation of visual cortex,

emotional salience linked to amygdala etc.

Do dreams have meaning? 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?) REM sleep as a ‘protoconscious’ state (Hobson 2009)

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 Narcolepsy (disordered sleep-wake

boundary) 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 Narcoleptic symptoms (not all may be present)

Sleep attack (intrusion of REM sleep into wakefulness?) Daytime sleepiness Microsleeps (continue automatic actions but asleep) Cataplexy (like REM atonia?)

sudden loss of muscle tone that can lead to collapse triggered by sudden intense emotional stimuli (laughter, anger etc.)

Sleep paralysis (like REM inhibition of voluntary movement?) inability to move when falling asleep or waking up

Hypnagogic or hypnapompic hallucinations (like REM dreaming?) associated with sleep paralysis dreamlike experiences occurring just as falling asleep (-gogic) or

waking (-pompic) (not unique to narcolepsy)

Treated with stimulants modafinil (Provigil) dexamphetamine (Dexedrine)

Sleep Disorders - parasomnias REM sleep behaviour disorder or REM

without atonia person acts out dreams may be associated with impaired inhibition of

motor neurons

Sleep Disorders - parasomnias Following all commonest in children and

associated with SWS Sleepwalking (somnambulism)

Not acting out of dreams Can be very complex actions

Night terrors (pavor nocturnus) Experiences of intense anxiety from which person may

awaken screaming Bedwetting (nocturnal enuresis)

may be cured with training

Brain mechanisms and sleep

Consider neural mechanisms in 1. Timing

2. Induction and Inhibition

1. Timing of sleep Endogenous circadian rhythms controlled

by internal clocks entrained by external cues (‘Zeitgebers’)

Free-running rhythms demonstrate intrinsic activity of clocks Isolated cave studies

(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 The pineal gland.

Light sensitive, releases melatonin. Melatonin regulates circadian rhythms and

seasonal reproductive behaviour 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 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 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 sleep-wake cycle (Ralph and Menaker 1988, Ralph et al 1990) 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

Desynchronisation can occur between free running sleep and temperature rhythms (Harrington et al 1994)

Separate clocks for circadian and ultradian rhythms Ultradian rhythms occur in animals with no free running

circadian rhythm (Takahashi 1995) 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 Thin strip of serotonin producing nuclei from

medulla to midbrain. Originally suggested that system induces sleep

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)

PCPA injections reduce sleep but recovery occurs even though serotonin levels stay low (Dement et al 1972)

2. Interacting neural mechanismsHowever: Serotonin injections don't promote sleep

PCPA antagonism only disrupts sleep in cats Stimulation causes cortical arousal Activity of serotonin nuclei is highest during

waking and falls through sleep stages (Aston-Jones and Bloom 1981)

Now thought that serotonergic activity promotes alertness and suppresses REM sleep

‘REM-off’ cells

(ii) Basal forebrain region and SWS 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

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

Interacting regions producing atonia, EEG desynchronisation, REM etc.

Pons crucial 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)

Moruzzi and Magoun 1949 System of neurons running from the medulla to the forebrain

(near the raphé system) (‘rete’ means net) ‘Active’ vs. passive theory of sleep

The cerveau isolé (‘isolated forebrain’) lesion produced prolonged SWS EEG. 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’? 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? Very strong motivation 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) Retained where it would seem maladaptive –

one eyed ducks and dolphins Bottlenose dolphin (Mukhametov 1984) Blind Indus dolphin (Pilleri 1979)

Sleep deprivation Affects cerebral not physical functioning (meta analysis by

Horne 1978)

Prolonged boring tasks become difficult (e.g. vigilance task,

Gillberg et al 1996)

Demanding tasks unaffected ( e.g abstract reasoning, Percival,

Horne & Tilley 1983)

Vision blurs, speech becomes incoherent, mild perceptual

hallucinations, irritability, disorientation

Most post deprivation recovery is of stage 4 and REM sleep

(common finding).

Horne (1998) suggests difference between ‘core’ and optional

sleep.

Adaptive or circadian theories A behaviour developed through evolution which keeps animal

safe during inactive periods and conserves energy (Meddis 1977)

REM sleep deprivation leads to loss of homeothermic control

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).

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.

Relaxed wakefulness seems to require a more advanced brain

(Horne, 2006).

A shift of function?

Restoration theories Sleep enables ‘repair’ (but of what?) Fail to account for between species differences in

length of sleep Effect of exercise

Sleep deprivation doesn’t affect physical performance

e.g. Takeuchi et al (1985)

Exercise increases SWS but only if brain temperature

increases (Horne 1988)

Suggests restoration is ‘cerebral’

Deprivation affects behaviour and cognitive ability

Cerebral effects

Horne – with increasing brain complexity and overall size,

sleep becomes less important for energy conservation

through immobilisation and more important for cerebral

recovery.

Increasing mental activity increases SWS (Horne and Minard, 1985)

suggesting recovery

Correspondence between task activity and subsequent activity of

related brain areas in sleep (e.g. bird song Dave & Margoliash 2000)

Ps reducing sleep time lose it from stages 1&2 not 3&4

(Mullaney et al 1977) – increasing sleep efficiency

REM sleep Sleep deprived subjects recover mainly REM and

stage 4 sleep. Dement (1960) - ‘Pressure’ for REM sleep

increases during REM sleep deprivation. ‘Rebound’ into REM seen in recovery.

But not essential Lavie et al, 1984, report on 33 yr old man injured who

engaged in almost no REM sleep Bottlenose dolphins have no REM sleep Fur seals have no REM sleep while at sea but regain it

on land (but without recovery of lost periods)

REM sleep and learning

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 “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

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 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 Complementary role in learning procedural

task 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? 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 Adaptive theories better in some key areas

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