Biological Rhythms

What are Body Rhythms?

• Body rhythms are biological processes that show cyclical variation over time…ranging from hours to years and reflect the influence of the earths rotation upon us… it's living inhabitants, along with plants and animals.

• There are three rhythms that we will focus our attention upon throughout this module.

• Circadian Infradian, and ultradian biological rhythms.

Body Rhythms (cont’d)…

• Circadian rhythms: (circa = approx and diem = day) go over 24hrs. Humans demonstrate a series of changes including temperature heart respiration and metabolism over this period. We (psychologists) are most interested in the sleep-wake cycle.

• Ultradian rhythms:(Meaning less than one day) Sleep is a good example of an ultradian rhythm, as you sleep you pass through differing stages of sleep (e.g. light and deep sleep lasting about 90 minutes.)

Body Rhythms (cont’d)…

• Infradian rhythm: (meaning more than 1 day). An example of a infradian rhythm would be a woman's menstrual cycle which lasts for 28 days.

• A circannial cycle occurs yearly/annually. An example of this would be non human animals hibernation and waking patterns.

Research Studies into Circadian Rhythms.

• If bodily rhythms show a similar daily pattern for people with different lifestyles it would seem these rhythms are ‘part of our nature’ and not our ‘upbringing or nurture’

• So..the next question would be is whether they are natural and triggered internally or whether they rely upon external cues in the environment.

Research Studies into Circadian Rhythms.

• Siffre (1975) Spent 6 months inside a cave and found that his natural Circadian rhythm was just over 24 hr, but would sometimes change to 48 hr.

• There were no zeitgebers such as natural light or sounds. He had no idea what time it was, although he did have contact with outside world via telephone. He had food and drink and so on. His behaviour such as when he slept/woke and when he ate his meals was monitored. From this study it was concluded our internal clock must have a 25-hr cycle and that our zeitgebers must reset the clock to our usual 24-hr day.

Research Studies into Circadian Rhythms…

• Another way to test circadian rhythms is to alter our environmental cues.

• Folkard (1985) 12 participants lived in ‘temporal isolation’ for 3 weeks…isolated from natural light and other time cues. They agreed to go to bed at 11.45 pm and get up when it said 7.45 am. The clock initially ran to time but gradually quickened until it indicated a passing of 24 hr for 22 hr. All but 1 of the participants kept pace with the clock…thus demonstrating a strong free-running rhythm.

Evaluation of Research Studies into Circadian Rhythms…

• Participants were isolated from exogenous cues (environmental) and we know these have an effect upon our circadian rhythms….but were not isolated from artificial light...it is now known these too can have an effect!!

• Individual differences- Are you a morning or evening person?

• Duffy et al (2000) found early risers prefer 6 am-10 pm cycles and late starters prefer 10 am - 1 am cycles.

Evaluation of Research Studies into Circadian Rhythms…

• What everyday application could we gain from studies such as these…(how useful is this stuff really???)

• Deciding the best time to study.

• Taking medication for serious medical conditions. (chronotherapeutics)

Research studies into infradian rhythms.

• Monthly cycles...the function of this cycle is to regulate ovulation.

Research Studies into Infradian Rhythms.

• Seasonal Affective Disorder (SAD). Research has shown that the hormone melatonin is secreted when it is dark...the more darkness...the more melatonin. This leads to severe disruption in mood.

Evaluation of Studies into Infradian Rhythms.

• Menstrual cycles can also be disrupted by other factors as well as hormones...research has shown that when a several women live in a house together and they are not taking oral contraceptives they tend to fall in line with each other and menstruate at the same time this be possibly due to pheromones being released chemically and giving a scent.

• SAD a greater understanding of this condition has lead to successful therapies such as phototherapy- very strong lights to increase the level of melatonin.

Research Studies into Ultradian Rhythms

• These are rhythmic cycles with a period of less than one day. Examples include levels of alertness throughout the day and the cycle of brain activity during sleep.

• NREM and REM: There are 4 stages (1 & 2) which are shallow into deep sleep/slow wave sleep (3 & 4). These cycles continue throughout the night with (SWS) becoming shorter and REM becoming longer as the night progresses. Cycles last for approx 60 min in early infancy and 90 min in adolescence.

• The use of an electroencephalogram (EEG) can show the electrical activity of the brain. There are different patterns of activity at different times during sleep (Rechtschaffen & Kales, 1968).

Circadian Rhythms

• Circadian = diurnal + nocturnal

• Zeitgebers and the SCN: Biological clock– Altering light/dark cycles produces phase shift

and entrainment

Suprachiasmatic Nucleus (SCN)

SCN - main control centerfor sleep and temperaturecircadian rhythms

Zeitgeber: a stimulus that resets the biological clock (e.g. bright light, exercise, temperature)

What sets the Clock?

Evidence for the SCN as biological clock

– Free-running rhythms and the 24+ hour period– SCN lesions disrupt circadian rhythms– SCN tissue maintained in vitro retains cyclicity– Transplanted SCNs set rhythms of donor animal– Recall the pathway in the visual system from

retina to SCN: These retinal ganglion cells contain a photopigment, melanopsin, and are light sensitive

The Role of Endogenous Pacemakers and Exogenous Zeitgebers.

• The main pacemaker for endogenous (internal) rhythms is the suprachiasmatic nucleus (SCN). This is a small group of cells located in the area of the brain called the hypothalamus. Its called the SCN because it lies just above the optic chiasm, therefore it can receive information directly from the eye and the rhythm can be rest by the amount of light entering the eye.

The Role of Endogenous Pacemakers and Exogenous Zeitgebers (cont’d)….

• The way the SCN works is as follows:

Production of protein for number of hours

The level inhibits further production, again for a number of hours.

The protein drops another level

and the SCN starts producing the protein again.

This rhythm then affects

the sleep wake cycle

via the pineal gland.

Stimulation of the pineal

gland produces the hormone melatonin

(sleepy) When light levels are

low we produce more

melatonin..

The Role of Endogenous Pacemakers and Exogenous Zeitgebers (cont’d)….

• So what about exogenous (external) pacemakers???

• Light is considered to be the most dominant zeitgeber. (see..Miles et al 1977)

• Opposing research also indicates that there are other factors that should be taken into consideration (see..Luce & Segal 1966)

• Overall it appears the sleep-wake cycle is strongly dictated by endogenous pacemakers but we can override these cues.

• It what circumstances might this happen?

The Role of Endogenous Pacemakers and Exogenous Zeitgebers Evaluation…

• It is adaptive for endogenous rhythms to be rest by external cues so that animals are in tune with seasonal variations and day/night time. This idea of adaptive ness comes from evolutionary perspective that refers to the idea that behaviours which persist are more likely to promote ones survival.

• It could be life threatening if we relied solely upon external cues, therefore we must not forget the significance of internal cues.

Optic nerve

Optic tract

Lateral geniculate nucleus

Optic radiation

Optic chiasm

Primary visual cortex

Pathways to SCN

Circadian Physiology

Circadian Rhythms• endogenous cycles• role of the suprachiasmatic nucleus• setting/resetting biological clocks

Sleep

• why sleep?• stages of sleep

Dreaming • why dream?

Endogenous circadian rhythms

• rhythms that last about a day• humans’ last around 24.2 h

Examples:-activity-temperature-waking and sleeping-secretion of hormones-eating and drinking

Circadian Rhythms

Light

• retinal ganglion cells send direct projections to the SCN• this provides information about light to the SCN

Melatonin

• secreted from the pineal gland• increased levels of melatonin make you sleepy• melatonin can act on receptors in the SCN to phase-advance the biological clock

What Resets the Clock?

Sleep

Neural Control of Sleep

• Is sleep a passive process?– The cerveau isole’ of Bremer (1936): SWS only– The encephale isole’ and the RAS: normal sleep– Partial transections leaving the RAS intact

• Ventrolateral Preoptic Area (VPA) triggers sleepiness and slow-wave sleep

• Warming the basal forebrain induces slow-wave sleep: GABA on tuberomammillary nucl.

• VPA receives input from thermoreceptors

More Neural Control

• PGO waves in the EEG from implanted electrodes

• Executive in the dorsolateral pons, called the peribrachial area.

• Kainic acid lesions of peribrachial area reduce REM sleep

• Carbachol, an ACh agonist, in ventral pons (medial pontine reticular formation) triggers REM phenomena.

The Sleep Cycle

• Electronic recording: EEG, EOG, EMG• EEG patterns divide sleep into four stages:

– 1: waves, 8 - 12 Hz, low amplitude, moderate frequency, similar to drowsy wakefulness

– 2: slower frequency, higher amplitude, plus• K complexes• Sleep spindles

– 3: waves appear, 1-2 Hz, large amplitude– 4: Dominated by waves

EEG patterns

2k

3

1 sec

EEG patterns...

1 sec

REM sleep phenomena

• Stage 1 EEG: Paradoxical sleep

• EOG (and corneal bulge) show frequent eye movements, as if scanning a visual field.

• EMG shows loss of muscle tonus due to downward inhibition of motor neurons, although muscles moving hands and feet may twitch.

• Many brain structures function as if awake.

More REM phenomena• SNS is partially activated: Increases blood

pressure, respiration, and heart rate.• Genital response• Narrative dreaming

– CBF is high to visual cortex, low to inferior frontal cortex (Madsen, 1991)

– Eye movements match dream events

– One EEG waveform is unique to REM and wakeful scanning

Sleep: Stages

A Typical Night

After 11 days of total sleep deprivation

Research studies into Ultradian rhythms….

Effects of sleep deprivation

• Sleep deprivation within a circadian cycle is followed by less sleep, not more

• Internal desynchronization: free-running body temperature cycle and sleep-wake cycle may desynchronize.

So, what goes on in the brain in SWS?

• Areas that arousal shut down.

• Primary sensory areas also shut down.

• Areas involved in memory consolidation and retrieval don’t shut down, but are isolated from sensory input.

So, what goes on in the brain in REM?

• INCREASE in sensory integration, motor, limbic, and memory areas.– Why don’t we move, if motor areas are

activated?

• One brain area sends inhibitory input to the spinal cord to prevent movement.

• Frontal cortex shuts down, disinhibiting limbic system.

Reticular formation (red) wakes the brain.Locus coeruleus (blue) inhibits muscles.

Basal forebrain (yellow) SWS.

Why Sleep?

Repair and Restoration Theory

– Sleep enables the body and brain to repair itself after working hard all day

– Brain is ~3% of total body weight, but uses almost ¼ of the energy.

– Going without sleep causes people to be irritable, dizzy, and to have hallucinations and impaired concentration

– Sleep-deprived rats’ bodies work harder– BUT, how much we sleep does not depend on how much

we worked that day

Who sleeps?

• Mammals and birds– Opossums, sloths, bats: 19-20 hours daily– Cats, dogs, rodents: 12-15 hours daily– Ruminant herbivores: 2-3 hours daily

• Reptiles, amphibians, fish, and insects have cycles of inactivity

• Note that sleep time does not correlate with waking activity levels, but does relate to waking vulnerability.

Evolutionary Theory

- we evolved to sleep so that we would conserve energy when we were least efficient

- during sleep body temperature decreases

- predicts that species will sleep different amounts depending on how much they must look for food and watch for predators

Why Sleep?

Dream research

• External stimuli may be incorporated into a dream.

• Dream events happen in real time.

• Everyone dreams; recall depends on when in the sleep cycle you awaken.

• Genital response is independent of dream content.

• Sleep-walking and talking are non-REM.

Interpretation of dreams

• Manifest content is symbolic of latent desires (Freud)

• Activation-synthesis theory: cf. incorporation of external events into dreams.

• Lucid dreams: Have you had one?

Why Dream?

Facilitate problem solving ?Facilitate memory consolidation ?

• Lots of REM sleep predicts better consolidation of emotional information.

•Lots of SWS predicts better consolidation of motor tasks.

•Lots of SWS+REM predicts better consolidation of perceptual information.

• Patterns of activation of hippocampal neurons are repeated

Sleep Disorders

• Waking phase disorders– Insomnia

• Drug-dependency insomnia• Sleep apnea: PAP or surgery• Fatal familial insomnia: thalamus damage

– Reduction of sleep spindles and K-complexes• SIDS

– Narcolepsy• Cataplexy• Decreased hypocretin neurons

– Sleep paralysis– Hypnagogic hallucinations

More sleep disorders: Sleeping phases

• REM sleep behavior disorder

• Slow-wave sleep problems– Nocturnal enuresis– Somnambulism– Pavor nocturnus (Night terrors)

Overall sleep deprivation

• Under total, voluntary sleep deprivation, sleepiness is cyclical– Greatest sleepiness from 3-6 a.m.– Waking sleepiness is countered by activity– Sleepiness increases only up to four days

• Active, complex tasks are not impaired• Easy, boring tasks are impaired• Microsleep emerges

Compensation for sleep deprivation

• Subsequent slow-wave, non-REM sleep is increased

• Stage 3 and 4 sleep is almost completely restored

• Involuntary sleep deprivation is stressful– Executive rats on a carousel apparatus died– Post-mortem exams showed few of the usual

stress symptoms

REM deprivation

• REM pressure• REM rebound• REM escape• Three theoretical effects

– Mental disorder– Amotivational syndrome– Memory processing deficits– But tricyclic antidepressants block REM with none

of these side effects.

Sleep Deprivation as a Stressor

• Hypothalamic corticotropin INHIBITING factor (CIF) SWS

• ~ I hr before waking: CRH, ACTH, and GCs rise and waking.

• If you don’t get enough sleep: decline in stress hormones doesn’t occur.– In fact, stress hormones increase.

• If sleep-deprived, frontal cortex and other areas work overtime:– “a bunch of unshaven gibbering neurons counting

on their toes, having to ask the rest of their cortical buddies to help out with this tough math problem.””

Sleep Deprivation as a Stressor

• Airline flight attendants: 5 vs. 15 days between transcontinental flights.– Attendants for airline with 5 day interval

had smaller temporal lobes, impaired explicit memory, higher GCs.

Stress as a Disruptor of Sleep

• CRH suppresses sleep – “throws ice water on those happily dozing neurons”– Direct effect on neurons– Also via SNS– Inhibits mostly SWS, which is needed more than more

shallow stages.– GCs impair memory consolidation.

• Random wakening higher CGs than predictable awakening:– “a sleeping brain is still a working brain.”

Resynchronization

• Jet lag and shift work

• Phase shift: Delay is better than advance– Morning melatonin phase-delays– Afternoon melatonin phase-advances– Evening melatonin is ineffective– Bright light exposure has the opposite effects

• Strengthen zeitgebers like light and activity early in the new waking period

The Consequences of Disrupting Biological Rhythms.

• When external cues change we have to re-adjust our internal clock…….

• JET LAG SHIFT WORK.

Shift Work…..

• Rising early or retiring to bed earlier than normal is an example of phase advance.

• Going to bed late or getting up late is an example of phase delay.

• By delaying/advancing our rhythms we are compromising our ability to cope in the short term.

• On average it takes approx 3 days to adjust to a 12 hour shift in time.

Shift Work…..

• We need doctors, nurses, policeman etc..so how do they cope?

• What happens to their cycle when it is disrupted by shift work?

• Well…we know what sometimes happens when they do work shifts..accidents!

• Lets look more closely at the facts!!

Shift Work…..The Facts!!

• Chernobyl occurred between 1am & 4am.• Most lorry accidents occur between 4am & 7am.• In the US $77billion annually as a result of accidents and

ongoing medical expenses due to shift work related illnesses.

• Therefore research in this area has important implications.

• Evidence: Hawkins and Armstrong-Esther(1978) studied 11 nurses during a 7 night rotation of their duty. Performance was significantly impaired on the first night but improved through the week. (Temps did not adjust until last night!)

Shift Work…How can we reduce the impact/effects of shift work?

• Monk and Folkard (1983) identified two major types of shift work:

• (a) Rapidly rotating shifts: One/two shifts max then they move to different time.

• (b) Slow rotating shifts: Rotate shifts on a weekly/monthly basis.

• Q: Which is the lesser of two evils??• A: Rapidly rotating….at least they allow the

worker to maintain a fairly constant circadian rhythm.

Shift Work…How can we reduce the impact/effects of shift work?

• Rapid rotation means your rhythms are constantly disrupted.

• Research has shown that it is possible to reset the internal clock by using bright lights as a substitute for sunlight.

• What will this reset?• Dawson and Campbell (1991) exposed workers to

a 4 hr pulse of very bright light. This appeared to work!

Shift Work…How can we reduce the impact/effects of shift work?

• Phase delay might also be more beneficial..

• Early Late

• Late Early

• Evidence: Czeisler et al (1982) tested phase delay. Workers in a chemical plant in Utah found phase delay made them feel better. The management also reported increased productivity and fewer errors.

It is better to rotate with the

clock than against it.

Jet Lag….The Facts.Jet Lag does not

occur form North-South and

vice versa!!Jet Lag only occurs when

flying from East-West or from West to East.in other words

when we change time zones.

ExampleYou fly from

Scotland –Boston (USA). You leave at 11am arrive

5pm British time actually it is

12pm in Boston...by 8pm

Boston time you’ll be tired as it is

1am to you normally!!

Jet Lag….The Facts.

• Klein et al (1972) found that adjustment was faster for westbound flights (going to states) than eastbound ones regardless of whether you were travelling home or going away.

• Eastbound = re-adjustment took 1 day per time zone crossed, therefore how long would it take to recover from a flight to Britain from Boston

Jet Lag….

• Its easier to adapt to jet lag when flying in a westerly direction because the day of travel is lengthen, whereas it is shortened when travelling east!

• As our endogenous cycle is about 25 hours we are more able to cope with phase delay than phase advance.

• Huh??? We can stay up when we should be a sleep but we don’t like being woken we want to sleep!

Jet Lag….• EvidenceSchwartz et al (1995) found that east coast US

baseball teams did better when travelling West (phase delay) than West coast teams who travelled East (phase advance). The time difference was 3 hours. This would give the East coast an advantage!!

• But what could be a possible problem with this evidence?

Jet Lag…How can we reduce the impact/effects of Jet Lag?

• Use melatonin to reset the body clock..• Should not be used unless intending to stay in

new time zone over 3 days.• Cabin crew tend to do overnight east-west then

24hrs on ground and west-east...taking melatonin in these cases may not be advisable.

• Timing is important too...individuals should be allowed to sleep after the melatonin or else they are prolonging their circadian rhythm.

• There is little scientific evidence on flying performance and melatonin however….cabin crew who have ingested melatonin are not allowed to fly within 36 hr ????

• Adopt local eating times etc to help reset the biological clock as soon as possible.

The Per-Cry-Tau complex

• In mammals, two SCN proteins (Clock and Cycle) form a dimer.

• The Clock/Cycle dimer acts on DNA to enhance transcription of Period (Per) and Cryptochrome (Cry).

• Per and Cry bind in a complex with Tau• The Per-Cry-Tau complex inhibits the Clock/Cycle dimer,

slowing Per-Cry production• Per-Cry breakdown over 24 hours allows a new cycle to

start.• Melanopsin-containing ganglion cells release glutamate in

the SCN, increasing per transcription and entraining the SCN.

Genetic variations

• Variations in the Clock gene may distinguish morning people from evening people

• Fatal familial insomnia is caused by a dual mutation involving a prion gene PrP.– Found in 40 families worldwide– Mean onset: age 50– Death ensues 7 to 36 months later.

Summary

• SCN is “biological clock”• A “Zeitgeber” is a regular stimulus that entrains the

circadian rhythm.• 90-minute cycles of 4 stages of SWS (1 through 4

and back) plus REM.• Sleep deprivation increases in stages 3 & 4 and

REM on subsequent nights.• The reticular formation in brain stem waking.• Locus coeruleus inhibits spinal motor neurons• Basal forebrain SWS

Summary

• Memory consolidation occurs during sleep– Emotional memories during REM– Motor memories during SWS– Perceptual memories during both SWS and REM

• Corticotropin INHIBITING factor (CIF) may SWS• CRH decreases sleep• Sleep deprivation increased GCs and

INCREASES cortical activity (inefficient).