25. Sleep and arousal

Question 1

What is meant by ‘consciousness’ or ‘arousal’?

Answer 1

This is the ability of an individual to react appropriately to stimuli in the outside world

Question 2

How is ‘consciousness’ or ‘arousal’ clinically assessed?

Answer 2

Assessed using the Glasgow Coma Score

Classified as either severe, moderate or mild unconsciousness

Question 3

What is important to remember about being unconscious vs. being conscious

Answer 3

Consciousness is not an all or nothing phenomena but it is a graded phenomena - need to ask how conscious is a person rather than are they conscious

Question 4

How is the electroencephalograph (EEG) used to measure consciousness?

Answer 4

Used to record very very small voltages from the brain through the scalp (hence it is subject to interference such as noise, muscle movements, eye movements)

Measures voltages of the cerebral cortex

Cannot be used to detect what individual neurones are doing but can show when the different regions of the brain are active

Question 5

How does an EEG trace appear when someone is asleep/awake and why

Answer 5

When aroused, excited and alert the EEG shows a low amplitude and a high frequency - there is a desynchronisation of neuronal firings
When drowsy and closer to sleep, the EEG shows a high amplitude and a low frequency - there is a synchronisation of neuronal firings

Question 6

Which part of the brain was originally thought to control consciousness and why is this no longer the case?

Answer 6

The cerebral cortex - thought this because when someone is in a coma, the EEG shows no electrical activity
BUT when at certain stages when asleep, the EEG of the cortex is almost identical to when we are awake

Question 7

What is normal sleep and why does sleep occur?

Answer 7

Normal sleep is known as slow-wave sleep or non-REM sleep
This is a heightened anabolic state during which there is increased growth and rejuvenation of the immune, nervous and muscular systems and the secretion of growth hormone

SO involved with growth (why you sleep when you are younger) and wound repair (why you sleep when you are injured)

There are also decreased cortisol levels whilst we sleep

Question 8

What adverse effects can occur due to a lack of sleep?

Answer 8

Will result in general behavioural problems such as a lack of concentration
Alters the blood pressure and can hence result in the development of cardiovascular disease, chronic kidney disease, diabetes
There is a reduced blood pressure during sleep due to reduced sympathetic output and a lack of sleep can result in a state of hypertension

Can result in obesity - a lack of sleep results in decreased secretion of leptin (secreted when asleep) and a lack of sleep results in an increased hunger (lack of satiety)

Question 9

What are the different stages of sleep?

How do these appear on an EEG?

Answer 9

There are four stages of normal/slow-wave sleep and then there is a stage of REM sleep
From stage 1 to stage 4, we become less and less conscious and so the EEG trace changes from a low amplitude and a high frequency to a high amplitude and a low frequency
Nb. The amplitude correlates with the ease of being able to awaken the person - this indicates synchronisation of cortical activity

Then have REM sleep (after stage IV) - rapid eye movement sleep
The eyes move back and forth and it is even harder to awaken the person
NB. during REM sleep is when you dream

Question 10

How is REM sleep shown on an EEG trace?

Answer 10

Interestingly, the EEG of someone in REM sleep is very similar to that of an awake person

Question 11

In sleep vs. wake - when is the cortical activity synchronised and when is it not?

Answer 11

In sleep - the cortical activity is synchronised

When awake - the cortical activity is desynchronised

Question 12

How often do the stages of the sleep cycle repeat?

Answer 12

Stages 1-4 repeats in 90 minute cycles throughout the night

Question 13

Which region of the brain is responsible for the control of sleep and wakefulness?

Answer 13

The reticular formation of the pons is the key control area for sleep and wakefulness
This is modulated by signals from the hypothalamus

Question 14

What are the different stimuli for sleep?

Answer 14

Chemicals in the blood

Diurnal rhythms

Question 15

How do chemicals in the blood act as a stimuli for sleep?

Answer 15

Around the preoptic nuclei, the BBB is leaky and large molecules can penetrate and act on local neurones

E.g. Ghrelin hunger hormone and low levels of blood glucose have an inhibitory action on sleep
E.g. Cholecystokinin associated with satiety increases sleepiness and induces sleep
E.g. High adenosine levels induce sleep (Caffeine is an antagonist at A1 adenosine receptors so keeps you awake)
E.g. Histamine firing from histaminergic neurones

Question 16

Where are the only histaminergic neurones located in the brain?

Answer 16

Located in the tuberomamillary nucleus

These neurones are active during wake and silent during sleep (so anti-histamines make you drowsy)

Question 17

How do diurnal rhythms act as a stimuli for sleep?

Answer 17

Retinal ganglia cells can integrate the level of light that is coming in over a certain number of hours
Transmits this information to the suprachiasmatic nucleus
Then transmitted to the reticular formation to decide whether you want to wake up or go to sleep

Question 18

What is narcolepsy and why does this occur?

Answer 18

This is where people fall asleep involuntarily during the day
Occurs due to a loss of orexins - this occurs due to an autoimmune attack from T-cell lymphocytes
The loss of orexin containing neurones means that you are unable to stay awake

Question 19

Which monoamine transmitters are involved in sleep/wake cycles and which particular regions of the reticular formation are these involved with?

Answer 19

Dopamine - cells in the ventral tegmental area
Acetylcholine - cholinergic cells in the pedunculopontine nucleus
Noradrenaline - cells in the locus coeruleus
Serotonin - cells in the raphe nuclei

These systems are all located around the (midbrain and the) pons and have diffuse projections to the cerebral cortex

Question 20

Other than in the reticular formation, where else are cholinergic neurones located and what pathology are they associated with?

Answer 20

Cholinergic neurones are also found in the basal forebrain nucleus (nucleus basalis)
Loss of neurones in this region can lead to the development of Alzheimer’s disease

Question 21

Describe the changes in noradrenaline, serotonin and acetylcholine levels when asleep compared to when awake

Answer 21

These three are all associated with being awake - there are high levels when awake and decreased levels when asleep
BUT when you go into REM sleep, the serotonin and noradrenaline levels decrease even further but the Ach levels increase (like when awake)
SO the REM sleep is associated with a turning on of the cholinergic system

Question 22

SO what is the proposed function of the ACh in the brain in terms of consciousness?

Answer 22

Proposed that the acetylcholine activates the thalamus and the cortex during waking and dreaming

Question 23

What is the general function of noradrenaline in terms of consciousness?

Answer 23

The central noradrenaline system activates our alertness and attention and so during all forms of sleep, these levels are decreased

Question 24

What is the function of dopamine in terms of consciousness?

Answer 24

During all forms of sleep, the activity in dopamine neurones is low
During waking, the nigrostriatal dopamine system activates the basal ganglia - allows fluent and smooth movement and the (mesolimbic and mesocortical dopamine systems) activate the frontal cortex and limbic system so we are alert and focussed to make plans and decisions

Question 25

How can amphetamines prevent sleep?

Answer 25

Amphetamines continually release dopamine and noradrenaline from nerve terminals and result in a dopamine overactivity - high levels of dopamine prevent sleep

Question 26

Describe the serotonin levels during REM sleep and how SSRIs can effect sleep

Answer 26

During REM sleep, the serotonin neurones completely cease and there is a zero level of serotonin activity

SO SSRIs can result in an interference in REM sleep

Question 27

What is the general effect of antidepressants on sleep?

Answer 27

Antidepressants e.g. tricyclic antidepressants promote sleep

This is because they are hisaminergic neurone antagonists

Question 28

What is the function of REM sleep?

When might your level of REM sleep increase?

Answer 28

Memory consolidation and the removal of junk and defragmentation of memories

REM sleep may increase when you have to adjust to a life event e.g. a bereavement or an impending marriage - the brain has to readjust to the new information

Question 29

How can insomnia be treated?

Answer 29

Lifestyle changes - fixed times to go to bed, create a relaxing bedtime routine, maintaining a comfortable sleeping environment, avoid caffeine at night
Cognitive behavioural therapy - help to relax and stress without the usage of drugs
Antihistamines - don’t disrupt REM sleep
Benzodiazepines - Increase GABA in the brain - have sedating/calming effects
Z-drugs - hypnotics

Question 30

What is sleep apnea and why might it occur?

Answer 30

When people stop breathing whilst dreaming in REM sleep
Generally REM sleep paralyses all muscles to prevent sleep walking apart from the eye muscles and the respiratory muscles
If the respiratory muscles are paralysed during REM sleep, they will stop breathing and will wake up gasping for air due to a build up of CO2 in the blood

Question 31

What are the different types of insomnia?

Answer 31

Transient e.g. jet lag
Short term - associated with illness, bereavement, stress
Chronic - lasts longer than 3 weeks - analyse the underlying cause

Question 32

What is the importance of insomnia in neurology?

Answer 32

Sleep disorders may be the first sensitive indicator of neurodegeneration or that something is wrong in the brain

Question 33

What are the ideal drugs for insomnia and why in particular?

Answer 33

Currently, the ideal drugs are benzodiazepines and z-drugs for insomnia

These both have mostly very short half lives and are short acting

Question 34

Which neurotransmitters are involved in wakefulness?

Answer 34

Cholinergic systems - pedunculopontine and laterodorsal tegmental nuclei
Monoaminergic projections

Question 35

Which neurotransmitters are involved in sleep?

Answer 35

GABA and galanin neurones - ventrolateral preoptic nucleus