S7) The reticular formation: control of consiousness

Question 1

What is arousal?

Answer 1

Arousal is the emotional state associated with some kind of goal seeking behaviour or avoidance of something noxious

Question 2

What is consciousness?

Answer 2

Consciousness has something to do with ‘awareness’ of both external world and internal states (difficult to define, but measurable)

Question 3

Consciousness requires two neural components to be functioning normally, and connected to each other.

What are they?

Answer 3

Consciousness = cerebral cortex + reticular formation

Cerebral cortex – the site where conscious thoughts arise
→ Receives many inputs, including from the reticular formation

Reticular formation (particularly the reticular activating system in the brainstem) – the circuitry that keeps the cortex ‘awake’
→ Receives many inputs, including from the cortex and sensory systems

If you lose one of these components → causes loss of consciousness

Question 4

The reticular formation and the cerebral cortex are needed for consciousness. They are said to cause a positive feedback loop. How?

Answer 4

The cerebral cortex + the reticular formation mutually excite each other.

Cortex and reticular formation are connected by reciprocal excitatory projections, forming a positive feedback loop
→ Positive feedback loops are seen when there is a binary outcome (e.g. sleep/awake, ovulating/not ovulating etc)

Question 5

What is the reticular formation?

Answer 5

The reticular formation is a population of specialised interneurones in the brainstem (throughout - midbrain, pons and medulla)

Question 6

Numerous inputs regulate the level of arousal.

Where do they come from?

Answer 6

• Sensory system
• Cortex

… makes sense when you think about it because you can’t get sleep if you have a lot of sensory input - as it is stimulating the reticular formation. Also can’t get sleep if you have a lot of thoughts in your head.

Question 7

The reticular formation has widespread excitatory outputs to the cortex via three major relay nuclei.

What are they?

Answer 7

• Thalamus (sensory gating- regulates amount of info flowing through the thalamus)
• Hypothalamus (projects to cortex)
• Basal forebrain nuclei
• Spinal cord (involved in regulation of muscle tone)

Question 8

What neurotransmitter is involved in the excitatory inputs from the reticular formation to the 3 different destinations (thalamus, hypothalamus and the basal forebrain nuclei)?

Answer 8

Acetylcholine - Reticular formation sends cholinergic (excitatory) projections to these relays

Question 9

What excitatory neurotransmitters are involved from the basal ganglia, hypothalamus and thalamus to the cortex? (in the positive feedback loop pathway between the reticular formation and the cortex)

Answer 9

Basal ganglia to cortex - AcH

Hypothalamus to cortex - Histamine

Thalamus to cortex - Glutamate

All are excitatory neurotransmitters being released in the cortex to maintain wakefullness.

Basal forebrain nuclei send excitatory cholinergic fibres to cortex (think sedative side effects of anticholinergics)

The hypothalamus sends excitatory histaminergic fibres to the cortex (think sedative side-effects of sedating antihistamines)

The thalamus sends excitatory glutamatergic fibres to the cortex

Question 10

What is the effect of antihistamines at the level of the cortex?

Answer 10

Antagonise histamine at the level of the cortex → take away excitatory inputs coming up from the hypothalamus to the cortex.: you make this positive feedback loop turn around a bit more slowly.: you can get drowsy. (less wakeful)

Likewise anticholinergic agents also have drowsiness as a side effect for the same reason.

Question 11

The reticular formation also sends projections down the cord. This is responsible for?

Answer 11

responsible for maintaining muscle tone

Question 12

What is the reticular activating system?

Answer 12

A large part of the reticular formation is devoted to arousal – the reticular activating system
The system contains largely of neurons that send projections up to the cerebral cortex as a high level of activity.

Question 13

Which assessment might one use to assess consciousness?

Answer 13

Glasgow Coma Scale (GCS)

Three components, looking for best response in each

Question 14

What are the 3 things that the GCS looks at?

Answer 14

1. Eye opening
2. Motor response
3. Verbal response

https://www.youtube.com/watch?v=Tc907CSlsFU

Question 15

Interpret each component of the ‘eye opening’ section in the GCS.

Answer 15

o Spontaneous eye opening (4) suggests normal cortical and brainstem function

o Response to speech (3) suggests slightly diminished cortical function but still functioning brainstem

o Response to pain (2) suggests impaired cortical function but brainstem preserved so that reflex opening can occur

o No response (1) suggests severe damage to brainstem +/- cortex

Question 16

Interpret each component of the ‘motor response’ section in the GCS.

Answer 16

o Obeys commands (6) suggests normal function with working connections from auditory system to brainstem/cord
o Localises to stimuli (5) suggests diminished higher cortical function but still connections working from sensory to motor cortex
o Withdraws to pain (4) suggests that there is still a ‘physiological’ reflex response to stimuli

o Flexor response to pain (3) suggests a lesion above the level of the red nuclei. This response is still ‘semi- physiological’
o Extensor response to pain (2) suggests a lesion below the red nuclei. This response is not physiological at all

o No response to pain (1) suggests severe damage to brainstem +/- cortex

Question 17

Interpret each component of the ‘verbal response’ section in the GCS.

Answer 17

o Oriented in time/place (5) suggests normal cortical function

o Confused conversation (4) suggests diminished higher cortical function but language centres are still functioning adequately

o Inappropriate words (3) suggests language centres have been damaged

o Incomprehensible sounds (2) suggests cortical damage with brainstem mediated groans

o No response (1) suggests severe damage to brainstem +/- cortex

Question 18

Which investigation might one use to assess consciousness?

Answer 18

The electroencephalogram (EEG) measures the combined activity of thousands of neurones in a given part of the cortex.

It has high temporal resolution, low spatial resolution.

Question 19

What is the EEG good at detecting for?

Answer 19

Good for detecting neuronal synchrony (a phenomenon which occurs commonly in the brain during both physiological and pathological processes such as sleep and epilepsy), and evidence of normal cerebral function

Question 20

What happens to the neurons in the brain if they are deprived of sensory input?

Answer 20

Neurons in the brain tend to fire synchronously.

Question 21

How many different stages are there in sleep? Explain

Answer 21

5 stages – during the night you typically pass through around 6 cycles of sleep, progressing from an awake state down through to stage 4 and then periodically going from stage 4 rapidly up into REM sleep.

Question 22

Provide a brief interpretation of the sleep on an EEG

Answer 22

Going down through the 4 stages (Non-REM sleep), the EEG shows decreasing frequency and increasing amplitude as neuronal populations in the cortex become synchronous

Question 23

Describe the following tracings of the different stages of sleep in this EEG:

Answer 23

• Awake (eyes open)– low voltage, random, fast (beta waves) – typical activity in the brain when it is doing something
• Drowsy – alpha waves -becomes a bit more ordered, amplitude increases - as large amount of sensory input taken from the brain .: all neuron firing becomes more synchronous – Eyes closed
• Stage I – theta waves - neurons are more synchronous and slow theta waves (background of alpha + interspersed theta waves)
• Stage II/III – sleep spindles and K complexes - (background of theta + interspersed sleep spindles + K complexes) , Sleep spindles are high frequency bursts arising from the thalamus, K-complexes represent the emergence of the ‘intrinsic rate’ of the cortex
• Stage IV – delta waves - v slow frequency activity, highly synchronous activity of the cortical neurons- represents intrinsic rhythms of the cerebral cortex as thalamus is largely inhibited and the cortex is being allowed to get on with what it needs to during sleep
• REM sleep (beta waves) - low voltage, random, fast with sawtooth waves – looks identical to the awake EEG. Stage where we dream - cortex maybe replaying events from the day - manifests as brain activity during awake period/ conscious pt

Question 24

Describe the neural mechanism of sleep

Answer 24

It is complex.

Sleep is about deactivating the reticular activating system (+ hence the cortex) and inhibiting the thalamus:

• The positive feedback loop between RAS and cortex is inhibited, leading to decreased cortical activity
• Inhibition of the positive feedback loop is assisted by removal of sensory inputs e.g. eyes closed, not too hot/cold, clearing mind of thoughts - fewer positive influences on positive feedback loop

Note: think about what your bedtime routine is and how this impinges on the pathway

Question 25

What initiates REM sleep?

Answer 25

REM sleep is initiated by groups of **neurones in the pons (i.e. initiation appears to be an** **active process)**

Question 26

Describe the EEG of REM sleep.

Answer 26

**Similar EEG to when awake with eyes open (beta waves)**, but **difficult to rouse** due to **strong thalamic inhibition**

Question 27

In four steps, describe the paradox of REM sleep

Answer 27

⇒ **EEG similar to that seen during arousal** (beta waves), but hard to rouse (wake up) due to s**_trong inhibition of the thalamus_** ⇒ **Majority of muscle tone is lost** due to **descending inhibition of LMNs** by **glycinergic fibres arising** from the reticular formation and running down the reticulospinal tracts (disorder of this can result in sleep walking) ⇒ **Preservation of eye movements** and some other cranial nerve functions (e.g. nocturnal bruxism - where trigeminal nerve function is preserved .: can cause grinding of teeth during sleep) ⇒ **Autonomic effects** are seen *e.g. penile erection, loss of thermoregulation*

Question 28

What is the importance of REM sleep?

Answer 28

REM sleep is essential for life - animals deprived of it will **die**

Question 29

What are the functions of sleep?

Answer 29

**Enigmatic:** - **Energy conservation and bodily repair** (good night's sleep = makes you feel better in the morning) - **Memory consolidation** (the reverbortory loops between the hippocampus and cerebral cortex on particularly active during sleep. get good night sleep - help consolidate those memories) - **Clearance of extracellular debris** (glymphatic system - passageway opens up during sleep and clears a whole load of extracellular debris. seems to be association with poor sleep + dementia - maybe not clearing amyloid .: could predispose ppl to dementia w lack of sleep) - **Resetting of the CNS**

Question 30

Identify three sleep disorders

Answer 30

- Insomnia - Narcolepsy - Sleep apnoea

Question 31

What is insomnia?

Answer 31

**Insomnia** is a sleep disorder where people have trouble sleeping and is often due to an underlying psychiatric/psychological cause e.g. anxiety and depression (.: assess mental health)

Question 32

What is narcolepsy?

Answer 32

- **Narcolepsy** is a long-term rare neurological disorder that involves a decreased ability to regulate sleep-wake cycles - It is characterised by excessive sleepiness, sleep paralysis, hallucinations

Question 33

What causes narcolepsy?

Answer 33

**orexin gene mutations for a neurotransmitter peptide known as orexin.** **orexin is a peptide transmitter involved in sleep.** **orexin → stops sensory input to the thalamus and therefore stops the positive feedback loop between the cerebral cortex and reticular formation.** This neurotransmitter helps to couple the perception of light to the thalamus. In these patients, they would report lower levels of light to the thalamus than in reality and therefore contributed to their tendency to spontaneously and uncontrollably fall asleep.

Question 34

What is sleep apnoea?

Answer 34

**Sleep apnoea** is a serious sleep disorder that occurs when a person's breathing is interrupted during sleep Common condition, often caused by excess neck fat leading to compression of airways during sleep and frequent waking Causes **excessive daytime sleepiness** Typically obese man, during the night - extra fatty tissue around the neck and tongue leads to temporary occlusion of the airway. (this occlusion can occur many times per night .: would constantly wake up)

Question 35

What advice would you give to someone with sleep apnoea?

Answer 35

Advise patient to lose weight/ exercise CPAP - continuous positive airway pressure

Question 36

Identify four disorders of consciousness

Answer 36

- Brain death - Coma - Persistent vegetative state - Locked in syndrome

Question 37

What is brain death?

Answer 37

**Brain death** is **widespread cortical and brainstem damage** (flat EEG - no activity - brain dead)

Question 38

What is a coma?

Answer 38

- A **coma** is a disorder of consciousness due to **widespread brainstem and cortical damage**, with **various** (disordered) EEG patterns detectable - The patient is **unarousable** and **unresponsive** to **psychologically meaningful stimuli** - **No sleep-wake cycle detectable** (the neurons are doing something but they are not really able to synchronize/communicate with each other well)

Question 39

What is PVS?

Answer 39

- **PVS** is a disorder of conscious due to **widespread cortical damage**, with various (disordered) EEG patterns detectable - Similar to **coma** but with some **spontaneous eye opening**, can even also **localise to stimuli via brainstem reflexes** - **Sleep-wake cycle detectable**

Question 40

What is locked in syndrome?

Answer 40

- **Locked-in syndrome** (rare) is a condition that can be caused by **basilar/pontine artery occlusion** - **Eye movements can be preserved,** but **all other somatic motor functions lost** from the **pons down** (can move their eyes, is conscious and aware but is not able to move any other part of their body. these pts can hear + can also communicate via these v clever devices which detects eye movements enabling them to produce verbal instructions)

Question 41

Glasgow Coma Scale … how to interpret it …

Answer 41