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Core
The reticular formation is a set of grey matter nuclei that are spread throughout the brainstem that are functionally linked (see below). The primary function of this is to keep the cerebral cortex ‘awake’ by maintaining behavioural arousal (not to be confused with sexual arousal) and consciousness.
Arousal is the state of being awake and is important to cause goal-seeking behaviour (such as looking for food, maintaining mobility and the fight or flight response).
Consciousness is the awareness of both the internal and external environments. The preservation of this requires the reticular formation and cortex to be functioning normally and appropriately connected to each other. Consciousness is a generally very slippery concept to grasp and understand fully, so it’s completely reasonable if you find it difficult to understand.
Diagram - The Reticular Formation found throughout the Brainstem
SimpleMed original by Dr. Keertana Anne
These functions are carried out by the activation of the ascending reticular activating system (ARAS), which is the pathway connecting the reticular formation to the cerebral cortex. This connection forms a positive feedback loop, meaning the output produced is always binary (either asleep or awake, for example).
The reticular formation functions on a system of inputs and outputs. It receives inputs from the sensory systems and the cortex itself, and sends outputs to the thalamus, hypothalamus and basal forebrain nuclei (and also to the spinal cord, which is responsible for maintaining muscle tone). The reticular formation sends these outputs via three major relay nuclei, and these then project onto the cortex (see below).
Diagram - The Reticular Activating System
SimpleMed original by Dr. Keertana Anne
The use of cholinergic and histaminergic fibres in the maintenance of the ‘awake’ state explains the action of drugs such as anticholinergics and antihistamines, and why they produce a sedative or drowsy effect on the person.
Massive lesions of the ARAS itself, or the connection between the ARAS and the cerebral cortex, can cause a variety of disorders of consciousness. These are explored later on in this article.
Clinical Assessment of Consciousness
There are three primary ways of assessing the conscious state of the brain, and each of them are used in different situations.
Note: ACVPU is a commonly used UK modification of the AVPU scale that includes assessment of new confusion.
The AVPU scale is used in emergency situations to assess a patient’s response to a variety of stimuli. It is a simple tool used in clinical settings like wards to quantify a patient’s conscious level, and on observation charts in the UK, a score of anything other than A for Alert prompts review by the medical team.
Alert - the patient is fully awake and shows no evidence of confusion. They will be able to spontaneously open their eyes, speak or move their body.
Confused - the patient is able to respond to you in some way, but is not orientated to place, person or time. This is a new change for the patient, and therefore indicates a potential deterioration in consciousness level.
Responsive to voice - the patient will respond in one of three ways when prompted by a voice. This could be opening the eyes; a verbal response such as a groan; or a slight movement of the limbs.
Responsive to pain - the patient will be able to respond in one of three ways when a painful stimulus is applied. Examples of this include squeezing the fingers or a trapezius squeeze. Central painful stimuli should be applied carefully to avoid injury.
Unresponsive - the patient is not responsive to any of the above stimuli.
The Glasgow Coma Scale records observed eye, verbal and motor responses. Record the individual components as well as any total, and check for factors that prevent a response from being assessed. A component score does not by itself localise anatomical damage.
Eye Opening
4 Spontaneous eye opening
3 Response to speech
2 Response to pain
1 No eye opening
Verbal Response
5 Orientated in time / place
4 Confused speech
3 Inappropriate words
2 Incomprehensible sounds
1 No verbal response
Motor Response
6 Obeys commands
5 Localises to a pressure/pain stimulus
4 Withdraws from pain
3 Abnormal flexion to a pressure/pain stimulus
2 Extensor response to pain
1 No motor response
Diagram - Glasgow Coma Scale responses. Interpret each component with examination findings and factors that interfere with testing.
SimpleMed original by Dr. Keertana Anne
Patients are given an overall score and also a breakdown of the individual components, for example GCS 11 = E3 M4 V4. A score of 15 is the highest possible, and 3 is the lowest (because for each category, no response results in a score of 1). The Glasgow Coma Scale is only used in living patients and does not apply to brain death.
GCS 15 means that the best observed responses score E4, V5 and M6. It does not prove that every neurological structure or function is normal. Interpret the responses alongside the history and examination, accounting for sedation, communication difficulties and other confounders. A non-testable component should be documented rather than assumed to score 1.
The Electroencephalogram (EEG)
The EEG is a test used to measure the electrical activity in the brain. It works by placing electrodes a few centimetres apart on the scalp, and these measure the activity of thousands of neurones in a specific region of the cortex. The EEG has a high temporal resolution (meaning it is good at measuring short periods of time - milliseconds), but a low spatial resolution (meaning that it is bad at visualising the impulses in 3D, owing to the distance between each sensor on the scalp - see below).
Diagram - An EEG Recording Cap
Licensed under Creative Commons, Source.
This piece of equipment is used to detect neuronal synchrony. This occurs when the neurones in the brain are deprived of sensory input, both physiologically (sleep) and pathologically (epilepsy) and begin to fire more regularly. EEG patterns can also be affected by changes in conscious states such as a coma or brain death.
Sleep is a physiological, recurring process that the human body undergoes and is considered a partially unconscious state of the mind. During the process, the mind and body are both unable to react to stimuli in a way they would normally do if awake, however the brain itself remains very active. The functions of sleep are mostly unknown, but some theories are that sleep has a role in memory consolidation, clearance of extracellular debris, and ‘resetting’ of the CNS.
It can be classified into two categories - Rapid Eye Movement (REM) and non-Rapid Eye Movement (non-REM) and the body cycles through these two stages while asleep (see below).
During REM sleep, the EEG pattern is similar to that of an awake person, and the sleeper is able to dream. The body has decreased muscle tone during this time due to the inhibition of lower motor neurons, however some functions are preserved (such as penile erection), despite widespread skeletal muscle atonia.
Non-REM sleep is classified as N1, N2 and N3; N3 is slow-wave sleep and combines the older stages 3 and 4. Non-REM sleep generally retains muscle tone. Sleep stages reflect changing activity across sleep–wake networks rather than a simple on/off switch in the arousal system.
Diagram - Historical hypnogram using stages 1–4. Current terminology is N1 and N2, with the older stages 3 and 4 combined as N3. This figure illustrates transitions through the night rather than current scoring labels.
Licensed under Creative Commons, Source.
Sleep cycles between non-REM stages N1, N2 and N3 and REM sleep. Deep N3 sleep has prominent high-amplitude slow waves, reflecting more synchronous cortical activity, whereas REM has low-amplitude mixed-frequency activity.
Diagram - Schematic EEG patterns in wakefulness, REM and non-REM stages N1, N2 and N3. Sleep spindles and K-complexes characterise N2; prominent slow waves characterise N3.
SimpleMed original by Dr. Keertana Anne
Awake - characterised by beta waves, typically in the range of around 13 to 30 Hz.
N1 sleep - light sleep, with reduced alpha activity and low-amplitude mixed-frequency activity, often predominantly theta.
N2 sleep - characterised by sleep spindles and K-complexes against the background EEG. These events help distinguish N2 from N1; N3 is identified by prominent slow-wave activity.
N3 sleep - deep non-REM sleep characterised by prominent high-amplitude slow waves. It combines the older stages 3 and 4.
REM sleep - low-amplitude mixed-frequency EEG activity, which can include sawtooth waves, alongside rapid eye movements and low muscle tone. It resembles wakefulness but is not defined by beta waves alone.
Insomnia - a condition involving difficulty getting to sleep or staying asleep. It is commonly due to an underlying psychiatric condition such as anxiety disorders.
Narcolepsy - a rare condition presenting with difficulty regulating sleep-wake cycles, resulting in a person being overcome by sleep at inappropriate times. Many narcoleptics also suffer from cataplexy, a sudden loss of muscle strength.
Sleep Apnoea - a common condition often caused by excess neck fat leading to compression of airways during sleep, and frequent waking. It causes excessive daytime sleepiness and is treated with weight loss and CPAP machines which introduce pressure to the airways to encourage the airways to remain open.
Disorders of consciousness involve impaired wakefulness, awareness or both. They can follow dysfunction of cerebral hemispheric or arousal networks. Locked-in syndrome is discussed here as an important differential diagnosis, because severe motor impairment can conceal preserved consciousness.
Brain injuries can be categorised into three mechanisms of injury:
- Traumatic, for example as a result of a car accident
- Non-traumatic, caused by acute health conditions such as a stroke or infections
- Progressive brain damages caused by conditions that gradually worsen over time, such as in Alzheimer’s disease or brain tumours).
These clinical states differ in wakefulness, awareness and the ability to demonstrate a response. They are not a single severity ladder, and locked-in syndrome must be distinguished from disorders that impair consciousness.
Locked-in syndrome: Awareness is preserved despite severe paralysis and inability to speak. Classic cases involve ventral pontine motor pathways with sparing of arousal networks. Vertical eye movements or blinking may permit purposeful communication, so lack of limb movement must not be mistaken for lack of consciousness.
Minimally conscious state: Limited but demonstrable awareness is shown by inconsistent yet reproducible purposeful responses, such as following commands. Diagnosis requires careful repeated assessment; one isolated movement is insufficient. Reliable functional communication or functional object use indicates emergence from this state.
Vegetative state (unresponsive wakefulness syndrome): Wakefulness, including eye opening and sleep–wake cycles, is present without behavioural evidence of awareness. Reflex and spontaneous movements can occur. Serial assessment is needed to distinguish these from purposeful responses.
Coma: Wakefulness and awareness are absent: the patient cannot be awakened and does not initiate purposeful responses. Reflex responses may remain. Coma can result from bilateral cerebral hemispheric dysfunction or dysfunction of the arousal system; combined cortical and brainstem structural damage is not required. Sedative or anaesthetic drugs can also produce profound unresponsiveness.
Brain death: This involves irreversible loss of brainstem function, with or without widespread cortical damage, and is a legally defined state. Diagnosis is based on strict clinical criteria rather than EEG findings.
Edited by: Dr. Maddie Swannack
Reviewed by: Adrian Judge
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