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CRANIAL NERVES AND
THE BRAINSTEM
Chapter summary
1. Twelve pairs of cranial nerves mediate input from special senses,
skin, muscles and joints of the head and neck, and parasympathetic
innervation to the salivary and tear glands.
2. Each nerve is functionally classified by fibre type as sensory, motor
or mixed; each fibre type has specific connections with brainstem
nuclei.
3. Individual cranial nerves innervate specific regions of the brainstem,
giving it functional significance. The midbrain is associated with
cranial nerves II–IV and is involved in eye movements and visual and
auditory reflexes. The pons is associated with cranial nerves V–VIII
and is involved in mastication, facial expression, facial sensations,
eye movements, hearing and balance, salivation, lacrimation and
taste. The medulla is associated with cranial nerves VIII–XII and
is associated with vital life support functions (cardiovascular and
respiration), taste, tongue movements, swallowing, talking, hearing,
nausea and vomiting, and coughing responses.
6
4. The brainstem is topographically organised. Cranial nerve nuclei are
located dorsally within the brainstem, descending tracts ventrally,
with ascending pathways and the reticular formation sandwiched
in between. Sensory cranial nerve nuclei are located laterally, motor
nuclei medially and mixed nuclei in between.
5. The reticular formation is a diffuse, multisynaptic meshwork of interconnected neurons involved in homeostasis, consciousness, alertness,
pain, automated cardiovascular and respiratory responses, muscle tone
and automated pattern generators (subconscious motor functions).
6. Vascular or physical lesions to cranial nerves or brainstem regions
produce distinct clinical signs, which can be diagnosed based on
knowledge of brainstem topography and cranial nerve function.
6
Introduction
To make an accurate diagnosis of the patient’s problem,
the doctor must carefully evaluate all the neurological findings. To do this, a clear knowledge of the organization and function of the various cranial nerves and
tracts within the brainstem is needed. The purpose of
this chapter is to build a three- dimensional picture of
the organisation of the brainstem. By understanding this
arrangement, one can use the signs and symptoms to
locate the level of the lesion.
The brainstem resides in the posterior fossa of the
skull and comprises the medulla, pons and midbrain.
The medulla is continuous with the spinal cord beyond
the foramen magnum, and the midbrain connects to the
thalamus and forebrain. The brainstem is essential for
life; while a human can survive if the cerebral cortex is
CRANIAL NERVES AND THE BRAINSTEM
irreversibly damaged or removed, damage to the brainstem can kill! It is also the origin of conscious perception
of different somatic and visceral sensations. The brainstem has three main functions:
1. Cranial nerve- related functions. It contains nuclei
associated with 11 of the 12 pairs of cranial nerves,
and cranial nerves III–XII emerge from its surface.
2. Conduit functions. It contains ascending and
descending pathways that relay sensorimotor
information to and from the cortex, cerebellum
and spinal cord, as well as other pathways that
originate within the brainstem.
3. Integrative functions. Cardiorespiratory
activities, complex motor patterns, oculomotor
functions, consciousness levels, sleep, alertness
and autonomic functions occur via the reticular
formation (RF) and the medial longitudinal
fasciculus (MLF) that run throughout the length of
the brainstem.
Knowledge of the basic organization and various
functions of the brainstem is important for understanding brainstem disorders. Signs of primary brainstem
injury (coma, irregular breathing, fixed and dilated
pupils and loss of oculovestibular reflexes or motor flaccidity) usually imply severe brainstem injury and have a
poor prognosis.
Anatomical organization of cranial nerves
and their nuclei
Understanding the functional anatomy of the cranial
nerves is of great clinical importance. Testing the integrity of the cranial nerves is a part of the neurological examination (see Chapter 3). If a sensory or motor
deficit is encountered, it is essential to determine if it
is a peripheral or a central problem. If it is a peripheral
problem, it is important to establish what nerve(s) are
involved, or if it is a central problem, to localize where
Box
Table 6.1 Classification of cranial nerves
Pure sensory
nerves Pure motor nerves Mixed nerves
Olfactory (I) Oculomotor (III)
Optic (II) Abducens (VI) Glossopharyngeal (IX)
Vestibulocochlear
Case history
6.1
A student comes into casualty one morning complaining
of an inability to see with his left eye. You notice that his
left upper eyelid droops. He says that he got very drunk
at a party and on the way home, he fell over and hit his
head hard on the pavement, losing consciousness for a
short while. Initially, he thought the eye closure was due
to swelling, but after a week, the eye had still not opened.
On inspection, his left eyelid was shut and, when it was
lifted, the eyeball deviated down and out. The left pupil was
fixed and dilated, whereas the right pupil responded normally to increased light intensity in either eye. When the student smiled, only minor elevation occurred on the right side
of the mouth. Further neurological examination revealed a
right- sided Babinski sign, right- sided weakness in the arms
and legs and hyperreflexia and hypertonia of the right side
limbs. General sensory examination proved normal.
This case gives rise to the following questions:
1. Why is the left eye closed and the eye deviated down
and out?
2. Why does only the right pupil respond to increased
light intensity in the left eye?
3. Why are there facial paralysis and limb motor deficits?
Trigeminal (V)
(VIII)
Trochlear (IV)
Accessory (XI)
Hypoglossal (XII)
Facial (VII)
Vagus (X)
the lesion is, and what other systems are affected. To
answer these questions, an understanding of the anatomy of the cranial nerves is required.
Cranial nerves have three main functions:
1. to provide the general motor and sensory
innervation of the skin, muscles and joints in the
head and neck region
2. to mediate special senses (vision, hearing, taste
and olfaction)
3. to regulate autonomic (visceral) functions via
parasympathetic innervation of autonomic
ganglia (e.g. breathing, heart rate, blood pressure,
coughing and swallowing)
Cranial nerves are classified as sensory, motor or
mixed (containing motor, sensory and autonomic fibres)
as summarized in Table 6.1.
120
SYSTEMS OF THE BODY
1
Closed
medulla
Open
medulla
Pons
2
3
4
5
Midbrain
6
CRANIAL NERVES AND THE BRAINSTEM
A
6
7
B
9
8
C
Fig. 6.1 Wiegert- Pal stained transverse sections of different levels of the human brainstem showing the location of some of the brainstem
nuclei, and major ascending and descending tracts. 1, Gracile nucleus; 2, Cuneate nucleus; 3, Spinal trigeminal nucleus; 4, Medial lemniscus;
5, Corticospinal tract; 6, CN XII, hypoglossal nucleus; 7, Inferior olivary nucleus; 8, CN VI, abducens nucleus; 9, Periaqueductal grey; 10, CN III,
oculomotor nucleus; 11, Red nucleus.
D
10
11
However, with modern imaging methods, it is now not
Internal organization of the brainstem
necessary to be able to recognize these internal features,
which are seen only in post mortem histological speciThe anatomy of the brainstem and organization of different cranial nerve nuclei is extremely complicated. It was
traditionally taught by recognizing features in histological
specimens from different levels of the brainstem (Fig. 6.1).
mens; however, one needs to be able to recognize their
shape to be able to identify them in medical images such
as magnetic resonance images. In order to diagnose brain-
stem lesions, one has to be familiar with its topographical
THE NERVOUS SYSTEM
121
6
A
Pure sensory
organization and with the deficits that occur with cranial
nerve lesions.
The brainstem is functionally associated with 11 of
the 12 pairs of cranial nerves. Cranial nerve I, the olfactory nerve, does not attach to the brainstem but projects
directly to the forebrain and is functionally associated
with the limbic system. Similarly, cranial nerve II does
not directly attach to the brainstem but does have afferent collaterals that terminate in midbrain nuclei. For the
other cranial nerves, their inputs are organized sequentially in a rostrocaudal fashion from nerve III to nerve XII
Fig. 6.3 shows a dorsal view of the brainstem, illus-
trating the relative mediolateral positions of the cranial
nerve nuclei in the brainstem. This is a schematic to
demonstrate the overall picture; in reality, some of these
nuclei would overlap. There are up to seven different
nuclei columns corresponding to the different cranial
nerve fibre types based on embryological development
(see Box 6.2 and Fig. 6.2B) that can be arranged in a
mediolateral row. In reality, the only place this occurs is
in the open (rostral) medulla, near its junction with the
pons. At the other levels, fewer columns are present.
(Fig. 6.2A). This gives the different subdivisions of the
brainstem functional significance (Table 6.2).
The basic organization of the brainstem is the same
for each region. Essentially, it is divided into three sections in the dorsoventral (transverse) axis (Fig. 6.2B). In
the dorsal part are located the cranial nerve nuclei; in the
ventral part are located fibres of descending pathways;
CRANIAL NERVES AND THE BRAINSTEM
in the middle (called the tegmentum) are located the
ascending pathways and various nuclei associated with
the reticular formation (see later).
In the mediolateral plane, cranial nerve nuclei are
organized with respect to function. Those nuclei associated with purely sensory nerves are located in the lateral brainstem, while purely motor nuclei are located
most medially. Cranial nerve nuclei with mixed sensory
and motor fibre input are located in between. Each of
these nerves has more than one nucleus of origin—at
II
III
IV
V
VI
VII
VIII
IX
X
XI
XII
Midbrain
Pons
Medulla
least one sensory and one motor. Sometimes, axons from
more than one nerve will terminate in a single nucleus.
For example, the sense of taste is shared by three nerves
(VII, IX and X) but merges into a single nucleus, the solitary nucleus. Another example is the spinal trigeminal
nucleus, which receives general sensations from the face,
muscles and ears (cranial nerves V, VII, IX and X).
The ascending tracts are similarly organized in a
mediolateral fashion within the tegmentum. Tracts
associated with motor function, such as the MLF or the
rubrospinal tract, are located more medially to those
B
Lateral Medial
Dorsal
(nuclei)
Ascending sensory pathways
(descending motor pathways)
Ventral
Key
Pure motor
nuclei
Mixed nerve
nuclei
nuclei
with sensory functions such as the medial lemniscus
(touch and vibration), the spinothalamic tract (pain and
temperature) or the lateral lemniscus (hearing). Although
their exact location varies at different rostrocaudal levels of the brainstem, the pattern of motor systems being
medially located to sensory systems is always preserved.
Fig. 6.2 Schematic representations of the brainstem viewed in the
rostrocaudal (A) and transverse (B) planes. (A) shows the input of
cranial nerves into the different regions of the brainstem. (B) shows
the organization of ascending, descending tracts and cranial nerve
nuclei within the brainstem.
Table 6.2 Main functions of the brainstem
Associated cranial
Brainstem region
Midbrain II–IV Auditory, visual and pupillary reflexes and eye movements
Pons V–VIII Mastication, eye movement, facial expression, blinking, salivation, equilibrium and
Medulla VIII–XII Equilibrium, audition, deglutition, coughing, vomiting, salivation, tongue movement,
nerve input Main functions
122 SYSTEMS OF THE BODY
Regulates cortical arousal
audition
respiration and circulation
6
Superior colliculus
Midbrain
sceral motor nuclei
CRANIAL NERVES AND THE BRAINSTEM
Inferior colliculus
mesencephalic nucleus
Principal trigeminal nucleus
Pons
(open)
Medulla
(closed)
Fig. 6.3 Superior view of the brainstem, showing the schematic organization of cranial nerve nuclei, separated for clarity. Sensory nuclei are
shown only on the left side and motor nuclei only on the right side.
Dorsal cochlear nucleus
Ventral cochlear nucleus
Spinal trigeminal nucleus
Trigeminal
Vestibular nuclei (4)
Nucleus solitarius
Thalamus
Edinger–Westphal nucleus
Oculomotor nucleus
Trochlear nucleus
Trochlear nerve
Trigeminal motor nucleus
Abducens motor nucleus
Facial motor nucleus
Superior salivatory nucleus
Inferior salivatory nucleus
Nucleus ambiguus
Dorsal motor vagal nucleus
Hypoglossal nucleus
Spinal accessory nucleus
Key
Somatic motor
nuclei
Vi
(parasympathetic)
Mixed nerve
nuclei
Purely sensory
nuclei
What is clear is that sensory nuclei are located laterally to
motor ones.
By understanding the basic rules relating to the top-
ographical organisation, the functional significance
Box
6.2
Comparison of spinal and cranial
nerves
becomes apparent: (1) that neurons with similar functions are in close proximity and (2) that different functional deficits occur depending on whether the lesion is
lateral or near the midline. As the location of ascending
and descending tracts and the mediolateral position of
cranial nuclei are relatively constant along their rostrocaudal distribution in the brainstem, specific combinations of signs can reliably indicate the site of a lesion.
Therefore, analysis of brainstem disorders is simplified
by answering two questions:
1. Is it lateral or medial—delineated by the presence/
absence of sensory and motor function?
2. What is the level of the lesion—delineated by
specific cranial nerves?
In order to determine this, it is important to know
what deficits are associated with each cranial nerve and
how to test for them. The specific tests for cranial nerves
are described in Chapter 3 and deficits associated with
specific cranial nerves or their nuclei are shown in Table
6.3.
Reticular formation
Running through the core of the brainstem tegmentum is
the RF, which consists of a diffuse network of neurons that
exert a widespread influence on central nervous system
(CNS) functions. Within this region, cells aggregate to form
Functionally, cranial nerves are analogous to spinal nerves
in that they contain motor, sensory and visceral afferents but there are differences between cranial and spinal
nerves:
• Cranialnervesdonotpossessdorsalandventral
roots.
• Cranialmotorafferentcellbodiesarelocatedin
brainstem nuclei (not in external ganglia).
• Cranialnervespossessfourtypesofsensoryafferents
(spinal nerves contain two). In addition to general
somatic and visceral afferents, special sensory
afferents also innervate specific sensory organs
located only in the head.
• Cranialnervespossessthreetypesofmotorbres,
whereas spinal nerves contain two (general motor/
visceral). General somatic efferents innervate the
extra- ocular muscles (nerves III, IV and VI) and
intrinsic tongue muscles (nerve XII). General visceral
efferents (controlling autonomic effectors) innervate
the sweat/tear glands and smooth muscles (nerves
III, VII, IX and X). Specialized visceral efferent fibres
controlling the striated (skeletal) muscles associated
with the facial expression, chewing, neck, larynx
and pharynx movements (nerves V, VII, IX, X and
XI) are derived from the branchial arches during
development.
• Eachbretypeprojectsto,orarisesfrom,aspecic
brainstem nucleus.
123THE NERVOUS SYSTEM
Table 6.3 Cranial nerve summary
Cranial nerve (CN)
(fibre type) Nucleus name
Olfactory (CN I)
(special sensory afferent) Olfactory bulb Olfactory tract Smell Anosmia
Optic (CN II)
(special sensory afferent) Lateral geniculate Thalamus Vision Blindness
Oculomotor (CN III)
(general somatic efferent)
(general visceral efferent)
Trochlear (CN IV)
(general somatic efferent) Trochlear Midbrain Eye movement (depression of
Trigeminal (CN V)
(general somatic afferent)
(general somatic afferent)
(general somatic afferent)
(special visceral efferent)
Abducens (CN VI)
(general somatic efferent) Abducens Pons Eye movement (abduction) Medial eye deviation
Facial (CN VII)
(special visceral efferent)
(special visceral afferent)
(general visceral afferent)
(general sensory afferent)
Vestibulocochlear (CN VIII)
(special sensory afferent) Vestibular
Glossopharyngeal (CN IX)
(special sensory afferent)
(general visceral afferent)
(general visceral efferent)
(special visceral efferent)
(general sensory afferent)
Vagus (X)
(special visceral efferent)
(general visceral efferent)
(special visceral afferent)
(general visceral afferent)
(general sensory afferent)
Cranial accessory (XI)
(special visceral efferent) Nucleus ambiguus Medulla Pharynx/larynx muscles Insignificant
Spinal accessory (special
visceral efferent) Spinal accessory Cervical cord Neck and shoulder movement Head turning/shoulder shrugging
Hypoglossal (XII)
(general somatic efferent) Hypoglossal Medulla Tongue movements Atrophy of tongue muscles, deviation
*Nuclei associated with the parasympathetic nervous system.
Oculomotor
Edinger–
Westphal*
Principal
Spinal
Mesencephalic
Motor
Motor
Solitary
Superior
salivatory*
Principal trigeminal
Cochlear
Rostral Solitary
Caudal solitary
(cardiorespiratory
centre)
Inferior salivatory*
Nucleus ambiguus
Spinal trigeminal
Nucleus ambiguus
Dorsal motor
vagal*
Rostral Solitary
Caudal solitary
(cardio-
respiratory
centre)
Spinal trigeminal
Nucleus
location Function Symptom/sign of damage
Midbrain
Midbrain
Pons
Medulla
Pons/midbrain
Pons
Pons
Pons
Pons
Pons
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Medulla
Eye movement (elevation,
adduction)
Pupil dilation
adducted eye)
Facial sensation (touch)
Facial sensation (pain) and
meninges
Proprioception
Mastication
Facial expression
Taste
Salivation, lacrimation
Posterior ear skin and outer ear
canal
Balance
Hearing
Taste
Control of blood pressure and
general sensations
Salivation
Stylopharyngeus muscle
Innervation of pharynx,
posterior one- third of
tongue, oropharynx, tonsils,
middle ear auditory tube and
ear drum
Swallowing and talking
Cardiac, respiratory and GI
tract smooth muscle
Taste, general sensations of
larynx and pharynx, cardio-
thoracic and abdominal cavi-
ties, blood pressure control
Innervation of posterior fossa
meninges, pharynx, posterior
ear skin and eardrum
Eye deviates down and out. Loss of
pupillary/ accommodation reflexes
Diplopia, lateral deviation of eye
Facial anaesthesia
Loss of facial pain sensation
Clinically insignificant
Weakness/loss of mastication
Paralysis of facial muscles; hyperacusis
Aguesia (loss of taste to anterior two-
thirds of tongue)
Dry mouth, loss of lacrimation
Loss of sensation
Vertigo, disequilibrium, nystagmus
Deafness
Aguesia (posterior one- third of tongue)
loss of blood pressure control and
gag reflex
Insignificant
Loss of gag reflex
Loss of sensations to these regions
Dysphagia and hoarseness of voice;
unilateral uvula deviation
Tachycardia, loss of cough reflex
Aguesia (epiglottis), loss of gag reflex
and blood pressure control
Loss of sensation
weakness
on protrusion, fasciculation
Table 6.4 Function of different parts of the reticular formation
A
Interpeduncular nucleus
B
6
CRANIAL NERVES AND THE BRAINSTEM
Location Function
Ascending reticular activating system (ARAS)
Periaqueductal grey region
Locus coeruleus
Raphe nuclei
Interstitial nucleus of Cajal, nucleus of Darkschewitz, rostral
interstitial nucleus of the MLF
Pontine paramedian reticular formation (PPRF)
Micturition centre
Pneumotaxic centre (medial parabrachial nucleus)
Salivatory nucleus
Supratrigeminal nucleus
Pedunculopontine nucleus
Dorsal and ventral respiratory nuclei
Cardiovascular nuclei
Raphe magnus nucleus
Area postrema
Chemoreceptor trigger zone
Lateral reticular nucleus
To diencephalon and telencephalon
Median (raphe) RF
(inhibitory)
Paramedian RF
(output)
Lateral RF
(input)
Midbrain Arousal
Rapid eye movement (REM) sleep/pain modulation
Arousal and attention
Wakefulness
Accessory nuclei associated with the vertical gaze centre
Pons Horizontal gaze centre
Bladder control
Respiration
Lacrimation/salivation
Mastication
Locomotor centre, REM sleep
Medulla Respiratory centres
Heart rate/blood pressure
Pain modulation
Vomiting pCO2/pH levels
Pattern generators for coughing and swallowing
Substantia nigra
Ventral tegmental
nucleus
Raphe nuclei
Locus coeruleus
Central reticular
nucleus
Fig. 6.4 (A) Schematic organization of the reticular formation (RF) showing the location of the various aminergic groups (B). (Adapted from
Fitzgerald MJT and Folan-Curran, J Clinical Neuroanatomy & Related Neuroscience, 4th ed. WB Saunders.)
nuclei that are associated with regulating various sensorimotor, cortical arousal and autonomic functions (Table 6.4).
They help to regulate, or fine tune, complex behaviours,
such as chewing, swallowing, coughing, sneezing, fighting
and copulation, using automated pattern generators.
The RF is functionally divided into three regions: a
midline region, containing the raphe nuclei, that has a
Nucleus raphe magnus
To spinal cord
Dopamine
Acetylcholine
Serotonin
Noradrenaline
Adrenaline
predominantly inhibitory function; a medial (magnocellular) region that provides the output pathways to the
spinal cord and forebrain regions; and a lateral (parvocellular) region that receives input from ascending sensory
pathways, from the cerebellum, basal ganglia, hypothalamus, cranial nerves and the cerebral cortex (Fig. 6.4). This
region provides input to the medial region.
Nucleus raphe magnus
125THE NERVOUS SYSTEM
6
The RF contains sets of neurons that utilize specific
amines that function as neuromodulators. The serotonergic (5- hydroxytryptamine [5- HT]) cells have the largest territorial distribution within the CNS and project to
the forebrain and spinal cord. Dopaminergic cells in the
midbrain project to the basal ganglia and limbic cortical
areas. Cells of the locus coeruleus contain noradrenaline
and project to the spinal cord and forebrain. Adrenalineproducing cells are rare and confined to the medulla;
they project to the hypothalamus and sympathetic preganglionic neurons in the spinal cord. Cholinergic cells of
the midbrain project to the thalamus and basal forebrain.
An imbalance in aminergic levels is associated with
depression, hyperactivity and agitation, or insomnia.
Principal functions of the RF
CRANIAL NERVES AND THE BRAINSTEM
Mediating behavioural responses: arousal, alertness and affect
The monoamine cell groups of the upper pons and midbrain form the ascending reticular activating system
(ARAS) that projects to the cerebral cortex, hippocampus,
amygdala, hypothalamus and thalamus. The ARAS regulates sleep and wake cycles, various emotional and behavioural responses, and orientation responses to various
stimuli. Clinically, this area is important in regulating levels
of consciousness; depletion of serotonin leads to insomnia
and tonic firing of locus coeruleus (noradrenaline) neurons
regulates general levels of arousal and attention. Damage
to the midbrain RF can lead to coma, stupor or a persistent
vegetative state. Certain drugs, anaesthetics or metabolic
disturbances also affect consciousness levels through their
actions on the RF. Levels of RF activity are reflected on an
electroencephalogram (EEG) by characteristic patterns that
vary with different states of consciousness.
Modulating pain perception
The raphe nuclei and locus coeruleus nuclei contain
neurons whose projections synapse onto interneurons
in the dorsal horn of the spinal cord, where they mediate stimulus- induced analgesia (see Chapter 5). The RF is
also involved in stress- induced analgesia and the diffuse
noxious inhibitory control of pain.
Modulating spinal and cranial motor functions (muscle tone, reflexes and body posture)
The RF influences motor activities through reciprocal connections with the red nucleus, basal ganglia
nuclei, vestibular nuclei, motor cortex and cerebellum.
Activation of the pontine RF and medullary RF has
antagonistic roles in the control of body posture, via
regulation of flexor and extensor reflexes. The pontine
RF gives rise to the medial reticulospinal tract (RST)
that facilitates extensor reflexes, inhibits flexor reflexes
and increases muscle tone in axial and proximal limb
muscles. The lateral RST originates in the medullary
RF, facilitates flexor reflexes, inhibits extensor reflexes
and decreases muscle tone in axial and proximal limb
muscles. Damage to the brainstem at different levels can
result in specific changes in posture, known as decerebrate or decorticate rigidity (see Chapter 9).
Gaze centres in the midbrain and pons control conjugate eye movements in the horizontal and vertical
directions via connections with the vestibular and ocular motor nerve nuclei in the brainstem and connections
from the frontal and posterior parietal eye fields.
Coordinating motor survival (autonomic) centres
The medulla contains the nuclei that control vital (survival) functions: the respiratory and cardiovascular centres, swallowing, blood pressure and vomiting (Box 6.3).
A key nucleus involved in these functions is the solitary nucleus (also called nucleus of the tractus solitarius
[NTS]). It is involved in the coordination of swallowing
and breathing so that one does not swallow air, or inhale
food or vomit. The caudal NTS also receives afferents
from stretch receptors in the lungs and from CSF chemoreceptors on the surface of the medulla. These fibres project
onto neurons situated in the respiratory centres located in
the medullary RF. The NTS also receives information from
aortic baroreceptors located in the carotid body in the
carotid artery (via cranial nerve IX) and relays this information to the cardiovascular control centres (in the medullary RF) to regulate blood pressure (see Box 6.4).
Blood supply to the brainstem
The entire brainstem derives its blood supply from the
posterior (vertebral- basilar) part of the cerebral circulation (Fig. 6.7). The medulla is supplied from the ventral
surface by the two vertebral arteries that then join to form
the basilar artery, which courses along the ventral surface
of the pons. Further rostrally, in the midbrain, the basilar
artery diverges to become the posterior cerebral arteries. Branches from these three main arteries supply both
the dorsal and ventral surfaces of the brainstem. These
branches subdivide into three groups that supply different
regions for each part of the brainstem (see Fig. 6.7).
There is a paramedian region on either side of the ventral midline that is supplied by short arteries. Next to
this region is an intermediate region, supplied by short
circumferential arteries. The lateral zone, which supplies the dorsal aspect of the brainstem, is supplied by
branches of long circumferential arteries, such as the posterior cerebral artery. The paramedian and lateral zones
are often involved in vascular accidents that give rise to
characteristic clinical deficits (see later).
Brainstem reflexes
The brainstem is involved in several reflexes (Table 6.5),
and their presence or absence is used to determine brainstem death in a patient (see Box 6.5).
126 SYSTEMS OF THE BODY
Box
6.3
6
CRANIAL NERVES AND THE BRAINSTEM
Nausea and vomiting
There are many causes of nausea and vomiting: pregnancy,
movement (e.g. travel sickness), vestibular disease, injury
and migraine. Treatment is based on the use of anti-emetics.
Nausea is easier to prevent than to stop after it has started.
Vomiting is coordinated by the vomiting centre located in the
lateral medullary reticular formation (Fig. 6.5). This region
receives input from the chemoreceptor trigger zone (CTZ),
located in the area postrema of the medulla, which is rich in
dopaminergic (D2) and serotonergic (5- HT3) receptors. This
region is not protected by the blood–brain barrier (BBB) and
is sensitive to circulating toxins or drugs. There is also input
from the limbic system (that responds to unpleasant smells
or sights), the spinoreticular tract (in response to physical
trauma), the NTS (involved in the gag reflex) and the stomach via the vagus nerve and the vestibular system. In motion
sickness, nausea is thought to arise due to conflicting signals from the visual and vestibular systems. Output from the
Limbic system
dopamine
D
2
antagonists
e.g. domperidone
metoclopramide
Spinal cord
(reticulospinal
tract)
VN
NTS
vomiting centre is to the spinal motor neurons innervating
the abdominal muscles.
Drugs used to fight diseases, such as Parkinson’s disease
and cancer, frequently cause nausea and vomiting because
they activate the CTZ. Dopamine receptor antagonists such as
domperidone and metoclopramide can be used to treat nausea. Domperidone does not cross the BBB and has few side
effects. Metoclopramide also has an effect on the gut, facilitating the absorption of many drugs, such as analgesics. 5- HT3
antagonists, such as ondansetron, inhibit receptors in the gut
and CTZ and reduce nausea but may result in constipation. D2
and 5- HT3 antagonists are ineffective in preventing motion
sickness. Anticholinergic drugs, such as hyoscine (a muscarinic
receptor antagonist), or anti-histamine drugs, such as cinnarizine, often prescribed for motion sickness, act directly on the
vomiting centre to reduce sickness.
Emetic agents
e.g. cytotoxins, opioids,
apomorphine
CTZ
VC
NTS
VN
Anti-emetics for motion sickness
Anticholinergic
e.g. hyoscine
Anti-histamine
e.g. cinnarizine
5HT
antagonists
3
e.g. ondansetron
Fig. 6.5 Pathways involved in nausea and their pharmacological modulation. 1, Excitatory; CTZ, chemoreceptor trigger zone; NTS, solitary
nucleus; VC, vomiting centre; VN, vestibular nucleus; X, vagus nerve; –, inhibitory. (Adapted from Neal MJ. (1997). Medical pharmacology at a
glance, 3rd ed. Blackwell Science Ltd.)
Pupillary light reflex
XX XX
Gut
Abdominal muscles
muscle occurs in response to autonomic parasympathetic
stimulation by postganglionic ciliary nerves. This reflex
Normally, shining a light into one eye causes both pupils
to constrict. In the stimulated eye, this is the direct light
reflex, and in the non- stimulated eye, it is the consensual
light reflex. Pupil constriction by the pupillary sphincter
is triggered by stimulation of optic nerve collaterals synapsing in the pretectal nucleus (in the superior colliculus)
that, in turn, stimulates neurons in the Edinger–Westphal
nucleus. From here, parasympathetic preganglionic fibres
127THE NERVOUS SYSTEM
6
Pons
Box
CRANIAL NERVES AND THE BRAINSTEM
Brainstem control of respiration and heart rate
6.4
The medulla houses the respiratory and cardiovascular nuclei
of the RF. These control the respiratory and heart rates in
response to peripheral stimuli or changes in the partial pressure of oxygen, carbon dioxide and blood pH (Fig. 6.6).
The medulla houses the dorsal (inspiratory) and ventral
(expiratory) respiratory groups in the nucleus of the solitary
tract (NTS) and nucleus ambiguus, respectively. Their function is to control the basic rhythm of breathing and they can
maintain breathing independently of the rest of the brain, as
occurs in a persistent vegetative state.
Other centres in the pons are involved in co- ordinating
breathing patterns. The pneumotaxic centre, located in the
medial parabrachial nucleus, inhibits inspiratory neurons to prevent the lungs becoming over inflated. It limits inspiration and
facilitates expiration. When this area is active, breathing rate
is more rapid. The apneustic centre stimulates the dorsal respiratory group, prolonging inspiration and reducing expiration.
When the pneumotaxic centre is active, the apneustic region is
inhibited.
Damage at different brainstem levels leads to altered patterns of respiration: damage above the pons leads to a normal
Midbrain
Colliculi
‘pneumotaxic centre’
breathing pattern whereas damage between the pneumotaxic and apneustic centres leads to apneusis (breathing with
prolonged inspiratory pauses) or Cheyne–Stokes respiration.
Damage between the apneustic centre and the respiratory
cell groups leads to irregular breathing patterns, and damage
below the respiratory groups eliminates the respiratory drive.
Breathing is also regulated by the blood levels of CO2 and
H+. Chemosensitive cells located in the ventrolateral part
of the medulla, close to where the choroid plexus projects
through the lateral aperture of the fourth ventricle, detect
local acidity or alkalinity changes in the CSF, and strongly
increase or decrease respiratory drive via connections with
the medullary respiratory centre.
The cardiovascular (baroreceptor) centre is located in the
medial NTS and is activated by the carotid sinus stretch (baro- )
receptors. Changes in heart rate or blood pressure stimulate
these centres resulting in activation of the (autonomic) cardioinhibitory neurons of the dorsal motor vagal nucleus to reduce
heart rate, or the lateral medullary RF to reduce peripheral arteriole sympathetic tone. These are the barovagal and barosympathetic reflexes that help to lower high blood pressure.
Vagus nerves
Intact Cut
Level of
PBN
4th
ventricle
D
R
V
R
G
G
(NA)
To diaphragm
(NTS)
CSF
‘apneustic centre’
‘inspiratory and
expiratory centres’
Cervical
spinal cord
CSF
Chemosensitive
area
Medulla
Fig. 6.6 The left and middle diagrams show lateral and dorsal views of the location of brainstem respiratory control neuron groups. The
pneumotaxic centre is located in the medial parabrachial nucleus (PBN). The dorsal respiratory group (DRG) located in the solitary nucleus
(NTS) and ventral respiratory group (VRG) of neurons located in the nucleus ambiguous (NA) house the inspiratory and expiratory centres,
respectively. The right panel shows the breathing patterns seen in decerebrate animals with damage at different brainstem levels. After
transection at the upper line, normal breathing can still occur without any influence from above the pons. After transection at the dashed
line, the pneumotaxic centre is disconnected from influencing the apneustic centre, so that prolonged inspiration takes place unless
inhibition occurs via stimulation of the lung stretch receptors (‘vagus intact’). Transection at the lower line removes all influences above the
level of the medulla and produces irregular breathing patterns. CSF, Cerebrospinal fluid; V, ventricle. (Adapted from Jenner S (1989). Human
Physiology. Churchill Livingstone.)
4th
ventricle
D
R
V
G
R
G
128 SYSTEMS OF THE BODY