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INTRODUCTION

The brainstem is the structure that connects the cerebrum of the brain to the spinal cord and cerebellum.
It is composed of three sections in descending order: the midbrain, pons, and medulla oblongata. It is
responsible for many vital functions of life, such as breathing, consciousness, blood pressure, heart rate,
and sleep. The brainstem contains many critical collections of white and grey matter. The grey matter
within the brainstem consists of nerve cell bodies and forms many important brainstem nuclei. The
white matter tracts of the brainstem include axons of nerves traversing their course to different
structures; the axons originate from cell bodies located elsewhere within the central nervous system
(CNS). Some of the white matter tract cell bodies are located within the brainstem as well. These tracts
travel both to the brain (afferent) and from the brain (efferent), such as the somatosensory pathways and
the corticospinal tracts, respectively. Ten of the twelve cranial nerves arise from their cranial nerve
nuclei in the brainstem. Clinicians can localize lesions of the brainstem with a thorough knowledge of
brainstem anatomy and functions. The brainstem contains many different nuclei and tracts. The
midbrain serves as the connection between the pons and the diencephalon. It also connects posteriorly to
the cerebellum via the superior cerebellar peduncles. The anterior part of the midbrain contains the crus
cerebri with the interpeduncular fossa located between them. The crus cerebri carry motor cortical spinal
fibers, corticonuclear fibers, and pontine fiber tracts. The midbrain contains the cerebral aqueduct
centrally, which connects the third ventricle superiorly with the fourth ventricle inferiorly. The
periaqueductal grey surrounds the cerebral aqueduct. The midbrain is separated relative to the cerebral
aqueduct, with the posterior portion being the tectum (floor) and anterior to the aqueduct serving as the
tegmentum (roof). The posterior surface of the midbrain contains the corpora quadrigemina, which are
composed of bilateral superior colliculi and bilateral inferior colliculi. The superior colliculi are
involved in visual reflexes such as saccadic eye movements. Each superior colliculus sends fibers to the
corresponding lateral geniculate body and optic tract through the superior brachium. The inferior
colliculi are involved in auditory processing and connect to their corresponding medial geniculate nuclei
through the inferior brachium. Just inferior to the inferior colliculi at the posterior midline of the
brainstem cranial nerve IV, the trochlear nerve emerges. The trochlear nerve is unique among cranial
nerves as it is the only one to emerge from the posterior surface of the brainstem. The other cranial
nerve that arises from the midbrain is cranial nerve III, the oculomotor nerve. The oculomotor nerve
arises from the midbrain in the oculomotor sulcus on the medial surface of the crus cerebri, within the
interpeduncular cistern.

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The midbrain also includes many other important nuclei, including but not limited to the substantia nigra
at the base of the midbrain, the red nucleus anterior medially at the level of the superior colliculus, and
the dorsal raphe nucleus. The largest of the raphe nuclei are in the anterior midline of the periaqueductal
grey, and the location of the ventral tegmental area is near the midline medial to the red nucleus. The
substantia nigra contains dopaminergic neurons that help to regulate movement associated with the basal
ganglia. The ventral tegmental area also contains dopaminergic neurons and plays a role in reward
pathways. The raphe nuclei contain serotonergic neurons and project widely throughout the brain. The
periaqueductal grey is thought to play a role in pain suppression. The red nucleus is involved with
movement and contains many connections with the cerebellum. The medial longitudinal fasciculus lies
anterior to the periaqueductal grey and plays a role in coordinating eye movements.

The pons connects the medulla oblongata inferiorly to the midbrain superiorly. The anterior portion of
the pons is convex and can be easily seen as a visible distention when viewing the brainstem anteriorly.
The surface of the anterior distention contains the basilar groove, which is where the basilar artery rests.
The posterior pons is connected to the cerebellum by the middle cerebellar peduncles, which are the
largest of the cerebellar peduncles. The posterior portion of the pons forms the superior portion of the
floor of the fourth ventricle. A groove is formed inferiorly where the pons meets the medulla from
which cranial nerves VI, VII, and VIII emerge medially to laterally. Cranial nerve V, the largest cranial
nerve, exits from the superior anterior lateral pons. Important nuclei of the pons include the cranial
nerve nuclei covered in the nerves section, the locus coeruleus, and pontine nuclei. The neurons of the
locus coeruleus produce norepinephrine and have projections that spread widely throughout the CNS.
The locus coeruleus is located in the posterior lateral pons at the lateral border of the periaqueductal
grey and is involved in the reticular activating system. The locus coeruleus also suffers compromise in
Alzheimer disease. The pontine nuclei are a collection of pontine motor nuclei in the anterior pons that
have many connections with the cerebellum via the middle cerebellar peduncle and assist with
coordinating movement and help to modulate breathing.

The most inferior portion of the midbrain is the medulla oblongata, which connects the pons to the
spinal cord. It meets the spinal cord at the level of the foramen magnum. The anterior portion of the
medulla oblongata contains the pyramids. The pyramids carry motor fibers from the precentral gyrus, or
motor cortex, to the grey matter of the spinal cord, where they synapse and continue to the muscles of
the body through the peripheral nervous system. The pyramids contain a decussation caudally in which
the majority of the motor fibers contained cross to the contralateral side of the body. The fibers that
decussate become the lateral corticospinal tract in the spinal cord, the fibers that do not decussate
become the medial corticospinal tract in the anterior portion of the spinal cord. The pyramids lie on

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either side of the anterior median fissure, a midline groove that continues caudally along the anterior
portion of the spinal cord. Lateral to the pyramids are the olivary bodies that are part of the
olivocerebellar system. The hypoglossal nerve, cranial nerve XII, emerges from the anterior surface of
the medulla from the sulcus between the olivary bodies and the pyramids. Posterior to the olivary bodies
is the postolivary groove. Cranial nerves IX (glossopharyngeal), X (vagus), and XI (accessory) emerge
from the postolivary groove in superior to inferior order. Posterior to the postolivary grooves are the
inferior cerebellar peduncles that connect the medulla to the cerebellum. The posterior portion of the
medulla oblongata inferiorly connects to the spinal cord. The posterior median sulcus is located in the
midline on the posterior aspect of the inferior medulla and continues caudally along the posterior spinal
cord. The posterior median sulcus in the posterior midline of the spinal cord is flanked by visible
localized prominences called the gracile tubercles. On each side, the gracile tubercle contains the gracile
nucleus. Similar bilateral localized prominences called the cuneate tubercles (containing the cuneate
nucleus on each side) are just lateral to each of the gracile tubercles on the posterior aspect of the spinal
cord. The gracile and cuneate tubercles carry second-order neurons of the dorsal column-medial
lemniscus system. The gracile nucleus carries fibers for the lower extremities and trunk, and the cuneate
nucleus carries fibers for the upper body above T6 except for the face and ears. The superior area of the
posterior medulla oblongata forms a portion of the floor of the fourth ventricle.

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 2

STRUCTURES IN THE MIDBRAIN

General Anatomy of Midbrain

The midbrain (also known as the mesencephalon) is the most superior of the three regions of the
brainstem. It acts as a conduit between the forebrain above and the pons and cerebellum below.

Figure 1 – The three major parts of the brainstem. (Crumbie, 2023)

External Anatomy of the Midbrain

The midbrain is the smallest of the three regions of the brainstem, measuring around 2cm in length. As it
ascends, the midbrain travels through the opening in the tentorium cerebelli.

It can be divided into two main parts:

 Tectum – located posterior to the cerebral aqueduct

 Paired cerebral peduncles – located anteriorly and laterally.

Internally, the cerebral peduncles are further separated by the substania nigra into the crus cerebri
(anterior) and the tegmentum (posterior).

Tectum

The tectum houses four rounded prominences named colliculi (collectively the corpora quadrigemina)
which sit directly inferior to the pineal gland. The colliculi are separated by the cruciform sulcus; there
are two superior and two inferior colliculi.

Extending laterally from each colliculi are the quadrigeminal brachium:

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 Superior quadrigeminal brachium forms a pathway between the superior colliculus and the retina
of the eye.

 Inferior quadrigeminal brachium conveys fibres from the lateral lemniscus and inferior colliculus
to the medial geniculate body.

Inferior to the colliculi, the trochlear nerve (CN IV) emerges before sweeping across to the anterior
surface.

Cerebral Peduncles

The paired cerebral peduncles extend from the cerebral hemispheres to converge as they meet the pons.
They are separated anteriorly in the midline by the interpeduncular fossa, the floor of which is termed
the posterior perforated substance (as many perforating blood vessels can be identified).

The oculomotor nerve (CNIII) is seen exiting from between the peduncles while the optic tract runs
around the superior border of the midbrain.

Fig 2 – Posterolateral view of the external anatomy of the midbrain. (Crumbie, 2023)

Internal Anatomy of the Midbrain

Two transverse sections of the midbrain will be discussed: the level of the inferior colliculus, and the
level of the superior colliculus.

Level of the Inferior Colliculus

The anteriolateral surface of the midbrain houses the paired crus cerebri. Four fibre tracts run within the
crus:

 Frontopontine fibres – located most medially.

 Corticospinal fibres – motor fibres from the primary motor cortex.

 Corticobulbar tracts – motor fibres from the primary motor cortex.

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 Temporopontine fibres – located posterolaterally.

Posteriorly is the substantia nigra – a pigmented nucleus that separates the two regions of the cerebral
peduncles. It is further broken down into the pars reticulata (anterior) and pars compacta (posterior).

The tegmentum is located posterior to the substantia nigra. It is continuous with that found in the pons
by the same name. It is important to note that unlike the crus cerebri, the tegmentum is continuous at the
midline.

The cerebral aqueduct is a midline structure surrounded by central gray matter – the periaqueductal gray
matter. Within this gray matter lies the mesencephalic nucleus of the trigeminal nerve, as well as the
trochlear nucleus with its fibres continuing around the gray matter to exit the midbrain. Anterior to this,
the medial longitudinal fasciculus can be seen.

The decussation of the superior cerebellar peduncles can be seen centrally at this level with some
reticular formation (noted throughout the brainstem) lying lateral.

Between the central gray matter and the substantia nigra are four lemnisci. Moving anterior to posterior
they are the medial, spinal, trigeminal, and lateral leminisci.

At the very posterior pole, we find the tectum which, at this level, contains the inferior colliculus.

Level of the Superior Colliculus

Much of the internal structure of the midbrain is unchanged at this level and should be assumed present
unless mentioned below.

The central portion which previously was occupied by the decussation of the superior cerebellar
peduncles now contains the large paired red nuclei with some decussation of the rubrospinal tract
occurring anterior to this. The reticular formation now fans around the posterior borders of the red
nuclei.

The trochlear nucleus is replaced with the oculomotor nucleus while the oculomotor nerve projects
anteriorly.

The medial, spinal and trigeminal lemnisci are all present in much the same location however the lateral
lemnisci do not reach to this level.

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Figure 3 – Cross-section of midbrain at the level of the superior colliculus. (Crumbie, 2023)

Vasculature

The midbrain receives vascular supply from the basilar artery and its branches. The major vessels are:

 Posterior cerebral artery and its peduncular branch

 Superior cerebellar artery

 Posterior choroidal artery

 Interpeduncular branches of the basilar artery.

Fig 4 – Vascular supply of the midbrain. (Netters, 2022)

GENERAL ANATOMY OF THE PONS

The pons is the largest part of the brainstem, located above the medulla and below the midbrain. It is a
group of nerves that function as a connection between the cerebrum and cerebellum (pons is Latin for
bridge).

The pons develops from the embryonic metencephalon (part of the hindbrain, developed from the
rhombencephalon), alongside the cerebellum.

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In this article, we will look at the anatomy of the pons – its location, structure and function, blood
supply and clinical relevance.

Anatomical Position

The pons is a horseshoe-shaped collection of nerve fibres located in the anterior part of the posterior
cranial fossa.

Its anatomical relations are as follows:

 Posteriorly – the cerebellum, separated by the fourth ventricle.

 Inferiorly – the medulla oblongata.

 Superiorly – the midbrain lies immediately above the pons.

External Anatomy

1. Anterior Surface

The anterior or ventral surface of the pons is marked by a bulging formed by the transverse
pontocerebellar fibres. These fibres wrap around the otherwise vertically oriented brainstem. It measures
around 2.5 cm in adults.
The basilar groove demarcates the midline of the ventral surface and is where the basilar artery is
located.
The pontomedullary junction is an important anatomical landmark defined by the angle between the
lower border of the pons and the superior border of the medulla.
Several cranial nerves originate from the ventral surface of the pons:

 Cranial nerve V: trigeminal – originates from the lateral aspect of mid pons
 Cranial nerve VI: abducens – originates from the pontomedullary junction, close to the midline
 Cranial nerve VII: facial – originates from the cerebellopontine angle, the more lateral aspect of
the pontomedullary junction.
 Cranial nerve VIII: vestibulocochlear – originates laterally to the facial nerve.

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 Fig 5 –Anterior surface of the midbrain. (crumbie, 2023)

2. Posterior Surface

The pons is intimately related to the cerebellum and is connected to it by the middle cerebellar
peduncles. Removal of the cerebellum will reveal the underlying fourth ventricle.

The floor of the fourth ventricle is composed of the dorsal surface of the pons and the medulla. There
are some important anatomical landmarks here:

 The medial eminence marks the midline of the floor.

 The facial colliculus is a bulging formed by the fibres of the facial nerve looping around the
abducens nucleus.
 The stria medullaris of the fourth ventricle is a bundle of nerve fibres crossing transversely from
the lateral aspect into the midline. They mark the posterior border between the pons and the medulla.

The angle formed at the junction of the pons, medulla, and cerebellum is another anatomical landmark
and is named cerebellopontine angle. Here, the cerebellar flocculus, the ventricular choroid plexus and
the emerging CNs VII and VIII surround the lateral apertures of the fourth ventricle (the foramen of
Luschka).

Fig 6 –Posterior surface of the midbrain. (crumbie, 2023)

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Internal Anatomy

The pons is comprised of two major components – the ventral pons and the tegmentum.

The ventral pons contains the pontine nuclei, which are responsible for coordinating movement. Fibres
from the pontine nuclei cross the midline and form the middle cerebellar peduncles on their way to the
cerebellum.

The tegmentum is the evolutionarily older part of the pons which forms part of the reticular formation –
a set of nuclei found throughout the brainstem that are responsible for arousal and attentiveness.
Damage to this part of the pons may result in anosognosia for hemiplegia, where patients are unaware of
their paralysis.

The rest of the pons is made up of tracts passing through the pons including:

 Descending corticospinal tracts – responsible for voluntary motor control of the body.

 Descending corticobulbar tracts – responsible for voluntary motor control of face, head and
neck.

 Ascending medial lemniscus tracts – responsible for fine touch, vibration and proprioception.

 Ascending spinothalamic tracts – responsible for pain and temperature sensation

Cranial Nerve Nuclei

The pons houses important cranial nerve nuclei.

The main sensory nucleus and the trigeminal motor nucleus are located in the midpons – at the level
where the fibres originate from the lateral aspect of the pons. The main sensory nucleus receives
somatosensory information from the face. There are two other nuclei that receive sensory information
from the trigeminal nerve:

 Spinal trigeminal nucleus – extends caudally towards the medulla.

 Mesencephalic nucleus – extends rostrally all the way to the midbrain.

The abducens nucleus controls the abducens nerve, which innervates the ipsilateral lateral rectus muscle.
It is located in the caudal pons, on the medial aspect of its dorsal surface.

At the same level of the abducens nucleus, the facial nucleus is located more anteriorly and laterally. It
controls the muscles of facial expression. Its fibres take an unusual course and loop around the abducens
nucleus before exiting the brainstem through its ventrolateral surface.

The cochlear and vestibular nuclei sit dorsolaterally from the inferior pons to the superior medulla.

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Vasculature

The blood supply of the pons is formed by branches of the vertebrobasilar system:

 Most of the pons is supplied by the pontine arteries, branches of the basilar artery

 A smaller part of its blood supply comes from the anterior inferior cerebellar artery and
the superior cerebellar artery (AICA and SCA).

The venous drainage of the pons consists of the anterior pontomesencephalic vein, which drains
superiorly into the basal vein, that in turn drains into the cerebral veins. Inferiorly, the pons drains into
the inferior petrosal sinus, which drains into the internal jugular veins.

GENERAL ANATOMY OF MEDULLA OBLONGATA

The medulla oblongata (medulla) is one of the three regions that make up the brainstem. It is the most
inferior of the three and is continuous above with the pons and below with the spinal cord. The medulla
houses essential ascending and descending nerve tracts as well as brainstem nuclei.

In this article, we shall look at the anatomy of the medulla – its external features, internal anatomy, and
blood supply.

External Anatomy of the Medulla

The medulla is conical in shape, decreasing in width as it extends inferiorly. It is approximately 3cm
long and 2cm wide at its largest point.

The superior margin of the medulla is located at the junction between the medulla and pons, while the
inferior margin is marked by the origin of the first pair of cervical spinal nerves. This occurs just as the
medulla exits the skull through the foramen magnum.

Anterior Surface

There are several structures visible on the anterior surface of the medulla – namely the three
fissures/sulci, the pyramids, the olives, and five cranial nerves.

In the midline of the medulla is the anterior median fissure, which is continuous along the length of the
spinal cord. However, it is interrupted temporarily by the decussation of the pyramids (see below). As
we move away from the midline, two sulci are visible – the ventrolateral sulcus and the posterolateral
sulcus.

The pyramids are paired swellings found between the anterior median fissure and the ventrolateral
sulcus. The olives are another pair of swellings located laterally to the pyramids – between the
ventrolateral and posterolateral sulci.

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Arising from the junction between the pons and medulla is the abducens nerve (CN VI). Extending out
of the ventrolateral sulcus is the hypoglossal nerve (CN XII). In the posteriolateral sulcus, three more
cranial nerves join the medulla (CN IX, CN X, and CN XI).

Posterior Surface

Unlike the anterior surface of the medulla, the posterior surface is largely obstructed from view and is
relatively devoid of features. In order to appreciate the posterior surface, the cerebellum must be
removed.

Similar to the anterior surface, the posterior surface has a midline structure – the posterior median
sulcus – which is continuous below as the posterior median sulcus of the spinal cord. Above, the sulcus
ends at the point in which the fourth ventricle develops.

As we move lateral from the midline, the fasciculus gracilis and fasciculus cuneatus are seen, separated
by the posterior intermediate sulcus.

Internal Anatomy of the Medulla

The internal structures of the medulla must be viewed in cross section to understand the
layout. Three levels of the medulla are typically discussed (inferior – superior):

 Level of decussation of the pyramids

 Level of decussation of the medial lemnisci
 Level of the olives

The medulla itself is typically divided into two regions: the open and the closed medulla. This
distinction is made based on whether the CSF-containing cavities are surrounded by the medulla (closed
medulla) or not (open medulla). The medulla becomes open when the central canal opens into the fourth
ventricle.

Some features are seen in all three cross sections. Anteriorly we can see the paired lumps representing
the pyramids which are separated by the anterior median fissure. Centrally, the central canal can be seen
as it rises to form the fourth ventricle in the final cross section.

Level of the Decussation of the Pyramids

This is the major decussation point of the descending motor fibres. Roughly 75% of motor fibres housed
within the pyramids cross diagonally and posteriorly, and continue down the spinal column as the lateral
corticospinal tracts.

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At this level, the central portion of the medulla contains gray matter, while the outer portions consist
of white matter. The posterior white matter contains the fasiculus gracilis and the more lateral fasiculus
cuneatus. Corresponding portions of gray matter extend to these regions and are the nucleus gracilis and
nucleus cuneatus respectively.

Unchanged from the spinal cord, the spinocerebellar tracts (posterior and anterior) are located laterally,
with the lateral spinothalamic tract situated between them. The large trigeminal nucleus and tracts can
be found posterior to these tracts. This is a continuation of the substantia gelatinosa of the spinal cord.

Level of Decussation of the Medial Lemniscus

This level marks the sensory decussation occurs of the medial lemniscus. (Fig. 5). Purple lines have
been used to represent the internal arcuate fibres as they run from the nucleus gracilis and nucleus
cuneatus around and anterior to the central gray matter to form the medial lemniscus.

Lateral to the medial lemniscus, the trigeminal nucleus and spinal tract can once again be seen, as can
the spinocerebellar tracts and the lateral spinothalamic tract. Similarly, the posterior structures are much
the same at this level.

Centrally, the hypoglossal nucleus and medial longitudinal fasciculus are seen. Moving laterally, the
nucleus ambiguous can be seen. Between this structure and the pyramids is the inferior olivary nucleus.

Level of the Olives

This level shows significant change in structure both externally and internally when compared with
previous levels. The central canal has now expanded into the fourth ventricle and as such makes this
region the open medulla.

The large inferior olivary nucleus is responsible for the external expansion of the olives. The related
medial and dorsal accessory olivary nuclei can be seen medial and posterior to this structure
respectively.

The large inferior cerebellar peduncles come into view and are surrounded by multiple nuclei. The
two vestibular nuclei (medial and inferior) are both found towards the midline while the two cochlear

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nuclei are found somewhat above and below the peduncles. Now a much smaller structure, the
trigeminal tract and nucleus is seen adjacent to the peduncle.

The nucleus ambiguous remains as it was previously, while the hypoglossal nucleus has migrated with
the central canal posteriorly, joined by the medial longitudinal fasciulus. An additional cranial nucleus
comes into view lateral to the hypoglossal – the dorsal vagal nucleus. Moving further lateral, the nucleus
of tractus solitarius comes into view.

Centrally, the medial lemniscus hugs the midline posterior to the pyramids, as does the tectospinal tract.

Between the peduncle and the olivary nuclei resides the lateral spinothalamic tract and the more lateral
anterior spinocerebellar tract.

Vasculature

The vasculature of the medulla is complex and is dependent on the level being viewed. The following
attempts to simplify this complexity. Despite this it may suffice the reader to know that the vessels that
supply the medulla include: the anterior spinal, the posterior spinal, the posterior inferior cerebellar, the
anterior inferior cerebellar, and vertebral arteries.

Throughout the medulla, the anterior spinal artery supplies a region beginning at the central canal (or
anterior border of the fourth ventricle), and fans out to encompass the pyramids.

Below the level of the olives the posterior half of the medulla is supplied by the posterior spinal artery.
No other regions are supplied by this vessel. The remaining portions are supplied by the posterior
inferior cerebellar and vertebral arteries.

In cross section through the olives both the posterior inferior cerebellar and vertebral arteries take on
greater territories posterolaterally and anterolaterally respectively. They continue to do so as the medulla
ascends.

At the highest point in the medulla, the anterior inferior cerebellar artery supplies the outermost portions
of the posterior region.

Major Brainstem Tracts

 The Reticular Formation

The reticular formation is found in the anterior portion of the brainstem and is composed of multiple
tracts that have a large number of connections. The reticular formation extends from the spinal cord

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through the brainstem to the diencephalon. It receives input from various tracts including spinothalamic
tracts, spinoreticular tracts, the dorsal column-medial lemniscus pathway, visual pathways, auditory
pathways, vestibular pathways, and cerebelloreticular pathways. The reticular formation sends efferent
fibers to the thalamic nuclei, cerebellum, red nucleus, corpus striatum, substantia nigra, hypothalamus,
and subthalamic nucleus. The vast connections of the reticular formation allow it to modulate many
different functions; some of these include movement coordination, autonomic regulation of blood
pressure, heart rate, and respiratory rate, postural reflexes, neuro-vegetative reflexes, and taste. It also
plays a role in wakefulness and sleep.

The Motor Tracts

1. Corticospinal Tracts

The majority of the upper motor neurons of the motor tracts originate in the precentral gyrus. The
corticospinal fibers descend through the posterior limb of the internal capsule to the crus cerebri and
then down the anterior pons to the pyramids of the medulla. At the pyramids, the majority of the
corticospinal fibers decussate and descend the spinal cord as the lateral corticospinal tract and eventually
continue to supply motor innervation to the limbs and digits. The majority of corticospinal fibers that do
not cross over at the medullary pyramids become the medial corticospinal tracts, located anteriorly in
the spinal cord, and provide innervation to the muscles of the trunk.

2. Corticobulbar Tracts

The corticobulbar tracts descend through the genu of the internal capsule and down through a similar
course as the corticospinal fibers; however, the corticobulbar fibers exit this course and synapse at the
appropriate cranial nerve nuclei at their respective levels. The majority of corticospinal fibers decussate,
while only some of the corticobulbar fibers decussate, as described in the nerves section of this article.
The corticobulbar tracts also contain connections with many of the sensory nuclei of the brainstem.

The Sensory Tracts

1. Spinothalamic Tract or Anterolateral System

The spinothalamic tract is responsible for conveying pain and temperature information from the body to
the brain. Peripheral neurons carry sensory information to the posterior column of the spinal cord. After
synapsing in the spinal cord, the axons ascend two to three levels before decussating. After decussating,
the fibers ascend as the lateral and anterior spinothalamic tracts in the anterior and lateral portions of the
spinal cord. When the tracts ascend through the medulla, they merge to form the spinothalamic tract and
course along the lateral portion of the medulla. The tract continues up the lateral portion of the anterior

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pons and midbrain to the ventral posterior lateral thalamus, where the axons synapse and continue up
through the posterior limb of the internal capsule to enter the post-central gyrus of the cortex.

2. Dorsal Column-Medial Lemniscus

The dorsal column-medial lemniscus tract is responsible for carrying afferent proprioception, fine touch,
two-point discrimination, and vibration to the cortex from the body. Peripheral neurons carry sensory
information to the posterior column of the spinal cord and ascend in the posterior portions of the spinal
cord as the gracile fasciculus and cuneate fasciculus. The neurons in these fasciculi will synapse of the
gracile nucleus and cuneate nucleus at the level of the inferior medulla, respectively. The second order
neurons will decussate at the level of the medulla and become the medial lemniscus. The medial
lemniscus maintains a medial position within the brainstem as it ascends to the ventral posterior lateral
thalamus. After synapsing in the thalamus, the fibers continue through the posterior limb of the internal
capsule to the post-central gyrus of the cortex.

3. Trigeminal Lemniscus and Spinotrigeminal Tract

Pain and temperature sensory input from the face enters the brainstem via cranial nerve V. The fibers
that carry this information enter the brainstem and descend parallel to the spinal trigeminal nucleus
before synapsing in it. Their descent forms the spinotrigeminal tract. After these fibers synapse, they
decussate to the contralateral side and ascend as a part of the trigeminal lemniscus.

The trigeminal lemniscus carries sensory axons from the second-order neurons of the principal sensory
nucleus of the trigeminal nerve, which contain discriminative touch and oral cavity proprioception.
These neurons do not descend before synapsing after entering the brainstem. Most of these fibers
decussate to the contralateral side on their course to the ventral posterior medial thalamus and then
proceed to the post-central gyrus of the cortex. The fibers of the trigeminal lemniscus ascend the pons
and midbrain posterior to the medial lemniscus.

4. Lateral Lemniscus

The lateral lemniscus carries auditory information from the cochlear nuclei at the level of the inferior
pons superiorly to the superior olivary complex, nuclei of the lateral lemniscus, inferior colliculi, and
eventually to the medial geniculate body, which sends the auditory information to the temporal lobes of
the cerebral cortex. Some of the fibers of the lateral lemniscus decussate while others do not. The lateral
lemniscus travels up the posterior lateral portion of the pons and is important for sensory input to the
brain.

Embryology

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All of the CNS derives from ectoderm. It develops through the process of neurulation, which is induced
by the notochord, which is of mesodermal origin. The notochord initially causes the formation of the
neural groove and releases noggin and chordin to inhibit ectodermally derived bone morphogenic
proteins and induce the creation of the neuroectoderm. The neural fold is formed by about day 20 after
conception and slowly folds over itself to form the neural tube. The tube closes both rostrally and
causally, with the complete rostral closure occurring near day 24 post-conception and the caudal closure
occurring near day 26 post-conception. Failure or other defects of the closure of the neural tube can
result in various forms of spina bifida caudally and anencephaly, and craniorachischisis rostrally. At 4
weeks gestation, the neural tube will have developed three outpouchings that will give rise to the
different components of the CNS. These outpouchings consist of the prosencephalon (forebrain), the
mesencephalon (midbrain), and the rhombencephalon (hindbrain). By 6 weeks gestation, the
prosencephalon will divide again into the telencephalon and diencephalon. The cerebral hemispheres
and lateral ventricles arise from the telencephalon. The diencephalon will form the thalamus,
hypothalamus, retina, and third ventricle. The mesencephalon will not divide any further and will give
rise to the midbrain and cerebral aqueduct. At 6 weeks, the rhombencephalon will have divided further
into the metencephalon and myelencephalon. The metencephalon will form the pons, cerebellum, and
part of the fourth ventricle. The myelencephalon will produce the medulla and part of the fourth
ventricle. The table below, Summary of Brainstem Embryology, contains this material in a simplified
form.

Blood Supply and Lymphatics

The significant conduits of blood to the CNS are the internal carotid arteries and the vertebral arteries;
they give rise to the many arterial branches that perfuse the CNS. The most inferior portion of the
brainstem is the medulla oblongata. Caudally it receives the majority of its blood supply from the
anterior spinal artery anterior-medially and the posterior spinal artery posterior laterally. Superiorly it
receives the majority of its blood supply from the vertebral artery laterally, basilar artery branches
anteriorly, and the posterior inferior cerebellar artery posteriorly.

Moving superiorly, the pons is the next brainstem structure encountered. Most of its blood supply
comes from branches of the basilar artery. Superiorly, it is also perfused on its posterior lateral portion
by branches of the superior cerebellar artery and branches of the anterior inferior cerebellar artery.

The next brainstem structure superior to the pons is the midbrain. It is perfused anterior medially by
branches of the basilar artery, anterior laterally by branches of the posterior choroidal arteries and

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quadrigeminal artery originating from the posterior cerebral artery, and posteriorly by the quadrigeminal
and superior cerebellar arteries.

The most superior brainstem structure, the diencephalon, is supplied anteriorly by branches of the
anterior cerebral artery. Its posterior portions receive supply from branches of the posterior cerebral
artery such as thalamogeniculate branches, thalamoperforating branches, and branches of the posterior
communicating artery.

The anatomical lymphatic drainage of the central nervous system was described over 100 years ago, but
until the last decade, the widely held consensus was that CNS lymphatics do not exist. The lymphatics
of the CNS are small channels within the meninges and differ from the basic structure of the peripheral
lymphatics. The CNS lymphatic system is still poorly understood but is thought to participate in
immune cell transport, cerebrospinal fluid drainage, and interstitial fluid drainage. The lymphatics of the
central nervous system continue to be a topic of investigation.

Clinical Anatomy

An understanding of the anatomical location of brainstem structures and their blood supply is critical for
localizing lesions on physical exam. Significant clinical problems can affect the brainstem such as
stroke, malignancy, demyelinating processes, and many more. Important conditions that can affect the
upper brainstem include but are not limited to thalamic pain syndrome from damage to the posterior
lateral thalamus, hemiballismus from damage to the subthalamic nucleus, and changes in appetite,
temperature regulation, blood pressure, growth and many more can suffer disruption by damage to the
hypothalamus. Injury to or degeneration of dopaminergic neurons in substantia nigra results in
Parkinson’s disease. Damage to the lower brainstem can result in many different syndromes that can be
localized using deficits in cranial nerves and the tracts that traverse the brainstem, including but not
limited to:

- Wallenberg stroke (spinothalamic tract, spinal trigeminal tract, hypothalamospinal tract,

vestibular nuclei)

- Cerebellar tonsillar herniation (sudden respiratory and cardiac arrest due to compression of the
medulla)

- Medial pontine syndrome (abducens nerve, corticospinal tract, medial lemniscus)

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- Another brainstem lesion that can occur is central pontine myelinolysis from the rapid correction
of hyponatremia, which can result in seizures, ataxia, and disturbed consciousness.

- Locked-in syndrome or pseudocoma is a rare neurologic condition that occurs when damage to
the brainstem occurs, most commonly caused by ischemic or hemorrhagic stroke resulting in damage to
the corticobulbar, corticopontine, and corticospinal tracts. This syndrome can result in patients with
quadriplegia and dysarthria but who maintain consciousness. They may appear to be in a persistent
vegetative state, but some patients may be able to communicate with eye movements or blinking and are
aware of their surroundings but cannot communicate freely. Patients can live for years with this
syndrome.

CRANIAL NERVES

The entire brainstem is composed of neural tissue. Ten of the twelve cranial nerves also emerge from the
brainstem. The cranial nerves are a set of twelve nerves that originate in the brain. Each has a different
function responsible for sense or movement. They include the olfactory nerve, which is essential for
detecting smells and the optic nerve, which enables a person to see.

The functions of the cranial nerves are sensory, motor, or both. Sensory cranial nerves help a person see,
smell, and hear. Conversely, motor cranial nerves help control muscle movements in the head and neck.

Each nerve has a name that reflects its function and a number according to its location in the brain.
Scientists use Roman numerals from I to XII to label the cranial nerves in the brain.

CRANIAL NERVES ASSOCIATED WITH BRAINSTEM

 Midbrain

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1. The Oculomotor nerve (cranial nerve III) – Arises from the oculomotor sulcus on the medial
portion of the crus cerebri. It is a motor nerve that receives inputs from two nuclei. The first nucleus is
the oculomotor nucleus; it serves as its main motor nucleus and is in the anterior midline of the
periaqueductal grey at the level of the superior colliculus. The second nucleus is the Edinger-Westphal
nucleus, which provides parasympathetic motor inputs. The somatic motor fibers from the oculomotor
nucleus provide innervation to all the extraocular muscles, with the exceptions of the superior oblique
and lateral rectus muscles. The parasympathetic motor fibers of the Edinger-Westphal nucleus provide
innervation to the ciliary muscles and constrictor pupillae after passing through the ciliary ganglion.
2. The Trochlear nerve (cranial nerve IV) – Exits from the posterior surface of the midbrain and
is the only cranial nerve to exit posteriorly. It is a motor nerve with its nucleus located in the midline of
the brainstem, also in the anterior portion of the periaqueductal grey, but inferior to the oculomotor
nucleus. The nerve innervates the superior oblique ocular muscle, which is responsible for moving the
eye downward and laterally. A unique feature of the trochlear nerve among the cranial nerves is that it is
the only cranial nerve decussating peripherally. The nerve decussates at the superior medullary velum
after leaving the brainstem, which causes cranial nerve nuclei deficits to appear as loss of function of the
contralateral superior oblique muscle. Injuries that happen to the nerve distal to the decussation result in
ipsilateral deficits to the superior oblique muscle.

 Pons
3. The Trigeminal Nerve (cranial nerve V) – Arises from the superior anterior lateral pons as the
largest cranial nerve. It contains both motor and sensory fibers. It arises as a smaller motor nerve and a
larger sensory nerve. The sensory fibers provide innervation to the face and head. The motor fibers
provide innervation to the muscles of mastication, mylohyoid, anterior belly of the digastric, tensor
tympani, and tensor veli palatini. The trigeminal motor nucleus situates in the superior posterior lateral
pons. The motor nucleus also receives corticobulbar fibers from both hemispheres as well as fibers from
the reticular formation, medial longitudinal fasciculus, and red nucleus. The nerve has contributions
from three sensory nuclei: The principal sensory nucleus of cranial nerve V, the mesencephalic nucleus,
and the spinal trigeminal nucleus. The principal sensory nucleus of cranial nerve V lies directly lateral to
the trigeminal motor nucleus and receives inputs from nerves that convey touch and pressure. The
mesencephalic nucleus is located on the lateral aspect of the periaqueductal grey, anterior lateral to the
fourth ventricle, and ascends to the height of the inferior colliculus. The mesencephalic nucleus
conveys proprioceptive input from the teeth, hard palate, temporomandibular joint, and muscles of
mastication. The spinal trigeminal nucleus is located in the inferior posterior lateral pons and extends

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inferiorly through the medulla into the superior spinal cord. The spinal trigeminal nucleus receives pain
and temperature input for the sensory distribution of the trigeminal nerve.
4. The Abducens nerve (cranial nerve VI) – Is a motor nerve that emerges anteriorly and
medially from the junction of the pons and medulla. The abducens nucleus is in the midline of the
inferior tegmentum of the pons just ventral to the fourth ventricular floor. It provides innervation to the
lateral rectus muscle, which is responsible for the abduction of the eye.
5. The facial nerve (cranial nerve VII) - Emerges from the junction of the pons and the medulla
lateral to the abducens nerve at the cerebellopontine angle. It is both a motor and a sensory nerve and
emerges as two separate roots; these include a medial motor root and a lateral sensory root. The facial
motor nucleus situates in the anterior lateral inferior pons, just anterior and medial to the spinal
trigeminal nucleus. The muscles of facial expression derive innervation from the motor nucleus of the
facial nerve. The upper face receives corticobulbar fibers that partially decussate from both
hemispheres, which allows sparing of deficits with lesions at the level of the cranial nerve nuclei while
the lower muscles corticobulbar fibers fully decussate. The sensory nucleus is the upper portion of the
solitary nucleus, which is located posterior and lateral to the facial nerve motor nucleus. It receives
afferent fibers for taste from the anterior two-thirds of the tongue and sensation for the skin near the
auricle of the ear. Its parasympathetic nucleus is the superior salivatory nucleus and is located laterally
to the abducens nucleus but posterior to the facial motor nucleus. It innervates the submandibular and
submental salivary glands.
6. The Vestibulocochlear nerve (cranial nerve VIII) – Arises from the brainstem directly lateral
to the sensory root of the facial nerve. Cranial nerve VIII has two distinct portions, the vestibular,
responsible for balance, and the cochlear, which is responsible for hearing. Cranial nerve VIII is purely
a sensory nerve, and both of its portions course together until they reach their nuclei within the
brainstem. The vestibular portion of the nerve provides input to the vestibular nuclei located along the
lateral portion of the fourth ventricle in the inferior pons. The vestibular nuclei are composed of four
different nuclei (superior, inferior, lateral, and medial.) These nuclei send tracts to three separate areas:
the cerebellum via the vestibulocerebellar tract, the spinal cord through the vestibulospinal tract, and the
nuclei of cranial nerves III, IV, and VI by the medial longitudinal fasciculus. The cochlear portion
provides input to the dorsal and ventral cochlear nuclei. These nuclei are in the anterior lateral portion of
the inferior pons. The posterior cochlear nucleus processes high-frequency sounds, while the anterior
cochlear nucleus processes low-frequency sound. The anterior cochlear nucleus projects fibers to the
ipsilateral superior olive and then to the lateral lemniscus. The posterior cochlear nucleus projects to the
contralateral lateral lemniscus.
 Medulla Oblongata

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7. The glossopharyngeal nerve (cranial nerve IX) – Emerges from the postolivary groove and
contains motor fibers, sensory fibers, and parasympathetic nerves. The nerve shares several cranial
nerve nuclei with cranial nerve X (the vagus nerve), the nucleus ambiguus, and the nucleus solitarius.
Cranial nerve IX also uses the inferior salivatory nucleus. The superior portion of the nucleus ambiguus
is located posterior to the inferior olivary nucleus and contains second order motor cell nuclei for the
glossopharyngeal nerve. The motor fibers from the superior nucleus ambiguus innervate the
stylopharyngeus muscle. The cranial nerve IX parasympathetic cranial nerve nucleus is the inferior
salivary nucleus; its postganglionic parasympathetic, visceral efferent fibers provide innervation to the
parotid gland. The inferior salivary nucleus is located posterior to the nucleus ambiguus and receives
afferent input from the hypothalamus, olfactory system, and nucleus solitarius. The last nuclei of the
glossopharyngeal nerve are the nucleus solitarius. It is a sensory nucleus that receives taste from the
posterior one-third of the tongue from the glossopharyngeal nerve. It also receives afferent impulses
from the carotid sinus.
8. The Vagus nerve (cranial nerve X) – Emerges from the postolivary groove and contains motor
fibers, sensory fibers, and parasympathetic fibers. The inferior portion of the nucleus ambiguus provides
motor output to the muscles of the pharynx and larynx. The parasympathetic nucleus of the vagus nerve
is the dorsal motor nucleus. The dorsal motor nucleus is located lateral to the hypoglossal nucleus and
receives afferent fibers from the upper gastrointestinal tract, liver, pancreas, heart, and bronchi. The
sensory nucleus for the vagus nerve is also the nucleus solitarius, similar to the glossopharyngeal nerve.
It receives afferent inputs from the carotid sinus as well.
9. The accessory nerve (cranial nerve XI) – Arises from the medulla between the olive and
inferior cerebellar peduncle and upper cervical spinal cord to C5. It forms from the combination of both
cranial and spinal nerve roots. This nerve supplies both the trapezius and sternocleidomastoid muscles
with motor innervation. Its efferent motor fibers arise from the nucleus ambiguus.
10. The hypoglossal nerve (cranial nerve XII) – Is a motor nerve and arises anteriorly from the
medulla. Its nucleus sits in the midline of the brainstem anterior to the fourth ventricle. The hypoglossal
nerve innervates the muscles of the tongue and the hyoglossus, genioglossus, and styloglossus muscles.
It receives innervation via cortico-nuclear fibers from both hemispheres of the brain. However, the
genioglossus muscle is innervated only by the contralateral side.

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Fig 7 –Image showing Cranial Nerves. (crumbie, 2023)

CRANIAL NERVES EMERGING TO THE CEREBRUM

The first two cranial nerves are not really nerves, but rather outdrawn parts of the central nervous
system. Only the peripheral bipolar nerve cells correspond with an ordinary nerve

11. The olfactory nerve (cranial nerve I): The first neurons are bipolar cells in the neuroepithelium
in the upper part of the nose. Their central processes gather themselves into about 20 olfactory
nerve filaments (for each olfactory nerve) that pass through foramina in the cribriform plate of
the ethmoid bone, piercing the dura and arachnoid mater of the anterior cranial fossa. They enter
the olfactory bulb from where the central processes of the second neuron pass in the olfactory
tract to the region of the anterior perforated substance, from where they proceed laterally to the

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 uncus and medially to parts of the limbic system. The arrangement is unique and ‘primitive’: the
second order neuron directly activates the conscious cortex, bypassing the thalamus. Other
olfactory pathways, by polysynaptic junctions, activate hypothalamic and brainstem nuclei (as is
the case with all sensory pathways) for visceral and somatic effects, distinct from conscious
appreciation.
12. The optic nerve (cranial nerve II): The rods and cones, near the choroidal surface of the retina,
activate the bipolar cells of the retina; these are the first sensory neurons. Their central processes
synapse on the large ganglion cells that lie on the vitreous surface of the retina. The central
processes of these second neurons emerge from the back of the eyeball as the optic nerve
surrounded by CSF and the meninges. The optic nerve enters the middle cranial fossa through
the optic canal and passes to the chiasma, where the nasal fibres from each retina decussate,
above the pituitary gland. From the chiasma the optic tract passes around the midbrain (cerebral
peduncle) to three destinations: (1) the lateral geniculate body (thalamus) for relay to the visual
cortex; (2) the pretectal nuclei for pupil constriction to light; and (3) the superior colliculus for
body reflexes to light. From the lateral geniculate body fibres of the third neurons of the visual
pathway pass through the retrolentiform part of the internal capsule and backwards by the optic
radiation to the visual (striate) cortex on the medial surface of the occipital lobe

Muscles

The brainstem is composed entirely of neural tissue and gets bathed in cerebrospinal fluid. The medulla
oblongata joins the spinal cord at the level of the foramen magnum and is not in close contact with any
muscles. The brainstem contains the cranial nerve nuclei for cranial nerves III-XII; therefore, the
innervation of the muscles controlled by the previously mentioned cranial nerves are dependent on the
brainstem.

CLINICAL ANATOMY OF THE CRANIAL NERVES

Cranial nerve palsy is characterized by a decreased or complete loss of function of one or more cranial
nerves. Cranial nerve palsies can be congenital or acquired. Multiple cranial neuropathies are commonly
caused by tumors, trauma, ischemia, or infections. While diagnosis can usually be made based on
clinical features, further investigation is often warranted to determine the specific cause. Contrast-
enhanced MRI is usually the preferred imaging modality to evaluate the affected nerve and any soft
tissue abnormalities. A CT scan may be indicated to evaluate for bony lesions and fractures that may be
compressing the nerve. Management is mainly aimed at treating the underlying cause. Surgery may be

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indicated for individuals with severe disability (e.g., acute traumatic cranial nerve palsies, persistent
symptoms despite conservative measures). Spontaneous resolution over months may occur, especially in
cranial nerve palsies secondary to microangiopathy.

Table 1: Table Showing Cranial Nerve Dysfunctions and coverage

CN name Main dysfunctions CNS coverage Skull base Face and neck
coverage coverage

I: Olfactory Anosmia Basal forebrain: Anterior skull Nasal mucosa

olfactory tracts, base:
bulbs, and striae. cribriform
Uncus, plate
parahippocampal
and cingular gyri

II: Optic Vision loss Basal forebrain: Anterior skull Orbit: eye ball retina
Prechiasmatic: optic radiation, base: optic
onilateral anopia chiasma, lateral canal
Chiasmatic: geniculate bodies,
bitemporal occipital calcarine
hemianopia sulci
Retrochiasmatic:
homonymous
hemianopia

III: Oculomotor Oculomotor palsy, Midbrain: Middle skull Orbit: oculomotor m.

ptosis, mydriasis interpedoncular base: (superior, medial,
fossa cavernous inferior recti, inferior
sinus, superior oblique), levator
orbital fissure palpebrae m., ciliary m.

IV: Trochlear Trochlear palsy Midbrain: tectum Middle skull Orbit: trochlear m
base:
cavernous
sinus, superior
orbital fissure

V: Trigeminal Facial anesthesia Pons: anterolateral Middle skull Face

Trigeminal base: V1: forebrain
neuralgia cavernous V2: chick
sinus; V1: V3: Jaw, sensory tongue
superior (2/3 ant)
orbital fissure

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CN name Main dysfunctions CNS coverage Skull base Face and neck
coverage coverage

V2: f.
rotundum
V3: f. ovale

VI: Abducens Abducens palsy Medullopontine s. Middle skull Orbit: abducens m.

(ant.) base:
cavernous
sinus, superior
orbital fissure

VII: Facial Facial palsy. Medullopontine s. Posterior skull Face m., lacrimal and
Hemifacial spasm (lat.) base: internal salivary glands
auditory canal,
stylomastoid f.

VIII: Hearing loss, Medullopontine s. Posterior skull Inner ear: cochlea and
Cochleovestibular tinnitus, dizziness (lat.) base: internal semicircular canals
auditory canal

IX: Ageusia, dysphagia, Medulla: Posterior skull Stylopharyngeus m.;

Glossopharyngeal throat anesthesia. retroolivary s. base: jugular sensory tongue (1/3
Glossopharyngeal foramen post)
neuralgia

X: Vagus Dysphagia, Medulla: Posterior skull Pharyngeal m.

dysphonia retroolivary s. base: jugular
foramen

XI: Accessory Impairment of head Medulla: Posterior skull Sternocleidomastoid,

rotation, scapula retroolivary s., base: jugular trapezius m.
elevation lateral cervical cord foramen

XII: Hypoglossal Palsy of the tongue Medulla: preolivary Posterior skull Tongue muscles
s. base:
hypoglossal
canal

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 4

ADVANCES IN NEUROANATOMY

Research in brainstem neuroanatomy has made significant strides in recent years, particularly in
understanding its role in regulating vital functions such as breathing, heart rate, and consciousness.
Techniques like diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI)
have enabled scientists to map neural pathways with unprecedented detail, shedding light on the
intricate connections within the brainstem. Additionally, advancements in molecular biology and
genetics have provided insights into the development and organization of brainstem structures, further
enhancing our understanding of its complex functions and potential implications for neurological
disorders.

Recent advancements in cranial nerve neuroanatomy have been fueled by various imaging modalities,
including high-resolution MRI, diffusion tensor imaging (DTI), and tractography. These techniques

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allow for the visualization and mapping of cranial nerve pathways in unprecedented detail, offering
insights into their anatomical variations, relationships with surrounding structures, and functional
connectivity. Additionally, advances in neuroimaging software and computational methods have
facilitated the creation of comprehensive atlases and databases of cranial nerve anatomy, which serve as
valuable resources for both research and clinical practice. Moreover, emerging studies combining
neuroimaging with molecular and genetic approaches are providing deeper insights into the
development, plasticity, and pathophysiology of cranial nerves, paving the way for improved diagnosis
and treatment of neurological disorders affecting these critical neural pathways.

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