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Brainstem 2 - Midbrain
Brainstem – Part 2: Midbrain
DAVID GRIESEMER, MD
Professor of Neurosciences and Pediatrics
Key Concepts:
1. On the ventral surface of the midbrain are the cerebral peduncles, and in the interpeduncular fossa
are the oculomotor nerves (CN III).
2. The oculomotor nerve (CN III) innervates all extraocular muscles except the lateral rectus and
superior oblique, and it has an autonomic nucleus called the Edinger-Westfal nucleus.
3. The Edinger-Westfal nucleus sends preganglionic parasympathetic fibers to the ciliary ganglion,
from which postganglionic fibers travel to innervate the papillary constrictor muscles and the
ciliary muscles (which alter the shape of the lens).
4. Pupillary fibers travel on the outside of the oculomotor nerve and are therefore more sensitive to
external compression.
5. On the dorsal surface of the midbrain is the quadrigeminal plate, consisting of the superior
colliculi and the inferior colliculi.
6. Neurons from the superior colliculus, which are involved in visual processing, project to the
lateral geniculate and thalamus.
7. Neurons from the inferior colliculus, which coordinate head and eye movement in response to
sound, project to the medial geniculate from which it receives feedback information.
8. The trochlear nerves (CN IV) leave the dorsal surface of the midbrain near the center of the
quadrigeminal plate.
9. The trochlear nerve, which is a pure motor nerve that innervates the superior oblique muscle, is
the smallest cranial nerve and the only one that decussates before leaving the brainstem.
10. Axons traveling between nuclei of CN III, IV and VI travel in the medial longitudinal fasciculus.
11. The pretectal area (rostral to the quadrigeminal plate) is involved in the pupillary light reflex.
12. The dorsal raphe nucleus is a source of serotonergic neurons which project throughout the brain.
13. The substantia nigra sends dopaminergic projections primarily to the dorsal striatum.
14. The red nucleus, which is primarily concerned with coordinating movement of the arms, receives
input from the cerebral cortex and the deep cerebellar nuclei. Its output is to the spinal cord,
cerebellum, reticular formation and inferior olive.
15. The periaqueductal gray nuclei modulate pain, respirations, behavior, and vertical gaze.
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Brainstem 2 - Midbrain
The midbrain contains many important structures and systems that coordinate eye movements, various
reflexes to light, and pathways and function of the basal ganglia.
EXTERNAL VIEW OF THE MIDBRAIN
The ventral surface of the midbrain (mesencephalon) is dominated by two massive, V-shaped columns at
the ventrolateral edges. These are the cerebral peduncles that consist mainly of axons originating in the
cerebral cortex that descend to synapse on brainstem and spinal cord nuclei. As the columns descend to
the level of the pons, they disappear into the prominent brachum pontis, and at the level of the medulla
they re-appear as the pyramids. The
roughly
triangular
depression
between the cerebral peduncles at
the level of the midbrain is called
the interpeduncular fossa. From
this fossa emanates the oculomotor
nerves (CN III). Just above the
oculomotor nerves can be seen the
mammillary bodies, which are
considered part of the diencephalon
rather than the midbrain. Note in
the cross-section view (on the left)
the “disorienting” view of the
midbrain; it appears upside down.
The traditional anatomic sections of
the brainstem are 180 degrees from
the standard radiologic view of the
brain.1
The trochlear nerve (CN IV)
emerges from the dorsal surface
(tectum) of the midbrain, slightly
below the level that the oculomotor nerve emerges on the ventral surface. Rostral to the trochlear nerve is
the quadrigeminal plate, which consists of two larger superior colliculi and two smaller inferior
colliculi. The former are involved in control of eye and head movements, and the latter participate in
ascending pathways that process auditory signals.
Also on the dorsal aspect is the brachium
conjunctivum (superior cerebellar peduncle)¸ which is the most rostral connection of the cerebellum to
the brainstem.
INTERNAL STRUCTURES OF THE MIDBRAIN
A cross section of the midbrain provides an axial view that demonstrates a very distinctive appearance of
the midbrain. The ventrolateral cerebral peduncles are massive, creating bulges almost as large as the
rest of the midbrain. The small cerebral aqueduct is seen as the later development of the central canal.
It is surrounded by periaqueductal gray matter. At the ventral margin of the periaqueductal gray matter
lie the trochlear nuclei (CN IV) in a midline position.
1
CT and MRI studies show the brain as if the patient is lying on his back and the viewer is standing at the foot of
the bed. The right side of the brain therefore appears on the left side of the radiographic image.
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Brainstem 2 - Midbrain
Dorsal to the cerebral aqueduct is the midbrain
tectum which contains the nuclei of the superior
and inferior colliculi (the four together creating the
“quadrigeminal plate”). The superior colliculi are
slightly higher (more rostral) than the CN IV nuclei,
and the inferior colliculi are slightly lower (more
caudal). The drawing on the left, while not showing
CN IV, demonstrates the relationship of the tectum
to the thalamus and lateral geniculate rostrally.
Ventral to the cerebral aqueduct and periaqueductal gray matter are two well-defined, “color coded”
nuclei:
 red nucleus – named for its pinkish appearance at autopsy. These are symmetric, large, round
nuclei located in the midbrain tegmentum. They fill the space between the periaqueductal gray
matter and the substantia nigra. The oculomotor nuclei (CN III) are medial to the red nuclei.

substantia nigra – named for neurons which contain black-colored melanin. These nuclei are
located in the midbrain basis.2 They are broad flat structures which separate the cerebral
peduncles from the rest of the midbrain.
It is beneficial to consider two cross-sectional (axial) views of the midbrain: one at the level of the
inferior colliculus and one at the level of the superior colliculus:

2
Level of the inferior colliculus
o In the tectum
 nucleus of the inferior colliculus – this receives afferents from the lateral
lemniscus, the cerebral (auditory) cortex and the contralateral inferior colliculus.
In addition it receives a feedback loop from the ipsilateral medial geniculate
body to which it sends efferent axons. It also sends efferents to the superior
colliculus to facilitate turning the head and eyes in response to sound.
The cerebral peduncles and the substantia nigra, which are located in the basis of the midbrain, are sometimes
called the basis pedunculi. The cerebral peduncles alone are sometimes called the crus cerebri.
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o
Brainstem 2 - Midbrain

mesencephalic nucleus of V -- this is homologous to a dorsal root ganglion for
the spinal cord, but it is uniquely positioned within the CNS. It is located medial
to the inferior colliculi. It processes proprioceptive signals from the gums and
muscles of mastication.

locus ceruleus – this nucleus was discussed with structures of the pons, but it
extends rostrally to the lower midbrain. It’s noradrenergic projections have a
role in the regulation of arousal, sleep and cognitive functions such as attention.
In the tegmentum

nucleus of the trochlear nerve (CN IV) – these nuclei are midline in location, at
the ventral margin of the periaqueductal gray matter. Axons from the nuclei
course dorsally around the central gray matter and once in the tectum cross to the
opposite side before exiting near the midline at the center of the quadrigeminal
plate. The trochlear nerve innervates the superior oblique muscle, which lowers
the eye when looking medially.

medial longitudinal fasciculus (MLF) – this ascending pathway is located
immediately ventral to the CN IV nuclei.

dorsal raphe nucleus -- this nucleus is located directly in the center of the four
“spots” created by the CN IV nuclei and the MLF, appearing like a 5-spot on one
of two dice. Neurons in this nucleus send serotonergic fibers to the substantia
nigra, the caudate and putamen, and throughout the cerebral cortex.

red nucleus – this nucleus receives fibers from deep nuclei of the cerebellum and
from the motor and pre-motor cortex of the brain. These latter projections are
somatotopically arranged. The corticorubral and rubrospinal tracts are often
considered an “indirect” corticospinal system. The red nucleus participates in
the control of arm movement. It sends efferents to the spinal cord, cerebellum,
reticular formation, and inferior olive.

other nuclei in the tegmentum include the ventral tegmental nucleus (which
deals with emotion and behavior), the dorsal tegmental nucleus (which projects
to brainstem autonomic nuclei), and the parabigeminal nucleus (which sends
cholinergic fibers to the superior colliculus and processes visual information).
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
Brainstem 2 - Midbrain
pathways that track through the tegmentum include:
 brachium conjunctivum (superior cerebellar peduncle) – these axons
originate in the deep nuclei of the cerebellum and project to the midbrain
where they cross to the opposite side in the tegmentum. Some of the
fibers synapse on neurons of the red nucleus and others continue
rostrally to the thalamus (VPL nucleus).

lemniscal pathways – these include the medial lemniscus (which
carries kinesthetic and discriminative touch information), the trigeminal
lemniscus (which carries sensation from the contralateral face), and the
spinothalamic tract (which carries sensation from the contralateral
body). All three originate from levels below the midbrain and are just
“passing through” to the thalamus (VPL nucleus). Lateral to the spinothalamic tract is the lateral lemniscus (which carries auditory fibers).

medial longitudinal fasciculus (MFL) – in addition to other functions,
this pathway provides a conduit of communication between cranial nerve
nuclei at different levels involved in the control of eye movements (CN
III, IV and VI).
central tegmental tract – this carries information from basal ganglia
and midbrain to the inferior olive
rubrospinal tract – located between the red nucleus and the substantia
nigra, this pathway carries fibers from the red nucleus to the spinal cord
and inferior olive


o
In the basis

cerebral peduncles -- corticospinal and corticobulbar fibers occupy a midposition in the cerebral peduncles. Corticopontine fibers that synapse on pontine
nuclei are located in the most ventral and dorsal positions. In a rostral direction
the cerebral peduncles become the internal capsule.

substantia nigra – this large nucleus has two regions: a dorsal region with
melanin-containing dopaminergic neurons (zona compacta) and a ventral region
containing iron pigment (zona reticulata). Pigmented neurons are twice as
numerous as non-pigmented neurons and project dopaminergic fibers to the
striatum of the basal ganglia. Destruction of these neurons leads to Parkinson’s
disease. Non-pigmented neurons from the zona reticulate project GABAergic
fibers to the thalamus, superior colliculus, and reticular formation. They likely
have a role in minimizing epileptic discharges.

Mesencephalic nuclei – there are other dopaminergic neurons at this level in
addition to those of the substantia nigra. They occur in lesser known areas: the
ventral tegmental area of Tsai and a retrorubral group of neurons close to the
red nucleus. Dopaminergic fibers from these cells also project to the striatum
and may have a role in reward processing and cognition.
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
Brainstem 2 - Midbrain
Level of the superior colliculus
o
In the tectum

nucleus of the superior colliculus – this is a laminated nucleus consisting of
alternating layers of gray matter and white matter. It’s highly structured
organization mirrors that of visual fields and represents a map of visual space. In
addition to the retina, it receives projections from the frontal and occipital
cortex, spinal cord, and inferior colliculus – all of which provide input necessary
for coordination of rapid visual pursuit and movement. Efferents from the
superior colliculus travel to:
 lateral geniculate, pulvinar, and lateral posterior nucleus (LPN) of
the thalamus via the tectothalamic tract
 lamina VII and VIII of the cervical spinal cord via the tectospinal tract,
which decussates in the midbrain tegmentum
 ipsilateral cerebellum via the tectopontocerebellar tract
 reticular nuclei in the midbrain via the tectoreticular tract

pretectal nucleus – this area is rostral to the superior colliculus at the junction of
the midbrain with the diencephalon. It is an important relay station in the
pupillary light reflex and vertical gaze. It receives fibers from both retinas and
projects to both oculomotor nuclei (CN III).
o
Periaqueductal gray – neurons in this region stimulate serotonergic neurons in the
medulla, which then project to sensory neurons in the dorsal horn of the spinal cord to
decrease pain. Other functions of this region include:
 control of vertical gaze
 initiation of voiding in response to bladder filling
 initiation of penile erection in response to stimuli from hippocampus, amygdala,
reticular formation, and spinal cord
 modulation of respiratory centers in the medulla
 activation of behaviors relating to fear and escape
 modulation of aggressive behavior
o
In the tegmentum
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3
Brainstem 2 - Midbrain

red nucleus – discussed above

oculomotor nucleus (CN III) -- this nucleus lies dorsal to the MLF. It is
composed of a lateral somatic motor column and a medial visceral column, each
about 1 cm in length. The latter is called the Edinger-Westfal nucleus, or
visceral oculomotor nucleus, and it mediates the light reflex.

The oculomotor nerve exits the brainstem between the superior
cerebellar artery and the posterior cerebral artery. It then runs anteriorly
in the subarachnoid space until it penetrates the dura at the roof of the
cavernous sinus. Here it divides into superior and inferior divisions.
The superior division provides innervation to the levator palpebrae
(which raises the eyelid) and to the superior rectus muscle (which
elevates the eye when looking laterally).

The inferior division innervates the inferior rectus (which lowers the
eye when looking laterally), the medial rectus (which adducts the eye),
and the inferior oblique (which elevates the eye when looking
medially).

Axons from the Edinger-Westfal nucleus course with other fibers until
the orbit where these preganglionic fibers synapse in the ciliary
ganglion. Postganglionic fibers innervate the papillary sphincter3
(which constricts the pupil) and the ciliary muscles (which change the
shape of the lens to permit focus at a closer distance).
Parasympathetic fibers responsible for the papillary light reflex travel on the outside of motor fibers in the
oculomotor nerve. This has two important clinical consequences. First, the pupillary fibers are more sensitive to
external compression. Thus pupillary reflexes are likely to be lost first in cases of tumors or masses compressing
CN III. Second, the oculomotor nerve receives its vascular supply from penetrating arterioles in the center of the
nerve. If disease processes (like diabetes) compromise these vessels, the interior of the nerve is likely to infarct.
The unmyelinated parasympathetic fibers are relatively resistant to ischemia and they are superficially located. This
leads to weakness of muscles of eye movement, with sparing the papillary light reflexes. This is referred to as a
“pupil-sparing third nerve palsy.”
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
Brainstem 2 - Midbrain
accessory oculomotor nuclei
 Interstitial nucleus of Cajal – located rostral to Edinger-Westfal nucleus,
this group of neurons coordinates vertical gaze and eye-head movement.
 Rostral interstitial nucleus of the MLF – located rostral to the
oculomotor nucleus and close to the red nucleus, this groups of “burst”
neurons is involved with upward and downward eye movements
 Other nuclei include the Darkschewitsch nucleus and the nucleus of the
posterior commissure.
BLOOD SUPPLY TO THE MIDBRAIN
The blood supply to the midbrain is complex, compared to that of the pons and medulla. In general, the
midbrain receives its blood supply from the basilar artery via the superior cerebellar artery and
branches from the posterior cerebral and posterior communicating arteries.