Anatomy of the diencephalon

Our central nervous system is made up of the cerebrum, the cerebellum and the brainstem, which
continues inferiorly with the spinal cord. The cerebrum consists of two cerebral hemispheres, which have
an external cerebral cortex made up of nuclei which form the gray matter and deep to that, the white
matter consisting of axons.

Embedded within the white matter, there are the basal ganglia, or basal nuclei. Removing them reveals
a part of the brain hidden between the hemispheres, called the diencephalon. Together, the cerebrum
and diencephalon form the forebrain, or prosencephalon. The diencephalon connects the cerebrum
superiorly with the midbrain of the brainstem inferiorly.

On a mid-sagittal section through the brain, we can see the cavity of the third ventricle and the
diencephalon around it. The two major parts of the diencephalon are the thalamus, which lies more
dorsally, and the hypothalamus, which lies more ventrally.

There are actually two thalami, one on each side, flanking the lateral aspect of the space created by the
third ventricle. Between the left and right thalami there’s a bridge of gray matter that connects them,
called the interthalamic adhesion, or connection. The hypothalamus forms the inferior part of the lateral
wall and the floor of the third ventricle. Between the thalamus and the hypothalamus there’s the
hypothalamic sulcus, which separates them. The diencephalon contains two endocrine glands as well:
the posterior lobe of the pituitary gland, below the hypothalamus, and the pineal gland, near the caudal
end of the thalamus.

Okay, let’s take a closer look at the thalamus first, which is an egg-shaped structure made of gray matter
that contains neuronal cell bodies. The thalamus is connected with almost all parts of the central
nervous system, like the brainstem and the cerebral cortex, enabling it to influence many different
processes in the brain. In fact, the thalamus is a part of almost every sensory pathway, where it serves
as a major relay station that gathers, combines and processes afferent information before forwarding it
to the cerebral cortex.

This way the thalamus can recognize that there is a hot object in our hands, but without the cortex, it
cannot process more detailed information, like the shape and weight of the object or compare it to
previous experiences. The only sensory pathway that doesn’t relay through the thalamus is the olfactory
system, which enables us to smell.

The thalamus plays a role in modulating movement through its connections with the basal ganglia,
cerebellum and frontal lobe. It can also influence motivated behaviors via connections between the
hypothalamus and the frontal lobe. The thalamus can even alter levels of consciousness by
communicating with the reticular formation of the brainstem. Talk about multitasking!

Now, to better understand its relation to adjacent structures, let’s make a transverse section of the brain.
Medial to the thalamus, there’s the lateral wall of the third ventricle. Anterior to the thalamus, there’s the
interventricular foramen, or foramen of Monro, through which the cerebrospinal fluid, or CSF, flows from
the lateral ventricles to the third ventricle. Lateral to the thalamus, there’s the posterior limb of the
internal capsule, while the posterior part of the thalamus, called the pulvinar, is not covered by other
structures and can be seen superior to the posterior aspect of the midbrain.

Now let’s switch to a coronal section of the brain. Here we can see that the dorsal surface of the
thalamus is free, sitting under the lateral ventricle and the fornix, while ventrally there’s the tegmentum of
the midbrain. Like on the transverse plane, the third ventricle lies medially and the internal capsule lies
laterally.

Switching to the sagittal plane, once again, inside the third ventricle, we can see the medial surface of
the thalamus and the interthalamic adhesion arising from it.

Now let’s take out the thalamus and zoom in on its superior surface. The first structure here is the
internal medullary lamina, which is a layer of white matter that looks like the letter Y and divides the
thalamus into three parts: medial, lateral and anterior. The gray matter of each part contains the various
thalamic nuclei.

Some of the most important nuclei of the lateral part are the ventral posterolateral nucleus, the ventral
posteromedial nucleus, and the ventral lateral nucleus. The ventral postero-lateral (VPL) nucleus
receives input from the medial lemniscus and the spinothalamic tract and projects to the primary
somatosensory cortex. In order to easily remember sensations that this nucleus transmits you can
remember that for VPL: V in ventral stands for the vibration; P in posterior for pain, pressure and
proprioception; L in lateral for the light touch; then just add the temperature.

The ventral postero-medial (VPM) nucleus receives input from the trigeminal and gustatory pathways
and projects to the primary somatosensory cortex as well. To remember the sensations that this nucleus
transmits, you can use the mnemonic: Makeup goes on the face. The M in makeup refers to the ventral
postero-medial nucleus while the face refers to somatosensations from the face as well as taste.

The ventral lateral nucleus receives input from the cerebellum and the basal ganglia, and it projects to
the motor and premotor regions of the cerebral cortex. This nucleus relays motor information and can
influence movements.

The last two nuclei are the medial and lateral geniculate bodies. The medial geniculate body is a small
bulge under the posterior end of the pulvinar. It receives input from the inferior colliculus via the inferior
brachium and from the superior olivary complex, and then projects to the auditory cortex of the temporal
lobe. To remember that it is involved in hearing, you can say the M in medial stands for music.

Lateral to the medial geniculate body is another small bulge called the lateral geniculate body. It
receives input from the retina, via the optic nerve, optic chiasm and optic tract, and then projects to the
primary visual cortex of the occipital lobe via the optic radiation. To remember that it transmits visual
information, you can say the L in lateral stands for light.

Let’s take a short break and see if you can identify the main nuclei of the thalamus.

Good, now let’s switch gears and have a closer look at the hypothalamus. Even though it’s small, the
hypothalamus is like a mastermind of the brain as it regulates homeostasis, which is the state of the
body where conditions are optimal for internal processes to function properly. The hypothalamus
achieves this by receiving various inputs, like visceral or somatic afferents, information related to the
special senses, as well as input from the cerebral cortex and the limbic system.

Using neural, blood and CSF connections, the hypothalamus can regulate a number of processes, which
you can remember using the TAN HATS mnemonic: thirst and water intake; endocrine organs and
hormone secretion of the pituitary gland, which consists of the adenohypophysis and neurohypophysis;
hunger and food intake; the autonomic nervous system; temperature; and sexual drive and emotional
expression.

Now, just like the thalamus, the hypothalamus has many nuclei that serve different purposes. Two of
them, namely the lateral and ventromedial nuclei, control appetite. Specifically, the Lateral nucleus
serves as a hunger center, increasing appetite and food intake - to remember that, think about a yummy
portion of lentil soup! The VentroMedial nucleus, on the other hand, serves as a satiety center,
decreasing appetite and food intake, so you can think of a Voluptuous Model to remember it better!

The next two nuclei, called the anterior and posterior nuclei, control the temperature of the body. The
Anterior nucleus serves as a Cooling center and uses the parasympathetic system to decrease body
temperature by producing sweat and dilating blood vessels in the skin. Think about AC! The posterior
nucleus, on the other hand, serves as a heating center that uses the sympathetic system to increase the
temperature by constricting blood vessels in the skin, thereby decreasing sweat production and causing
shivering. Think of a Hot Pot to remember this one!

Then, there is the suprachiasmatic nucleus, which receives input from the retina about the presence or
absence of light and uses the information to regulate many biological circadian rhythms, like the
sleep-wake cycle. Therefore, you can remember the suprachiasmatic nucleus as the Sun-censing
nucleus.

The next two nuclei, namely the supraoptic and paraventricular nuclei, are in charge of hormone
production. The supraoptic nucleus produces vasopressin, also known as the antidiuretic hormone, or
ADH. This hormone causes constriction of blood vessels, increasing peripheral vascular resistance and
it also makes the kidneys reabsorb more water from their tubules into the bloodstream. These two
actions ultimately increase blood pressure.

The paraventricular nucleus, on the other hand, makes oxytocin, which stimulates contractions of the
uterus while in labor, and later stimulates milk secretion while breastfeeding. To remember these nuclei
and their hormones you can use the SAD POX mnemonic, where S stands for supraoptic, AD for ADH,
P for paraventricular and OX for oxytocin.

Lastly, there is the preoptic nucleus, which is involved in thermoregulation and sexual behavior. It also
produces gonadotropin-releasing hormone that stimulates the adenohypophysis to release the follicle
stimulating hormone, or FSH, and the luteinizing hormone, or LH, which are necessary for normal gonad
functioning.

Okay, let’s wrap up the hypothalamus by making a mid-sagittal section through the brain. Remember
that the hypothalamus creates the floor and the inferior part of the lateral walls of the third ventricle.
Superiorly is the thalamus, which is separated from the hypothalamus by the hypothalamic sulcus.
Anteriorly, there’s the optic chiasm. The hypothalamus also has a region called the preoptic area, which
is located rostrally in the hypothalamus near the lamina terminalis, with the optic chiasm inferiorly and
the anterior commissure superiorly. Most inferiorly, there’s the tuber cinereum, which contains a small
bump called the median eminence that connects with the stalk of the posterior lobe of the pituitary gland.
Posteriorly, the hypothalamus includes the mammillary bodies and spreads to the border of the
interpeduncular fossa of the midbrain, with the floor of this fossa known as the posterior perforated
substance.

The mammillary bodies are two rounded structures that are a part of the limbic system. They contain
mammillary nuclei that receive input from the hippocampus via the fornix. The mammillary nuclei then
project to the anterior nuclei of the thalamus via the mammillothalamic tracts. There is also a connection
between the mammillary bodies and the midbrain tegmentum via the mammillary peduncles.

On the ventral aspect of the brain, the mammillary bodies can be seen anterior to the posterior
perforated substance, between the cerebral peduncles and posterior to the tuber cinereum. Functionally,
the mammillary bodies are believed to play a role in learning and memory.

Let’s take another short break and see if you can identify the main nuclei of the hypothalamus.
Ok now, let’s take a closer look at the pituitary gland, also known as the hypophysis, which is actually
made up of two parts: the neurohypophysis and the adenohypophysis. The neurohypophysis is the
posterior part of the gland, which develops from the ventral side of the hypothalamus. It contains axons
of the supraoptic and paraventricular nuclei, which carry ADH and oxytocin to the neurohypophysis to be
stored. When needed, the neurohypophysis releases these hormones directly into the bloodstream via
its fenestrated capillaries.

The anterior part is called the adenohypophysis and develops from Rathke’s pouch, which is an
ectodermal diverticulum from the roof of the primitive oral cavity. Unlike the neurohypophysis, the
adenohypophysis is connected to the hypothalamus through a system of blood vessels called the
hypophyseal portal system.

This system starts with the superior hypophyseal artery located on both sides of the gland, which is a
branch of the internal carotid artery. It enters the median eminence and forms the first capillary plexus.
Blood from the first plexus is gathered into hypophyseal portal veins that enter the adenohypophysis and
form the second capillary plexus. Then the blood drains into the hypophyseal veins and joins the
systemic circulation.

The adenohypophysis makes hormones itself, but their release into the bloodstream is controlled by the
hypothalamus. The neurons of the hypothalamic nuclei produce releasing hormones and
release-inhibiting hormones, pack them into granules and transport them via their axons to the median
eminence where they release them into the first capillary plexus. These hormones reach the second
capillary plexus and instruct the adenohypophysis to increase or decrease hormone release.

The main hormones of the adenohypophysis are: growth hormone, or GH, that stimulates cell growth;
thyrotropic or thyroid-stimulating hormone, TSH for short, that stimulate the thyroid gland;
adrenocorticotropic hormone, or ACTH, that stimulates the adrenal glands; follicle stimulating hormone,
or FSH, and luteinizing hormone, or LH, that stimulate the gonads; and the luteotropic hormone, or LTH,
also known as the prolactin, that stimulates milk production and secretion.

On a midsagittal section of the brain, the pituitary gland sits in the middle of the sphenoid bone, in a
depression called the sella turcica. Superiorly, there’s the median eminence of the hypothalamus. Now,
the posterior lobe of the pituitary gland has a stalk, called the infundibulum, that connects to the median
eminence. These three structures form the neurohypophysis. Anterior to the pituitary gland there’s the
optic chiasm, while posterior to it, there are the mammillary bodies. The pituitary gland is closely related
to the cavernous sinuses, which almost enclose the pituitary gland on each side.

Since this is the only visible part of the diencephalon, if we switch to the ventral side of the brain, we can
see the infundibulum sitting between the optic chiasm, anteriorly, and the mammillary bodies, posteriorly.

Lastly, let’s cover the second endocrine gland of the diencephalon, which is the pineal gland, named so
because of its pine cone shape. The main function of the pineal gland is regulation of the sleep-wake
cycle by production of melatonin, a hormone that helps us fall asleep. It receives information from the
retina about the presence or absence of light, which allows it to know if it is day or night. Once it gets
darker, the pineal gland starts releasing melatonin into the bloodstream and the CSF of the third
ventricle, which prepares us for sleep. It is also believed that the pineal gland can influence the hormone
secretion of other endocrine glands, like the pituitary, parathyroid, endocrine pancreas, adrenal glands
and gonads.

On a midsagittal section through the brain, the pineal gland has a central, midline position. It sits just
caudal to the thalamus and is attached to it by a hollow stalk filled with CSF from the third ventricle. The
pineal gland protrudes posteriorly, lying superior to the superior colliculi. It is also a part of the central
nervous system that doesn’t have the blood-brain barrier.
Alright, as a quick recap... The diencephalon is a part of the forebrain that sits between the cerebral
hemispheres, connecting the cerebrum with the midbrain. It contains the thalamus, dorsally, and the
hypothalamus, ventrally. These form the lateral walls and floor of the third ventricle.

The thalamus serves as a relay station for almost all sensory pathways and afferent signals that are
targeting the cerebral cortex. Major nuclei of the thalamus are: ventral postero-lateral (VPL), which
relays information from the spinothalamic tract and medial lemniscus; ventral postero-medial (VPM),
which relays information from trigeminal and gustatory pathways; lateral geniculate body, which relays
visual system information; medial geniculate body, which relays auditory information; and the ventral
lateral nucleus, which relays information from motor systems.

The hypothalamus regulates homeostasis and controls hormone production of the pituitary gland. It has
several nuclei: lateral and ventromedial nuclei that regulate appetite; anterior and posterior nuclei that
regulate body temperature; suprachiasmatic nucleus that regulates circadian rhythms; supraoptic and
paraventricular nuclei that produce ADH and oxytocin; and the preoptic nucleus that is related to
thermoregulation and sexual behavior.

The pituitary gland contains the neurohypophysis, which is a part of the diencephalon and secretes ADH
and oxytocin, and the adenohypophysis that develops from Rathke’s pouch. It secretes hormones that
influence other endocrine glands in the body. The pineal gland secretes melatonin and regulates the
sleep-wake cycle.

Anatomy of the cerebral cortex

Now, we know what you are thinking. Don’t worry, here at Osmosis we are not telepathic, but by
watching this video on the cerebral cortex, we know you have the brain on your mind, so let’s get to it!

The human central nervous system basically consists of the spinal cord and the brain, which includes
the cerebrum, diencephalon, cerebellum, and brainstem.

Taking a closer look at the cerebrum, it consists of two nearly symmetrical halves, called the cerebral
hemispheres, and the basal ganglia, also referred to as basal nuclei. Furthermore, each cerebral
hemisphere is divided into four main lobes, the frontal, parietal, temporal, and occipital, as well as what
has become to be known as the fifth lobe, the insula, or insular cortex.

If we were to cut through the cerebral hemispheres in the coronal plane, which means transecting from
left to right and dividing the brain into rostral and caudal divisions, we would see the cerebral cortex.
This is the outermost area of the cerebral hemispheres, and is composed of gray matter containing
billions of nuclei, or neuronal cell bodies.

A cell body and its dendrites, along with its axon and synaptic terminal, collectively make-up a structure
called a neuron. Neurons thus allow for information processing and communication with other neurons
within the nervous system. The gray matter gets its name from its dark appearance during gross
inspection.

Deep to the gray matter is the subcortical white matter, which is made up of myelinated axons
connected to the nuclei of the gray matter. White matter gets its name because the myelination of the
axons gives this area a white appearance on gross inspection.

The largest white matter tract is the corpus callosum, which sends signals between the two cerebral
hemispheres essentially connecting them together.
Found throughout the subcortical white matter are further collections of gray matter masses containing
neuronal cell bodies referred to as the basal ganglia, also called the basal nuclei.

The basal ganglia consist of the caudate and putamen, the globus pallidus, the subthalamic nucleus and
the substantia nigra. Note that the term striatum refers to the caudate and putamen; the term lentiform
nuclei, or lenticular nuclei, refers to the putamen and globus pallidus; and the term corpus striatum refers
to all three structures, the caudate, putamen and the globus pallidus. All of the structures of the basal
ganglia have their own unique functions and pathways.

Running in between these basal ganglia are more white matter afferent and efferent axon tracts, the
most notable being the internal capsule. The internal capsule is a collection of densely packed white
matter, or axons, which divides the corpus striatum and acts like a highway for information flow between
the cerebral cortex and the brainstem and spinal cord.

Generally, the right cerebral hemisphere sends and receives signals from the left side of the body, while
the left hemisphere sends and receives signals from the right side of the body.

Now taking a step back and looking at the external surface of the brain, we can see that the cerebral
cortex is not flat, but covered with many folds called gyri, which are separated by shallow grooves called
sulci, or by deeper grooves or clefts called fissures.

One function of these gyri and sulci is to allow the nearly two and a half square feet of the cerebral
cortex to fold in on itself, allowing it to fit within the small space of the neurocranium, just like the folds of
an accordion when it is closed!

A second advantage of this cortical folding is that it effectively increases the surface area, allowing more
nuclei to be packed into the cortex. This greater number of nuclei allows for more signaling and therefore
more advanced processing and higher cortical function.

The deep fissures also help to separate the brain into lobes. Even though the brain looks like it has a
random configuration of ridges and clefts, the gyri, sulci, and fissures actually create a relatively constant
pattern from person to person. This pattern can be used to identify certain external landmarks of the
brain, which have very specific functions.

We not only can define the cerebral cortex by lobes or functionality, which we will talk about soon, but
the cerebral cortex can also be divided into histologically similar regions called Brodmann’s areas.

This means that the neurons within a particular Brodmann’s area are all arranged in the same manner
and partake in a similar function. Approximately 180 Brodmann’s areas have been identified in the
human brain through MRI and other mechanisms! We will mention Brodmann's areas for some of the
primary areas of cortex shortly.

So, let’s take a closer look at the different sulci and deep fissures that separate the brain into the five
lobes; the frontal lobe, parietal lobe, temporal lobe, occipital lobe, and insula. When seen from above,
the cerebrum has a deep midline sagittal fissure called the longitudinal fissure, which divides the brain
into left and right cerebral hemispheres. Deep within this fissure is the already mentioned corpus
callosum.

Still looking from above, around the middle of the longitudinal fissure and moving laterally, is the coronal
central sulcus, also known as the fissure of Rolando, which separates the frontal lobe rostrally, or
anteriorly, from the parietal lobe caudally, or posteriorly. The rostral most point of the frontal lobe is called
the frontal pole.
The central sulcus can also be seen on a lateral view of the brain travelling inferiorly across the lateral
aspect of the hemispheres. From this lateral view, beneath the frontal and parietal lobes is the lateral
fissure, also known as the lateral sulcus or Sylvian fissure.

The lateral fissure is found mainly on the lateral and inferior surface of the cerebral hemispheres, and
separates the frontal and parietal lobes above from the temporal lobe below.

The lateral fissure extends in three directions, rostrally as the anterior ramus, superiorly as the
ascending ramus, and caudally as the posterior ramus. The most rostral point of the temporal lobe is
called the temporal pole.

Furthermore, the area of cortex called the insula, or insular cortex, lies at the bottom of the lateral
fissure, hidden from the external surface of the brain, so we need to open up the folds of the lateral
fissure or dissect them in order to see it. The insula has the central sulcus of the insula running through
it, forming both short gyri rostral to the sulcus, and long gyri caudal to the sulcus.

Looking at the brain from a posterior view, around the posterior middle portion of the cerebral
hemisphere, there is a fissure called the parieto-occipital fissure, which travels inferiorly and anteriorly.

The parieto-occipital fissure separates the parietal lobe rostrally, from the occipital lobe caudally, and
from a medial view of the hemisphere the parieto-occipital sulcus is joined halfway by the calcarine
sulcus. The most caudal point of the occipital lobe is called the occipital pole.

Now that we have outlined the general boundaries of each lobe, let's look at the components of each
lobe in more detail, starting with the frontal lobe. On the lateral aspect, rostral to the central sulcus is the
precentral sulcus that runs parallel to it. Together, the central sulcus and the precentral sulcus form the
borders of the precentral gyrus.

From the rostral side of the precentral sulcus arise two more horizontal sulci, the superior frontal sulcus
and the inferior frontal sulcus, which extend toward the frontal pole. These divide the rest of the frontal
lobe into three gyri, and going from medial to lateral these are the superior, middle and inferior frontal
gyri.

The inferior frontal gyrus is divided into three parts by the branching rami of the lateral fissure. First,
inferior to the anterior ramus is the orbital part, or pars orbitalis. Then between the anterior ramus and
the ascending ramus is the triangular part, or pars triangularis. Finally, posteriorly between the
ascending ramus and the precentral sulcus is the opercular part, or pars opercularis.

If we cut a sagittal section, meaning cutting the brain in half along the longitudinal fissure, and look at the
frontal lobe from a medial view, we can also see another sulcus called the cingulate sulcus; as well as
the anterior paracentral lobule, which forms the medial aspect of the precentral gyrus; and the posterior
paracentral lobule, which forms the medial aspect of the postcentral gyrus, which we will mention later.

By understanding the different anatomical landmarks of the lobes, we can start to identify the different
functionally specialized regions of the cerebral cortex. For example, the regions of our cortex that are
responsible for controlling motor or sensory functions that assist with our everyday lives.

When considering the functional areas of the frontal lobe, it contains the primary motor cortex,
Brodmann’s area 4, that occupies the area of the precentral gyrus and extends over to the medial aspect
of the hemisphere as the anterior paracentral lobule. The primary motor cortex houses neurons
responsible for carrying out voluntary movements of different parts of our body, mainly to the
contralateral, or opposite, side.
Extending anteriorly from the primary motor cortex, and over the posterior parts of the superior, medial
and inferior frontal gyri is the premotor cortex, or Brodmann’s area 6. This premotor cortex receives input
from other parts of the cerebral cortex, the thalamus, the basal ganglia, and directly communicates with
the primary motor cortex.

Its function is to assist the primary motor cortex plan and carry out voluntary movements and therefore it
is called an association cortex. The premotor cortex essentially stores and processes information about
past activity, and helps to integrate sensory and motor information for planning of future voluntary
movements.

Rostral to the premotor cortex and extending into the middle frontal gyrus is the frontal eye field,
Brodmann’s area 8, which controls voluntary eye movement, and allows us to move our eyes together in
the same direction at the same time, known as conjugate gaze.

The next area we are going to look at is Broca’s area and Brodmann’s area 44/45, which is formed by
two regions of the inferior frontal gyrus, namely the pars opercularis and the pars triangularis.

Broca’s area is usually located in the dominant hemisphere, which in most individuals is the left
hemisphere. This area has connections to the nearby motor cortex, specifically to the areas that control
the muscles of the larynx, mouth, soft palate, and the tongue, as well as respiratory muscles, to assist in
the formation, or production, of words and speech.

And lastly, we have the prefrontal cortex, which is located anterior to the premotor cortex and overlies
the anterior portions of the superior, middle, and inferior frontal gyri.

The prefrontal cortex has rich connections to other parts of the brain, and is responsible for mainly what
has been coined as executive functions, which include reasoning, planning, social behavior, judgement,
and much more.

Let’s take our attention back specifically to the primary motor cortex, which again is responsible for
controlling voluntary movements of our body. The nuclei of neurons that will control a certain region of
the body are organized together, so that all the nuclei that will control the muscles of the face are
organized in one specific region of cortex, while all of the nuclei associated with controlling the foot are
organized in another.

This unique and elegant arrangement of body parts in the cortex is called somatotopy. This can be
visually represented by drawing the body part above the cortical area that controls it, so it looks like this,
where each body part is noted on top of its corresponding cortical area.

Now, the proportion of the primary motor cortex, or the number of neurons dedicated to a particular
movement depends upon how much that muscle, or group of muscles, is actually used! So, the more a
muscle is used, the more nuclei will be dedicated to it within the cortex.

The number of nuclei is independent upon the size or mass of the muscle performing that movement,
but it is based on how important that muscle is to your everyday life and functioning!

So, when we quantify the proportions of neurons in the primary motor cortex utilized by the muscles in
each individual body part, we get a strange looking humanoid figure that is called the motor homunculus,
which in latin means ‘little human’.

As you can see, this primary motor cortex map creates an awkwardly large representation of the hands,
fingers and face. This means that more cortex, and hence more neurons, are dedicated to those
regions, since we use them more often in our daily lives to explore our world.
Going back to our primary motor cortex map, we can see that the location of the body parts is essentially
inverted, anatomically, on the primary motor cortex.

Starting at the superior medial part of the primary motor cortex in the anterior paracentral lobule, the
toes are represented first, and then as one moves laterally through the primary motor cortex, the more
superior parts of the body are progressively represented, with the more lateral and inferior part of the
primary motor cortex representing the most superior parts of the body, such as the head and neck.

Okay, let’s move on to the parietal lobe. On the lateral view, just caudal to the central sulcus running
parallel to it is the postcentral sulcus. Together, the central sulcus and the postcentral sulcus form the
borders of the postcentral gyrus. Running caudally from the middle of the postcentral sulcus, or near it,
is the intraparietal sulcus, which divides the rest of the parietal lobe into the superior parietal lobule
above it, and the inferior parietal lobule below it.

Remember the posterior ramus of the lateral fissure? Well, there is a part of the inferior parietal lobule
that folds over the end of the posterior ramus and is called the supramarginal gyrus, and behind it is the
angular gyrus that folds over the end of the superior temporal sulcus found in the temporal lobe.

This takes us to the functional regions of the parietal lobe. Similar to the primary motor cortex, there is
also a primary somatosensory cortex, Brodmann’s area 3,1,2, which is located in the postcentral gyrus
and extends medially to the posterior paracentral lobule.

The primary somatosensory cortex receives sensory input from the opposite side of the body through
the ventral posteromedial, or VPM, and ventral posterolateral, or VPL, nuclei of the thalamus, enabling
us to process and interpret sensory information from our body like touch or pain.

And similar to the motor homunculus, we have a sensory homunculus to visually represent the
proportion of sensory fibers that the primary somatosensory cortex receives from a particular part of the
body. The more sensitive a body part is, the more neurons it requires for processing sensory stimuli, and
therefore it occupies a larger area of the somatosensory cortex.

And again, similar to the primary motor cortex, starting from the deeper, more medial aspect of the
primary somatosensory cortex in the posterior paracentral lobule, the first body part represented here is
the anogenital area, followed by the foot, leg, and thigh.

As we cross over to the lateral side and move inferiorly along the postcentral gyrus, the thigh is followed
by the trunk, upper limb, the head and neck, and then, the intra abdominal organs.

Then, located over the superior parietal lobule is the somatosensory association cortex, which has many
connections with other sensory regions of the cerebral cortex.

The somatosensory association cortex is believed to allow the ability to integrate different sensory
modalities, such as being able to recognize objects through touch without visual input, like reading
braille, by comparing and associating the sensations to past sensory experiences.

That was a lot of brain to take in for the brain! Let's take a moment to pause and see if you can identify
some of the different regions of the brain.

Now, can you label these functional areas of the brain?

Now, let's continue our journey and examine the temporal lobe, which lies inferior to the lateral fissure
and extends posteriorly to the occipital lobe. The lateral surface of the temporal lobe includes the
superior temporal sulcus and the middle temporal sulcus, which divide the temporal lobe into the
superior, middle, and inferior temporal gyri.
Deep inside the lateral fissure, there is also the transverse temporal gyri of Heschl, which is found on the
deep upper surface of the superior temporal gyrus.

Now let’s look at the functional regions of the temporal lobe. Located in the transverse temporal gyri of
Heschl is the primary auditory cortex, Brodmann’s area 41/42, which receives auditory input from the
medial geniculate body of the thalamus and interprets auditory information, or sound, such as when the
next door neighbours are being way too loud.

Then, on the dominant hemisphere, which again is most often the left, we have Wernicke’s area,
Brodmann’s area 22/39/40, which encompasses a part of the superior temporal gyrus along with the
supramarginal and angular gyri of the parietal lobe.

Wernicke’s area is responsible for the processing and understanding of both written and spoken
language, allowing us to read a sentence, understand it, and say it out loud comprehensively. It is also
connected to Broca’s area by a bundle of axons called the arcuate fasciculus, which allows us to tie
together speech comprehension from Wernicke’s area, and speech production from Broca’s area.

A second important function of the temporal lobe, and specifically the medial aspect of the temporal
lobe, is that it houses limbic system structures related to learning, memory and emotion, which we will
get to later.

We also spoke previously about the insula, known as the fifth lobe of the brain, which is found deep in
the lateral fissure. The insula is usually divided into anterior and posterior aspects. Functions are diverse
and complex with convergence of inputs from temporal, parietal, and frontal lobes. The insula has been
associated with processing viscero-autonomic sensations, limbic and emotional elements,
somatosensation, and possibly motor elements too.

Moving on, let's get to the final lobe on our journey, the occipital lobe, which lies caudal to the
parietal-occipital sulcus. The occipital lobe contains the cuneus, a wedge-shaped area bounded by the
parieto-occipital fissure rostrally, and by the calcarine sulcus inferiorly. Inferior to the cuneus and the
calcarine sulcus is the lingual gyrus.

When considering the functionality of the occipital lobe, this area of cortex is dedicated to vision and
hence a substantial part is occupied by the primary visual cortex, Brodmann’s area 17.

The primary visual cortex is located on the medial aspect of the hemispheres, and lines both the
superior and inferior banks of the calcarine sulcus. It also extends around the occipital pole onto the
lateral surface of each hemisphere. This area receives, processes, and interprets visual input from the
lateral geniculate body of the thalamus.

Finally, on the medial side of each hemisphere, there is a region of cortex surrounding the corpus
callosum that is a part of the limbic system. This region contains the subcallosal gyrus, located below the
rostral part of the corpus callosum; as well as the cingulate gyrus, which begins beneath the rostral end
of the corpus callosum and continues superiorly and caudally until it reaches the posterior end of the
corpus callosum.

The parahippocampal gyrus, which is part of the medial temporal lobe, lies rostral to the lingual gyrus of
the occipital lobe and ends rostrally as the uncus, also a component of the limbic system.

These cortical structures, along with the olfactory cortex, the amygdala, the hypothalamus, and the
hippocampus, constitute the major structures of the limbic system. They are responsible for functions
related to the “preservation of the species”, such as fight or flight responses, emotion, memory, and
reproductive, endocrine, and other behavioral responses.
All right, as a quick recap… The cerebrum consists of two cerebral hemispheres, where the cerebral
cortex is the outermost layer and consists of gray matter, which contains neuronal cell bodies, or nuclei.

Located beneath the gray matter is the subcortical white matter, which is composed of myelinated
axons. Found within the subcortical white matter are further gray matter masses, such as the basal
ganglia or basal nuclei.

The external surface of the cerebral cortex is formed by gyri, sulci, and fissures. The longitudinal fissure
separates the two cerebral hemispheres, which are connected via the corpus callosum.

The central sulcus, parieto-occipital fissure, and the lateral fissure divide each cerebral hemisphere into
four main lobes: frontal, parietal, occipital, and temporal lobes.

The cerebral cortex can also be divided into histologically similar regions called Brodmann’s areas,
which provides a map of the primary cortices and functional regions.

The main anatomical regions of the frontal lobe are: the precentral sulcus, precentral gyrus, and the
superior and inferior frontal sulci, which delineate the superior, middle, and inferior frontal gyri.

The frontal lobe has five functional regions: primary motor cortex, premotor cortex, the frontal eye field,
Broca’s area, and the prefrontal cortex.

The motor homunculus is a visual representation of the areas of primary motor cortex dedicated to the
voluntary motor control of body parts.

The parietal lobe contains the postcentral sulcus and intraparietal sulcus that border the postcentral
gyrus, superior parietal lobule, and inferior parietal lobule.

Its functional regions are the primary somatosensory cortex, the somatosensory association cortex, and
the supramarginal and angular gyri that both contribute to Wernicke’s area.

The sensory homunculus is a visual representation of the proportion of sensory axons the primary
somatosensory cortex allocates to a particular part of the body.

The temporal lobe contains the transverse temporal gyrus of Heschl, which includes the primary auditory
cortex and the superior temporal gyrus that contributes to a part of Wernicke’s area. Structures in the
medial temporal lobe are important to learning, memory, and emotion.

The occipital lobe contains the cuneus and lingual gyrus separated by the calcarine sulcus, and these
areas comprise the primary visual cortex.

Deep within the lateral fissure is the insula, or fifth lobe, and finally, around the corpus callosum, we
have a strip of cortex, the subcallosal gyrus, and cingulate gyrus, that are both part of the limbic system.

Anatomy of the limbic system

The limbic system consists of several parts within the telencephalon, also known as the cerebrum; the
diencephalon, which includes the thalamus and hypothalamus; and the midbrain.

The term “limbic” means “border” in latin, so this system’s name originated from its location at the border
between the telencephalon and diencephalon.
One way to remember the limbic system is to think of the word HOME; Homeostasis, Olfaction, Memory,
Emotion.

This is because limbic system structures are involved in olfaction, or smell, in the regulation of emotions,
like anger and fear, and other behaviors, like aggression and sexual behaviour.

Memory formation and the recollection of those memories are supported by the limbic system, and It can
even influence responses of the autonomic nervous system, like cardiovascular or gastrointestinal
functions.

To easily recall some of the functions, you can remember the famous 5 F’s, which are: Feeding, Fleeing,
Fighting, Feeling and...Fornicating, the last one being, really, just a fancy word for Sex.

Structures that are included in the limbic system include the: hypothalamus, olfactory cortex,
hippocampal formation, amygdala, subcallosal area, cingulate gyrus, parahippocampal gyrus,
mammillary bodies and the basal forebrain.

Let’s take a closer look at each of them, starting with the hippocampal formation, which is crucial for
converting short-term memory into long-term memory, shipping those memories into other cortical
regions for long-term storage and assisting in retrieval of memories when needed.

It is also involved in spatial orientation, which is the ability to identify the position of our body relative to
the objects around us.

The hippocampal formation consists of the hippocampus, the dentate gyrus, subiculum and entorhinal
cortex.

Now, on a mid-sagittal section of the brain, the hippocampal formation is hidden within the medial
temporal lobe.

It lies posterior to the amygdala and spreads caudally all the way to the splenium of the corpus callosum.

On a transverse section of the temporal lobe, we can see the hippocampal formation forming the floor of
the inferior horn of the lateral ventricle. But, the best plane for the visualisation of this structure is
actually the coronal plane.

Here, we can see the hippocampal formation located within the medial temporal lobe and swooping
beneath the inferior horn of the lateral ventricle.

The most inferior part of the hippocampal formation is the subiculum, and it is continuous caudally with
the parahippocampal gyrus.

The hippocampus, meaning seahorse in latin, is so named as its contours resemble the shape of a
seahorse. The dentate gyrus is contained within the hippocampus, just superior to the subiculum.

The hippocampus is involved in long-term memory formation and helps decide what should be stored
within the cerebral cortex as a memory.

It has connections with the olfactory cortex, hence why smells can elicit memories very easily, and also
connections with the amygdala to remember emotionally significant events!

The next three structures that belong to the limbic system are the subcallosal area, the cingulate gyrus
and the parahippocampal gyrus. These structures influence emotional reactions and support learning
and memory formation.
On a mid-sagittal section of the brain, we can see the subcallosal area on the medial side of the frontal
lobe, just anterior to the lamina terminalis and inferior to the rostrum of the corpus callosum.

Anteriorly, it is continuous with the cingulate gyrus, which arches over the genu, body and splenium of
the corpus callosum.

Superior to the cingulate gyrus there is the cingulate sulcus that separates it from the rest of the cerebral
cortex.

On a coronal section of the brain, we can see the corpus callosum connecting the hemispheres and the
cingulate gyrus just superior to it, at the bottom of the longitudinal fissure.

On the ventral and medial aspect of the temporal lobe, spreading anteriorly from the splenium of the
corpus callosum, we see the parahippocampal gyrus, which is separated from the rest of the temporal
lobe by the collateral sulcus.

The anterior portion of the parahippocampal gyrus curves medially and posteriorly, like a hook, and is
called the uncus.

And now let’s look at the mammillary bodies, which are a pair of round nuclei, belonging to the
hypothalamus, that can be seen on the ventral surface of the brain.

They are located posterior to the tuber cinereum of the hypothalamus, anterior to the midbrain and
between the cerebral peduncles.

Similarly, in the mid-sagittal plane of the brain, they can be seen posterior to the tuber cinereum and
anterior to the tegmentum of the midbrain. In the coronal plane, we can see the mammillary bodies
inferior to the third ventricle.

Now, all of the hypothalamic nuclei are part of the limbic system, as “homeostasis” is one of their major
functions, but the mammillary bodies are especially important as they play a role in learning and memory
and are connected to the hippocampus.

These structures assist in episodic memory, which is the ability to recall specific situations, or episodes,
from our lives, like the place and time of our first kiss and the emotional reaction associated with it.

Great! Now let’s take a closer look at the amygdala, which means “almond” in latin. The amygdala
contains numerous nuclei and is connected with various parts of the nervous system, but the important
connections with other limbic system structures include the hypothalamus, olfactory cortex, hippocampal
formation, frontal lobe and the sensory association cortices.

Because of this, the amygdala is involved in emotional responses, especially fear, rage and aggression,
modulation of memory and influences attention and decision making.

Interestingly, the connections between the amygdala and the hypothalamus can elicit various
physiological responses to emotional experiences!

On a mid-sagittal section of the brain, the amygdala is located in the medial temporal lobe, just deep to
the uncus.

On a rostral coronal plane, we can also see the amygdala in the medial temporal lobe, deep to the
uncus with the tail of the caudate just superior to it.
Remember that the hippocampus and parahippocampal gyrus would be found more caudally in relation
to the amygdala.

Let’s take a short break and see if you can recall the role of the hippocampal formation!

Ok, now that we saw the primary structures that make up the limbic system, let’s go through just a few
more structures that are connected to and work together with it.

First, there’s the orbitofrontal cortex of the frontal lobe, which is involved in planning and decision
making in relation to emotion and reward.

It’s connected with the dorsomedial nucleus of the thalamus, which gathers information from other
cortical and limbic system structures like the hypothalamus and amygdala.

It relays this information to the orbitofrontal cortex to aid in decision making; reward learning; affective
behaviour; emotional reactions; subjective feeling states and personality.

Another part of the thalamus that is connected to the limbic system includes the anterior nuclei of the
thalamus.

They receive input from the mammillary bodies and project to the cingulate gyrus, supporting the
pathway for long-term memory storage.

Two more groups of structures that are connected to the limbic system and the basal ganglia include:
the basal forebrain nuclei and limbic nuclei in the brainstem.

The basal forebrain nuclei include the basal nucleus of Meynert, the nucleus accumbens and the septal
nuclei.

On a coronal section of the brain, the basal nucleus of Meynert can be seen just below the basal
ganglia. It contains neurons that release acetylcholine as their neurotransmitter.

The nucleus accumbens can be seen within the basal ganglia, next to the septal area. It contains
neurons that release GABA as their neurotransmitter.

The septal nuclei are believed to be a pleasure area of the brain involved in reward and reinforcement.

These nuclei are part of the basal forebrain and are connected to other limbic system structures such as
the amygdala, the olfactory cortex, the hippocampus and the hypothalamus.

In the mid-sagittal plane, we see them located inferior to the rostrum of the corpus callosum, superior to
the lamina terminalis and around the anterior commissure.

Moving on to the limbic nuclei in the brainstem, these nuclei include the ventral tegmental area, the
raphe nuclei and the locus ceruleus.

The ventral tegmental area is located in the ventral midbrain, medial to the substantia nigra, and its
neurons are dopaminergic.

The raphe nuclei can be found throughout the brainstem as part of the reticular formation and their
neurons produce serotonin.

The locus ceruleus is located in the pons and contains norepinephrine-producing neurons. All of these
act as diffuse modulators within the nervous system.
Let’s take another short break and see if you can recall the parts of the limbic system!

Lastly, let’s cover a few of the axon tracts that connect the parts of the limbic system and allow for
overall communication and function!

Although connections are rich and varied, a few of the major tracts include: the fornix, the
mammillothalamic tract, and the stria terminalis.

The fornix is made up of fibers that run from the hippocampus to the mammillary bodies, and it has
several parts. First, there are the fimbria, which are fibers that arise from the hippocampus.

They gather and leave the hippocampus posteriorly as the crus of the fornix. The left and right crura of
the fornix curve posteriorly and then superiorly, passing posterior to the thalamus and inferior to the
splenium of the corpus callosum.

They come together to form the body of the fornix, which lies beneath the corpus callosum and superior
in relation to the third ventricle.

Before they merge into the body, the crura are connected by a membrane called the commissure of the
fornix, or the hippocampal commissure. It contains fibers that connect the left and right hippocampi.

The body of the fornix then curves anteriorly and inferiorly with the septum pellucidum located superior
to it.

The septum pellucidum is a membrane between the lateral ventricles and on a medial view we see it
extending between the fornix and the corpus callosum. Near the anterior commissure, the body of the
fornix splits into two columns of the fornix.

These pass over the interventricular foramina, and pass through the hypothalamus, before reaching the
mammillary bodies where it will terminate.

The second major bundle of axons is the mammillothalamic tract, that connects the mammillary bodies
with the anterior nuclei of the thalamus.

The last pathway is the stria terminalis, which connects the amygdala with the basal forebrain and the
hypothalamus.

The fibers of the stria terminalis originate in the amygdala and pass along the medial side of the tail of
the caudate nucleus, following it through the floor of the body of the lateral ventricle, before reaching the
hypothalamus.

Alright, as a quick recap… The limbic system consists of several parts of the telencephalon,
diencephalon and midbrain that together influence emotions, behaviour and learning and memory.

The hippocampal formation consists of the hippocampus, dentate gyrus, subiculum and entorhinal
cortex, and it’s involved in long term memory formation and spatial orientation.

These structures, along with the mammillary bodies help to support the consolidation and storage of
memories.

Then, there is the subcallosal area, the cingulate gyrus and the parahippocampal gyrus, which support
emotional responses and learning and memory.
The amygdala regulates emotions like fear and aggression and can elicit physiological responses to
emotion via its connections with the hypothalamus.

Then, there are areas that are functionally connected to the limbic system, and these include: the
orbitofrontal cortex, and the dorsomedial nuclei and anterior nuclei of the thalamus.

The basal forebrain include the basal nucleus of Meynert, the nucleus accumbens and the septal nuclei.

And finally, the limbic midbrain area that includes the ventral tegmental area, which produces dopamine,
the raphe nuclei, which produce serotonin, and the locus ceruleus, which produces norepinephrine.

The major pathways that connect the structures of the limbic system include the fornix, the
mammillothalamic tract and the stria terminalis.

Anatomy of the ventricular system

An adult human brain weighs about 1.5 kgs, but we don’t really feel it weighing us down!

That’s because the brain is cushioned by cerebrospinal fluid or CSF, which can be found within brain
cavities called ventricles.

These cavities are involved in the production, transport and removal of CSF, and they are connected to
each other. So, as a whole they are often referred to as the ventricular system of the brain.

CSF doesn’t only fill the ventricles, but also the subarachnoid space, which surrounds the brain and
spinal cord. This way, CSF cushions and protects the brain from head trauma, and it also provides
buoyancy so that the brain doesn’t compress blood vessels and cranial nerve roots against the cranium.
It also provides protection against sudden intracranial pressure changes.

CSF can also transport nutrients for nervous tissue,

as well as remove metabolic waste products.

It can also transport hormones, and

influence the brain's excitability by regulating its ionic composition. .

Now, the ventricular system consists of four ventricles: two lateral ventricles, the third ventricle and the
fourth ventricle.

CSF flows from the lateral ventricles through the left and right interventricular foramina, also called the
foramina of Monro, to the third ventricle.

From here, it passes through the cerebral aqueduct to reach the fourth ventricle. CSF can then flow
caudally into the central canal of the spinal cord.

The fourth ventricle also has two lateral apertures, called the foramina of Luschka,

and a median aperture, called the foramen of Magendie, both of which allow CSF to reach the
subarachnoid space.
The lateral ventricles are the largest. They occupy both cerebral hemispheres, and they’re present all
four lobes, This is best seen on coronal sections of the brain,

cutting through the frontal lobe,

the parietal lobe, and temporal lobes,

and finally the occipital lobe.

On a mid-sagittal section of the brain, you can see the third ventricle centrally. Rostrally and superiorly,
there is a depression that narrows into the interventricular foramen, which connects the third ventricle to
the two lateral ventricles. Inferiorly, the third ventricle continues into the cerebral aqueduct, which is a
narrow canal that passes through the midbrain and reaches the fourth ventricle, which is a pyramid-like
cavity sitting dorsal to the brainstem and ventral to the cerebellum. Caudally, the fourth ventricle
continues to the central canal of the spinal cord and just inferior to the cerebellum, there is the foramen
of Magendie. Laterally, at the level of the cerebellum, there are two foramina of Luschka. These
foramina allow CSF to leave the fourth ventricle and enter the subarachnoid space.

The subarachnoid space has CSF-filled dilations called subarachnoid cisterns. Some of these cisterns
contain proximal parts of cranial nerves and blood vessels. On a mid-sagittal section of the brain, we can
identify the main subarachnoid cisterns.

Between the cerebellum and the medulla, there is the posterior cerebellomedullary cistern, also known
as cisterna magna. It receives CSF from the foramen of Magendie, and can even be accessed for
obtaining a CSF sample in some rare cases.

On both sides of the cisterna magna, there are two lateral cerebellomedullary cisterns that can’t be seen
in this section. They receive CSF from the foramina of Luschka and contain cranial nerves seven and
eight.

Then, ventral to the pons, there is the pontocerebellar, or pontine cistern, which contains the basilar
artery and continues inferiorly into the spinal subarachnoid space.

Next is the, or basal cistern, which sits between the cerebral peduncles of the midbrain.

Rostrally, there is the chiasmatic cistern, or the cistern of the optic chiasma, which lies below the optic
chiasm.

And lastly, the quadrigeminal cistern sits inferior to the caudal part of the corpus callosum and superior
to the cerebellum. It is also referred to as the cistern of the great cerebral vein, since it contains the great
cerebral vein of Galen. No surprises here!

Next let’s go over the choroid plexus. Now, CSF is produced by the epithelial cells of the choroid plexus
contained in all four ventricles. The choroid plexus is a cauliflower-like structure that consists of many
fringes and folds of vascular pia mater that protrude into the ventricles. And surrounding the pia mater,
there are cuboidal epithelial cells. These are actually modified ependymal cells, similar to those that line
the inner surface of the ventricles.

The choroid plexus can be found protruding from the floor of the lateral ventricles

and the roof of the third and fourth ventricles.

As CSF flows from the ventricles to the subarachnoid space, it continues superiorly to reach the superior
sagittal sinus, which is a channel between two layers of dura mater that holds venous blood. The
arachnoid mater forms small protrusions, called arachnoid villi, that penetrate the dura and enter the
sinus. The subarachnoid space extends into these villi, which are therefore filled with CSF. The CSF
then passes through the thin lining of the villi and drains into the venous system to be recycled.

Interestingly, the villi tend to group together and form arachnoid granulations.

You can even see the impressions of these granulations, called the granular foveolae, on the inferior
surface of the calvaria.

Okay, now let’s look at each ventricle in a bit more detail. First up, the lateral ventricles! Each of them is
shaped like the letter C, and they each have a body, or a central part, and three horns, the anterior horn,
posterior horn and inferior horn, also called the frontal, occipital and temporal horns, respectively.

To begin, there’s the body of the lateral ventricle,

and can be found deep within the parietal lobe.

The body of the lateral ventricle has a distinct roof, a floor and a medial wall. On a coronal section of the
brain, you can see that the roof is formed by the inferior surface of the corpus callosum.

The floor, on the other hand, from medial to lateral, is formed by the fornix, choroid plexus, lateral part of
the dorsal side of the thalamus and the caudate nucleus.

Medially, the septum pellucidum extends from the corpus callosum to the fornix, separating the left and
right lateral ventricles.

On more caudal coronal sections, the septum pellucidum slowly disappears as the corpus callosum and
fornix come closer together.

Rostrally, the body connects to the interventricular foramina, which can be seen on a transverse section
of the brain.

Each interventricular foramen is bounded by the anterior column of the fornix, rostrally, and the anterior
aspect of the thalamus caudally.

As we follow the body of the lateral ventricle caudally we see that it stretches along the medial aspect of
the body of the caudate nucleus and eventually becomes continuous with the posterior and inferior
horns.

On a mid-sagittal section of the brain, we can easily identify the corpus callosum and the septum
pellucidum extending from it to the fornix. Caudally, the septum pellucidum becomes smaller, as the roof
and the floor of the lateral ventricles come closer together.

If we look at a three quarter view of the brain,

And remove the cerebrum

We can see how the body of the lateral ventricle curves around the thalamus,

And caudate nucleus,

and the corpus callosum is located superior to it.

Rostrally, the body is continuous with the anterior horn.

Now, the anterior horn continues from the body at the interventricular foramen,

and extends into the frontal lobe.

On a coronal section, we can see that the anterior horn has a roof, a floor and a medial wall. The roof is
also formed by the corpus callosum, while the floor is formed by the head of the caudate nucleus. The
medial wall is formed by the septum pellucidum and the anterior columns of the fornix.

Again, if we look at a three quarter view of the brain, and remove the cerebrum. We can appreciate the
relationship between the lateral ventricle and the basal ganglia.

Here we can see how the anterior horn is above the head of the caudate nucleus and below the corpus
callosum.

As the rostral part of the corpus callosum curves inferiorly and caudally, it also forms the rostral border of
the anterior horn, and even a small portion of its floor.

On a transverse section at the level of the interventricular foramina, we can follow the anterior horn from
the foramen along the medial side of the head of the caudate nucleus.

The posterior horn continues from the body at the posterior end of the thalamus,

and extends into the occipital lobe.

The posterior horn has a roof, or a lateral wall, and a floor, or a medial wall.

On a coronal section, you can see the roof is formed by the fibers spreading laterally from the corpus
callosum, called the tapetum.

Lateral to the tapetum, there are fibers of the optic radiation. The floor has a superior and an inferior
bump. The superior bump, also known as the bulb of the posterior horn, is formed by the fibers of the
corpus callosum, called the forceps major, spreading posteriorly.

The inferior bump, also known as the calcar avis, is formed by the underlying calcarine sulcus.

On a transverse section, the optic radiation borders the posterior horn laterally. And on a mid-sagittal
section, if we ghost the ventricles, we can see how the calcarine sulcus reaches the posterior horn.

Finally, the inferior horn continues from the body inferiorly and then rostrally, extending into the temporal
lobe.

This horn also has a roof and a floor, both of which are visible on a coronal section. The roof is formed
by the tapetum spreading laterally from the corpus callosum. On the medial and superior aspect, there’s
the tail of the caudate nucleus.

The lateral part of the floor is formed by the collateral eminence, which is an elevation caused by the
collateral sulcus underneath it.

The medial part of the floor is formed by the hippocampus. The ventricular surface of the hippocampus
is lined by the alveus, which is formed by the fibers of the neurons inside the hippocampal cortex. Fibers
of the alveus group together to form the fimbria, which are positioned medial to the hippocampus.

On a transverse section, the hippocampus extends along the medial part of the floor of the inferior horn.
Rostrally, it expands and becomes a bit wrinkly, forming the pes of the hippocampus.
Looking at a three quarter view, we can see that the inferior horn is bordered rostrally by the amygdaloid
nucleus. Also, the tail of the caudate nucleus on the roof extends all the way to the amygdala as well.

Ok, time for a quick break! Can you remember the names of the three horns of the lateral ventricles?

Great! Now let’s look at the third ventricle, which is a very narrow cavity in the middle of the
diencephalon.

On a mid-sagittal section, the superior part of the lateral wall is formed by the thalamus, while the inferior
part is formed by the hypothalamus. The third ventricle is bordered rostrally by the anterior commissure
and the lamina terminalis. On the anterior and superior part of the lateral wall, there’s the interventricular
foramen, while in the middle, there’s the interthalamic adhesion, which is a bridge of tissue connecting
the two thalami.

The third ventricle also has small extensions that form recesses near adjacent structures. These include
the optic recess, between the lamina terminalis and the optic chiasm; the infundibular recess, towards
the pituitary gland; the pineal recess, towards the pineal gland; and the suprapineal recess, above the
epithalamus.

On a coronal section you can see that the roof is formed by choroid plexus, the floor is formed by the
hypothalamus, and laterally there are the thalami.

On a transverse section, the third ventricle looks like a slit, or cavity, between the thalami, that continues
into the lateral ventricles at the level of the interventricular foramen.

Now, on a mid-sagittal section, the third ventricle connects inferiorly and caudally with the cerebral
aqueduct, or the aqueduct of Sylvius. The cerebral aqueduct stretches through the dorsal part of the
midbrain, inferiorly towards the fourth ventricle. This is the narrowest passage of the ventricular system
that the CSF flows through, and it doesn’t usually have choroid plexus.

On a coronal section we can see it as a central opening, or canal, extending down the brainstem.

On a transverse section of the midbrain, the cerebral aqueduct is positioned in the middle, between the
tectum posteriorly and the tegmentum anteriorly. Surrounding it is the periaqueductal gray matter.

Lastly, let’s cover the fourth ventricle. It has a dorsal wall, or a roof. On a mid-sagittal section, the fourth
ventricle looks like a tent. Its roof has a central part, called the apex or the fastigium, that extends toward
the cerebellum. From the apex, the superior medullary velum extends superiorly. This is a thin layer of
white matter between the superior cerebellar peduncles. There’s also an inferior medullary velum, that
extends from the apex inferiorly. This structure holds the choroid plexus of the fourth ventricle, and it
also contains the foramen of Magendie in the midline, where most of the CSF leaves the fourth ventricle
into the subarachnoid space.

The ventral wall, or floor of the fourth ventricle, on the other hand, is formed by the dorsal sides of the
pons and the medulla. In the midline, the median sulcus can be seen, extending from the cerebral
aqueduct rostrally to the central canal of the spinal cord caudally.

To better visualize the floor of the fourth ventricle we should expose the dorsal surface of the brainstem.
The floor is diamond, or rhomboid, shaped, so it’s called the rhomboid fossa. The dorsal aspect of the
pons, which is triangular shaped, creates the rostral half of the floor

Laterally there are the superior cerebellar peduncles. Running vertically, down the midline, is the median
sulcus and just parallel to it, on each side, the sulcus limitans. Between the median sulcus and sulcus
limitans, there are two elevations called the medial eminences, whose caudal parts enlarge to form the
facial colliculi. The facial colliculi are two bumps, which are made up of axons from the facial nuclei that
wrap around the abducens nuclei. Caudal to the superior cerebellar peduncles we see the middle
cerebellar peduncles.

Now, on the dorsal aspect of the medulla oblongata, we can see that the rostral medulla creates the
dorsal half of the floor of the fourth ventricle.

Laterally, there are the inferior cerebellar peduncles, which contain fibers that travel between the
medulla and the cerebellum. The ventricle, or fossa, tapers at its caudal aspect to a point called the
obex,

and near this caudal limit is the entrance to the central canal of the spinal cord. In this region, CSF can
travel from the fourth ventricle into the central canal.

Lastly, let’s look at the area postrema, which can be found on the dorsal surface of the medulla on the
floor of the fourth ventricle, just before the entrance to the central canal. It holds the chemoreceptor
trigger zone, or CTZ, that can initiate the vomiting reflex by sending input to the vomiting center in the
medulla.

The CTZ doesn’t have a well developed blood-brain barrier which means that it can be exposed to
chemical substances found in the blood and CSF. These substances include toxins, hormones, alcohol,
and drugs such as chemotherapy drugs. The substances can in turn directly activate and initiate the
vomiting reflex.

It also receives input from visceral afferent fibers coming from the GI tract via the vagus nerve. For
example, chemotherapy drugs can stimulate receptors on vagal afferent nerve fibers in the bowel wall of
the gastrointestinal tract, which ascend and trigger the vomiting reflex in the CTZ. Additionally, it also
receives input from the vestibular system, which can explain car or sea sickness.

Alright, as a quick recap… The ventricular system produces CSF via the choroid plexuses, and
transports it to the subarachnoid space.

The lateral ventricles have a body in the parietal lobe and three horns, the anterior, posterior and inferior
horns, that extend into the frontal, occipital and temporal lobes, respectively.

The CSF flows from the lateral ventricles through the interventricular foramina of Monro to the third
ventricle that is located in the middle of the diencephalon. The CSF then flows through the cerebral
aqueduct of Sylvius of the midbrain into the fourth ventricle found between the brainstem and the
cerebellum. The CSF then enters the central canal of the spinal cord, or the subarachnoid space through
the median foramen of Magendie and two lateral foramina of Luschka.

From the subarachnoid space, the CSF gets recycled into the venous system via the arachnoid villi and
granulations.

Anatomy of the cranial meninges and dural

venous sinuses
The brain and spinal cord are covered by the meninges, which are three layers or membranes of
connective tissue that not only protect the brain and spinal cord, but also form a framework for vessels
and venous sinuses.
Just think of this as the brain needing three layers of blankets when going to bed at night to make sure it
is extra cozy and secure! These three layers, from superficial to deep, are the dura mater, arachnoid
mater, and pia mater.

The dura mater is a tough, thick, fibrous external meningeal layer. Deep to the dura mater is the
arachnoid mater. The dura and arachnoid mater are separated from each other by a potential space
called the subdural space.

Deep to the arachnoid mater is the pia mater. The pia mater is a delicate vascular layer that is intimately
adhered to the brain, covering the gyri and extending along the different sulci and fissures.

Together, the arachnoid and pia mater are collectively known as the leptomeninges. Between the
arachnoid mater and the pia mater is the subarachnoid space, also known as the leptomeningeal space,
which is a true space between the arachnoid and pia mater which contains cerebrospinal fluid or CSF for
short, as well as major vessels and cranial nerves.

Okay, let's dive in and take a closer look at the dura mater, which is the thickest, outermost meningeal
layer. The dura mater itself is further divided into two layers. The first, more superficial layer is called the
endosteal layer, or periosteal layer of the dura mater. It is located on the interior surface of the skull
bones and ends at the foramen magnum.

The endosteal layer does not continue with the dura mater of the spinal cord, but instead becomes
continuous with the periosteum on the external aspect of the skull bones. Between the endosteal layer of
the dura mater and the skull bones, there lies a potential space called the extradural, or epidural space,
which is not a natural space, but may become a pathological space during bleeding.

The second, deeper layer of the dura mater is the inner meningeal layer, which is continuous with the
dura mater of the spinal cord and ends at the level of the S2 vertebra. For the most part, these two dural
layers are fused together and cannot be separated, but there are two main exceptions to this.

One, there are locations where spaces are created between the layers to house the dural venous
sinuses. Secondly, the inner meningeal layer of the dura mater reflects away from the endosteal layer at
certain regions to create dural infoldings, or reflections, which divide the cranial cavity into
compartments.

These dural infoldings, or reflections, consist of the falx cerebri, falx cerebelli, tentorium cerebelli, and
diaphragma sellae. The largest dural infolding is the falx cerebri, which lies in the longitudinal fissure and
separates the two cerebral hemispheres from each other.

It attaches anteriorly to the frontal crest of the frontal bone and the crista galli of the ethmoid bone. It
contains the superior sagittal sinus in its fixed superior margin and attaches posteriorly to the internal
occipital protuberance, where it also blends with the upper surface of the tentorium cerebelli.

Speaking of the tentorium cerebelli, this crescent shaped reflection is the second largest dural infolding,
with a fixed margin posterolaterally and a free margin more anteriorly. The fixed margin is attached at
three sites; bilaterally at the posterior clinoid processes, to the superior parts of the petrous portion of the
temporal bone, and to the grooves of the transverse sinus on the inner surface of the occipital bone.

In contrast, the anterior part of the tentorium cerebelli is connected to the clinoid process of the sphenoid
bone at its most rostral end. Otherwise, its margins are free, forming a U-shaped space.
This space between the free margins of the tentorium cerebelli is called the tentorial notch, and it allows
for passage of the brainstem. The tentorium cerebelli spans a transverse plane over the cerebellum,
which forms a roof over the posterior cranial fossa.

This effectively separates the cerebellum from the cerebrum, and divides the cranial vault into an
infratentorial compartment below the tentorium cerebelli and a supratentorial compartment above. As
you can see, the falx cerebri blends with the tentorium cerebelli posteriorly, helping to maintain its
position.

Now, inferior to the tentorium cerebelli, we will find the falx cerebelli. This small dural infolding attaches
to the internal occipital crest and contains the occipital sinus in its fixed posterior margin. It extends in
the sagittal plane and partially separates the cerebellum into two cerebellar hemispheres.

The diaphragma sellae is the last and smallest dural infolding. It is a flat layer between the clinoid
processes that forms an incomplete roof over the hypophyseal fossa of the sella turcica, which is a part
of the sphenoid bone and contains the pituitary gland. The diaphragma sellae has a circular opening in
the middle, which allows the passage of the pituitary stalk, or infundibulum, to connect the hypothalamus
above to the pituitary gland below.

Now, as we said before, the two layers of the dura mater, for the most part, are strictly fused together.
However, there are areas between the endosteal and meningeal layers that form spaces to
accommodate the dural venous sinuses.

These dural venous sinuses contain venous blood from the cerebral veins and also cerebrospinal fluid
from the subarachnoid space. The cerebrospinal fluid enters the sinuses through structures called
arachnoid granulations, which protrude through the meningeal dura mater into the dural venous sinuses.
The contents of the dural venous sinuses ultimately drain into the internal jugular vein.

The dural venous sinuses can be either paired or unpaired. Paired sinuses include the transverse sinus,
cavernous sinus, superior petrosal sinus, inferior petrosal sinus, sphenoparietal sinus, and sigmoid
sinus.

On the other hand, unpaired sinuses include the superior sagittal sinus, inferior sagittal sinus, straight
sinus, occipital sinus, and intercavernous sinus.

The superior sagittal sinus is the largest dural venous sinus and, throughout its course, it receives
venous blood from the superior cerebral veins. As the name suggests, it runs in the sagittal plane, along
the border of the falx cerebri. The superior sagittal sinus extends from the foramen cecum of the frontal
bone, rostrally, to the internal occipital protuberance, caudally, where it drains into the confluence of
sinuses.

Keep in mind that the confluence of sinuses is also the point where the straight and occipital sinuses
merge with the superior sagittal sinus. It then deviates to one side, usually the right, to connect with the
transverse sinus.

The left transverse sinus and right transverse sinus begin at the internal occipital protuberance, from the
confluence of sinuses, and pass laterally to run in the lateral border of the tentorium cerebelli.

While doing so, these sinuses create impressions in the occipital and parietal bones. The transverse
sinuses also receive blood from the superior petrosal sinuses. The two transverse sinuses eventually
continue as the right and left sigmoid sinuses on each side.
The right and left sigmoid sinuses follow an S shaped course in the posterior cranial fossa. During their
course, they turn anteriorly and continue inferiorly as the internal jugular veins, which travel through the
jugular foramen.

Deeper to the superior sagittal sinus lies the smaller, unpaired inferior sagittal sinus, which runs along
the inferior free border of the falx cerebri. Similar to the superior sagittal, it has a rostral to caudal extent.
During its course, it receives venous blood from small veins draining the medial surface of the cerebral
hemispheres and ultimately drains into the straight sinus.

The straight sinus is formed by the merger of the inferior sagittal sinus and the great cerebral vein. The
straight sinus runs posteroinferiorly along the attachment between the falx cerebri and tentorium
cerebelli to eventually meet the superior sagittal and occipital sinuses at the confluence of sinuses.

Speaking of the occipital sinus, this sinus is located on the interior aspect of the occipital bone, along the
caudal attached border of the falx cerebelli. It ends posterosuperiorly at the confluence of sinuses.

Up next, we have the cavernous sinuses, which are located within the middle cranial fossa on either side
of the sella turcica of the sphenoid bone. The cavernous sinus extends from the superior orbital fissure
to the apex of the petrous part of the temporal bone. The left and right cavernous sinuses are connected
to each other via intercavernous sinuses, which are quite variable, but usually consist of anterior and
posterior parts.

The cavernous sinuses then diverge into the superior petrosal sinus and inferior petrosal sinus. The
superior petrosal sinus drains into the transverse sinus at the site where it continues as the sigmoid
sinus, and the inferior petrosal sinus drains into the sigmoid sinus at its transition to becoming the
internal jugular vein.

Off note, there are bridging vessels called emissary veins that connect the dural venous within the
cranium to veins outside of the cranium. One example is the parietal emissary vein, which runs through
the parietal foramen and connects the superior sagittal sinus with veins in the scalp.

Okay, that was a lot! Let’s take a short break and see if you can recall these dural venous sinuses.

Of all the sinuses that we have talked about, the cavernous sinus is the most clinically relevant because
there are several important structures related to it. Again, the cavernous sinus lies on both sides of the
sella turcica of the sphenoid bone.

The pituitary gland lies in between the sinuses, along the midline, within the hypophyseal fossa. Looking
at a coronal section, the cavernous sinus contains numerous fibrous trabeculae that result in the sinus
having a spongy “cave-like” appearance.

The cavernous sinus has a medial and lateral border, a floor, and a roof. The medial border of the
cavernous sinus is formed by the sphenoid bone, and the lateral border is formed by the meningeal layer
of the dura mater.

The roof of the cavernous sinus is the diaphragma sellae, which is also the meningeal layer of the dura
mater, and lastly, the floor is formed by the endosteal layer of the dura mater overlying the sphenoid
bone.

There are several key anatomical structures that travel either through the cavernous sinus or very close
to it. The structures passing through the cavernous sinus are the internal carotid artery and the
postganglionic sympathetic fibers of the carotid plexus that run with it, as well as the abducens nerve, or
cranial nerve six.
In contrast to running through the cavernous sinus, the oculomotor nerve or cranial nerve three, the
trochlear nerve or cranial nerve four, and the ophthalmic or V1 and maxillary or V2 branches of the
trigeminal nerve, or cranial nerve five, travel along the lateral wall of the sinus.

Now, the dura mater is highly vascularized with its own intricate arterial circulation. The major artery that
supplies the dura is the middle meningeal artery, which is a branch of the maxillary artery. It passes
through the skull in the foramen spinosum and enters the middle cranial fossa.

From here, the middle meningeal artery runs laterally and then superiorly on the greater wing of the
sphenoid bone, where it divides into the frontal or anterior branch, and the parietal or posterior branch.

The parietal branch runs posteriorly and superiorly to supply the posterior part of the dura and cranium.
On the other hand, the frontal branch heads superiorly to the pterion, and eventually runs posteriorly to
give off several branches that distribute throughout the dura up to the vertex of the skull.

The dura mater also has an extensive nerve supply, which directly or indirectly comes from the
trigeminal nerve, or cranial nerve five. The dura overlying the anterior cranial fossa is innervated by
branches of all three divisions of the trigeminal nerve. The dura overlying the middle cranial fossa is
innervated mainly by branches of the mandibular nerve or V3, with some innervation from the maxillary
nerve or V2.

Furthermore, the supratentorial dura covering the posterior cranial fossa is innervated by branches of
the ophthalmic nerve or V1. The infratentorial dura is innervated by branches of the cervical plexus
arising from C2 and C3, as well as the vagus nerve, or cranial nerve ten. Pain signals from the dura
travel along the sensory fibers of these nerves and can be referred to the cutaneous areas that are also
supplied by the same nerve fibers.

For example, irritation of the dura from an infection in the anterior cranial fossa can be referred to any of
the cutaneous areas that are also supplied by those same branches of the trigeminal nerve, such as the
skin around the orbit or face.

Okay, let’s move on to the two layers that form the leptomeninges; the arachnoid mater and the pia
mater. The arachnoid mater is situated between the dura and pia mater, creating two spaces.

The first is the subdural space, which is a potential space between the dura and arachnoid mater. The
second is the subarachnoid space between the arachnoid and pia mater, which is filled with CSF, as well
as cerebral arteries, veins, and cranial nerves.

The arachnoid mater forms protrusions called arachnoid granulations, which pierce the dura mater to
enter the dural venous sinuses. These protrusions allow the CSF to flow from the subarachnoid space
into the dural venous sinuses, and from there, into the venous circulation.

The largest granulations are present along the length of the superior sagittal sinus, located just below
the calvaria. These granulations may erode the inner surface of the skull, creating small pits known as
the granular foveolae.

The arachnoid mater is also loosely connected to the pia mater through thin strands of fibrous tissue
known as arachnoid trabeculae. These strands create a meshwork that looks similar to a spider web,
hence the name “arachnoid” for these structures. Where the various cranial nerves exit the skull, the
arachnoid mater fuses with their outside layer called the epineurium.
Finally, we have the pia mater, which is the deepest meningeal layer, and we don't mean the most
profound! This is the most delicate and the thinnest meningeal layer, and it tightly adheres to the entire
surface of the brain.

The cranial pia mater is the only meningeal layer that closely follows the contours of the brain. The pia
mater dives into all of the sulci and fissures, blending for a short time with the sheaths of arteries as they
enter the brain, and fuses with the epineurium of the cranial nerves within the subarachnoid space.

In this video, we have focused on the cranial meninges. However, please note that there are slight
differences between the cranial meninges and the meninges surrounding the spinal cord.

Basically, the dura mater of the cranial meninges is double layered with both endosteal and meningeal
layers, while the spinal meninges only have a single meningeal layer. Also, the epidural space, in
relation to the cranial meninges, is a potential space, while the epidural space, superior to the dura of
the spinal cord, is a real space.

All right, as a quick recap, there are three meningeal layers that consist of membranous connective
tissue that covers the brain and the spinal cord. The outermost and toughest layer is the dura mater,
which has two layers: the outer endosteal and the inner meningeal layer.

The endosteal layer is an extension of the periosteal layer of the interior skull bones, whereas the
deeper meningeal layer creates projections that form dural infoldings or reflections. The arachnoid mater
is found deep to the dura mater, and between them is the subdural space.

The arachnoid mater contains arachnoid granulations, which pierce the dura mater to enter into the dural
venous sinuses. The deepest meningeal layer is the pia mater, which closely adheres to the contours of
the brain.

The arachnoid mater is loosely connected to the pia mater through the arachnoid trabeculae. Between
these two layers is the subarachnoid space, which contains CSF, cerebral vessels, and cranial nerves.

The main dural infoldings are the falx cerebri, the tentorium cerebelli, the falx cerebelli, and the
diaphragma sellae. These two dura mater layers are normally attached to each other, however there are
areas where pockets occur between them forming the dural venous sinuses that drain cerebral venous
blood and cerebrospinal fluid.

The dura has extensive sensory innervation from different branches of the trigeminal nerve, as well as
the vagus nerve and branches from cervical nerves C2 and C3.

Anatomy of the basal ganglia

Generally speaking, our central nervous system is made up of three parts; the cerebrum, the
cerebellum, and the brainstem. The cerebrum consists of two nearly symmetrical halves called the
cerebral hemispheres, and deep within these hemispheres lie the basal ganglia.

On a coronal or axial section of the brain, the outermost area represents the cerebral cortex, which is
made up of gray matter that consists of billions of neuronal cell bodies. The axons that are connected to
these cell bodies create the white matter of the brain, which is the innermost area.
One prominent white matter fiber bundle is the internal capsule, which is like a highway that allows
signals, and thus information, to flow to and from the cerebral cortex. On both sides of the internal
capsule, we can see areas of subcortical gray matter that form the basal ganglia.

The basal ganglia are very important for providing a feedback mechanism to motor cortices for initiation
and control of voluntary movements. So, for example, you want to write your name on a piece of paper.

First, you plan the movements using your prefrontal cortex, and that sends a signal to the motor cortex
as well as the basal ganglia. The basal ganglia now help the motor cortex prepare for, and initiate the
action. The result is that you position your arm so that you can start writing.

Then, the basal ganglia ensure that your hand movements are as precise and executed as planned, and
while doing so, they also maintain your posture. In addition to this, the basal ganglia can help you learn
new procedural motor skills, like riding a bicycle.

The basal ganglia are a collection of nuclei that include the caudate nucleus, the putamen, the globus
pallidus externus and the globus pallidus internus. These nuclei have highly complex connections with
other parts of the central nervous system, like the cerebral cortex, the thalamus and the brainstem. But
the two most important structures that are closely related to the basal ganglia are the substantia nigra of
the midbrain and the subthalamic nuclei of the diencephalon.

Now, let’s look at each of these structures in detail. First up is the caudate nucleus, which is shaped like
the letter C. The caudate nucleus can be divided into three parts: the head, the body and the tail. It
follows the lateral ventricle of the brain, which is medial to it, and curves around the thalamus. Laterally,
the caudate nucleus is bounded by the internal capsule.

On a transverse section of the brain, the head can be seen forming the lateral wall of the anterior horn of
the lateral ventricle. On a coronal section, the body of the caudate can be seen along the wall of the
body of the lateral ventricle. The tail of the caudate curves around the posterior end of the thalamus and
follows the inferior horn of the lateral ventricle, forming its roof.

The putamen and the globus pallidus externus and internus are sometimes collectively referred to as the
lentiform, or lenticular, nucleus. This is a wedge-shaped nucleus with the wide base pointing laterally.

On transverse and coronal sections of the brain, we can see that the internal capsule is medial to the
lentiform nucleus and separates it from the caudate nucleus and the thalamus. Lateral to the lentiform
nucleus is the external capsule. Thin sheets of white matter pass vertically through the lentiform nucleus,
dividing it into its three components.

First, the most medially positioned nucleus is the globus pallidus, which has a lighter appearance
because it contains more myelinated nerve fibers. The globus pallidus is further divided by a sheet of
white matter into the globus pallidus internus, lateral to the internal capsule, and the globus pallidus
externus, which is medial to the putamen.

The putamen is the most lateral of the lentiform nuclei and has a darker appearance. It is positioned
lateral to the globus pallidus externus and medial to the external capsule.

The putamen and the caudate nucleus are sometimes referred to as the corpus striatum, or just the
striatum. These two nuclei are separated by the internal capsule, except anteriorly where the head of the
caudate nucleus is continuous with the putamen.

Superior to this connection, small bridges of gray matter between these nuclei pass through the internal
capsule, giving it the striated appearance, hence the name corpus striatum.
Let’s take a short break and see if you can identify the function of the basal ganglia, as well as the basal
nuclei that comprise the basal ganglia.

Let’s switch gears now and talk about other nuclei that are closely related to the basal ganglia. Inside the
midbrain, ventrally, between the tegmentum and the crus cerebri, there is a darkly pigmented area called
the substantia nigra, which is Latin for “black substance”. It contains cells that store granules in their
cytoplasm, filled with a pigment called neuromelanin, making this region look darker in color.

The substantia nigra can be divided into two parts: the substantia nigra pars compacta, or SNpc, and the
substantia nigra pars reticulata, or SNpr. SNpc contains dopaminergic neurons that project their axons to
the corpus striatum, forming the nigrostriatal pathway, where they release dopamine.

Then, there is the subthalamus, which is a part of the diencephalon located ventral to the thalamus,
lateral to the hypothalamus and medial to the internal capsule. It contains the subthalamic nuclei, or STN
for short, which assists the basal ganglia in the regulation of movements. The STN receive afferent
fibers mainly from the globus pallidus externus, and project efferent fibers mainly to the globus pallidus
internus.

Now that we have covered the main basal nuclei, let’s see how they work together to assist the motor
cortex in control of movements.

In order to pass messages between each other, neurons of the basal nuclei use different
neurotransmitters. They either release excitatory neurotransmitters, like glutamate, or inhibitory
neurotransmitters, like the gamma-aminobutyric acid, or GABA for short.

The basal ganglia don’t have any direct connection with lower motor neurons, so they can’t control the
muscles directly. However, they influence the motor cortex through the thalamus. Basically, information
enters the basal ganglia through the corpus striatum and leaves it through the globus pallidus internus,
or GPi for short, which has an output on the thalamus.

The information flow can follow two different pathways: the direct pathway and the indirect pathway. The
normal connectivity of the direct pathway results in the excitation of the motor cortex, while the normal
connectivity of the indirect pathway results in the inhibition of the motor cortex. To remember which
pathway produces which effect, just recall that the INdirect pathway INhibits the motor cortex.

Now to better understand how they function, let’s dive into both of these pathways, step by step. The
direct pathway starts with the substantia nigra pars compacta, which contains neurons that project to the
corpus striatum.

These neurons release dopamine from their axons, which binds to D1 receptors found on the neurons of
the corpus striatum. Neurons that have D1 receptors project directly to the GPi and inhibit it by releasing
GABA.

Normally, the GPi projects to the thalamus where it releases GABA, thus inhibiting the thalamus and
preventing it from releasing glutamate and stimulating the motor cortex.

However, because the GPi is inhibited by the corpus striatum, the thalamus is then dis-inhibited and can
stimulate the motor cortex, thereby assisting with the initiation and execution of the desired voluntary
movements.

At the same time the direct pathway is activated, the information passes through the indirect pathway as
well. The indirect pathway also begins with the neurons of the SNpc that project to the corpus striatum,
where they release dopamine.
This time, dopamine binds to the D2 receptors, found on the neurons that project to the GPe first. Once
activated, these neurons release GABA, which inhibits the globus pallidus externus, or GPe for short.

Normally, the GPe projects to the subthalamic nuclei and releases GABA to inhibit it. This prevents the
STN from releasing glutamate and stimulating the GPi. But, because the GPe has been inhibited by the
indirect pathway, the STN breaks free and starts releasing glutamate to stimulate the GPi. This
excitation causes the GPi to release more GABA, which inhibits the thalamus and results in the inhibition
of the motor cortex.

Even though it might seem like the indirect pathway wants to sabotage the direct one, it actually helps
the motor cortex by suppressing the unwanted muscle contraction while producing voluntary
movements.

All right, as a quick recap… The basal ganglia regulate initiation and execution of movements, regulate
posture and assist in learning new motor skills. They are found deep within the white matter of the
cerebrum and consist of: the caudate nucleus, the putamen, the globus pallidus externus and the globus
pallidus internus.

The caudate nucleus and putamen are sometimes referred to as the corpus striatum, while the putamen,
globus pallidus externus and internus are sometimes referred to as the lentiform nucleus.

The basal ganglia are closely related to the substantia nigra of the midbrain and the subthalamic nuclei
of the diencephalon. Information in the basal ganglia passes through two different pathways. The direct
pathway leads to the stimulation of the motor cortex, while the indirect pathway leads to inhibition of the
motor cortex.

Anatomy of the blood supply to the brain

The human brain is one of the most important and sophisticated organs of the human body. In fact,
every minute, it receives about 15% of the total blood pumped by the heart to our entire body! Cerebral
circulation is a complex circulatory system, formed by the two internal carotid arteries, the two vertebral
arteries, and their branches. The terminal branches of both the internal carotid arteries and the vertebral
arteries lie in the subarachnoid space, which is a space between two meningeal layers called the
arachnoid mater and pia mater. Anatomoses between these two arteries and their branches give rise to
the Circle of Willis, which is a system of vessels at the base of the brain that helps to ensure adequate
blood flow to this vital organ.

Let’s start off with the internal carotid arteries, or ICAs, which are the terminal branches of the common
carotid arteries, and form the anterior part of the cerebral vascular system. The ICAs ascend on both
sides of the neck to reach the base of the skull, where they enter a passageway in the petrous part of
the temporal bone, called the carotid canal. Within the carotid canal, the ICA is close to venous plexuses
as well as the carotid plexuses of sympathetic nerves. Within the canal, each ICA turns 90 degrees
anteromedially, then another 90 degrees superiorly to exit the carotid canal and enter the cranial cavity.

Inside the cranial cavity, the ICA runs through the cavernous sinus, which is, in fact, a dural venous
sinus. So the ICA, an artery, actually runs through a sinus filled with venous blood! Within the cavernous
sinus, the ICA travels alongside the abducens nerve, and lies in proximity to the oculomotor nerve, the
trochlear nerve and the ophthalmic and maxillary divisions of the trigeminal nerve. Then, the ICA
emerges from the cavernous sinus and divides into the anterior cerebral artery, the middle cerebral
artery and several smaller branches.
To simplify this complex course, the ICA can be divided into 4 parts: the cervical part, that extends from
common carotid to the carotid canal; the petrous part, that extends from the carotid canal to the foramen
lacerum; the cavernous part, meaning the part of the ICA within the cavernous sinus; and the cerebral
part, after it exits from the cavernous sinus.

The cerebral part of the ICA ends by bifurcating into two major terminal branches: the anterior cerebral
artery and middle cerebral artery. Now, the cerebral part of the ICA gives off several other collateral
branches that supply various structures in the head - including the brain. Anteriorly, right after it exits
from the cavernous sinus, it gives off the ophthalmic artery. This artery, intuitively, enters the orbit and
gives off the central retinal artery which is the main blood supply to the retina. Posteriorly, the ICA gives
off two branches: the posterior communicating artery and the anterior choroidal artery. The posterior
communicating artery arises right before the terminal bifurcation of the ICA, and connects the middle
cerebral and posterior cerebral artery in the Circle of Willis. The anterior choroidal artery, also arises
close to the terminal bifurcation, and courses posteriorly to enter the lateral ventricle of the brain, to end
in the choroid plexus, supplying it and several other cerebral structures along its course.

And now let’s use an image of the medial side of one cerebral hemisphere to look at the two terminal
branches of the ICA: the anterior cerebral artery and the middle cerebral artery. From its origin, the
anterior cerebral artery runs anteriorly and then turns superiorly and travels posteriorly arching over the
corpus callosum. Throughout this course it supplies the medial aspect of the frontal lobe and the parietal
lobe by giving off numerous small cortical branches. These cortical branches will also arch over to the
lateral aspect of the hemisphere and supply the supero-lateral part of the frontal and parietal lobes. The
two anterior cerebral arteries on each side are connected through the anterior communicating artery,
forming the anterior part of the circle of willis.

Next, after branching from the internal carotid artery, the middle cerebral artery travels laterally along the
lateral sulcus. While it traverses the lateral aspect, it gives off deep penetrating branches called central
arteries which supply the deeper structures of the brain like the corpus striatum, which is made up of the
caudate and lenticular nucleus. This is why these central arteries are often referred to as lenticulostriate
branches of the middle cerebral artery.

After reaching the lateral surface, the middle cerebral artery provides a few branches that supply the
lateral surface of the temporal lobe and part of the infero-lateral surface of the frontal and parietal lobe.
Now, both the anterior and middle cerebral arteries are often referred to as terminal arteries as there is
no collateral circulation in areas supplied by them. Thus any blockage in these arteries may prevent
blood from reaching that part of the brain completely.

Okay, that was a lot! Let’s take a short break and see if you can recall the collateral and terminal
branches of the internal carotid artery.

Alright! Now let’s switch gears and look at the vertebral arteries, which arise from the subclavian arteries
and form the vertebro-basilar system. The vertebral arteries ascend through the transverse foramina of
the cervical vertebrae to enter the skull through the foramen magnum, and then they pierce the dura
mater to get into the subarachnoid space. Here, the vertebral arteries start their intracranial course, by
moving forward, upward and medially over the medulla oblongata. At the ponto-medullary junction,
which is where the pons and medulla meet, the two vertebral arteries merge with each other and form a
single basilar artery - hence the term “vertebro-basilar” system.

Now, before the two vertebral arteries merge, they give off two important branches: the anterior spinal
artery and the posterior inferior cerebellar artery. The anterior spinal artery is formed by two separate
branches of the vertebral artery, which travel inferiorly and medially and subsequently form the singular
anterior spinal artery at the level of the foramen magnum.
The anterior spinal artery then courses in the anterior, median aspect of the spinal cord, supplying its
rostral anterior two-thirds.

The posterior inferior cerebellar artery, or PICA, on the other hand, originates from the vertebral artery
and winds posteriorly around the upper part of medulla oblongata, travels along the inferior aspect of the
cerebellum and divides into medial and lateral branches. The medial branch continues posteriorly, while
the lateral branch supplies the inferior part of the cerebellum. Now, there is another branch called the
posterior spinal artery which in one fourth of the population arises from the vertebral artery and in the
other three fourths of the population from the PICA. The posterior spinal artery mainly supplies the
posterior aspect of the spinal cord.

Now let’s look at the basilar artery. After its origin, it ascends along the ventral surface of the pons. On
its way, it gives off four paired collateral branches: the anterior inferior cerebellar arteries, or AICA; the
labyrinthine arteries; the pontine arteries; and the superior cerebellar arteries. Then, just superior to the
origin of the oculomotor nerve, the basilar artery ultimately divides into a pair of terminal branches called
the posterior cerebral arteries. The left and right posterior communicating arteries originate from these
posterior cerebral arteries and merge with the internal carotid arteries, thereby closing the posterior
portion of the circle of willis.

The anterior inferior cerebellar arteries course postero-laterally, and mainly supply the inferior aspect of
the cerebellum, as well as part of the pons and middle cerebellar peduncle. Next, the labyrinthine
arteries course laterally, along with the seventh and eighth cranial nerves, to the internal acoustic
meatus to enter and supply the inner ear. Next up, the pontine arteries are numerous small branches
that course laterally to supply the pons. Last, just before the bifurcation of the basilar artery, there are
the superior cerebellar arteries, which course laterally and then travel around the cerebral peduncle to
reach and supply the superior aspect of cerebellum, the pineal gland, part of the pons and part of the
third ventricle.

Okay, that was a lot! Let’s take a short break and see if you can recall the branches of the vertebral
artery!

Great! Now let’s put all this information together and look at the circle of Willis, named after the English
physician Thomas Willis. See, the anterior communicating artery connects the two anterior cerebral
arteries, while the posterior communicating arteries connect the posterior cerebral arteries with the
internal carotid arteries on each side. This forms the circle of Willis in the subarachnoid space at the
base of the brain, right in front of the midbrain. This circle helps create a collateral arterial circulation, so
complete or partial blockage of any one of the cerebral arteries can be compensated by other arteries. In
this way, cerebral perfusion is more likely to be maintained which helps to prevent ischemic and hypoxic
brain injury from occurring.

The circle of willis is closely related to some important surrounding structures. For example, the anterior
communicating artery travels just anterior to the optic chiasm, while the posterior communicating artery
courses just medial to the third cranial nerve on each side. Thus any abnormal dilatation or aneurysm in
a particular artery may lead to compression of a related nerve or other associated structure, causing
specific neurological deficits.

On a quick side note, even though the major cerebral arteries participate in the formation of the circle of
Willis, each of them predominantly supplies one part of the cerebral cortex. The anterior cerebral arteries
supply the anteromedial surface of the cerebral cortex. The middle cerebral arteries are located laterally,
supplying the majority of the lateral surface of the cerebral cortex. Finally, the posterior cerebral arteries
supply both the posterior and inferior surfaces of the cerebral cortex.
An important concept to remember when considering vasculature supply and infarcts is the cortical
homunculus. The homunculus is a kind of neurological map that depicts the neurons in a particular area
of the cortex that process a particular body region, as well as the density of neurons that are dedicated
to that region of the body. The motor homunculus is located in the frontal lobe, while the sensory
homunculus is just caudal to it, in the parietal lobe. The cortical homunculus can be represented as a
body lying on top of the brain, where each body part lies on top of its corresponding brain area. The toes
are represented first on the medial aspect of the cerebral hemisphere. Then moving superiorly and then
laterally, more superior parts of the body are progressively represented, until we see the face most
lateral. The motor and sensory homunculi on each side of the brain correspond to motor and sensory
functions on the opposite side of the body. The medial area of the homunculus, representing the lower
body, is supplied by the anterior cerebral artery, while the lateral area representing the upper body and
face is supplied by the middle cerebral artery.

Now, as we move away from the origin of the anterior, middle and posterior cerebral arteries and more
towards the areas of cerebral cortex that border the cortical branches of these arteries, blood supply by
these cerebral arteries gradually decreases. As a result, these border areas are more prone to ischemic
injuries. In these cases, the pattern of injury is called a watershed infarct or watershed stroke, where
healthy tissue continues to extract what it needs from the blood flowing by, leaving little or no oxygen
and nutrients for the tissue furthest away and as a result, the tissues that are the furthest downstream
are affected the most. The “furthest downstream” tissues are the watershed areas, which are at the
border of blood supply from two separate groups of cerebral arteries.

There are three main watershed areas, where watershed infarcts typically occur: between the anterior
cerebral and the middle cerebral arteries; between the posterior cerebral and the middle cerebral
arteries; and between the superficial and deep branches of the middle cerebral arteries.

Finally, let’s briefly look at the venous drainage of the brain, which starts as a series of small superficial
veins. These veins drain into dural venous sinuses, which are venous channels located between the two
layers of dura mater: the periosteal layer and meningeal layer. The superior sagittal sinus runs along the
longitudinal fissure, where it absorbs cerebrospinal fluid from the meninges. It drains to the confluence of
sinuses, along with the straight sinus and occipital sinuses, which then empties into the transverse
sinuses. The transverse sinuses drain to the sigmoid sinuses, which then drain to the internal jugular
veins, ultimately returning to the heart.

Alright, as a quick recap. The anterior part of the cerebral circulatory system is created by the internal
carotid arteries. The ICA has 4 parts: the cervical part, the petrous part, the cavernous part, and the
cerebral part. Collateral branches of the internal carotid artery include the ophthalmic artery, the
posterior communicating artery, and the anterior choroidal artery. The terminal branches of the ICA are
the anterior and middle cerebral arteries. The anterior cerebral arteries are connected via the anterior
communicating artery.

The posterior aspect of the cerebral circulatory system arises from the vertebral arteries which merge to
form the basilar artery. Before they join, they give off the anterior spinal artery and the posterior inferior
cerebellar artery. The basilar artery gives off four paired collateral branches: the anterior inferior
cerebellar arteries, or AICA; the labyrinthine arteries; the pontine arteries; and the superior cerebellar
arteries. Ultimately, the basilar artery divides into a pair of terminal branches called the posterior cerebral
arteries, which in turn give off the left and right posterior communicating arteries. The circle of willis is
formed by the anterior cerebral arteries, that are connected by the anterior communicating artery, and
the posterior cerebral arteries and the internal carotid arteries, which are connected by the posterior
communicating arteries.
The three main watershed areas of the brain are between the anterior cerebral and the middle cerebral
arteries; between the posterior cerebral and the middle cerebral arteries; and between the superficial
and deep branches of the middle cerebral arteries. Blood returns from the brain to the systemic
circulation through a series of venous channels called dural venous sinuses that ultimately drain into the
internal jugular veins.

Anatomy clinical correlates: Anterior blood

supply to the brain
Your brain is awake and working hard all day, every day, even when you’re sleeping! So it makes sense
that it needs a lot of oxygen and energy, which is why it is well supplied from several major arteries. The
circulation of the brain can ultimately be divided into the anterior and posterior circulation, and
understanding their anatomy can help us understand the clinical consequences and management of
various issues that can arise! So let’s delve into the anterior circulation of the brain!

Remember that the anterior circulation supplies the anterior portion of the brain, and comes from the
internal carotid arteries which divide into the anterior and middle cerebral arteries. The anterior
circulation then connects to the posterior circulation through the posterior communicating arteries. The
posterior circulation comes from the vertebral arteries, which combine to form the basilar artery.
Together, the connection between the anterior and posterior circulation form the circle of Willis, which is
an anastomotic network of arteries at the base of the brain which ensure adequate blood flow to the
brain, even in cases where part of this circulation becomes occluded! However, there are still instances
where obstruction of these arteries and their branches disrupts blood flow to the brain, causing a stroke,
which can lead to irreversible neuronal damage.

Now, a stroke can be classified as either ischemic or hemorrhagic. Ischemic strokes are much more
common, and they happen because of an acute blockage of one of the blood vessels supplying the
brain. Ischemic strokes can be thrombotic, embolic or hypoxic. A thrombotic stroke occurs when there’s
a blood clot in the artery, formed directly at the site of infarction, which typically occurs because of a
ruptured atherosclerotic plaque. An embolic stroke, on the other hand, is where an embolus from
another part of the body travels to the site of infarction to cause obstruction. For example, with atrial
fibrillation, a blood clot can form in the heart, where it then travels through the circulation to eventually
obstruct brain vessels. Then there are hypoxic strokes, where there is not a direct blockage of a vessel
but systemic hypoperfusion or hypoxemia of the brain. This can cause inadequate oxygenation of the
brain, especially in watershed areas which are supplied by the terminal branches of two large vessels,
and are therefore more prone to hypoperfusion injuries.

Hemorrhagic strokes, on the other hand, occur when there is a bleed within the brain tissue called an
intracerebral or intraparenchymal bleed, or a bleed in the subarachnoid space called a subarachnoid
hemorrhage. This happens most often as a result of chronic untreated hypertension, and associated
hypertensive vasculopathy. Other causes include amyloid angiopathy, a ruptured vascular aneurysm
and vascular malformations.

Now, we can typically identify which artery of the anterior circulation is affected during a stroke based on
clinical symptoms. Let’s start with the middle cerebral artery, or MCA for short, which supplies most of
the lateral cerebral cortex of the frontal, parietal and temporal lobes, the insular cortex, as well a large
portion of the basal ganglia and internal capsule. Depending on what portion of the MCA is occluded,
clinical presentation can vary.
Now, the MCA supplies a large portion of the primary motor and sensory cortex, which can be found
along the precentral and postcentral gyrus, respectively. Looking at the motor homunculus, we can see
that the MCA supplies the area for the face, trunk and upper extremity. Therefore, lesions of the motor
cortex cause weakness or paralysis of the contralateral side of the face and arm and eventual upper
motor neuron signs such as hyperreflexia. Looking at the sensory homunculus we can see that the MCA
also supplies the face and upper extremity area. Because of this, lesions of the sensory cortex produce
loss of sensations in the contralateral side of the face and arm.

The MCA also supplies the posterior part of the inferior frontal gyrus. This area is in the dominant
cerebral hemisphere, which is the left hemisphere for right handed people and right hemisphere for left
handed people, and is where Broca’s area is located. Lesions of this area cause Broca’s aphasia, where
individuals have difficulties planning and executing movements necessary for the production of speech,
while their comprehension of speech is not affected. Furthermore, the MCA also supplies the posterior
part of the superior temporal gyrus. In the dominant hemisphere this is where Wernicke’s area is
located. When injured, it causes Wernicke’s aphasia, where individuals are fluent and may even speak
faster than usual, but their comprehension and repetition of spoken and written language is impaired and
their speech appears meaningless. So, in a right handed individual presenting with Broca’s or
Wernicke’s aphasia, we would suspect a lesion to the left MCA!

An MCA artery stroke can also affect other regions of the brain, such as the frontal lobe which contains
the frontal eye field in the middle frontal gyrus. This is the center for voluntary control of eye movements
and conjugate gaze to the contralateral side. So when injured, it causes both eyes to deviate towards
the ipsilateral side, as if they are looking at the lesion.

The frontal lobe also contains the prefrontal cortex, and its injuries lead to frontal lobe syndrome, where
individuals experience personality changes such as problems with planning, initiative, and judgement,
while the individual also exhibits socially unacceptable behaviour.

Next, lesions of the angular gyrus of the parietal lobe on the dominant cerebral hemisphere lead to
Gerstmann syndrome, which presents with 4 key features: left-right disorientation; finger agnosia,
acalculia, and agraphia. Involvement of the parietal cortex on the non-dominant cerebral hemisphere, on
the other hand, would cause hemispatial neglect syndrome. This means that individuals have agnosia,
or inability to process sensory information, of the contralateral side of the body and the space around it.

Finally, the MCA supplies the subcortical area of the temporoparietal lobe which contains the optic
radiation, where depending on which hemisphere is affected, a lesion here would result in contralateral
homonymous quadrantanopia.

Let’s take a short break and see if you remember the most common clinical syndromes associated with
a middle cerebral artery stroke.

Okay, now let’s switch gears and discuss the anterior cerebral artery, or ACA for short, which supplies
the medial aspect of the frontal and parietal lobes as well as anterior portions of the basal ganglia and
internal capsule.

The ACA supplies specific portions of the primary motor and somatosensory cortex, in particular the
anterior and posterior paracentral lobule. When we look at the motor and sensory homunculi, we can
see that the ACA mainly supplies the areas for the lower extremities and genitalia.

Therefore, occlusion of the ACA leads to paresis or motor loss of the contralateral leg with eventual
upper motor neuron signs such as lower limb hyperreflexia and positive Babinski sign, while lesions of
the sensory cortex lead to sensory loss of the contralateral leg. To make matters worse, the left and right
ACA can sometimes get occluded at the same time, causing bilateral damage to both hemispheres.
Motor control to the urinary sphincters is also located in the anterior paracentral lobule, so bilateral
lesions can result in urinary incontinence.

Now, as we recall, the brain is contained within the rigid boney cranium, which provides great protection,
but doesn’t allow the intracranial space to expand. Because of this, any mass-occupying lesion, such as
a hemorrhagic stroke or a tumor, increases the intracranial pressure and pushes the brain tissue of the
frontal, parietal, or temporal lobe away from the lesion.

In a setting like this, the cingulate gyrus of the affected cerebral hemisphere is forced under the falx
cerebri which separates the hemispheres, leading to a subfalcine or cingulate herniation. As herniation
progresses, the cingulate gyrus pulls the ipsilateral anterior cerebral artery together with it under the falx,
where it can be compressed or occluded. This leads to infarction in the regions of the cerebral cortex
supplied by the ACA, and its characteristic clinical features, which are hemiplegia and hemisensory loss
of the contralateral leg. Subfalcine herniation can also obstruct the foramen of Monro which allows
passage of cerebrospinal fluid from the lateral ventricles to the third ventricle, causing obstructive
hydrocephalus, or a buildup of cerebrospinal fluid in the brain.

Now let’s discuss a particular type of stroke, known as a lacunar stroke, which involves small blood
vessels arising from the MCA and ACA called the lenticulostriate arteries. The lenticulostriate arteries
arising from the MCA are sometimes referred to as the lateral lenticulostriate arteries, and the ones
arising from the ACA are sometimes referred to as the medial lenticulostriate arteries. They penetrate
the brain and supply deep subcortical structures, like the striatum, composed of the caudate and
lentiform nucleus; and the internal capsule. These arteries are susceptible to injury secondary to
uncontrolled hypertension. The high blood pressure damages their endothelial cells and leads to the
development of hyaline atherosclerosis, thickening the arterial wall which reduces their lumen size and
blood flow, setting the stage for a lacunar stroke.

Lesions that develop from a lacunar stroke commonly affect the posterior limb of the internal capsule
and damage the descending corticospinal and corticobulbar tracts. This causes hemiplegia of the
contralateral side of the body with eventual signs of upper motor neuron lesion, such as hyperreflexia,
hyperspasticity and positive Babinski sign. The thing that differentiates lacunar stroke from other types of
strokes is the absence of cortical signs such as aphasia, visual field defects, hemineglect syndrome and
others. This is why lacunar strokes are sometimes referred to as “pure motor” strokes.

Let’s take one more break and see if you can recall the areas of the brain supplied by the anterior
cerebral artery!

Now let's move onto the concept of watershed zones of the brain. A watershed zone is a cortical or
subcortical area supplied by two major arteries, for example between the MCA and ACA, or between the
MCA and PCA. Watershed zones get their blood supply from the terminal branches of both adjacent
arteries, so if there’s systemic hypoperfusion or hypoxemia, these terminal branches cannot provide
enough blood supply to this area. This is why watershed zones are especially prone to infarction.

Some of the most common causes of hypoperfusion include cardiovascular surgery and cardiac arrest,
which cause bilateral lesions; or major arterial stenosis, such as the internal carotid artery stenosis,
which often cause unilateral lesions.

Going back to the motor homunculus, we can see that the cortical area for the proximal part of the upper
and lower extremities is a watershed zone between the ACA and MCA. Because of this, infarction of the
watershed zones between the ACA and MCA causes proximal muscle weakness of both upper and
lower extremities, which is sometimes referred to as the man in a barrel syndrome.
On the other hand, infarction of the watershed zones between the MCA and PCA damages areas
around the visual cortex that are in charge of processing visual information. This presents as a higher
order visual dysfunction, such as prosopagnosia, or the inability to recognize people’s faces, visual
agnosia, or loss of ability to recognize objects, alexia, or the loss of ability to comprehend written
language, and achromatopsia which is a form of color blindness.

Finally, let’s look at the different types of brain bleeds that can occur. Depending on where the bleed
occurs in relation to the dura, arachnoid and pia mater, brain bleeds can be divided into epidural,
subdural and subarachnoid hemorrhages.

So let’s start with the epidural hematomas, which typically develop after injury of the middle meningeal
artery following a traumatic event and possible skull fracture. The most common site of fracture is the
pterion, which is the thinnest area of the skull. It can be found in the lateral region of the skull, where the
frontal, parietal, temporal and sphenoid bones come together. Sharp bone fragments can lacerate distal
branches of the middle meningeal artery coursing in the area of the pterion after it enters the foramen
spinosum to act as the major blood supply for the cranial dura mater.

Once ruptured, the artery then bleeds causing a fast growing hematoma to accumulate in the space
between the outer or periosteal dura layer and the inner skull.

On a head CT, the hematoma presents as a hyperdense, biconvex or classical ‘lens shape’ blood
collection that does not cross the suture lines of the skull. To remember that epidural hematomas are
outside of the dura, think that when you go outside, you need to wear sunglasses with lenses in them to
protect yourself from the sun! Individuals can sometimes present with a ‘lucid interval’ where they
experience an interval of no symptoms, but these hematomas can progress quickly in a matter of hours
and be fatal.

Next up, there are subdural hematomas, which can be either acute or chronic. Acute injuries can
develop following a traumatic event or blow to any part of the skull. This blow displaces the brain,
damaging the bridging veins found in the subdural space that drain the superior cerebral veins into the
superior sagittal sinus. Individuals that are at higher risk of developing subdural hematomas are elderly
individuals and alcoholics. These people are prone to brain atrophy, which shrinks the brain down
creating more space and putting more stress on longer bridging veins within the subdural space, so
even minor traumas can cause subdural hematomas. In children, subdural hematomas are also a sign of
‘shaken baby syndrome’ which is an indicator of child abuse.

Once damaged, these veins bleed below the dura in the subdural space between the dura and
arachnoid. On a head CT, there’s a crescent shaped hematoma that crosses the suture lines, making it
distinguishable from an epidural hematoma.

Finally, there are subarachnoid hemorrhages. These can occur after trauma, aneurysmal rupture, or
arteriovenous malformation of the major arteries at the base of the brain. With a ruptured aneurysm,
individuals may experience what's called a ‘thunderclap headache’, typically described as the worst
headache of their life. The bleeding occurs between the arachnoid and pia mater, in the subarachnoid
space that is normally filled with the cerebrospinal fluid. On a head CT, a subarachnoid hemorrhage can
be seen as hyperdense areas of blood collected in the subarachnoid space, which can be found in the
major brain fissures and sulci, along the falx cerebri, tentorium cerebelli, and falx cerebelli, or the
cisterns of the brain.

Ok, final quiz! Can you name all the arteries of the anterior circulation?
Summary
Alright, as a quick recap… The anterior circulation supplies the anterior part of the brain. The MCA
supplies the lateral side of the brain. A stroke in this area usually leads to the contralateral hemiparesis
and sensory loss of the face and arm. A stroke in the dominant hemisphere can also lead to Broca’s or
Wernicke’s aphasia, or Gerstmann syndrome, while in the non-dominant side it leads to hemineglect
syndrome. The ACA supplies the medial side of the brain and when occluded, that causes contralateral
hemiparesis and hemisensory loss of the leg. When occlusion is bilateral it also leads to urinary
incontinence.

Subfalcine herniation is when the cingulate gyrus is forced under the falx cerebri to the contralateral side
of the brain, and if severe enough the ACA can become compressed and occluded. A lacunar stroke
involves the lenticulostriate arteries and leads to the hemiparesis of the contralateral side of the body,
and can manifest as a ‘pure motor’ stroke. Lesions of the watershed zones between ACA and MCA lead
to the proximal muscle weakness of the arms and legs, while lesions of those between MCA and PCA
produce higher order visual dysfunctions. Intracranial bleeds can also be categorized as epidural,
subdural and subarachnoid hemorrhages depending on their location.

Anatomy clinical correlates: Posterior blood

supply to the brain
Blood supply to the brain can be divided into an anterior and a posterior circulation. The posterior
circulation supplies the cerebellum, brainstem, occipital lobes, and inferomedial temporal lobes, and
comes from the vertebral arteries. The vertebral arteries combine to form the basilar artery, which
eventually divides into the posterior cerebral arteries. The posterior circulation then connects to the
anterior circulation through the posterior communicating arteries. Remember that the anterior circulation
comes from the internal carotid artery which divides into the anterior and middle cerebral arteries.
Together, the connection between the posterior and anterior circulation form the Circle of willis, which is
an anastomotic network of arteries at the base of the brain that ensure adequate blood flow even in
cases where part of this circulation becomes occluded! However, there are still instances where
obstruction of these arteries and their branches can disrupt blood flow to the brain, so understanding
their anatomy and what parts of the brain they nourish can help us better understand the clinical
manifestations and management.

When blood flow to the brain is obstructed, that causes a stroke, which can be either ischemic or
hemorrhagic. Ischemic strokes can be caused by thrombi, emboli, and hypoperfusion injuries, with the
latter most commonly affecting the watershed areas of the brain. Hemorrhagic strokes, on the other
hand, occur when there is a bleed within the brain tissue called an intracerebral or intraparenchymal
hemorrhage, or a bleed in the subarachnoid space called a subarachnoid hemorrhage. The posterior
circulation of the brain is susceptible to all of these, and the clinical signs and symptoms depend on
which artery is occluded.

Let’s look at the vertebral arteries first, starting with the subclavian steal phenomenon. This is when the
vertebral artery on the same side as an occluded, or blocked subclavian artery “steals” blood from the
contralateral subclavian artery circulation. This happens when the occlusion is proximal to the vertebral
artery, so blood from the contralateral vertebral artery flows to the basilar artery and then continues as
retrograde flow through the ipsilateral vertebral artery to the blockage. This allows blood flow to the area
supplied by the occluded subclavian vessel, and is often asymptomatic. The most common cause of
subclavian stenosis is an atherosclerotic plaque, but other less common causes include Takayasu
arteritis and complications from cardiovascular surgery, like an aortic coarctation repair surgery. When
subclavian steal phenomenon becomes symptomatic, it is considered subclavian steal syndrome.

Clinical features usually occur during an exercise, when blood flow to the occluded arm is not enough to
meet the demand, causing muscle weakness and claudication, meaning pain or cramping of the
muscles. Individuals can also have neurological symptoms such as light headedness, dizziness and
vertigo.

Next up, let’s look at the anterior spinal artery, which arises from the vertebral arteries. The anterior
spinal artery, together with the vertebral arteries, give paramedian branches for the anteromedial parts
of the medulla. This region of the medulla includes many important structures such as the lateral
corticospinal tract within the pyramids, medial lemnisci, and the hypoglossal nucleus and fibers coming
from it.

So when the paramedian branches of the anterior spinal arteries don’t provide adequate blood flow, the
structures within the anteromedial parts of the medulla are damaged, leading to Medial Medullary
syndrome. Clinically, damage to the lateral corticospinal tracts at this level causes contralateral
hemiparesis of the upper and lower extremities. Damage to the medial lemniscus pathway at this level
leads to contralateral hemisensory loss of proprioception, fine touch, and vibratory sensations from the
trunk and extremities. And finally damage to the hypoglossal nucleus or nerve fibers leads to ipsilateral
flaccid paralysis of the tongue that can be seen as deviation to the paralyzed side when protruded.

A good way to remember the symptoms of Medial Medullary syndrome is to think of 3 Midline structures.
The M in midline stands for medial, and all 3 structures start with an M: 1) Motor pathway (corticospinal
tract) 2) Medial lemniscus 3) Motor fibers of hypoglossal nerve.

Okay, now let’s look at the posterior inferior cerebellar artery, or PICA for short, which is a branch of the
vertebral artery that supplies the lateral part of the medulla and regions of the cerebellum. This region of
the medulla it supplies contains many important structures such as the vestibular nuclei, spinal
trigeminal nucleus, spinothalamic tract, nucleus ambiguus, the inferior cerebellar peduncle, and
sympathetic fibers.

Now, infarction to the PICA can lead to lateral medullary syndrome, also known as PICA, or Wallenberg,
Syndrome. Clinically, damage to the vestibular nuclei leads to nystagmus, vertigo, nausea and vomiting.
Damage to the spinal trigeminal nucleus leads to loss of pain and temperature sensation from the
ipsilateral side of the face, where damage to the spinothalamic tract that has already crossed over at the
spinal cord leads to loss of pain and temperature sensation from the contralateral side of the trunk and
extremities. Damage to the nucleus ambiguus, which houses the motor nuclei for the cranial nerves IX,
X and XI, leads to dysphagia, dysphonia or hoarseness, dysarthria, and loss of gag reflex. Damage to
the nucleus ambiguus is actually specific to PICA syndrome, distinguishing this condition from similar
ones.

Next up, damage to the inferior cerebellar peduncle leads to ipsilateral ataxia, or lack of muscle control
and coordination when performing voluntary movements; dysmetria, or inappropriate voluntary action
execution, such as overreaching for a glass of water; and dysdiadochokinesia, or an inability to perform
rapid alternating muscle movements. Finally, damage to descending sympathetic fibers can result in
Horner syndrome which includes ptosis, anhidrosis and miosis.

In order to remember the structures damaged in this syndrome, we can remember that the lateral Side
of the medulla that has 6 ‘S’s: 1) the veStibular nuclei 2) the Spinal trigeminal nucleus 3) the
Spinothalamic tract 4) Speech and Swallowing representing the nucleus ambiguous 5) Inferior
‘S’erebellar peduncle...ok we know that starts with a C but it sounds like an S…..and 6) Sympathetics.
Another mnemonic that you can use to recall the most common clinical features of the lateral medullary
syndrome is: Don’t pick a (PICA) horse (hoarseness) that can’t eat (dysphagia).

Okay, now after the vertebral arteries combine to form the basilar artery, there is a branch called the
anterior inferior cerebellar artery, or AICA for short, which supplies the lower lateral part of the pons, and
the inferior and middle cerebellar peduncles. Infarction of the AICA can lead to something called Lateral
Pontine syndrome, also known as the AICA syndrome. Now, in this region, there are structures like the
facial motor nucleus, the vestibular nuclei, the spinothalamic tract, spinal trigeminal nucleus, sympathetic
fibers, the middle and inferior cerebellar peduncles, and the labyrinthine artery.

Damage to the facial motor nucleus results in ipsilateral facial paralysis due to lower motor neuron
damage, along with decreased tear and saliva production, loss of taste from anterior two thirds of the
tongue, and loss of corneal and stapedial reflexes. Vestibular nuclei lesions result in nystagmus, vertigo
and vomiting. Spinothalamic tract and spinal trigeminal nucleus damage lead to loss of temperature and
pain sensations in the ipsilateral side of the face and contralateral side of the trunk and extremities.

Damage to the inferior and middle cerebellar peduncles result in ipsilateral ataxia, dysmetria and
dysdiadochokinesia. Finally, damage to the sympathetic fibers can cause ipsilateral Horner syndrome.
Bear in mind that the AICA typically gives rise to the labyrinthine artery that supplies the inner ear, so
infarction of the AICA also causes ipsilateral sensorineural deafness, accompanied with tinnitus and
vertigo. Now, when trying to differentiate between all of these syndromes, in particular from lateral
medullary syndrome which shares similar features, facial paralysis is specific to AICA territory infarcts.

Let’s take a short break and see if you can remember the difference between PICA and AICA infarction.

Great! Now let’s move on to the Basilar artery, which supplies the lower midbrain, the anterior medial
part of the pons and the anterior parts of the medulla. Infarction of the basilar artery causes locked-in
syndrome, which is a scary condition where the individual may have full consciousness but is paralysed.

More specifically, there is bilateral damage to the descending corticospinal tracts, leading to
quadriplegia. There is also bilateral damage to the descending corticobulbar tracts, leading to paralysis
of the facial, mouth, and tongue muscles. There is damage to the paramedian pontine reticular
formation, also known as the lateral gaze center, resulting in loss of horizontal gaze, in addition to
damage of the nuclei to cranial nerve 4 and 6 leading to deficits in ocular movement.

Now, with locked-in syndrome the reticular activating system, or RAS for short, which spans across the
brainstem can be spared, making the individual conscious and aware of their surroundings, however
they are unable to move and interact with the outside world due to damage of the previously mentioned
structures. The only way of communication is through blinking as the oculomotor nucleus in the midbrain
is spared, and vertically eye movements as the vertical gaze center is located more superiorly in the
midbrain. Respiratory muscles are also paralysed, so individuals need to be ventilated. To easily recall
that the locked-in syndrome is caused by the basilar artery infarction, just remember the mnemonic:
locked in the basement.

Okay, and last but not least, there’s the posterior cerebral artery, or PCA for short, which is the terminal
branch of the basilar artery and supplies areas such as the occipital lobe, inferomedial temporal lobe,
splenium of the corpus callosum, thalamus, as well as the hippocampal formation and amygdala located
within the temporal lobe.

During a PCA infarct, one commonly affected area is the primary visual cortex found in the occipital lobe,
and lesions here cause contralateral hemianopia, where individuals lose vision in the contralateral
halves of the visual fields of both eyes. However, the central part of the visual field is usually preserved,
a phenomenon known as macular sparing. This is thanks to the collateral branches of the middle
cerebral artery supplying the part of the visual cortex that receives input from the macula of the eye.
Bilateral damage to the occipital lobes results in cortical blindness, however the pupils are still reactive
to light since the light reflex does not involve the visual cortex.

Furthermore, a PCA territory infarct can also affect the splenium of the corpus callosum, which connects
the occipital lobes and also allows visual input to reach the parietal language centers of the dominant
hemisphere. Damage to the dominant hemisphere can result in dyslexia, as well as alexia without
agraphia, meaning that they lose the ability to read but can still write. Non dominant hemisphere lesions
include, visual agnosia which is the inability to recognize objects, and prosopagnosia which is the
inability to recognize faces.

If the thalamus is affected during a PCA territory infarct, the individual may experience numbness and
paraesthesia of the contralateral face, trunk, and limbs.

Finally, lesions of the dominant or bilateral temporal lobes, hippocampal formations and amygdalas, lead
to the development of amnesia, where individuals can’t form new long-term memories.

Ok, final quiz! Can you name all the arteries of the posterior circulation?

Alright, as a quick recap…the brain is supplied by the posterior and anterior circulation, where the
posterior circulation comes from the vertebral arteries, which combine to form the basilar artery, and
eventually branch as the posterior cerebral arteries, all which are susceptible to stroke or infarct.

Stenosis of the subclavian artery can cause subclavian steal phenomenon where we get retrograde flow
through the vertebral artery on the affected side in order to maintain perfusion of the affected subclavian.
Anterior spinal artery infarction leads to medial medullary syndrome, damaging the lateral corticospinal
tract, the medial lemnisci and the hypoglossal nucleus or fibers coming from it.

Infarction of the posterior inferior cerebellar artery, or PICA, leads to lateral medullary syndrome, or
Wallenberg syndrome, causing damage to the vestibular nuclei, spinal trigeminal nucleus, spinothalamic
tract, nucleus ambiguus, the inferior cerebellar peduncle, and sympathetics. Damage to the nucleus
ambiguus is specific for this syndrome, and symptoms include dysphagia, hoarseness, dysarthria and
loss of gag reflex.

Infarction of the anterior inferior cerebellar artery, or AICA, causes lateral pontine syndrome, which is
when there’s damage to the facial motor nucleus which is specific to this syndrome, the vestibular nuclei,
the spinothalamic tract, spinal trigeminal nucleus, sympathetic fibers, the middle and inferior cerebellar
peduncles, and the labyrinthine artery.

Infarction of the basilar artery leads to locked-in syndrome that includes: quadriplegia, paralysis of the
facial, mouth and tongue muscles, and loss of horizontal gaze, but the individual may still retain
consciousness and can only communicate through blinking and limited eye movements.

The PCA supplies the occipital lobe, medial temporal lobe, splenium of the corpus callosum, and
hippocampal formation. A PCA stroke can lead to the contralateral hemianopia with macular sparing.
PCA territory infarct can also lead to dyslexia, alexia without agraphia, visual agnosia, prosopagnosia,
and numbness of the contralateral face, trunk, and limbs.
Anatomy clinical correlates: Cerebral
hemispheres
The cerebral hemispheres are two symmetrical halves of the brain that contain billions of neurons and
their connections, forming an amazing network of cells which help govern our everyday actions. These
cerebral hemispheres consist of the cerebral cortex, subcortical white matter, and gray matter masses
called the basal ganglia found throughout the subcortical white matter. Due to the complexity of our
brains, the clinical conditions affecting our cerebral hemispheres lead to a variety of abnormal and
strange symptoms, so understanding the anatomy of the cerebral hemisphere is crucial in understanding
these conditions.

Let’s start with lesions of the cerebral cortex, which is the superficial gray matter of our brains containing
billions of neurons responsible for processing information. Depending on which part of the cortex these
lesions occur in, it can cause different clinical manifestations.

First, there are lesions of the prefrontal cortex, which is an area responsible for the makeup of a
person’s personality and governs social behaviour. So, prefrontal cortex lesions cause frontal lobe
syndrome which generally result in personality changes, and can specifically cause problems with
planning, initiative, judgment, and social behaviour. Individuals have difficulty making decisions, and may
become impulsive and aggressive. Individuals can also exhibit socially unacceptable behavior, where
they no longer restrain from saying or doing inappropriate things, and may also no longer care about
their clothing and appearance.

Injury to the prefrontal cortex may also contribute to the reemergence of primitive reflexes, such as the
grasp reflex, suckling reflex, and groping reflex. Bilateral damage of the prefrontal cortex may lead to
incontinence, gait apraxia, and can even lead to akinetic mutism, where awake individuals lack the will
or motivation to move or speak, but will follow you with their eyes in response to noise.

Next up, there are injuries to the frontal eye fields which can be found on the middle frontal gyrus -
specifically, in Brodmann's area 8. Possible causes of lesions to the frontal eye fields include stroke
involving the middle cerebral artery, brain tumors, or injury during neurosurgery.

This area allows voluntary control of eye movements and conjugate gaze to the contralateral side. As
fibres crossover to the contralateral lateral gaze center which is located in the paramedian pontine
reticular formation in order to govern contralateral gaze.

Damage to the frontal eye field of one of the cerebral hemispheres will cause both eyes to deviate
towards the same side as the lesion, and the inability to voluntarily move the eyes toward the
contralateral side. This is in contrast to a lesion of the paramedian pontine reticular formation, which will
cause the eyes to deviate to the contralateral side of the lesion, away from the injury. So, for example,
when eyes are deviated to the right, the lesion can either involve the left paramedian pontine reticular
formation or the right frontal eye field.

Let’s take a short break and see if you can remember clinical features associated with the prefrontal
cortex lesions? What about the frontal eye field lesion?

Continuing with lesions of the cerebral cortex, let’s cover those that can lead to aphasia, which is the
inability to understand and produce speech. These lesions usually affect the dominant hemisphere,
which is the left hemisphere for right handed individuals and the right hemisphere for the left handed
individuals.
First let's look at lesions to Broca’s area, or Brodmann’s area 44/45, which is the motor area responsible
for controlling the muscles that allow us to produce words and speak. Located at the inferior frontal
gyrus, a lesion to this area results in Broca’s aphasia, also known as motor, non fluent, or expressive
aphasia.

In Broca’s aphasia, individuals have difficulties planning and executing movements necessary for the
production of speech. Therefore, they would talk slowly with poor fluency, and there will be increased
effort and pauses between words. The individual's comprehension of speech is intact, since Wernicke’s
area is preserved, but repetition is usually impaired. Individuals can have difficulty naming objects and
are usually aware of their problem, which can be very frustrating for them. You can use Broca to remind
yourself of the Broken Boca, where Boca means “mouth” in Spanish. When Broca’s area is damaged,
the nearby primary motor cortex may also be affected, so patients may also have accompanying
symptoms of weakness or paralysis to the contralateral face and upper limb.

Then we can have a lesion to Wernicke’s area, or Brodmann’s area 22/39/40, which is responsible for
processing and understanding both written and spoken language, allowing us to understand a sentence
and say it back comprehensively. Wernicke’s area is located in the superior temporal gyrus, so a lesion
here results in Wernicke’s aphasia, also known as sensory or receptive aphasia.

In Wernicke’s aphasia, individuals are fluent, well articulated, and may even speak faster than usual, but
their comprehension and repetition of spoken and written language is impaired. Because of this, they
don't find the right words to use and their speech appears meaningless, which has been described as
“word salad”. Quick tip, you can use Wernicke to remember Word salad. Unlike Broca’s aphasia,
individuals with Wernicke’s aphasia are unaware of their deficits, so they will speak as if nothing is
wrong. On a quick note, the optic radiation is in close proximity to Wernicke’s area, so individuals can
also have accompanying symptoms of contralateral superior quadrant visual field defects.

Both Broca’s and Wernicke’s areas are connected by a bundle of white matter tracts called the arcuate
fasciculus, which is located beneath the supramarginal gyrus and the frontoparietal operculum. Lesions
of the arCuate fasciculus cause Conduction aphasia. In conduction aphasia, individuals have preserved
fluency and comprehension of speech, but the repetition of spoken language is severely impaired. They
can also have difficulty naming objects and they are aware of their deficits.

And finally, when lesions are so extensive that they affect both Broca’s and Wernicke’s areas, that
causes global aphasia. With global aphasia, there’s a loss of speech production, and loss of
understanding of both written and spoken words. Individuals are not able to formulate, comprehend, or
repeat both spoken and written language.

Let’s take another break and see if you can remember the common symptoms of Broca’s aphasia? What
about Wernicke’s aphasia?

Okay, now let’s switch gears and look at lesions of the medial aspect of the precentral gyrus, also known
as the anterior paracentral lobule. This area is responsible for motor control of the lower limbs. Damage
to the paracentral lobule causes contralateral lower limb weakness and upper motor neuron lesion signs,
such as hyperreflexia and positive Babinski sign. Because the falx cerebri extends between the
hemispheres to the corpus callosum, a common and usually benign type of tumor called a parasagittal
meningioma can compress and affect the paracentral lobules of both hemispheres. Motor control to the
urinary sphincters is also located in the anterior paracentral lobule, so bilateral lesions can result in
urinary incontinence.

Now, let’s switch gears and cover Gerstmann syndrome, which is caused by a lesion of the angular
gyrus, located in the inferior parietal lobe of the dominant hemisphere. The angular gyrus is an area that
integrates visual, acoustic and somatosensory information in order to understand and solve problems,
particularly in regards to speech and number processing. The angular gyrus is supplied by the angular
and posterior parietal arteries, which are branches of the middle cerebral artery, and occlusion of these
arteries can result in Gerstmann Syndrome.

Gerstmann syndrome typically has 4 key features, which are left-right disorientation which is confusion
differentiating the left and right side of the body; finger agnosia which is the inability to recognize
individual fingers on your hand; acalculia which is the inability to perform mathematical calculations, and
agraphia which is the inability to write. Furthermore, some lesions may also result in aphasia, as well as
alexia which is the inability to read.

Now a similar lesion in the inferior parietal lobe of the non dominant hemisphere typically results in
hemispatial neglect syndrome. This area also receives its blood supply from angular and posterior
parietal arteries of the middle cerebral artery. Clinical features associated with this syndrome is spatial
neglect of the contralateral side of the body. Simply put, if the non-dominant hemisphere is the right one,
as is the case for right handed individuals, a lesion in the inferior parietal lobe results in a lack of
awareness of the left half of the body and the space around it. An example of this is construction
apraxia, where when asked to draw a clock, the individual only draws the right half of the clock but is
unaware they have not drawn the whole thing, or dressing apraxia where they only dress half of their
body. The individual also suffers from anosognosia, which is an indifference or lack of ability to
recognize their condition.

And just briefly, let’s cover the hippocampus, which is part of the limbic system and is involved in
memory formation. Individuals with bilateral hippocampal damage develop anterograde amnesia, which
means they are unable to make new memories, but they can still recall old ones. Neurons of the
hippocampal cortex are extremely vulnerable to ischemic damage, and injury begins just 5 minutes after
the onset of hypoxia. The hippocampus is so vulnerable to ischemia because it constitutes a watershed
area, which means it receives its blood supply from the terminal branches of two different arteries, the
anterior choroidal artery and the posterior cerebral artery, with limited collateral blood supply. Therefore,
there is a high risk for hippocampus injury in clinical situations which are more likely to damage these
vessels, such as hypertension, smoking, dyslipidemia and diabetes and situations with excessive
metabolic demand, like during an epileptic seizure,

Let’s take another short break and see if you can remember what are the syndromes and clinical
features of a dominant parietal cortex lesion? And what about non-dominant?

Ok, let's take a look at a lesion that affects the function of the basal ganglia, particularly a lesion of the
subthalamic nucleus. Normally, the subthalamic nucleus assists the basal ganglia in the regulation of
movements by exciting the globus pallidus internus, which inhibits the thalamus. Once the subthalamic
nucleus gets damaged, the globus pallidus internus stops inhibiting the thalamus, which overstimulates
the motor cortex, causing a condition called hemiballismus.

Hemiballismus usually presents as the sudden, involuntary and large amplitude flailing of one or both
extremities on the side of the body that is contralateral to the side of the lesion. To remember this, you
can use the word hemi-ball-ismus to recall that “half of the body goes ballistic”. The subthalamic nuclei
mainly receives blood from the small penetrating arteries of the middle cerebral arteries called the
lenticulostriate arteries and small branches from the posterior circulation. Due to the small size of these
arteries they are prone to blockage, especially in the setting of hypertension or diabetes. Strokes
occurring from these small arteries are called lacunar strokes.

Okay, now let’s discuss another condition called Kluver-Bucy syndrome, which can be caused by
bilateral lesions of each amygdala and surrounding cortex of the temporal lobe. These lesions usually
develop as a complication of viral encephalitis typically caused by herpes simplex virus type 1, which
usually affects the temporal lobe. Some other possible causes include temporal lobe surgery that aims
to treat epilepsy, head trauma that leads to temporal lobe contusions, or hypoperfusion of the bilateral
anterior choroidal arteries supplying the amygdala. Kluver-Bucy syndrome usually presents with three
types of disinhibited behavior: hypersexuality, or increased sexual drive; hyperphagia, or uncontrollable
desire to eat; and hyperorality, which is an urge for exploring objects by mouth. Other symptoms that can
develop are visual agnosia, or psychic blindness, where individuals can not recognize objects that they
see, in addition to personality changes, like passivity or docility.

Speaking about hunger, the hypothalamus contains two more nuclei that regulate hunger, which are the
lateral hypothalamic nucleus and the ventromedial nucleus. The lateral nucleus stimulates hunger and
represents the hunger or feeding center. Lesions of the lateral nucleus therefore cause loss of appetite,
and anorexia and starvation. The ventromedial nucleus, on the other hand, monitors blood glucose and
mediates satiety, and stimulation of this area reduces hunger. Injury or a lesion to this area can lead to
hyperphagia and obesity. In order to easily differentiate between these lesions, just remember that
Lateral Lesion makes you Lean, while the VentroMedial injury makes you Very Massive. Injuries which
can affect these nuclei include tumors, like a craniopharyngioma, infection, trauma, and vascular
disorders.

Finally, let's finish off by taking a look at the thalamus and its role in relaying somatosensory information.
The ventral posterolateral nucleus of the thalamus receives input from the spinothalamic tract and dorsal
columns of the contralateral side of the trunk and extremities, while the ventral posteromedial nucleus
receives input from the trigeminal pathway of the contralateral side of the face, and projects this
information to the cortex via the thalamocortical fibers in order to be processed. Therefore damage to
these two nuclei may result in complete contralateral sensory loss. This means that the individual loses
the sense of touch, tactile discrimination, vibration, proprioception, pain and temperature from the
contralateral side of the body, and may even lead to unsteady gait. Damage to these thalamic nuclei can
be due to vascular compromise or local compression from things such as tumours.

Quiz time! What happens when there is an injury to the subthalamic nucleus? Also, can you recall, injury
to which hypothalamic nuclei can cause anorexia and hyperphagia?

Alright, as a quick recap… Lesions of the prefrontal cortex can lead to personality changes, often
causing issues in decision making, socially unacceptable behaviour, and apathy towards appearance. A
lesion of the frontal eye field leads to deviation of the eyes to the ipsilateral side, while lesion of the
paramedian pontine reticular formation leads to deviation of the eyes to the contralateral side. Lesions to
Broca’s area can cause motor or expressive aphasia resulting in difficulty producing words and word
repetition. Wernicke’s area lesions can cause sensory or receptive aphasia, where individuals have
fluent speech but have difficulty with language comprehension. Damage to the arcuate fasciculus leads
to conduction aphasia leading to difficulties in repetition of spoken language, while damage to all these
areas leads to global aphasia.

Damage to the paracentral lobule causes contralateral lower limb upper motor neuron signs, with
bilateral damage also causing incontinence. Lesions of the dominant parietal cortex cause Gerstmann
syndrome which presents with left-right disorientation, finger agnosia, acalculia and agraphia, while
lesions of the non-dominant parietal cortex cause hemispatial neglect. Bilateral damage to the
hippocampus causes anterograde amnesia. Injury to the subthalamic nucleus results in hemiballismus.
Kluver-Bucy syndrome is caused by bilateral damage to both of the amygdala. Lesions of the lateral
hypothalamic nucleus lead to anorexia while lesions of the ventromedial nucleus lead to obesity.
Damage to the ventral posterolateral and posteromedial nuclei of the thalamus leads to the total
contralateral sensory deficit.
Anatomy clinical correlates: Cerebellum and
brainstem
The cerebellum, which is latin for ‘little brain’, is a part of the brain that plays a major role in posture,
balance, maintenance of muscle tone and coordination of skilled voluntary motor activities. The
brainstem, on the other hand, is a trunk-like structure that connects the higher parts of the central
nervous system with the spinal cord and serves as a center for life sustaining reflexes, such as breathing
and our heartbeat. Injury and disease to these parts of our brain can result in a variety of complex
neurological problems, which can even have life threatening consequences.

First off, let’s look at lesions of the cerebellum, which can be caused by a variety of things such as
stroke, space occupying lesions, infections, or drug toxicities. Remember that the cerebellar cortex can
be divided into three functional regions that are positioned longitudinally: the lateral zone; the
intermediate or paravermal zone; and the median or vermal zone.

One type of lesion is a lateral lesion of the cerebellum, which affects the lateral and intermediate zone of
the cerebellum and their associated cerebellar nuclei, which impairs voluntary movements of the
extremities. Think Lateral lesions affect Lateral structures! The lateral zone assists in motor planning,
and the intermediate zone has been shown to control muscles of the distal parts of the limbs, particularly
the hands and feet.

Clinically, lateral cerebellar lesions can cause ipsilateral limb ataxia, meaning loss of coordination of the
limb on the same side as the lesion. This can manifest as: intention tremor, which are involuntary,
trembling movements that occur with voluntary targeted movements; dysmetria, which is when
individuals overshoot or undershoot an intended position of the extremities for example during the finger
to nose test; dysdiadochokinesia which is the inability to perform fast alternating movements; a loss of
balance with a tendency to fall to the same side as the lesion, and finally reduced muscle tone on the
ipsilateral side.

Next, there are medial lesions to the cerebellum, which affects the vermis or median zone; the
flocculonodular lobe, or the fastigial nucleus. These areas modulate posture and coordination of the
trunk and proximal limbs, which are medial structures. So now remember a Medial lesion affects the
Medial structures!

Clinically, medial lesions cause truncal ataxia, which is when individuals have an unsteady and wide
based gait, sometimes referred to as drunken sailor gait. Lesions of the flocculonodular lobe tend to
cause vestibular symptoms, such as nystagmus, vertigo and vomiting. One of the most common causes
of medial cerebellar degeneration in adults is chronic alcohol abuse, while in children damage is often
caused by brain tumors such as medulloblastomas or ependymomas.

Let’s take a short break and see if you can compare clinical symptoms of the lateral versus medial
lesions to the cerebellum.

Now, the cerebellum sits in the posterior cranial fossa, covered by a fold of dura mater called the
tentorium cerebelli. This fold separates the cranial cavity into the infratentorial space containing the
cerebellum and parts of the brainstem, and the supratentorial space containing the cerebrum. On the
anterior part of the tentorium, there is an opening called the tentorial incisure or notch, through which the
brainstem passes. Since the cranium is a hard structure that can’t expand, if supratentorial intracranial
pressure rises, it can force parts of the brain to protrude through the tentorial incisure, causing a
transtentorial herniation.
In a central or downward transtentorial herniation, the whole brainstem is pushed downward, or caudally,
through the tentorial notch. This can occur because of severe cerebral edema, like after a traumatic
head injury. Other possible causes are space occupying lesions of the brain particularly in the
supratentorial space, such as tumors or hemorrhages. When herniation develops rapidly, it can tear off
small paramedian basilar artery branches that supply the medulla and pons. These small parenchymal
bleedings are called Duret hemorrhages. Unfortunately, these are usually fatal, seeing as the brainstem
plays a vital role in breathing and regulating heartbeat.

Another type of transtentorial herniation is called an uncal herniation, where the medial part of the
temporal lobe, called the uncus, is pushed through the tentorial notch where it compresses on the
midbrain of the brainstem. It’s usually caused by an expanding mass such as hematomas, tumors, or
abscesses in the temporal lobe.

One of the first structures that can become compressed is the oculomotor nerve, or cranial nerve III, on
the ipsilateral side. This nerve arises from the midbrain between the cerebral peduncles, providing motor
control to the eye muscles, as well as relaying parasympathetic innervation for the constriction of the iris
and accommodation of the lens. Since the parasympathetic fibers are positioned superficially to the
motor fibers, they’re the first to become compressed, resulting in a dilated and fixed pupil often referred
to as a ‘blown pupil’ and paralysis of accommodation of the ipsilateral eye.

As compression progresses, the motor fibers get affected as well, causing oculomotor nerve palsy,
resulting in the eye being pulled downwards and outwards due to unopposed action of the superior
oblique and lateral rectus muscles which are innervated by cranial nerve IV and cranial nerve VI
respectively. This can cause symptoms like double vision, diplopia, as well as potential ptosis as the
oculomotor nerve supplies the upper eyelid muscle. The uncus can also compress on the cerebral
peduncle where descending corticospinal fibers decussate, which may lead to contralateral hemiparesis.

In severe cases of midline shift due to uncal herniation, the brainstem can become compressed on the
contralateral edge of the tentorium cerebelli, called the Kernohan notch. This can result in the Kernohan
phenomenon, resulting in damage to the contralateral oculomotor nerve and cerebral peduncle which
causes a fixed and dilated contralateral pupil with oculomotor palsy, and ipsilateral hemiparesis.

Last but not least, there’s cerebellar tonsillar herniation, which can be caused by tumours or bleeds
leading to elevated intracranial pressure in the posterior cranial fossa. This increased intracranial
pressure causes the cerebellar tonsils to herniate down through the foramen magnum. The tonsils can
then compress the brainstem and its respiratory and cardiac centers, leading to coma and potential
death.

Let’s take another short break and see if you can recall three most common types of herniations
involving the brainstem and cerebellum.

Let’s switch gears and talk about the lesions of the brainstem, starting with the midbrain. Lesions or
compression of the tectum or dorsal part of the midbrain at the level of the superior colliculi can lead to
dorsal midbrain syndrome, also known as the Parinaud syndrome. They involve the vertical gaze center
causing vertical gaze palsy, where individuals are unable to perform upward or downward conjugate
gaze. Lesions also involve the Edinger Westphal nuclei, causing light-near dissociation, where pupils do
not react to light but react to accommodation.

Damage to the dorsal midbrain in Parinaud Syndrome can also cause bilateral eyelid retraction,
revealing the sclera above the superior corneal limbus, which is known as the Collier sign. This
mechanism is not fully understood, but is thought to be due to overstimulation of the upper eyelid
muscles. Finally when an individual tries to look upwards, there may be irregular, jerky nystagmus that is
associated with convergence and retraction of both eyes, particularly with upward gaze, and this is
called convergence-retraction nystagmus. This can happen because of sustained contraction of the
medial rectus and other extraocular muscles. Parinaud syndrome can be caused by a stroke to the
dorsal midbrain, a tumour of the pineal gland, called a pinealoma, and hydrocephalus.

Now, the midbrain is home to many structures, one of which is the medial longitudinal fasciculus, or MLF
for short. Damage to the MLF can cause what's called internuclear ophthalmoplegia, which is an
impairment of horizontal conjugate gaze. Remember that for horizontal gaze, the frontal eye field sends
a signal to the contralateral paramedian pontine reticular formation, which then communicates with the
abducens nucleus on that side to act on the contralateral lateral rectus muscle of the frontal eye field
where the signal was sent. Simultaneously, fibers from that abducens nucleus also sends fibers through
the MLF tract to communicate with the oculomotor nucleus on the ipsilateral side of the original signal
from the frontal eye field to act on the medial rectus muscle of the ipsilateral eye, allowing both eyes to
coordinate horizontal gaze together in the same direction.

Unilateral damage to the MLF causes the inability to adduct the ipsilateral eye, while the contralateral
eye can still perform abduction. So, for example, if the right MLF gets damaged and the individual tries
to look to the left, the right eye stays fixed while the left eye abducts, causing diplopia. The abducted eye
may also undergo nystagmus.

Unilateral damage of the MLF is usually due to lacunar infarcts of pontine arteries from the basilar artery
in the area of the midbrain and dorsal pons. Bilateral MLF damage can also occur, and it’s usually
associated with multiple sclerosis. Bear in mind that convergence and pupillary light reflex are not
affected by MLF damage, because they use different pathways.

Lower in the pons, we can also have a lesion to the paramedian pontine reticular formation, or PPRF,
which is the subcortical lateral gaze center. As we said, the PPRF receives input from the contralateral
frontal eye field and sends signals to the abducens nucleus on the same side to stimulate the lateral
rectus muscle of that ipsilateral eye. The signal is simultaneously sent through the medial longitudinal
fasciculus to the contralateral oculomotor nuclei to stimulate the medial rectus muscle of the
contralateral eye. When there is a lesion to the PPRF both eyes deviate to the contralateral side, away
from the brainstem lesion. This is in contrast to frontal eye field lesions where both eyes will deviate to
the ipsilateral side of the lesion, or towards the side of the lesion.

So, for example, when eyes are deviated to the right, the lesion can either involve the left PPRF or the
right frontal eye field. Some possible causes for lesions to the PPRF include ischemic or hemorrhagic
stroke involving the paramedian branches of the basilar artery that supply it.

Now, let’s take a look at the ventricular system, which is a network of cavities housing cerebrospinal
fluid, or CSF for short, within the brain. When there is an increase of CSF volume, this can lead to a
dilation of the ventricles resulting in a condition called hydrocephalus.

Normally, CSF is produced by the choroid plexuses of the ventricles and flows from the two lateral
ventricles, through the third and fourth ventricles, and ultimately to the subarachnoid space to be
reabsorbed. The narrowest aspect of the ventricular system is the cerebral aqueduct, also called the
aqueduct of Sylvius, which can be found within the midbrain and connects the third to the fourth
ventricle. This is the most common site of obstruction that can lead to buildup of CSF and subsequent
hydrocephalus.

The cerebral aqueduct can be blocked due to intraventricular hemorrhages, bacterial and fungal
infections, or due to congenital aqueductal stenosis. Other possible causes are tumors or masses, like a
glioma or a colloid cyst, that compress and further narrow the cerebral aqueduct. Clinically, this can
result in noncommunicating or obstructive hydrocephalus, which causes headaches, nausea, vomiting,
papilledema, coma and even death.
Let’s take another break and see if you can recall two conditions and their clinical features that can
develop from the compression of the dorsal midbrain by pinealoma.

Alright! Now let’s move on to the reticular activating system, or RAS for short, which is a complex
processing center found in the midbrain in an ill defined area called the reticular formation. The reticular
formation is responsible for controlling consciousness and arousal, receiving afferent information from
multiple sensory pathways such as auditory, visual, and somatosensory centers, and relaying this
information to the cerebral cortex which processes this information. It is thought our degree of
wakefulness and awareness of oneself in the environment is related to the degree of activity coming
from the reticular formation, where things such as pain sensation may stimulate the reticular formation
and subsequently increase arousal. Therefore, lesions of the midbrain, such as bilateral pontine
hemorrhage, can damage the RAS, reducing levels of arousal and consciousness. This can cause
lethargy, stupor, and coma.

Okay, let’s look at another midbrain structure called the red nucleus, which helps coordinate muscle tone
and body posture. The red nucleus is located in the tegmentum or ventral part of the midbrain, and gives
rise to the rubrospinal tract that descends and acts on the flexor muscles of the upper limb. Severe
lesions of the proximal midbrain above the red nucleus damages the descending inhibitory signals from
the cortex to the spinal cord and red nucleus. As a result, the red nucleus is overstimulated, sending
signals to the flexor muscles of the upper extremities through the rubrospinal tract, increasing their tone.
Furthermore, other descending motor tracts such as the vestibulospinal and reticulospinal tracts also
lose inhibitory control, and they also overstimulate the extensor muscles of the body. This leads to a
characteristic pathological posturing, called decorticate, or flexor posturing, where upper extremities are
flexed with the wrists and hands flexed into fists near the chest, while the lower extremities are extended
and internally rotated with foot plantarflexion.

On the other hand, lesions at or below the red nucleus damage the rubrospinal tract, so the flexors of
the upper limbs are no longer stimulated. In turn, the vestibulospinal and reticulospinal tracts
overstimulate the extensor muscles of the entire body, causing the characteristic decerebrate, or
extensor posturing, where the upper extremities are adducted, extended and in hyperpronation, while
the lower extremities are also extended with foot plantarflexion. Decerebrate posturing is associated with
a worse prognosis. Pro tip: to easily differentiate between these two postures, just remember that in
decorticate posturing the arms are close to the heart, or cor in latin.

Let’s take a final break and see if you can differentiate between lesions to the frontal eye field,
paramedian pontine reticular formation and medial longitudinal fasciculus.

Lastly, let’s look at the vomiting center of the brain, which is responsible for our vomiting reflex. The
vomiting center is coordinated by the nucleus tractus solitarius, or solitary nucleus, found in the medulla
oblongata, and it receives input from multiple sources to initiate the vomiting reflex. First, it receives
information from the chemoreceptor trigger zone, or CTZ which is located on the dorsal surface of the
medulla on the floor of the fourth ventricle in an area called the area postrema, or area ‘puke’- strema.
The CTZ doesn’t have a well developed blood-brain barrier which means that it can be exposed to
chemical substances found in the blood and CSF which can directly activate it and initiate the vomiting
reflex. These substances include toxins, hormones, and drugs such as chemotherapy drugs, as well as
alcohol. It also receives input from visceral afferent fibers coming from the GI tract via the vagus nerve.
For example, Chemotherapy drugs can stimulate vagal afferent nerve fibers receptors in the bowel wall
of the gastrointestinal tract, which ascend and trigger the vomiting reflex in the CTZ. Additionally, it also
receives input from the vestibular system, which can explain car and boat sickness.

Summary
Alright, as a quick recap… Lateral lesions to the cerebellum cause limb ataxia and loss of balance, while
the medial lesions cause truncal ataxia and nystagmus. Increased intracranial pressure can cause
central or downwards transtentorial herniation of the brainstem, tearing basilar artery branches supplying
the medulla and pons, and may be life threatening. In uncal transtentorial herniation, the uncus
compresses the ipsilateral oculomotor nerve and the descending motor pathways to the contralateral
body in the midbrain. In cerebellar tonsillar herniations, the respiratory and cardiac centers of the
brainstem are compressed, which can lead to coma and death.

Parinaud syndrome refers to a lesion of the dorsal midbrain that causes vertical gaze palsy, light-near
dissociation, Collier sign and convergence-retraction nystagmus. Lesions of the medial longitudinal
fasciculus cause internuclear ophthalmoplegia and impaired horizontal gaze characterized by inability to
adduct the ipsilateral eye, diplopia and nystagmus of the contralateral eye. Lesion of the paramedian
pontine reticular formation leads to the deviation of the eyes to the contralateral side.

Blockage of the cerebral aqueduct in the midbrain can lead to noncommunicating hydrocephalus that
presents with headaches, nausea, vomiting, papilledema, coma and even death. Lesions of the reticular
activating system of the midbrain reduce level of consciousness and may lead to coma. Lesions above
the red nucleus present with decorticate posturing while lesions below it present with decerebrate
posturing. The vomiting center of the brain activates our vomiting reflex, and receives input from the
chemoreceptor trigger zone in the area postrema which senses emetogenic substances from blood and
CSF, visceral afferents from the GI tract, and the vestibular system.