Basal ganglia

The basal ganglia, or basal nuclei, are a group of subcortical structures found deep within the
white matter of the brain. They form a part of the extrapyramidal motor system and work in
tandem with the pyramidal and limbic systems.

The basal ganglia consist of five pairs of nuclei: caudate nucleus, putamen, globus pallidus,
subthalamic nucleus, and substantia nigra. These nuclei are grouped into broader clusters;

 Striatum, which further consists of the: 

 o Dorsal striatum, made by the caudate nucleus and putamen
o Ventral striatum, composed of nucleus accumbens and olfactory tubercle (this part of
the striatum is considered part of the limbic system)
 Globus pallidus, that consists of an internal segment (GPi) and an external segment (GPe)
 Subthalamic nucleus
 Substantia nigra

The function of the basal ganglia is to fine-tune the voluntary movements. They do so by
receiving the impulses for the upcoming movement from the cerebral cortex, which they process
and adjust. They convey their instructions to the thalamus, which then relays this information
back to the cortex. Ultimately, the fine-tuned movement instruction is sent to the skeletal
muscles through the tracts of the pyramidal motor system. Basal ganglia mediate some and other
higher cortical functions as well, such as planning and modulation of movement, memory, eye
movements, reward processing, and motivation.

Key facts about the basal ganglia

Definition A group of subcortical nuclei that fine-tune the voluntary motor activity

Striatum
Dorsal striatum (caudate nucleus and putamen)
Ventral striatum (nucleus accumbens and olfactory tubercle)
Parts
Globus pallidus
Subthalamic nucleus
Substantia nigra

Planning and modulation of movement, memory, eye movements, reward processing,

Function
motivation

Overview

The basal ganglia are one of the components in the neural chain that controls the voluntary motor
activity. The supreme component of this chain is the cerebral cortex. It generates the commands
that define the motor activity of all skeletal muscles in the body. These commands descend
through the pathways of the pyramidal system and synapse with the cranial nerve nuclei and
motor neurons of the spinal cord. From here, the motor commands travel via the cranial and
spinal nerves in order to reach the target muscles.
However, some extent of modulation and refinement of these cortical signals is necessary so that
their motor execution at the muscular level happens as smoothly and precisely as planned. These
adjustments are performed in the “accessory motor centers”, with the most important one being
the basal ganglia. Despite being physically separated from each other, the basal ganglia are
interconnected with many pathways making them a strong functional unity. Functionally, the
basal ganglia are referred to as the extrapyramidal motor system although this term nowadays
is not used widely. They receive and process the inputs from wide areas of the cerebral cortex,
after which they relay it back to the thalamus. The thalamus then forwards those refined inputs
further across the brain, mainly back to the cortex, and to the brainstem.

Phylogenetically, the oldest motor centers are the spinal cord and the reticular formation of the
brainstem. With the development of the vertebrates, the brain gained new motor centers; the
paleostriatum (globus pallidus) and neostriatum (caudate nucleus and putamen), which grew
together with the cerebral cortex. Over time, the cerebral cortex and pyramidal system grew
larger and developed a myriad of functional properties. With this, the extrapyramidal system fell
under the control of the new, pyramidal, motor system, being left with the autonomy to control
the nuances of cortical activity, i.e. to modulate the movements.

Components
Striatum

The striatum is a complex nucleus located deep in subcortical structures of the forebrain, inside
the insular lobe. 
In the introduction, we mentioned that the striatum is composed of the dorsal and ventral parts.
The ventral striatum is considered part of the limbic system, thus we will not describe it
furthermore.  

The dorsal striatum on the other hand is a component of the basal ganglia and usually, it is this
part that is called “striatum” in the literature, when we describe the basal ganglia. The dorsal
striatum (or simply the striatum) consists of two parts: the caudate nucleus and putamen. The
parts of striatum are separated by the internal capsule, whose myelinated fibers radiate through
striatum, giving it a characteristic striped appearance.  Together with the globus pallidus, the
striatum forms a structure called corpus striatum.

The striatum is the main input unit of the basal ganglia. It receives excitatory glutamatergic
inputs from the cerebral cortex, whose synapsing pattern reflects the topography of the cortex.
This means that the caudal parts of the cortex project to the caudal part of the striatum, while
the rostral parts of the cortex project to the rostral part of the striatum.

The substance of the striatum is mainly (80-95%) composed of projection neurons (medium-
sized spiny neurons) and minor interneurons. The projection neurons are covered by numerous
spines, hence their name. Functionally, they are inhibitory neurons that use GABA as a
neurotransmitter. The axons of these neurons form the direct and indirect pathways of basal
ganglia, which project into the globus pallidus and substantia nigra
The interneurons of the striatum lack spines and are classified into four groups: 

 Cholinergic large aspiny neurons

 Parvalbumin-containing GABAergic neurons 
 Somatostatin/nitric oxide synthase-containing GABAergic neurons
 Calretinin-containing GABAergic 

These neurons project to the thalamus, SNc, cerebral cortex, and control the activity of those
regions.

Caudate nucleus

The caudate nucleus is an elongated C-shaped nucleus that lies anterior to the thalamus, just
lateral to the lateral ventricles and medial to the internal capsule.

The caudate nucleus consists of the head, body and tail.  The head of the nucleus contributes to
the lateral wall of the lateral ventricle. The tail of the caudate nucleus forms the roof of the
inferior horn of the lateral ventricle. It arches over the ventral surface of the thalamus, enters the
temporal lobe and terminates by connecting with the amygdala. The rostral portion of the
caudate nucleus is continuous with the putamen, and inferiorly it’s bordered by nucleus
accumbens.

The functions of the caudate nucleus lie within the spectrum of functions that we described
previously in the section about the striatum. More specifically, the caudate nucleus integrates
sensory information about the spatial position of the body and according to that, it sends the
information about the necessary fine tunes of the motor response to that stimulus to the thalamus.
Additionally, it contributes to body and limb posture and the speed and accuracy of directed
movements.

Besides motor control, the caudate nucleus is involved in many tasks, such as memory, goal-
pursuit, learning, language processing, emotions, etc.

Putamen

The putamen is a round structure situated at the base of the forebrain. It is the most lateral of the
basal ganglia on the axial section of the brain. The putamen lies laterally to the globus pallidus
and medially to the external capsule, covering it like a shell and extending both rostrally and
caudally. It is encircled by the caudate nucleus, from which it is separated by the internal
capsule. 

The putamen and globus pallidus are separated by a thin layer of white matter called the medial
medullary lamina.

The main function of the putamen is to regulate motor functions and influence various types of
learning and it employs dopamine to perform its functions.
Nucleus accumbens and olfactory tubercle

Nucleus accumbens and olfactory tubercle are paired structures, situated at the base of the
forebrain. They are components of the ventral striatum and component of input nuclei for the
ventral tegmental area (VTA). 

The nucleus accumbens is found in the rostral forebrain, where the head of the caudate nucleus
and putamen meet. The olfactory tubercle, however, is situated ventral to the nucleus accumbens,
between the optic chiasm and olfactory tract.

Both structures are not involved in the movements regulation, rather they play an important role
in the “reward circuit” and are referred to as “limbic-motor interface”. When we do anything
rewarding (e.g. food, drugs, sex), dopamine neurons in an area of the brain called the ventral
tegmental area (VTA) are activated. These neurons project to the nucleus accumbens and the
olfactory tubercle, and when they are activated it results in an increase in dopamine levels.

Globus pallidus

The globus pallidus is a paired subcortical structure, situated medially to the putamen and
composed of inhibitory GABAergic projection neurons, which fire spontaneously and irregularly
at high frequency. It is divided by a vertically placed sheet of white matter, the medial (internal)
medullary lamina, into external (GPe) and internal  (GPi) segments. 

The superior and medial aspects of the globus pallidus are in contact with the internal capsule.
The capsule separates the caudate nucleus from the globus pallidus. The inferior surface of the
globus pallidus is in contact with the subthalamic nucleus and zona incerta, which separate it
from the thalamus. Anteriorly, the globus pallidus is closely related to the substantia
innominata and the hypothalamus. More caudally, it is in close proximity to the optic tract. And
because the putamen and globus pallidus are in close connection, with their combined shapes
resembling a bean, they are referred to as the lenticular nucleus.

Both the GPe and GPi play an essential role in the modulation of the motor program, more
specifically in the direct and indirect pathways.

They both receive inhibitory GABA-ergic input from the striatum, through striatopallidal
fibers, also known as Wilson’s pencils. Fibers that project from the striatum to the internal part
of the globus pallidus are part of the indirect pathway of the motor loop. Meanwhile, fibers that
connect the striatum with the external part of the globus pallidus are part of the direct pathway of
the motor loop.

The output fibers of the globus pallidus are the pallidothalamic tracts. They divide into: ansa
lenticularis, lenticular fascicles and thalamic fasciculus. Together they are part of the Forel’s
field. These structures are responsible for connecting the globus pallidus and thalamic nuclei.
The globus pallidus is involved in the constant subtle regulation of movement to create smooth
and precise motor actions and has a primarily inhibitory action that balances the excitatory action
of the cerebellum.

Subthalamic nucleus
Subthalamic nucleus
Nucleus subthalamicus
Synonyms: Nucleus of Corpus Luysii, Nucleus of Luys

The subthalamic nuclei (STN), also known as Luys’ bodies, are small biconvex paired
structures located within the subthalamus. The subthalamic nucleus is not an anatomical part of
the basal ganglia. However, given their functional connection, the subthalamus is listed as a
functional part of the basal ganglia. 

The subthalamic nucleus lies at the junction of the diencephalon and midbrain, ventral to the
thalamus and ventro-lateral to the red nucleus. Anteriorly its bordered by the substantia nigra and
medially by the internal capsule. STN is closely related to the Forel’s fields and the
pallidothalamic fibers, which entwine around its ventral and medial borders before arching
back over its dorsomedial surface as the thalamic fasciculus. These fibers thus tend to separate
the zone incerta from the subthalamic nucleus below and the thalamus above. 

The subthalamic nuclei are composed of excitatory glutamatergic projection neurons. It

receives excitatory inputs from the frontal cortex in a somatotopically organized manner. Based
on this, the subthalamic nucleus is divided into three parts: 

 The dorsal (motor) part, which receives inputs from the primary motor cortex
 The ventrolateral (associative) part, which receives inputs from the prefrontal cortex and
frontal eye fields, and
 The ventromedial (limbic) part, which receives inputs from the anterior cingulate cortex.

The function of the subthalamic nucleus is unknown, but some theories suggest its crucial role in
the hyperdirect pathway in order to modulate the planned motor program. Additionally,
considering the nucleus firing pattern, the subthalamic nucleus is considered the “pace-maker” of
the basal ganglia.

Substantia nigra

The substantia nigra is a small motor nucleus, within the anterior part of the midbrain, between
the cerebral peduncle and tegmentum of the midbrain. Despite its location in the midbrain,
function-wise it is considered part of basal ganglia. 

The substantia nigra consists of two parts with very different connections and functions: the pars
compacta (SNc) and the pars reticulata (SNr). It divides the cerebral peduncles from the
tegmentum within both sides of the midbrain. Dorso-medially it is bordered by the subthalamic
and red nuclei, and laterally by the medial lemniscus and the geniculate bodies. 
The pars compacta comprises the dorsal portion of the substantia nigra. It consists of numerous
closely packed melanin-filled neurons that give the substantia nigra its distinctive dark color. The
pars reticulata lie ventral to pars compacta. It is larger than the pars compacta, but it contains
fewer cells than it. 
Medially to the substantia nigra is a zone called the ventral tegmental area. It is a small group of
scattered cells that have similar functions to the pars compacta and may really be considered as
an extension of this part.

The pars compacta serve mainly as an output to the basal ganglia circuit, supplying the striatum
with dopamine, through specific D1 and D2 neurons within the nigrostriatal pathways. The pars
reticulata, though, serves mainly as an input, conveying signals from the basal ganglia to the
thalamus.

The loss of dopamine neurons in SNc is believed to be the reason for the development of
Parkinson's disease and some other parkinsonic syndromes.

Struggling with remembering the function of each basal nuclei? Try to understand the
importance of active recall in learning anatomy.

Connections

The major efferents (outputs) of the basal ganglia consist of the neurons that project towards
the thalamus and brainstem from the internal part of globus pallidus and the reticular part of the
substantia nigra. These are ansa lenticularis and lenticular fasciculus.
Afferents (inputs) to the basal ganglia include the following:

 From the entire cerebral cortex - through the corticostriatal pathway, which is the largest
afferent connection of the basal ganglia. The fibers are glutamatergic – releasing the
neurotransmitter glutamate to excite the striatal neurons.
 From the substantia nigra - fibers arising in the pars compacta of the substantia nigra reach the
striatum, forming the nigrostriatal connections. This very important connection of the basal
ganglia ensures a continuous supply of dopamine to the striatum, which promotes the
regulation of direct and indirect pathways. 
 From the thalamus - fibers from the thalamus to the basal ganglia form the thalamostriatal
connections or the thalamostriatal afferents. Those connections or pathways are glutamatergic
and responsible for excitatory effects on the cerebral cortex and brainstem.
 From the reticular formation of the brainstem (specifically from the midbrain) - afferents from
the reticular formation are noradrenergic and responsible, besides vital functions, for
modulation and regulation of flexor and extensor muscles tonus in voluntary movements.

In summary, the basal nuclei can be grouped functionally into four categories:

1. Input nuclei: striatum and subthalamic nucleus, which receive cortical inputs
2. Output nuclei: internal part of globus pallidus and reticular part of substantia nigra, which
project outside the basal ganglia to the thalamus and brainstem
3. Connecting nucleus: external part of globus pallidus, which connects the input nuclei to the
output nuclei.
 4. Modulatory nucleus: compact part of substantia nigra, which modulates the activity of the basal
ganglia.

Pathways

The basal nuclei modulate motor function through various pathways in order to initiate,
terminate, or modulate the extent of the movement.

These are the following:

 Direct pathway: which is responsible for the initiation of the movement. In order to make this
happen, the direct pathway funnels the information from the striatum to GPi/SNr via GABAergic
inhibitory projections. This inhibition releases the firing from the thalamocortical neurons to
initiate the movement.
 Indirect pathway, which has a net excitatory effect on the same structures. The neurons from
the external part of globus pallidus send inhibitory fibers to the subthalamic nucleus instead of
sending directly to the thalamus (hence its name “indirect”). From the subthalamic nucleus,
neurons send their axons to the internal part of the globus pallidus and reticular part of the
substantia nigra and then continue as the direct pathway with GABAergic inhibitory neurons to
the thalamus and glutamate excitatory efferents to the cortex. So, functionally, the striatum
inhibits the external globus pallidus, and that causes disinhibition of the subthalamus.
 Hyperdirect pathway, via which the internal part of globus pallidus and reticular part of the
substantia nigra receive strong excitatory signals from the cortex directly through STN and has a
shorter conduction time compared to the direct and indirect pathways. The hyperdirect
pathway consists of neurons projecting from the cortex directly to the subthalamic nucleus
(STN), skipping the striatum. Therefore, the glutamatergic excitatory neurons of the STN can
then excite the GPi/SNr thus suppressing thalamic activity on the cerebral cortex and increasing
inhibitory influences on the upper motor neurons.

Considering the conduction path and time, we can say that the hyperdirect and indirect
pathways make clear initiation and termination of the selected motor program, while at the same
time canceling other competing motor programs.

 If you want to learn more about the pathways of the basal ganglia please read the article about
the direct, indirect and hyperdirect pathways of basal ganglia.

Functions

There is a growing number of studies focused on the functions of the basal ganglia, as its
functions are yet to be fully understood. However, the following are functions have been clearly
established by now:

 Planning and modulation of movement pathways

 Reward processing and motivation
 Decision making
 Working memory
  Eye movements

Moreover, the basal nuclei use proprioceptive feedback from the periphery to compare the
movement patterns generated by the cerebral cortex with the actual movement, so that the
movement is subject to ongoing refinement by a continuous servo-control mechanism.

Also, the basal ganglia have been shown to play an important role in motivation. Considering
that the basal ganglia circuits are influenced heavily by extracellular dopamine, high levels of it
have been linked to satiated “euphoria”, medium levels with seeking and low with aversion. The
activation of the basal nuclei pathway that causes the disinhibition of the thalamus, leads to
activation of the prefrontal cortex and ventral striatum. There is also evidence that other basal
ganglia structures including the globus pallidus, pars medialis and subthalamic nucleus are
involved in reward processing.

Regarding memory, the same structures in the prefrontal cortex are shown to be involved in the
memory gates and focus. By using the basal ganglia’s direct and indirect pathways as a relay
between the input information from surroundings to the cerebral structures involved in memory
storage.

Clinical notes

Degeneration of the basal ganglia and, consequently, its dysfunction can lead to several
neurological conditions. The characteristic feature of the basal ganglia lesion is a movement
disorder in which there is either too little movement (hypokinesia), too much (hyperkinesia), or a
combination of both, depending on the location and extent of the affected structure.

Bradykinesia represents a generalized slowness of movement and is the most common

hypokinesia. The prototypical hypokinetic movement disorder is Parkinson's disease. Parkinson's
disease results from the degeneration of the dopaminergic nigrostriatal projection. In substantia
nigra pars compacta, dopaminergic neurons are decreased, so the dopaminergic output to the
striatum is decreased. This leads to the reduction of the inhibition of the indirect (inhibitory)
pathway and reduction of the excitation of the direct (excitatory) pathway resulting in
bradykinesia, which is the main symptom of Parkinson's disease. The condition is also
characterized by resting tremor, rigidity and postural instability.

Parkinsonism is the umbrella term used to describe the symptoms of bradykinesia, tremor, and
rigidity. Parkinson's disease is the most common type of parkinsonism, but there are also some
rarer types where a specific cause can be identified (ex. drug-induced parkinsonism, progressive
supranuclear palsy).

The hyperkinetic movement disorders, unlike Parkinson's disease, are characterized by too much
movement. The different clinical types of hyperkinesia include dystonia, chorea, ballism,
athetosis tremor, myoclonus, tics, and others.
Dystonia is characterized by involuntary, sustained muscle contraction that leads to abnormal
postures of the neck, toes, hands, or other parts of the body. The exact mechanism of dystonia is
not completely clear. However, the best evidence suggests that there is relevant hypoactivity in
the indirect (inhibitory) pathway resulting in less inhibition and more unwanted movement. The
clinical types of dystonia classify as either focal, that affects only isolated muscle groups (ex.
Spasmodic Torticollis), or generalized, that typically affects muscles in the torso and limbs, and
sometimes the neck and face (ex. DYT1 mutation).

Chorea, ballism, and athetosis are irregular, involuntary, jerky, and purposeless, "dance-like"
movements. They are relatively similar in physiology. Ballism has a more proximal (shoulder
and hip) origin and is slower than chorea. Athetosis, in nature, is slower and more twitching.

Several disorders are presenting with chorea, and the most common is Huntington's disease. It is
characterized by the degeneration of striatal GABAergic neurons, causing atrophy of the head of
the caudate nucleus. Huntington's disease is a genetic, autosomal dominant disease manifested by
chorea, dementia and psychiatric abnormalities, bulbar symptoms, and gait disturbance.

Hemiballismus (ballism on the one side of the body) typically occurs after a lesion (ex. stroke,
neoplasm) adjacent to the subthalamic nucleus.

Tremor is an abnormal involuntary, rhythmic and oscillatory movement of the hand, head, or
other parts of the body. Usually, the basal ganglia, cerebellum, and the subthalamic nucleus are
involved. However, intention tremor is also seen in disorders of the cerebellum, in which case,
the tremor comes when the individual tries to perform a voluntary movement (intention tremor).

Myoclonus is a jerky, involuntary, and usually arrhythmic movement. To imagine how

myoclonus looks like, think of body jerks as one is falling asleep, this is physiological
myoclonus. A full list of myoclonus-related disorders is very long. Myoclonus can present in
some hereditary diseases (ex. Juvenile myoclonic epilepsy) and any central nervous syndrome
lesions like tumor, hemorrhage, stroke or abscess.

Tics are brief, stereotyped semi-voluntary movements, which means that unlike other movement
disorders, they are partially suppressible. Tics can be either motor (motor tics) or sounds (vocal
tics). They are common in children and can appear as the result of direct brain injury (ex. head
trauma or encephalitis). However, most of them are idiopathic and are part of the spectrum of
Gilles de la Tourette syndrome or another idiopathic tic disorder.

Most of the diseases typically have a large phenomenology of movement disorders, which
includes both hypo- and hyperkinesia. In any case of young-onset parkinsonism, dystonia or
other movement disorders, Wilson's disease should be considered as this disorder is treatable and
the effects of non-recognition may be severe. An autosomal recessive defect causes this disease
in copper transport and the neurological manifestations are due to the accumulation of copper in
basal ganglia, especially in the putamen. Because copper also accumulates in other tissues, like
eyes, Kayser–Fleischer rings, a brown-green pigmentation of the Descemet membrane of the eye
are diagnostic signs of Wilson's disease.