Basal ganglia pathways

Each day we are doing thousands of movements, from walking to writing and so many more. Have
you ever wondered which system is responsible for organizing and smoothening all these
movements? The answer to that question lies within the structure called basal ganglia.

The basal ganglia are a collection of subcortical structures consisting of several connected nuclei
located in the brain. They are called the caudate nucleus, putamen, globus pallidus, subthalamic
nucleus, and substantia nigra (the last two are only functionally connected and related to this
system).

Three major pathways emerge from the basal ganglia, which project onto various structures of the
brain, communicating with them. They are called the direct (excitatory), indirect (inhibitory)
and hyperdirect (inhibitory) pathways. The activity of the direct and indirect pathways are
modulated by D1 and D2 dopamine receptors contained in the substantia nigra, pars compacta. The
hyperdirect pathway bypasses the striatum and therefore the substantia nigra compacta does not
play a role in its regulation. 

TThe “basal ganglia” or basal nuclei, refers to a group of nuclei situated deep within the cerebral
hemispheres and form a major portion of the “extrapyramidal system”. This system receives inputs
from wide areas of the cerebral cortex and returns it, via the thalamus, to the cortex and brainstem.

The major structures that compose the basal ganglia are:

 the striatum (Str), which includes the caudate nucleus and the putamen, 

 the globus pallidus (GP) which is divided into two segments, the internal (GPi) and external parts
(GPe), 
 the subthalamic nucleus (STN)
 the substantia nigra (SN) which is also divided into two parts, the reticular part (SNr) and the
compact part (SNc).
All these structures lay in the core of the cerebral hemispheres, wrapped around by
the ventricular system and separated between them with an abundant network of descending and
ascending pathways that connect the cerebral cortex and the brainstem.

The basal ganglia or nuclei are heavily interconnected and play an important role in motor
planning and modulation. By choosing the intended movement, the basal ganglia use different
pathways to initiate and terminate the motor program, by controlling the muscle tone, muscle
length, speed, and strength of the movement by using the pyramidal system as the executor.

To make this possible, the basal ganglia use three pathways: the direct, indirect and hyperdirect
pathway.

Direct pathway Type: Excitatory

 Pathway: cortex -> striatum -> globus pallidus, pars interna -> thalamus ->
motor cortex -> spinal cord / brainstem
Function: movement initiation

Indirect pathway Type: Inhibitory

Pathway: cortex -> striatum -> globus pallidus, pars externa -> subthalamic
nucleus -> globus pallidus, pars externa -> thalamus -> motor cortex ->
spinal cord / brainstem
Function: movement termination
Direct pathway

The direct pathway starts from the cortex and projects to the striatum (caudate nucleus and
putamen) with excitatory glutamatergic (glu) neurons. The neurons from the striatum, which are
inhibitory GABAergic, send their axons to the medial (internal) globus pallidus and substantia
nigra, pars reticulata (SNr). 

The neurons from the internal globus pallidus and SNr send their axons to the thalamus, and they
are also inhibitory. The fibers that travel from the pallidum to the thalamus, form two white matter
fascicles called ansa lenticularis and lenticular fasciculus, that fuse into one pathway called
thalamic fasciculus just before they enter the thalamus.

From the thalamus, excitatory pathways go to the cortex (prefrontal, premotor and supplementary

cortex) where they affect the planning of the movement by synapsing with the neurons of
the corticospinal and corticobulbar tracts in the brainstem and spinal cord

.
 In summary, we have the following connections:

 Cortex - Striatum (glu)

 Striatum - GPi/SNr (GABA)
 GPi/SNr - Thalamus (GABA)
This entire system functions on the principle of positive feedback. Since the two of the inhibitory
synapses are serially connected, that means that the first inhibitory neuron (striatum) suppresses the
activity of the second inhibitory neuron (globus pallidus). The result of this is a reduction of the
inhibitory influence that the globus pallidus has over the thalamus, so-called disinhibition of the
thalamus, which is equivalent to the excitation of the motor cortex. So the final function of the
direct pathway of the basal ganglia is to excite the motor cortex or to increase the motor activity.
Indirect pathway

This pathway begins (like the direct pathway) from the cortex, projecting to the striatum. Instead of
sending axons directly to the GPi and SNr, they project to the external globus pallidus. 

The neurons from the GPe 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 GPi/SNr 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. For that reason, the neurons of the subthalamus become more active, and they
excite the internal segment of the globus pallidus which in the end, inhibits the thalamic
nuclei. The final result of this pathway is a decreased activity of the cortical motor neurons and
consequential suppression of the extemporaneous movement.
Disorders of the basal ganglia are classified into two categories:

hypertonic-hypokinetic and hypotonic-hyperkinetic.

Hypertonicity is an abnormal increase of the muscle tone in response to passive stretch. As we

have learned so far, when the indirect pathway of the basal ganglia is stimulated, it sends signals to
the motor cortex and brainstem, which ultimately inhibit muscle tone. Following a lesion of the
basal ganglia, this inhibitory influence is lost and hypertonicity is manifested contralateral to the
side of the lesion.

Dyskinesia is a presence of the unintentional purposeless movements. Dyskinesias are classified

further as:

Hypokinesia

Hyperkinesia

Hypotonic-hyperkinetic disorders

These disorders are caused by a disturbance of the indirect loop that causes a loss of the inhibition
of the thalamic neurons, which ultimately results in excess cortical activity and movement. They
are presented as:

 Tremor, that is a rhythmic, low amplitude movement that may be manifested as the
nodding of the head, or in the hands and feet.
 Chorea is a sequence of rapid involuntary movements involving mostly the hands and feet,
the tongue, and facial muscles.
 Hemiballismus is a condition where the patient exhibits involuntary ballistic (violent
striking) movements on only one side of the body, that affect only the proximal muscles of
a limb.
 Ballismus is the equivalent to the hemiballismus, with the difference that it affects the
entire body. It is the most extreme type of dyskinesia.
 Huntington’s disease is a rare inherited condition that manifests with severe chorea and
hemiballismus that develop over time. The neuropathological substrate of the disease is the
degeneration of the striatal neurons that give rise to the indirect pathway.
  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.
 Dystonia is characterized by involuntary, sustained muscle contraction that leads to
abnormal postures of the neck, toes, hands, or other parts of the body.
 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.

Hypertonic-hypokinetic disorders

These disorders result from the degeneration of the neurons that form the direct pathway. Since this
is the pathway that serves for the planning of the movement, the problems that patients will have
been presented in two forms:

Bradykinesia that is presented with slow movement

Akinesia is presented with the inability to move at all because the individual is unable to plan or to
direct a movement toward a desired position or target.

Parkinson’s disease is the most prevalent disorder associated with basal ganglia. It is the result of
the degeneration of the dopaminergic neurons of the pars compacta of the substantia nigra. This is
actually the place of origin of the nigrostriatal pathway that is essential for the promotion of the
direct pathway of the basal ganglia. Because of its damage, the excitation of the supplementary
motor area which is of key significance for the movement planning is lost.

Essential tremor (ET) is a medical condition characterized by symmetrical involuntary rhythmic

contractions and relaxations of certain muscle groups. It usually affects the arms, hands, or fingers;
but sometimes involves the head, vocal cords, or other body parts, and it intensifies when one tries
to use the affected muscles during voluntary movements such as eating and writing.