This article discusses a part of the brain called the basal ganglia and the role it is thought to play in dystonia. The exact cause of dystonia is unknown and there are a number of theories about how dystonia arises – below we discuss one of them. There are other theories – some of which are discussed here and here. How these theories fit together and which will turn out to be most important remains to be seen.

What are the basal ganglia?

The basal ganglia are clusters of nerve cells deep in the brain which are tightly interconnected. They are involved in selecting muscles for movement. This article focuses on the theory that dystonia is caused by a failure of the basal ganglia to trigger the right balance of muscle selection.

How does the brain normally initiate movement?

The part of the brain that initiates a movement is called the pre-frontal cortex. The cortex is the outermost layer of the brain and, as its name suggests, the pre-frontal cortex is the part of the cortex located at the front of the brain. The pre-frontal cortex sends messages to the motor cortex, which generates impulses involved in the planning, control, and execution of voluntary movements. To refine the choice of muscles which participate in the movement the motor cortex sends messages through the basal ganglia.

For a movement to be executed smoothly and successfully, the muscles that cause the movement (known as the agonist muscles) need to contract while, at the same time, the muscles that oppose or interfere with the movement (known as the antagonist muscles) need to relax. For example, when the head is turned to the left, the muscles that rotate the head to the left (the agonists) contract, while those that rotate the head to the right (the antagonists) relax.

The role of the basal ganglia in movement

The role of the basal ganglia is to amplify activity in the areas of the motor cortex that control the agonist muscles (this is called excitation) while simultaneously silencing the areas that control the antagonist muscles (this is called inhibition).

The quantity of activity in the motor cortex is adjusted using two distinct pathways – the direct pathway and the indirect pathway. Both pathways run from the cortex through the basal ganglia then back to the motor cortex via the thalamus but they have opposite effects:

• The direct pathway causes the thalamus to send excitatory signals back to the motor cortex and so increases activity. The muscles controlled by the parts of the motor cortex receiving signals from the direct pathway become more active, causing the muscles to contract, thereby, reinforcing the desired movement

• The indirect pathway causes the thalamus to send inhibitory signals to the motor cortex and so suppresses activity. The muscles controlled by areas of the motor cortex receiving inhibitory signals relax, preventing muscle action that would interfere with the movement.

A part the basal ganglia called the striatum is responsible for selecting which pathway is used. It receives input from the cortex that indicates the required movement and converts this into signals that trigger the direct pathway for the areas of the motor cortex that need to be excited and the indirect pathway for areas that need to be inhibited.

Depending on which pathway is triggered, the signals then pass through a number of other nerve clusters in the basal ganglia (one of which is the globus pallidus) with the result that either basal ganglia releases the thalamus to trigger the muscle contraction (in the direct pathway) or prevents it from doing so (in the indirect pathway).

Signals are passed between the different areas of basal ganglia using neurotransmitters – chemical messengers that pass information between neurons, which either excite or inhibit activity. Two examples are GABA which passes messages inhibiting activity and glutamate which passes excitatory messages.

The basal ganglia and dystonia

Usually, when a movement is made, excitation and inhibition work in harmony so contraction of the agonist muscles is coordinated with relaxation of the antagonist muscles. In patients with dystonia there is deficient inhibition of the antagonist muscles. This can result in co-contraction, where the agonist and antagonist muscles contract together.

Research has identified that the major role of the basal ganglia is to balance excitation and inhibition (just like a pair of scales). However, in dystonia this delicate balance is not attained. It is not yet certain whether the problem is with the direct pathway, the indirect pathway or both. However, as dystonia appears to result from insufficient inhibition in the muscles, it may be that the indirect pathway is failing, resulting in impaired suppression of muscle activity. The lack of inhibition of antagonist or surrounding muscles ultimately causes the co-contraction or overflow phenomena seen in dystonia.

One area of focus has been to look at whether dystonia is caused by a shortage of the inhibitory neurotransmitter GABA. It seems plausible that a shortage of an inhibitory neurotransmitter such as GABA may play a role, since dystonia seems to be a failure of inhibition. At present this is a theory that remains unproven; however, one of the treatments for dystonia, which helps in some cases, is to prescribe medications that increase the quantity of GABA such as benzodiazepines, gabapentin or baclofen.

Where does DBS fit in with all this?

Deep Brain Stimulation (DBS) is a surgical procedure in which fine electrodes are inserted into the brain. They are connected to a power source implanted in the chest.

An area often targeted by the electrode in DBS is the internal Globus Pallidus (GPi) area of the basal ganglia, which primarily has an inhibitory action, therefore decreasing muscular activity. The electrode delivers a constant, painless, signal which aims to block the signals that cause the disabling symptoms of dystonia.

Findings suggest that modulating the activity of the basal ganglia and in particular the GPi may normalise levels of inhibition, allowing for the gradual replacement of abnormal activity with more normal physiological patterns of activity.

Cortex images (which have been slightly modified) provided by