Basal ganglia diseases are characterized by deficits in movement, muscle tone, and initiating movement. Dyskinesia, cogwheel rigidity, and bradykinesia are observed. Abnormal movement includes tremor, athetosis, chorea, ballism, and dystonia. Tremor is a 3-Hz "pill-rolling" tremor at rest. Athetosis involves slow, writhing movement of distal limb parts, while chorea is characterized by rapid, flicking movement of extremities and facial muscles. Ballism is associated with violent, flailing movement of the limbs, while dystonic movements cause distorted body postures.

Parkinson's disease is a common disorder characterized by tremor, rigidity, and bradykinesia. It results from the loss of neurons in the substantia nigra's pars compacta, leading to severe dopamine loss in the striatum. There is also loss of neurons in the locus coeruleus, raphe nuclei, and other monoaminergic nuclei. The reduction in dopamine diminishes the activity of the direct pathway and increases the activity of the indirect pathway. This leads to increased activity of neurons in the internal segment of the globus pallidus, resulting in greater inhibition of neurons in the VA and VL nuclei and less activation of motor cortical areas. As a consequence, movement becomes slowed.

Levodopa administration can temporarily relieve motor deficits in Parkinson's disease before complete loss of dopaminergic neurons occurs. Levodopa is a dopamine precursor that can cross the blood-brain barrier. Research is also exploring the possibility of transplanting dopamine-synthesizing neurons into the striatum. Human embryonic stem cells may hold therapeutic potential in the future.

Huntington's disease is another basal ganglia disorder caused by a genetic defect. It leads to the selective loss of striatal GABAergic and cholinergic neurons that project to the GPe as part of the indirect pathway. Degeneration of the cerebral cortex also occurs, resulting in dementia. Loss of inhibition of the GPe leads to decreased activity of neurons in the subthalamic nucleus. Consequently, the excitation of GPi neurons is reduced, disinhibiting neurons in the VA and VL nuclei. This enhances activity in the motor areas of the cerebral cortex, potentially explaining the choreiform movements seen in Huntington's disease. Over-treatment of Parkinson's disease patients with levodopa can result in chorea, which can be considered as the opposite of rigidity.

Hemiballism is caused by a lesion in the subthalamic nucleus on one side of the brain. It manifests as involuntary, violent flailing movements of the limbs on the contralateral side of the lesion. As the subthalamic nucleus excites GPi neurons, a lesion reduces their activity. This leads to decreased inhibition of neurons in the VA and VL nuclei, resulting in increased activity of neurons in the motor cortex.

In all basal ganglia disorders, motor dysfunction occurs on the contralateral side of the affected component. This is because the main output of the basal ganglia to the body is mediated through the corticospinal tract.
The deficits seen in the various basal ganglia diseases include abnormal movement (dyskinesia), increased muscle tone (cogwheel rigidity), and slowness in initiating movement (bradykinesia). Abnormal movement includes tremor, athetosis, chorea, ballism, and dystonia. The tremor of basal ganglion disease is a 3-Hz “pill-rolling” tremor that occurs when the limb is at rest. Athetosis consists of slow, writhing movement of the distal parts of the limbs, whereas chorea is characterized by rapid, flicking movement of the extremities and facial muscles. Ballism is associated with violent, flailing movement of the limbs (ballistic movement). Finally, dystonic movements are slow involuntary movements that may cause distorted body postures.
Parkinson’s disease is a common disorder characterized by tremor, rigidity, and bradykinesia. This disease is caused by loss of neurons in the pars compacta of the substantia nigra. Consequently, the striatum suffers a severe loss of dopamine. Neurons of the locus coeruleus and the raphe nuclei, as well as other monoaminergic nuclei, are also lost. The loss of dopamine diminishes the activity of the direct pathway and increases the activity of the indirect pathway (see
Fig. 9.25B ). The net effect is an increase in the activity of neurons in the internal segment of the globus pallidus. This results in greater inhibition of neurons in the VA and VL nuclei and less pronounced activation of the motor cortical areas. The consequence is slowed movement (bradykinesia).
Before the dopaminergic neurons are completely lost, administration of levodopa can relieve some of the motor deficits in Parkinson’s disease. Levodopa is a precursor of dopamine, and it can cross the blood-brain barrier. Currently, the possibility of transplanting dopamine-synthesizing neurons into the striatum is being explored. Future research will no doubt focus on the potential for human embryonic stem cells to play such a therapeutic role.
Another basal ganglia disturbance is Huntington’s disease, which results from a genetic defect that involves an autosomal dominant gene. This defect leads to the preferential loss of striatal GABAergic and cholinergic neurons that project to the GPe as part of the indirect pathway (and also degeneration of the cerebral cortex, with resultant dementia). Loss of inhibition of the GPe presumably leads to diminished activity of neurons in the subthalamic nucleus (see
Fig. 9.25C ). Hence, the excitation of neurons of the GPi would be reduced. This would disinhibit neurons in the VA and VL nuclei. The resulting enhancement of activity in neurons in the motor areas of the cerebral cortex may help explain the choreiform movements of Huntington’s disease. The rigidity in Parkinson’s disease may in a sense be the opposite of chorea because overtreatment of patients with Parkinson’s disease with levodopa can result in chorea.
Hemiballism is caused by a lesion of the subthalamic nucleus on one side of the brain. In this disorder, involuntary, violent flailing movements of the limbs may occur on the side of the body contralateral to the lesion. Because the subthalamic nucleus excites neurons of the GPi, a lesion of the subthalamic nucleus would reduce the activity of these pallidal neurons. Therefore, neurons in the VA and VL nuclei of the thalamus would be less inhibited, and the activity of neurons in the motor cortex would be increased.
In all these basal ganglia disorders, the motor dysfunction is contralateral to the diseased component. This is understandable because the main final output of the basal ganglia to the body is mediated by the corticospinal tract.