One possible factor could be the natural accumulation of iron in the basal ganglia, causing neurodegeneration due to its involvement in toxic, free-radical reactions.

[5] Proper striatal dopamine release is integral in the suppression of the basal ganglia output, which is needed for increased activity of the thalamic neurons.

The indirect pathway inhibits unwanted movements by simultaneous increase in excitatory input to other GPi and SNr neurons.

This is generally attributed to higher than normal basal ganglia output causing inhibition of thalamocortical motor neurons.

[6] Other motor deficits and common non-motor features of Parkinson's such as autonomic dysfunction, cognitive impairment, and gait/balance difficulties, are thought to result from widespread progressive pathological changes commencing in the lower brain stem and ascending to the midbrain, amygdala, thalamus and ultimately the cerebral cortex.

[1] Huntington's disease stems from a defect that consists of an expanded CAG repeat in the huntingtin gene (HTT) located on the short arm p of chromosome 4.

[8] This degeneration of striatal neurons projecting to GPe leads to disinhibition of the indirect pathway, increased inhibition of the subthalamic nucleus, and therefore, reduced output of the basal ganglia.

Again, it was thought that this dysfunction led to a decrease in basal ganglia output to the thalamus and a resultant increased disinhibition of the thalamic projections to the premotor and motor cortex.

Patients with seizures display some abnormal electrophysiological activity and structural changes like atrophy, altered blood perfusion and metabolism within their basal ganglia.

; demonstrated receptor derangement or hyposensitivity in the basal ganglia dopamine pathways plays a critical role in the diathesis for Tourette syndrome.

The basal ganglia, a cerebral structure involved in controlling movement, is believed to be one of the sites vulnerable to dopamine abnormalities and is implicated in the pathogenesis of TS.

It is thought that dopamine, norepinephrine, and serotonin neurotransmitters are not able to exchange messages properly between nerve cells in a person diagnosed with Tourette’s.

Sydenham's chorea is a disorder characterized by rapid, uncoordinated jerking movements primarily affecting the face, hands and feet.

[14] It is a result of an autoimmune response that occurs following infection by group A β-hemolytic streptococci (GABHS)[15] that destroys cells in the corpus striatum of the basal ganglia.

The syndrome is believed to be due to damage to areas of the basal ganglia or frontal cortex, specifically the striatum and globus pallidus, responsible for motivation and executive functions.

[27] Within the first few years of life, extrapyramidal involvement causes abnormal involuntary muscle contractions such as loss of motor control (dystonia), writhing motions (choreoathetosis) and arching of the spine (opisthotonus).

[28] Wilson's disease is an autosomal recessive genetic disorder caused by a mutation in the copper-transport gene ATP7B, leading to excess copper build-up.

About half of those affected have neurological symptoms, including parkinsonism (most commonly cogwheel rigidity, bradykinesia or slowed movements and a lack of balance)[29] with or without a typical hand tremor, masked facial expressions, slurred speech, ataxia or dystonia.

[30] Fahr's disease is a rare, genetically dominant, inherited neurological disorder characterized by abnormal deposits of calcium, primarily in the basal ganglia.

It is believed that the success of pallidotomies in reducing the effects of movement disorders may result from the interruption of abnormal neuronal activity in the GPi.

[1][4] The most effective structures used for implantations for deep brain stimulation are the internal globus pallidus (GPi) and the subthalamic nucleus (STN).

Evidence suggests that benefits of STN deep brain stimulation is due to the activation of efferents and the modulation of discharge patterns in the GPi that are propagated throughout the thalamocortical pathways.