Basal ganglia disorders

Motor disorders occurring from dysfunction of the basal ganglia, whether caused by lesions, or by disease in animal studies, fall into two different categories, hyperkinesias and hypokinesias:

- Hyperkinesias. These are disorders in which the motor overactivity takes place. Characteristically these disorders consist of regular, arbitrary, twitch-like or writhing movements, similar to fragments of normal movements, known as choreoathetosis. It is the principal symptom of Huntington’s disease, and of tardive dyskinesia, an unnecessary effect of the treatment of Parkinson’s disease with l-DOPA, or infarcts of subthalamic nucleus. The Huntington’s disease (HD) is a progressive neurodegenerative disorder in which motor and cognitive symptoms start between 40 to 50 years of age. It is an autosomal leading disease caused by an extreme number (> 36) of CAG repeats in the coding area of the gene for huntingtin (Htt) that accordingly has a long string of glutamine residue near its N terminus. The common functions of Htt and how the abnormal protein kills cells are uncertain, but mainly afflicted are the GABA/ENK medium spiny neurons of the striatum. Their death causes extreme inhibition of the subthalamic nucleus, therefore increased and unsuitable firing of thalamocortical neurons. In summing up, the chorea is a failure of the indirect pathway to block unnecessary movement series.

- Hypokinesias. The prototypical hypokinetic disorder is Parkinson’s disease, illustrated by bradykinesia, rigidity, bradykinesia, and tremor. Here the main lesion is the massive loss of dopaminergic cells in the SNpc. As the normal circumstances is that dopamine tonically activates the direct pathway through D1 receptors but restrains the indirect pathway through D2 receptors, loss of the nigrostriatal pathway directs to an increase in the action of GABAergic striatal neurons in the indirect pathway and a reduce in the GABAergic striatal neurons in the direct pathway. The total effect is increased inhibition on the thalamocortical connections which are needed for movement. However this model accounts for the bradykinesia it does not elaborate the tremor.

Disorders of other basal ganglia-thalamocortical circuits appear to involve obsessive-compulsive disorder (OCD). This is a chronic psychiatric disorder in which a person is not capable to prevent themselves endlessly repeating similar actions or thoughts. The afflicted individual might spend many hours each day acting out pointless rituals, like hand washing as of an obsessional fear of contamination. The OCD emerges to be extreme perseveration. Brain imaging illustrates a decrease in cerebral blood flow in the orbitofrontal cortex which correlates with the harshness of the disorder in patients. A lesion of the orbitofrontal cortex in primates causes perseveration. This recommends that the cause of OCD might lie with dysfunction of the lateral orbitofrontal basal ganglia-thalamocortical circuit.