Physiologic basis of dyskinesia

The current functional model of the basal ganglia suggests that dyskinesia results from abnormally low activity at the output of the system. This view appears incomplete. The recent literature suggests other factors. Thus, dyskinesia may result from disturbance of surround inhibition: a physiologic mechanism to select neuronal responses. A major criterion for selection in the basal ganglia is prediction of reward, materialized by release of dopamine. However, much of this release is independent of impulse flow, and controlled presynaptically, at a myriad of terminals, whose presence is then essential. Thus, levodopa in parkinsonism is likely to exaggerate imbalance between regions of the basal ganglia more or less deprived of dopaminergic terminals. The cortex and thalamus may be viewed as equally important afferents to the basal ganglia. Each of them appears to influence preponderantly its own half of striatal projection neurons. Those of the indirect pathway would be part of a mainly transcortical loop, specialized for the precise weighing, and selection of cortical information. Those of the direct pathway would be part of a predominantly subcortical loop, more likely concerned by changes in alertness and attention. Dyskinesia could thus result from imbalance between cortical and thalamic functions, between selection and attention.