Cortico-basal ganglia-cortical circuitry in Parkinson's disease reconsidered

The classical model of the cortico-basal ganglia-cortical circuit, with its indirect and direct pathways, was developed to explain the phenomenon of hypokinesia in Parkinson's disease (PD). The model has undergone refinement, but the emphasis on the basal ganglia side of the equation (dopamine deficiency in the dorsal striatum) remains. Here, a revised version of the basic model incorporates key non-dopaminergic connectivities known to become affected in the course of PD and, thus, the cortico-basal ganglia-cortical circuit appears within the context of the larger pathological process. The central roles of the corticostriatal projection, corticosubthalamic projection, and lower brainstem nuclei are emphasized. (C) 2008 Elsevier Inc. All rights reserved.