A neural network model of Parkinson's disease bradykinesia

Abstract

Parkinson's disease (PD) is caused by dopamine (DA) depletion consequent to cell degeneration in the substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA). Although computational analyses of PD have focused on DA depletion in DA-recipient parts of the basal ganglia, there is also extensive DAergic innervation of the frontal and parietal cortex as well as the spinal cord. To understand PD bradykinesia, a comprehensive network model is needed to study how patterns of DA depletion at key cellular sites in the basal ganglia, cortex and spinal cord contribute to disordered neuronal and spinal cord activity and other PD symptoms. We extend a basal ganglia-cortico-spinal circuit for control of voluntary arm movements by incorporating DAergic innervation of cells in the cortical and spinal components of the circuit. The resultant model simulates successfully several of the main reported effects of DA depletion on neuronal, electromyographic (EMG), and movement parameters of PD bradykinesia.