Disturbances of learning processes in the basal ganglia in the pathogenesis of Parkinson's disease: a novel theory.

A hypothesis is proposed that the cortico-basal ganglia-thalamocortical circuit is a neural optimal control system containing a model of the controlled object. To predict the behaviour of the object, the model uses the language of afferent signals that enter the system. Based on these ideas, it is suggested that the skeletomotor basal ganglia-thalamocortical circuit serves to model the motor behaviour of the body of an individual and its environment during motor planning and performance. Association basal ganglia-thalamocortical circuits are capable of modeling the behaviour of abstract objects such as thoughts. Within the limits of the proposed theory, the dopaminergic system serves to distribute an error signal within the striatum. These error signals contain information about mismatch between model (predicted) afferent flow and real afferent flow coming from the controlled object. An error signal is necessary to tune the model on the object, and is delivered to a structure within the circuit that is responsible for the production of the error signal. An error signal is minimal when the model properly describes the object behaviour. The process of learning is initiated when an error signal increases and is complete when the error signal is minimized. Parkinson's disease is thus considered to be the consequence of modeling disfunction because of progressive functional and structural degeneration of the error distribution system in the substantia nigra pars compacta. Other clinical applications of the proposed theory are also discussed.