The goal of this project is to understand how the prefrontal- and motor-basal ganglia-thalamocortical loops contribute to motor skill learning in humans. The project specifically addresses a form of motor skill learning where movement speed and accuracy is scaled to visual input over time with practice, as in learning to use a computer mouse. The studies will evaluate the hypothesis that the prefrontal-basal ganglia loop signals the need to change movement and that cortical-basal ganglia motor circuit acts later to implement the movement adaptation required. The basal ganglia is hypothesized to be the site where the cortical information from the two loops is synthesized, with the globus pallidus pars interna and the subthalamic nucleus initiating the velocity changes. FMRl methods will be used to compare cerebral regions activated during motor skill learning in normal humans and movement disorders patients (parkinson's and dystonia), where learning may be compromised. Next, simultaneous, multiple single cell recordings will be made in either the premotor or dorsolateral prefrontal cortex, globus pallidus and subthalamic nucleus, and thalamus during these same motor behaviors to identify neural changes associated with signal and set related changes in the two cerebral loops. A unique opportunity to carry out behavioral neurophysiology experiments in human forebrain is now possible in movement-disordered subjects, who undergo neurophysiological mapping to guide placement of a deep brain stimulator. Direct evaluation of the role of cortical and deep cerebral structures in learning can be carried out because subjects can perform visually guided arm movements during recording. This project will help provide important information about the ways in which the frontal cortical and basal ganglia circuits interact during motor skill acquisition. Because we are comparing subjects with Parkinson's disease and dystonia to control subjects, important new information about the cortical and subcortical processes contributing to these motor disorders will be obtained.

K01NS049040

2005-08-01

2010-08-31