The overall goal of this project is to demonstrate, through the study of cortical activation on functional MRI (fMRI), that the cognitive and motor effects of deep brain stimulation (DBS) in the basal ganglia are mediated through the selective activation of discrete regions of the frontal lobe to which the basal ganglia are connected. Recent work in non-human primates has demonstrated that the basal ganglia and frontal cortex are reciprocally connected by segregated, parallel circuits that subserve distinct motor and cognitive functions. Focal surgical therapies such as ablative lesioning or DBS may impart specific effects depending on the particular circuits they impinge upon.
The specific aims of the project are to demonstrate (1) the existence of segregated frontal-subcortical circuitry within the basal ganglia of humans, by studying the cortical activation on fMRI resulting from stimulation of discrete regions of the subthalamic nucleus and globus pallidus internus, (2) that stimulation of discrete regions of these two nuclei selectively affects cognitive or motor performance, and (3) that the distinct cognitive and motor effects elicited by stimulation of neighboring regions of these basal ganglia nuclei are due to the discrete frontal cortical regions that are thereby activated. The basic strategy of this research is to utilize fMRI and cognitive and motor assessments in patients undergoing placement of quadripolar deep brain stimulating electrodes in the various structures comprising these frontal-subcortical pathways. Each of the four contacts on the DBS electrode will be individually activated during various complementary experiments. First, fMRI will be performed immediately following surgery while activating individual contacts both at rest and during motor and cognitive activation tasks. This will demonstrate that neighboring contacts are located in and selectively activate segregated fronto-subcortical circuits. Next, tests of motor and neuropsychological performance will be obtained during stimulation through individual electrode contacts. These experiments will demonstrate that selectively activated segregated circuits have distinct effects on cognition and motor function. Finally, the relationship of regional cortical activation to cognitive and motor performance during stimulation through individual electrode contacts will establish that the effects of DBS are mediated through the specific cortical activation thus imparted. These experiments will establish the existence of segregated, parallel fronto-subcortical pathways that selectively mediate cognitive and motor functions in the human. The results will have important implications for the specific targeting of distinct subregions of the subthalamic nucleus and globus pallidus during the implantation of deep brain stimulating electrodes for the treatment of Parkinson's -disease and other movement disorders.
