Subthalamic Nucleus Stimulation and Basal Ganglia Circuits: Dissociable Neurophysiological and Behavioral Effects

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Neurobiology and Anatomy, 2012.Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting over four million people worldwide. The loss of dopamine producing cells in the midbrain causes the characteristic tremor, rigidity, and slow movements of PD. Pharmacological approaches, such as dopamine replacement therapy, are currently the first line of treatment for PD. Although these medications generally provide initial reduction in motor symptoms, the benefits are not typically maintained and extended use can lead to detrimental side effects. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted surgical treatment for PD motor symptoms, and in conjunction with medications, may extend the useful window of the pharmaceutical benefits. Recently, however, adverse non-motor effects of STN DBS have been identified and it is becoming clear that STN stimulation for PD-related motor disability also affects cognitive functions supported by prefrontal cortical regions. A more complete understanding of how STN DBS affects striato-frontal circuits supporting cognition is needed in order to maximize the therapeutic efficacy of this promising surgical approach. The overall goal of this project was to gain a deeper understanding of the role of striato-frontal circuits supporting complex behavior. Parkinson’s patients with STN DBS provided us a model to examine modulation of these circuits and the stimulation effects on prefrontal neurophysiology and behavior. We examined DBS effects on cortical neuronal activity by recording EEGs while subjects perform tasks of motor control, working memory and cognitive flexibility. We also analyzed the relationship between electrode locations with downstream behavioral effects. We hypothesized that cognitive changes following STN DBS are due to stimulation fields affecting non-motor striato-frontal circuits. We also expected to observe regional differences in prefrontal cortical responses to STN stimulation that corresponded to behavioral performance. Our findings suggest that STN DBS causes dissociable effects on underlying neurophysiology and behavioral performance. The results from this study could provide critical information for neurosurgical target planning and guide the programming of DBS for optimal motor benefit while minimizing adverse effects. More broadly, these results may help refine the application of DBS for other disorders