The common goals of this program project are to understand how the basal ganglia contribute to the control of sensorimotor functions and to assess the pathophysiologic basis of human parkinsonism. The three research projects in this proposal are conceptually framed by the model of basal ganglia function formulated by DeLong and colleagues. In this model, widespread cortical inputs ultimately converge in the globus pallidus. Inhibitory pallidal output project to thalamus and brainstem. This concentrated will be an integrated investigation of basal ganglia sensorimotor function using two physiologic approaches (direct single unit recording at the neural level and PET functional imaging of regional brain activity) applied across four clinical states (normal, dopamine deficiency of Parkinson's disease (PD), dopamine replacement of PD, and surgical pallidotomy for PD). These groups will be assessed with consistent sensory, motor and control states. The experiments are distributed among three research projects, supported by two cores; one to manage subject recruitment and the other to orchestrate data analysis and modeling. The human imaging studies of this proposal form a critical bridge between the animal model of parkinsonism and clinical application of techniques such as pallidotomy to PD patients. They provide a large scale perspective of adaptation in the setting of neurodegeneration and reorganization after surgical pallidotomy that cannot be examined at the single unit level, by imaging on-human primates or behavioral assessment alone. The results could directly impact on the rational design of surgical therapies for patients with movement disorders. Integration of the imaging and physiologic data could be used to optimize lesion localization in surgical pallidotomy. Correlation of the physiological data could be used to optimize lesion localization in surgical pallidotomy. Correlation of the physiological data could be used to optimize lesion localization in surgical pallidotomy. Correlation of the physiological data with clinic scores may establish if functional imaging or intraoperative recording are reliable predictors of patient outcome.
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| Vanlancker-Sidtis, Diana; McIntosh, Anthony Randal; Grafton, Scott (2003) PET activation studies comparing two speech tasks widely used in surgical mapping. Brain Lang 85:245-61 |
| Turner, Robert S; Desmurget, Michel; Grethe, Jeff et al. (2003) Motor subcircuits mediating the control of movement extent and speed. J Neurophysiol 90:3958-66 |
| Grea, Helene; Pisella, Laure; Rossetti, Yves et al. (2002) A lesion of the posterior parietal cortex disrupts on-line adjustments during aiming movements. Neuropsychologia 40:2471-80 |
