Basal Ganglia Cortical Coupling and Connectivity Changes in PD and DBS

University Of Minnesota, Minneapolis MN

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Abstract

DESCRIPTION (provided by applicant): Synchronized oscillations in the pallido-thalamo-cortical circuit have been hypothesized to underlie the development of parkinsonian motor signs by altering connectivity between the basal ganglia and cortical structures. Deep brain stimulation (DBS) improves parkinsonian motor signs; but how it changes basal ganglia cortical interactions remain unclear. The goal of this proposal is to characterize the changes in synchronization and effective connectivity that occur between the basal ganglia and motor and supplementary motor cortices (MC and SMA, respectively) in the parkinsonian state and during therapeutic DBS of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN). A second goal of this study is to examine the feasibility of exploiting the presence of these oscillations in the pathological state for use as biomarkers in the development of a closed loop control system for DBS. These goals will be accomplished by simultaneously recording from populations of neurons in both subcortical and cortical areas at rest and during movement; characterizing the physiological changes in synchronized oscillatory activity and effective connectivity between the basal ganglia and MC and SMA in the parkinsonian state and during therapeutic DBS in the nonhuman primate MPTP model of Parkinson's disease (PD). Putative biomarkers, identified as part of the first phase of the study, will be evaluated as triggers for closed loop stimulation delivery during a goal directed reaching task in the final stuy phase. The results of this study will provide critical new information to help us to understand the changes in interactions that occur across the MC, SMA and basal ganglia network in PD, identify biomarkers that can be used as triggers for closed loop control of DBS and compare the relative effect of STN versus GPi DBS on basal ganglia cortical interactions and as sites for triggers in a closed loop control system.