Project 1

The goals of this study are to advance our understanding of the role of basal ganglia thalamocortical (BGTC) (subcortical-cortical) and cortical-cortical circuits in the development of PD, the changes that occur with DBS and L-dopa, and to use this understanding to advance current and develop new DBS approaches for its treatment. We will define the relationship between synchronized oscillations, coherence and connectivity within the broader BGTC circuit (STN, GPi, sensory, motor, premotor and dorsolateral prefrontal cortices) to the development of PD motor signs, define their role in motor performance, cognitive function, and corresponding changes with DBS, L-dopa and DBS+L-dopa. By defining the strength and direction of connectivity patterns at rest and during movement we will characterize the role of individual circuits within the BGTC network and define their respective roles in motor performance and cognitive function paving the way for future development of optimization algorithms for DBS that take advantage of this understanding. By correlating the degree of coherence between multiple single cells and local field potential (LFP) activity we will also advance our understanding of the role of spike-phase locking to the development of motor signs. Through high resolution imaging techniques and parcellation analyses we will define the optimal site for DBS within the STN and GPi correlating motor and cognitive outcomes to biomarker activity and lead location, leading to patient specific DBS and development of automated programming algorithms based on each patient’s phenotype and lead location. The proposed aims will be conducted using directional DBS leads, multiple independent current controlled (MICC) devices, high resolution imaging and electrophysiological recordings in PD patients with electrocorticography (ECoG) arrays undergoing microelectrode mapping, postoperatively in patients with ECoG arrays and externalized leads, and following optimization of DBS parameters.