New approaches to DBS employing closed-loop paradigms or novel stimulation patterns remain in early stages of development, largely due to a lack of understanding of the basic mechanisms underlying PD motor signs. In order to advance DBS and provide the rationale upon which to implement these innovative approaches we need a better understanding of the physiological changes that underlie PD motor signs, the topographic distribution of these changes within current DBS targets, how they correlate to individual motor signs, and how this understanding can be used to implement novel DBS approaches.
Project 1 will address these concerns by:
1) identifying and characterizing the distribution of physiological biomarkers of disease in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) from patients undergoing intraoperative microelectrode mapping (MEM) (SA1)
2) characterizing the presence and distribution of synchronized oscillatory activity in the STN and GPi in patients under conditions that modulate the presence and severity of motor signs (i.e., at rest and during movement, off/on medication; off/on DBS) (SA2)
3) determining the relative effect of DBS timed to disrupt low beta/HFO (high frequency oscillation) phase amplitude coupling (PAC) to standard DBS on motor function (SA3)
4) assessing the acute and carryover effect of coordinated reset (CR) DBS on motor signs and LFP activity in the region of the STN using the Activa© RC+S ‘brain radio’ (SA4).