Neuroengineering Seminar: “Advancing Deep Brain Stimulation Therapy in Movement Disorders: from surgical implantation to behavior-based responsive therapeutic stimulation” (Enrico Opri)

Sponsored by the Center for Neuroengineering and Therapeutics, and the Departments of Neurosurgery and Bioengineering.

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https://pennmedicine.zoom.us/j/97483734781

Meeting ID: 974 8373 4781

Deep brain stimulation (DBS) has become standard therapy for medically refractory patients with Parkinson’s disease (PD), essential tremor (ET), and other neurological disorders. The two main challenges for DBS standard-of-care are rooted in the accurate positioning of the DBS leads during intraoperative implantation and the postoperative programming of the implanted DBS device, both needed to achieve the sought optimal therapeutic benefit. However, both processes rely on subjective patient exams, on expert neurophysiologists to optimize implant trajectory and programming, and on time-consuming trial-and-error approaches. Furthermore, existing commercially available stimulation approaches (continuous stimulation, also known as open-loop stimulation) lack integration with patient behavior and environmental factors. We sought to address these shortcomings in the ET population, by demonstrating the feasibility of on-demand responsive stimulation using only thalamocortical neuromarkers that modulate movement related-behavior. This led to the design and implementation of the first fully embedded closed-loop algorithm for chronic neurostimulators (CL-DBS) in humans affected by ET, which achieved an equally effective treatment compared to current DBS approaches while having a more efficient stimulation energy profile. Furthermore, CL-DBS demonstrated potential in decreasing DBS-related side effects (e.g. speech impairments). Additionally, the unique window provided by intraoperative acute recordings, allowed us to further our understanding of the thalamocortical network. We showed that there is significant cross-rhythm communication between thalamocortical regions and that changes in motor behavior correspond to changes in thalamocortical phase-amplitude coupling (PAC) profiles, demonstrating it is a crucial mechanism for gating motor behavior. We then sought to improve intraoperative DBS implantation for the PD population by leveraging a novel biomarker, DBS local evoked potential (DLEP), which strongly correlates with the location of the typical target-subregions of the nuclei of interest, the subthalamic nucleus (STN) and globus pallidus internus (GPi). Most importantly, the proposed methodology requires no patient interaction and could be leveraged for implementing an objective, real-time guided placement of the DBS lead, with a less time-consuming process and subjectivity compared to traditional mapping procedures.