PROJECT SUMMARY - JOHNSON Deep brain stimulation (DBS) is a promising FDA-approved therapeutic for advanced Parkinson’s disease (PD), a disease that increases with age, affecting 1% of the population over the age of 60 and 10% of the population over the age of 80. There is a critical need to automate DBS parameter selection for optimal therapy and greatly reduce clinician burden. Clinical DBS, however, creates long-lasting stimulation artifacts that obscure and distort the detection of neural biomarkers that could be used to automate therapy. This study will address this challenge by making innovative advancements to our closed-loop neuromodulation technology called WAND (wireless artifact-free neuromodulation device) that can reliably sense neural signals with concurrent electrical stimulation. Our long-term goal is to develop a miniaturized DBS device that closes the loop by sensing biomarkers and computing stimulation parameters for automatic, patient-specific treatment. Our overall objective is to adapt WAND for rodent studies and use a machine learning search strategy to find the best stimulation settings based on biomarkers in a rodent model of PD. Closed-loop DBS, enabled by WAND and by a machine-learning based parameter optimization, can produce longer-lasting and more energy- efficient motor rescue as compared to standard DBS therapy. The central hypothesis will be tested pursuing three specific aims: 1) Optimize WAND for rodent studies to create a next-generation research platform; 2) Validate WAND’s ability to extract neural biomarkers during DBS therapy and gait analysis in a rat model of PD; and 3) Design and evaluate an optimization system to dynamically control neural biomarkers in a rat model of PD. This work is significant because it will make substantive advancements to a next-generation neurotechnology research platform (WAND). This smaller device will be more automated because of our emphasis on the critical technical challenge of improving patient-specific DBS parameter selection. Outcomes not only advance PD research and clinical outcomes, but we can also extend knowledge given that DBS has shown promise as a treatment for many other neurological disorders, including epilepsy, depression, and memory impairment. Further, the effort is well-suited to this COBRE as it addresses the Biomedical Devices, Sensors, and Systems theme.