Characterizing Evoked Potentials of Deep Brain Stimulation for Parkinson's Disease

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Deep brain stimulation (DBS) is a surgical intervention used to treat the cardinal motor symptoms of Parkinson’s disease (PD) when medical interventions fail. While DBS for the motor symptoms of PD has been used for decades, there are still gaps in our knowledge on the underlying mechanism of action, which, if resolved, might enhance DBS outcomes further. One point of improvement in DBS can be found in the process of DBS lead placement. DBS lead placement is a challenging, time-intensive procedure based on radiographic criteria, then refined by confirming motor symptom reduction and assessing side effects intraoperatively in awake patients. DBS lead placement may be improved using evoked potentials (EPs) as objective, surrogate biomarkers linked to neural activity and appropriate symptom relief. EPs have potential to guide appropriate placement of DBS leads more rapidly and accurately, possibly even in patients under anesthesia, particularly in subthalamic nucleus (STN) implants. The use of EPs as a biomarker may reduce surgical time, improve patient outcomes, and improve patient comfort. The goal of this proposal is to characterize the effect of stimulation amplitude, lead location, and anesthesia on local and distant EPs to identify more reliable and efficient methods of lead placement. This will be particularly impactful if EPs correlate with symptom relief, removing the need for behavioral characterization and expediting awake and/or asleep DBS lead placement. The first aim is to quantify the effect of DBS amplitude and location on local and distant EPs during awake DBS lead placement. Experiments will occur in concert with partnering neurosurgeons and neurologists. Local and distant EPs will be recorded simultaneously during DBS at the target of the dorsal STN and off- target at the ventral STN. DBS stimulation trials will include sub-therapeutic, therapeutic, and supra-therapeutic intensities. Before and during the DBS trials, I will concurrently quantify bradykinesia and tremor. Next, I will repeat DBS trials in follow-up clinic one month later to determine the predictive value of intraoperative EP recordings on post-op symptom treatment. The second aim will repeat these steps in patients undergoing asleep surgery. These studies are expected to quantitatively establish the causal relationship between DBS and EPs, and the correlative link between EPs and behavior critical for the use of EPs in the clinical setting. This proposal will ultimately support my training as a dual-degree MD/PhD student, in preparation for a career as an independent physician-scientist at the intersection of the bench and the bedside. The training plan will include attending conferences, gaining further clinical experience, and further developing my scientific reasoning skills. The training environment is well-equipped to prepare me for my future career as a physician- scientist. My primary sponsor (PI) has a long record of mentoring trainees and is an expert in the field of DBS, and the lab has a long record of successful collaboration with partnering physicians, several of which will also provide direct mentoring support, to help guide my long-term clinical career.