Study Rationale: Deep brain stimulation is an effective therapy for motor symptoms of late-stage Parkinson’s disease. It works like a pacemaker to interrupt abnormal patterns of brain activity that cause motor symptoms. We discovered a novel pattern of DBS stimulation that provides long-lasting therapeutic effects on brain activity patterns and movement. Here, we will use a small pre-clinical model of PD to assess the optimal stimulus location and duration for our novel protocol that will speed its translational application to humans.
Hypothesis: We hypothesize that the GPi is the optimal surgical target for our novel DBS protocol and that treatment epochs as short as 10 minutes long can work to attenuate motor symptoms for hours after stimulation.
Study Design: Our optimization study for Burst-DBS will be conducted in small pre-clinical models of Parkinson’s disease. One model is optimized for the study of DBS effects on bradykinesia while the other model is optimized for the study of DBS effects on tremor and gait disturbances. Models displaying parkinsonian symptoms will be implanted with DBS electrodes into either the STN or GPi (the main surgical targets for DBS in humans). We will perform a systematic analysis of the therapeutic efficacy of DBS delivered to each target to provide a set of recommendations for neurosurgeons looking to translate our novel DBS protocol to humans.
Impact on Diagnosis/Treatment of Parkinson’s disease: Our novel DBS protocol promises to deliver the equal or better therapeutic effects compared to conventional stimulation with only a fraction of the active stimulation time. This would greatly reduce the risk of side effects and has the potential to repair, rather than mask circuit dysfunction in disease.
Next Steps for Development: Several neurosurgical teams have expressed interest in testing our novel DBS protocol in humans. Our proposed experiments will help to better design these translational studies by providing input on which patients are most likely to respond to treatment (based on electrode placement and symptoms descriptions).