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Article

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disorder that affects over 10 million people worldwide. Deep Brain Stimulation (DBS) has been a successful treatment for advanced PD, however, can be accompanied with current spread related side effects. Coordinated Reset (CR) DBS is a novel therapeutic approach that could reduce the risk of side-effects by using lower current. Previous research has shown therapeutic effects of CR DBS on PD motor symptoms including akinesia, bradykinesia, rigidity, and tremor that sustained after stimulation cessation (i.e., carryover effect), however its effect on gait dysfunction is unknown even though it can be one of the most difficult symptoms to treat. The goal of this study is to investigate the carryover effect of subthalamic CR DBS on PD gait. Two non-human primates (NHP) were rendered parkinsonian and implanted with a DBS lead in the subthalamic nucleus (STN). Each subject received STN CR DBS for 2 hours per day for 5 consecutive days. Gait was quantitatively assessed before and after the stimulation using a gait testing apparatus. A modified clinical rating scale (mUPDRS) was used to monitor carryover effects on other motor symptoms. Moreover, in one NHP, the differential effects of CR DBS using two additional burst frequencies were also explored. Our results showed that STN CR DBS induced carryover improvement in gait as well as in other symptoms. We also identified a significant impact of varying burst frequency on the effect of CR DBS in gait given that one burst frequency produced greater gait improvement than the others. Although preliminary, this study encourages the further advancement of CR DBS and emphasizes the importance of customizing parameter settings of CR DBS to treat specific symptoms of PD.

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