RESUMO
Background: Freezing of gait (FOG) is a debilitating symptom of Parkinson's disease (PD) that is often refractory to medication. Pathological prolonged beta bursts within the subthalamic nucleus (STN) are associated with both worse impairment and freezing behavior in PD, which are improved with deep brain stimulation (DBS). The goal of the current study was to investigate the feasibility, safety, and tolerability of beta burst-driven adaptive DBS (aDBS) for FOG in PD. Methods: Seven individuals with PD were implanted with the investigational Summit™ RC+S DBS system (Medtronic, PLC) with leads placed bilaterally in the STN. A PC-in-the-loop architecture was used to adjust stimulation amplitude in real-time based on the observed beta burst durations in the STN. Participants performed either a harnessed stepping-in-place task or a free walking turning and barrier course, as well as clinical motor assessments and instrumented measures of bradykinesia, OFF stimulation, on aDBS, continuous DBS (cDBS), or random intermittent DBS (iDBS). Results: Beta burst driven aDBS was successfully implemented and deemed safe and tolerable in all seven participants. Gait metrics such as overall percent time freezing and mean peak shank angular velocity improved from OFF to aDBS and showed similar efficacy as cDBS. Similar improvements were also seen for overall clinical motor impairment, including tremor, as well as quantitative metrics of bradykinesia. Conclusion: Beta burst driven adaptive DBS was feasible, safe, and tolerable in individuals with PD with gait impairment and FOG.
RESUMO
BACKGROUND: Pathologically prolonged bursts of neural activity in the 8-30â¯Hz frequency range in Parkinson's disease have been measured using high power event detector thresholds. NEW METHOD: This study introduces a novel method for determining beta bursts using a power baseline based on spectral activity that overlapped a simulated 1/f spectrum. We used resting state local field potentials from people with Parkinson's disease and a simulated 1/f signal to measure beta burst durations, to demonstrate how tuning parameters (i.e., bandwidth and center frequency) affect burst durations, to compare burst duration distributions with high power threshold methods, and to study the effect of increasing neurostimulation intensities on burst duration. RESULTS: The baseline method captured a broad distribution of resting state beta band burst durations. Mean beta band burst durations were significantly shorter on compared to off neurostimulation (pâ¯=â¯0.0046), and their distribution shifted towards that of the 1/f spectrum during increasing intensities of stimulation. COMPARISON WITH EXISTING METHODS: High power event detection methods, measure duration of higher power bursts and omit portions of the neural signal. The baseline method captured the broadest distribution of burst durations and was more sensitive than high power detection methods in demonstrating the effect of neurostimulation on beta burst duration. CONCLUSIONS: The baseline method captured a broad range of fluctuations in beta band neural activity and demonstrated that subthalamic neurostimulation shortened burst durations in a dose (intensity) dependent manner, suggesting that beta burst duration is a useful control variable for closed loop algorithms.