At home adaptive dual target deep brain stimulation in Parkinson disease with proportional control

Abstract

Abstract Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus (GP) is an effective treatment for the motor symptoms of Parkinson’s Disease (PD). The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. CDBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and GP (dual target DBS) in a prospective within-participant, clinical trial in six PD patients (n = 6, 55 to 65 years, two women). Dual target cDBS was tested for PD symptom control annually over 2 years, measured by motor rating scales, ON time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral (PI) aDBS using a novel distributed (off-implant) architecture. In the home setting we collected tremor and dyskinesia scores as well as individualized beta and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by UPDRS to a greater degree than either region alone (p < 0.05, Linear Mixed Model) in the cohort. The amplitude of beta oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (p < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artifacts and demonstrated a correlation between STN beta amplitude and DBS amplitude. PI control of aDBS reduced average power, while preserving Unified Parkinson’s Disease Rating Scale Motor Examination (UPDRS III) scores in the clinic (p = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n =3, p > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of PD over DBS of either the STN or GP alone. When combined with PI aDBS, stimulation power may be reduced while preserving the increased benefit of dual target DBS.