Efficient suppression of parkinsonian beta oscillations in a closed-loop model of deep brain stimulation with amplitude modulation.

Introduction: Parkinson's disease (PD) is a movement disorder characterized by the pathological beta band (15-30 Hz) neural oscillations within the basal ganglia (BG). It is shown that the suppression of abnormal beta oscillations is correlated with the improvement of PD motor symptoms, which is a goal of standard therapies including deep brain stimulation (DBS). To overcome the stimulation-induced side effects and inefficiencies of conventional DBS (cDBS) and to reduce the administered stimulation current, closed-loop adaptive DBS (aDBS) techniques were developed. In this method, the frequency and/or amplitude of stimulation are modulated based on various disease biomarkers. Methods: Here, by computational modeling of a cortico-BG-thalamic network in normal and PD conditions, we show that closed-loop aDBS of the subthalamic nucleus (STN) with amplitude modulation leads to a more effective suppression of pathological beta oscillations within the parkinsonian BG. Results: Our results show that beta band neural oscillations are restored to their normal range and the reliability of the response of the thalamic neurons to motor cortex commands is retained due to aDBS with amplitude modulation. Furthermore, notably less stimulation current is administered during aDBS compared with cDBS due to a closed-loop control of stimulation amplitude based on the STN local field potential (LFP) beta activity. Discussion: Efficient models of closed-loop stimulation may contribute to the clinical development of optimized aDBS techniques designed to reduce potential stimulation-induced side effects of cDBS in PD patients while leading to a better therapeutic outcome.