Closed-loop deep brain stimulation in Parkinson’s disease: Explore the superiority and mechanism

Continuous high frequency deep brain stimulation (DBS) at subthalamic area (STN) is an effective treatment for patients with advanced Parkinson’s disease (PD), with improvement of cardinal motor symptoms, such as tremor, rigidity radykinesia and postural instability. However, the efficacy of STN DBS is limited by the undesirable adverse effect, partial improvement of parkinsonism symptoms and cost of battery. The mechanism of action of DBS remains unclear. Converging evidences suggest that the high frequency stimulation suppresses the pathological activity in basal ganglia. Nevertheless, the residual physiological activity at the same target would be over-ridden inevitably with the conventional fixed and continue stimulation system. Accordingly, a more optimal stimulation paradigm would be a closed-loop stimulation system that can sense a reliable feedback signals relating to pathological and clinical state of PD, and delivers stimulation when it is necessary. Recently, there are two experimental studies compared the effect of closed-loop Stimulation and conventional open-loop DBS in motor symptoms in parkinsonsian primate and patients with PD, spikes recorded from motor cortex and local field potentials (LFPs) recorded from STN are used as feedback signals, respectively. Both showed that closed-loop stimulation is superior in ameliorating akinesia. In this proposed study, I plan to use a novel signals analysis paradigm to reconstruct the LFPs, which will be recorded directly from the electrodes implanted to STN of PD. The reconstructed LFPs will be used to trigger the stimulation of this target. To this end, I will test whether the therapeutic effects of closed-loop stimulation is superior to conventional DBS in postural instability and gait disturbance in patients with PD.

Project ID:PG10501-0298
External Project ID:NHRI-EX105-10413NC