Restoring the basal ganglia in Parkinson's disease to normal via multi-input phase-shifted deep brain stimulation

摘要

Deep brain stimulation (DBS) injects a high frequency current that effectively disables the diseased basal ganglia (BG) circuit in Parkinson's disease (PD) patients, leading to a reversal of motor symptoms. Though therapeutic, high frequency stimulation consumes significant power forcing frequent surgical battery replacements and causing widespread influence into other brain areas which may lead to adverse side effects. In this paper, we conducted a rigorous study to assess whether low frequency signals can restore behavior in PD patients by restoring neural activity in the BG to the normal state. We used a biophysical-based model of BG nuclei and motor thalamus whose parameters can be set to simulate the normal state and the PD state with and without DBS. We administered pulse train DBS waveforms to the subthalamic nucleus (STN) with frequencies ranging from 1-150Hz. For each DBS frequency, we computed statistics on the simulated neural activity to assess whether it is restored to the normal state. In particular, we searched for DBS waveforms that suppress pathological bursting, oscillations, correlations and synchronization prevalent in the PD state and that enable thalamic cells to relay cortical inputs reliably. We found that none of the tested waveforms restores neural activity to the normal state. However, our simulations led us to construct a novel DBS strategy involving low frequency multi-input phaseshifted DBS to be administered into the STN. This strategy successfully suppressed all pathological symptoms in the BG in addition to enabling thalamic cells to relay cortical inputs reliably.