Control mechanisms of pathological low-frequency oscillations under different targets in Parkinson's disease

Abstract

Deep brain stimulation (DBS) inhibiting excessive low-frequency (7–35 Hz) synchronization can treat Parkinson's disease (PD), although the therapeutic mechanism remains unclear. To explore the mechanism of DBS in controlling the pathological low-frequency oscillations, we stimulate the globus pallidus pars interna (GPi), globus pallidus pars externa (GPe), subthalamic nucleus (STN), indirect medium spiny neurons (iMSN) and direct medium spiny neurons (dMSN) in basal ganglia (BG) to analyze the discharge mode of each nucleus. The transition between healthy and PD condition can be achieved by whether to add dopamine-level current based on the cortex-basal ganglia-thalamus (CTx-BG-TH) loop model. In this study, we propose two mechanisms to control the abnormal oscillations, namely, increase and decrease mechanisms of oscillation frequency. The simulation results show that stimulating GPi, STN or iMSN can make the discharge frequency of GPi reach more than 35 Hz, while stimulation of dMSN or GPe targets can reduce the frequency to less than 7 Hz, indicating that the discharge frequency presents two opposite changes to eliminate the beta oscillations. Moreover, GPi-DBS and dMSN-DBS are the optimal choices that can minimize the oscillation energy in the low-frequency band under the two control mechanisms, respectively. Therefore, simultaneous stimulation in GPi and dMSN to coordinate the two control mechanisms may provide a new idea for the DBS targets selection under parkinsonian state.