Evaluation of Frequency-Dependent Effects of Deep Brain Stimulation in a Cortex-Basal Ganglia-Thalamus Network Model of Parkinson's Disease.

Abstract

Parkinson's disease (PD) is a chronic neurodegenerative disease whose motor symptoms are accompanied by an exaggerated power in the alpha-beta (7-35Hz) band and an increased synchronization of neurons encompassing the cortex-basal ganglia-thalamus network. Currently, deep brain stimulation (DBS) is used as an effective therapy for reducing the excessive power and synchrony observed in brain circuits, thereby ameliorating the PD symptoms. In the present study, we used a biologically plausible computational model of cortex-basal ganglia-thalamus network, which represents both healthy and PD conditions, to systematically investigate the effects of DBS frequency on the model outputs. DBS was applied to the subthalamic nucleus (STN) at different stimulation frequencies (40Hz to 300Hz). Spike train variability and spectral power in the 7-35Hz band were measured from the several nuclei represented in the model. In addition, the magnitude squared coherence between the nuclei was assessed. An increased DBS frequency tended to produce interspike intervals (ISIs) with higher variability as compared to PD condition. Also, DBS significantly reduced the alpha-beta power for almost all brain nuclei. The median of the magnitude-squared coherence matrix (which is a metric of global network synchronization) decreased significantly with the increase of DBS frequency.