Effects of the temporal pattern of subthalamic deep brain stimulation on the neuronal complexity in the globus pallidus.

Abstract

Deep brain stimulation (DBS) is a surgical treatment for Parkinson's disease (PD) but, despite clinical efficacy, the mechanisms of DBS still require investigation. Recent evidence suggests that the temporal pattern of the electrical pulses may be critical to the therapeutic merit of DBS and carefully-designed, non-regular patterns could ameliorate some of the motor symptoms in PD. It is unclear, though, how different stimulation patterns affect the neural activity in the basal ganglia and whether this is related to the pathophysiology of PD. In this study, a non-human primate was treated with DBS of the subthalamic nucleus while single-unit recordings were collected in the animal's globus pallidus internus (GPi). Three stimulation patterns were applied (one regular, two non-regular) and the stimulation effects on the GPi spike trains were assessed via point process modeling. On a preliminary set of 23 GPi neurons, we show that regular DBS maximized the neuronal complexity, which is a measure of the amount of information that a single neuron can encode, and significantly increased the dependency of the neurons' spike trains on the background ensemble activity through an articulated balance of excitation and inhibition. Overall, regular DBS caused the largest modulation in the neurons' spiking pattern and the largest increment in encoding capabilities. Both results may be relevant to the mechanisms of therapeutic DBS.