April 29, 2008 - 1:00 p.m.

Location: Main Auditorium, Toronto Western Hospital
**Note change of day, time and location for this seminar**

David Terman, Mathematical Biosciences Institute & Ohio State University
A data-driven computational model of subthalamic nucleus deep brain stimulation

The delivery of high-frequency stimulation has become a widely used therapeutic option for the treatment of Parkinson's disease (PD). The mechanisms underlying the effectiveness of deep brain stimulation (DBS), however, remain unclear. Studies have shown that pathological rhythmicity emerges in certain subsets of cells within the basal ganglia in Parkinsonism. Therefore, DBS for PD may work by eliminating such pathological signals. Recent experimental results, however, suggest that neurons directly downstream from stimulated regions may in fact be activated by DBS. These results support the alternative idea that DBS works by replacing pathological rhythms with regularized firing activity. Here, we present a computational implementation of this idea. Our simulations and analysis demonstrate a mechanism by which pathological oscillatory inhibition from the internal segment of the globus pallidus (GPi) to thalamocortical (TC) cells could compromise the fidelity of TC relay of excitatory signals, whereas elimination of the pathological oscillations within this inhibitory signal could restore TC cells' relay capabilities. We use GPi spike trains recorded from normal control monkeys and from parkinsonian monkeys with or without DBS of the subthalamic nucleus region as the source of inhibitory inputs to our model TC cells. Our results show that there is a significant decline in the ability of the TC cells to relay the excitatory stimuli when they are exposed to GPi signals recorded under parkinsonian conditions in the absence of DBS or with sub-therapeutic DBS, defined by its failure to induce a therapeutic effect on motor symptoms, relative to GPi data recorded from normal monkeys. Moreover, relay effectiveness is restored to non-parkinsonian levels by GPi signals recorded under parkinsonian conditions in the presence of therapeutic DBS, which induced a measurable improvement in motor symptoms.