Short pulse width widens the therapeutic window of subthalamic neurostimulation

Abstract

We explored the impact of pulse durations <60 μsec on the therapeutic window of subthalamic neurostimulation in Parkinson's disease. Current thresholds for full rigidity control and first muscle contractions were evaluated at pulse durations between 20 and 120 μsec during a monopolar review session in four patients. The average therapeutic window was 2.16 mA at 60 μsec, which proportionally increased by 182% at 30 μsec, while decreasing by 46% at 120 μsec. Measured chronaxies and model data suggest, that pulse durations <60 μsec lead to a focusing of the neurostimulation effect on smaller diameter axons close to the electrode while avoiding stimulation of distant pyramidal tract fibers.

Figure 1

(A) linearized strength–duration curves for rigidity control and muscle contractions. (B) Bar graph depicting the relative change in therapeutic window compared to 60 μsec pulse duration (TW_60 μsec). Error bars indicate the standard error of mean in both graphs.

Figure 2

Model derived strength–duration curves for action potential initiation in smaller (2 μm) diameter axons located closer (1–2 mm) the electrode as compared to larger (5.7 μm) diameter axons located farther from (4–5 mm) the electrode. At shorter pulse duration the two curves diverge explaining an increased “therapeutic window” if benefit was associated with stimulation of the nearby fibers and adverse effects with the distant thick myeliniated axons.