Modeling the response of small myelinated and unmyelinated axons to kilohertz frequency signals

The effects of kilohertz frequency signals on action potential conduction in small myelinated (1 to 5.7 μm diameter) and unmyelinated axons are poorly understood, but could have important therapeutic applications. We developed a finite element model of a compound peripheral nerve and quantified the effects of a 5 kHz signal delivered via cuff electrode on conduction in small myelinated and unmyelinated axons. We compared the results from this realistic model to responses to the same signal delivered by an extracellular point source in a homogeneous isotropic extracellular medium. Using typical clinical parameters, the primary effect of the 5 kHz signal was excitation of the 5.7 μm diameter myelinated fibers in both models. The unmyelinated fibers were mostly unaffected by the applied signal. Axonal conduction block occurred only for certain parameter sets in the 5.7 μm diameter myelinated fibers. Our model reveals the complexity of possible responses to kilohertz frequency signals, and suggests that mechanisms of therapeutic efficacy other than conduction block need to be considered. A better understanding of the effects of kilohertz frequency signals is needed to inform clinical parameter selection for electrical devices targeting conduction block in small fibers.