Abstract
OBJECTIVE: Computational modeling is an important tool for developing and optimizing implantable neural stimulation devices, but requires accurate electrical and geometrical parameter values to improve predictive value. We quantified the effects of perineurial (resistive sheath around each fascicle) and endoneurial (within each fascicle) parameter values for modeling peripheral nerve stimulation. APPROACH: We implemented 3D finite element models of compound peripheral nerves and cuff electrodes to quantify activation and block thresholds of model axons. We also implemented a 2D finite element model of a bundle of axons to estimate the bulk transverse endoneurial resistivity; we compared numerical estimates to an analytical solution. MAIN RESULTS: Since the perineurium is highly resistive, potentials were approximately constant over the cross section of a fascicle, and the perineurium resistivity, longitudinal endoneurial resistivity, and fascicle diameter had important effects on thresholds. Activation thresholds increased up to ~130% for higher perineurium resistivity (~400 versus 2200 Ω m) and by ~35%-250% for lower longitudinal endoneurial resistivity (3.5 versus 0.75 Ω m), with larger increases for smaller diameter axons and for axons in larger fascicles. Further, thresholds increased by ~30%-180% for larger fascicle radii, yielding a larger increase with higher perineurium resistivity. Thresholds were largely insensitive to the transverse endoneurial resistivity, but estimates of the bulk resistivity increased with extracellular resistivity and axonal area fraction; the numerical and analytical estimates were in strong agreement except at high axonal area fractions, where structured axon placements that achieved tighter packing produced electric field inhomogeneities. SIGNIFICANCE: We performed a systematic investigation of the effects of values and methods for modeling the perineurium and endoneurium on thresholds for neural stimulation and block. These results provide guidance for future modeling studies, including parameter selection, data interpretation, and comparison to experimental results.