Subthreshold Effects of Low-Frequency Alternating Current on Nerve Conduction Delay

Background/Objectives: Low-frequency alternating current (LFAC) has been shown to induce nerve conduction block (LFACb). However, the effects of LFAC on conduction delay prior to block remain unclear. This study investigates the impact of LFACb on conduction velocity and blocking thresholds in myelinated and unmyelinated fibers using experimental and computational models. Methods: Four models were employed to analyze LFACb effects: (1) in-vivo experiments in earthworms examined conduction delays across nerve bundles with distinct conduction velocities; (2) ex-vivo experiments in canine vagus nerves assessed the upstream and downstream effects of LFAC waveforms ranging from 50 mHz to 500 mHz; (3) in-silico simulations using the Horn, Yoshida, and Schild (HYS) model for unmyelinated fibers explored size-dependent conduction delays and blocking thresholds; and (4) in-silico simulations using the McIntyre, Richardson, and Grill (MRG) model extended to 504 Nodes of Ranvier characterized myelination effects, localized nodal interactions, and diameter-dependent thresholds. Results: LFAC-induced conduction delays were independent of LFAC frequency but strongly influenced by fiber diameter and conduction velocity. Larger fibers exhibited lower block thresholds and shorter delays before block onset. In contrast, smaller fibers demonstrated prolonged subthreshold conduction delays before achieving full block. Conclusions: These findings suggest that LFACb could serve as a neuromodulation tool for selectively blocking larger fibers while preserving smaller fiber function. This has potential applications in functional electrical stimulation (FES) and temporary, non-destructive nerve blocks for clinical and research applications.