Horn Michael Ryne, Lazorchak Nathaniel Liam, Khan Usama Kalim, Yoshida Ken
Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Biomedicines. 2025 Apr 13;13(4):954. doi: 10.3390/biomedicines13040954.
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. 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. 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. 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.
低频交流电（LFAC）已被证明可诱发神经传导阻滞（LFACb）。然而，LFAC对阻滞前传导延迟的影响仍不清楚。本研究使用实验和计算模型，研究了LFACb对有髓和无髓纤维传导速度和阻滞阈值的影响。采用了四种模型来分析LFACb的作用：（1）在蚯蚓体内进行实验，检测不同传导速度的神经束的传导延迟；（2）在犬迷走神经上进行离体实验，评估50 mHz至500 mHz范围内LFAC波形的上游和下游效应；（3）使用Horn、Yoshida和Schild（HYS）模型对无髓纤维进行计算机模拟，探讨尺寸依赖性传导延迟和阻滞阈值；（4）使用扩展到504个郎飞结的McIntyre、Richardson和Grill（MRG）模型进行计算机模拟，表征髓鞘形成效应、局部节点相互作用和直径依赖性阈值。LFAC诱导的传导延迟与LFAC频率无关，但受纤维直径和传导速度的强烈影响。较大的纤维表现出较低的阻滞阈值，在阻滞开始前延迟较短。相比之下，较小的纤维在完全阻滞之前表现出延长的阈下传导延迟。这些发现表明，LFACb可作为一种神经调节工具，用于选择性地阻断较大的纤维，同时保留较小纤维的功能。这在功能性电刺激（FES）以及用于临床和研究应用的临时、非破坏性神经阻滞方面具有潜在应用。
