Fig. 5: Interferential stimulation activates vagal fibers in a specific spatiotemporal pattern, in experiments in swine and in swine vagus nerve models.

A Example laryngeal EMG responses to a 0.25 ms long sinusoidal stimulus (red) and i²CS (green) at different steering ratios (total amplitude 1 mA) and beat durations (0.25, 1, and 2 ms, from left to right). B Difference in latency of onset of laryngeal EMG in response to 0.25 ms-long sinusoidal stimulation (red) and i²CS (green) of different beat durations (0.25, 1, and 2 ms, from left to right), across all steering ratios, in 5 animals. Median response onset latencies to sinusoidal stimulation are shorter compared to i²CS of beat durations of 1 and 2 ms (p < = 0.112 for sin. stim. vs. i²CS 0.25 ms, p = 0.024 for sin. stim. vs. i²CS 1 ms and p = 0.0002 for sin. stim. vs. i²CS 2ms, Kruskal–Wallis test). C Modeled action potentials (APs) in a fast fiber located in a deep, RL fascicle (black-outlined fascicle in inset i1), in response to sinusoidal (red) and i²CS (green), at different steering ratios (total amplitude 2 mA) and beat durations (0.25, 1 and 2 ms, from left to right), same as those used in A. D Difference in latency of onset of modeled APs calculated from simulations of fast fibers located in all RL fascicles (inset: orange-filled fascicles), for sinusoidal stimulation (red) and i²CS (green), at different beat durations (0.25, 1, and 2 ms, from left to right), across all steering ratios. Median AP latencies to sinusoidal stimulation are shorter compared to i²CS of any beat duration (p < 0.001, Kruskal–Wallis test). E Onset latency of APs for modeled, fast fibers inside fascicles located at different distances from the middle of the steering axis, in response to sinusoidal stimulation (red data points) or i²CS with beat durations of 0.25 ms (filled green data points) and 1 ms (open green data points); the current was steered at the center of the nerve (steering ratio = 0; total amplitude 2 mA). Inset i2 shows modeled fascicles color-coded according to their distance from the mid-point of the steering axis. F Same as (E), but for a steering ratio of −0.5 (total amplitude 2 mA), resulting in a maximum interferential field on the right side of the nerve cross-section.