In vivo peripheral nerve activation using sinusoidal low‐frequency alternating currents

Abstract

Background The sinusoidal low‐frequency alternating current (LFAC) waveform was explored recently as a novel means to evoke nerve conduction block. In the present work, we explored whether increasing the amplitude of the LFAC waveform results in nerve fiber activation in autonomic nerves. In‐silico methods and preliminary work in somatic nerves indicated a potential frequency dependency on the threshold of activation. The Hering‐Breuer (HB) reflex was used as a biomarker to detect cervical vagus nerve activation. Methods Experiments were conducted in isoflurane‐anesthetized swine (n = 5). Two stimulating bipolar cuff electrodes and a tripolar recording cuff electrode were implanted on the left vagus nerve. To ensure the electrical stimulation affects only the afferent pathways, the nerve was crushed caudal to the electrodes to eliminate cardiac effects. (1) Standard pulse stimulation (Vstim) using a monophasic train of pulses was applied through the caudal electrode to elicit HB reflex and to identify the activated nerve fiber type. (2) Continuous sinusoidal LFAC waveform with a frequency ranging from 5 through 20 Hz was applied to the rostral electrode without Vstim to explore the activation thresholds at each LFAC frequency. In both cases, the activation of nerve fibers was detected by a HB reflex‐induced reduction in the breathing rate. Results LFAC was found to be capable of eliciting an HB response. The LFAC activation thresholds were found to be frequency‐dependent. The HB threshold was 1.02 ± 0.3 mAp at 5 Hz, 0.66 ± 0.3 mAp at 10 Hz, and 0.44 ± 0.2 mAp at 20 Hz. In comparison, it was 0.7 ± 0.47 mA for a 100 μs pulse. The LFAC amplitude was within the linear limits of the electrode interface. Damage to the cuff electrodes or the nerve tissues was not observed. Analysis of Vstim‐based compound nerve action potentials (CNAP) indicated that the decrease in breathing rate was found to be correlated with the activation of slower components of the CNAP suggesting that LFAC reached and elicited responses from these slower fibers associated with afferents projecting to the HB response. Conclusions These results suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic nerve fibers and potentially provide a new modality to the neurorehabilitation field.

The International Functional Electrical Stimulation Society (IFESS): Highlights from the IFESS conference at Rehabweek 2023

“…It is a phenomenon we named LFAC activation (LFACa). 20,21 In-silico models and subsequent in-vivo experiments show that LFAC block and activation have interesting properties. 22 It blocks without onset activation and activates nerve fibers in a size-wise order.…”

“…In 2018, in another experiment aiming to maximize LFAC block, we discovered that the waveform at higher amplitudes activated nerve fibers that led to strong, fatigue‐resistant muscle contractions. It is a phenomenon we named LFAC activation (LFACa) 20,21 . In‐silico models and subsequent in‐vivo experiments show that LFAC block and activation have interesting properties 22 .…”

Impact of anesthesia on micromagnetic stimulation (μMS) of the vagus nerve

“…Of the several sVNS techniques developed in the past, special mention includes -fiber-selective stimulation [20,21], spatially selective stimulation [18,22], anodal block [23,24], kilohertz electrical stimulation (KES) block [25,26], reversible AC nerve conduction block [27] and neural titration [28,29]. Such techniques have primarily focused on studying the impact of stimulation pulse [30], the electrode array geometry [31,32], and the stimulation protocol.…”