Exploration of Sinusoidal Low Frequency Alternating Current Stimulation to Block Peripheral Nerve Activity

Abstract

Sinusoidal low frequency alternating current (LFAC) stimulation is a novel mode of electrical modulation observed in the Bioelectroics Lab in 2017. LFAC is capable of blocking the single fiber action potentials (APs) of the earthworm with only a few 100’s of µA. The goal of this dissertation was to further explore and characterize the LFAC waveform to determine it’s feasibility as a method for block in the mammalian peripheral nervous system (PNS). To better understand the mechanisms of LFAC block (LFACb), a blend of in-silico modeling work was explored and the predictions were validated with ex-vivo and in-vivo experiments. This dissertation is divided into five chapters. The first chapter will explore the history of bioelectricity, the current state of in-silico modeling and methods of nerve block used in the PNS. The second chapter explores a major modeling assumption, the conductivity and permittivity of the nerve laminae of a mammalian nerve bundle. Four point electrochemical impedance spectroscopy (EIS) was performed on excised canine vagus nerve to evaluate the electrical properties of the perineurium and epineurium. This study’s result, found that the corner frequency of the perineurium (2.6kHz) and epineurium (370Hz) were much lower than previously assumed. This explain a major difference between LFACb and the more established kilohertz frequency alternating current (kHFAC) block. The third chapter revisits the initial earthworm experiments during the discovery of LFACb. The effect of conduction slowing was observed in these earthworm experiments and were also seen in a mammalian canine vagus nerve and in the Horn-Yoshida-Schild (HYS) autonomic unmyelinated axon mode. These experiments showed that LFACb occurs as a cathodic block in which the sodium channels are held inactive. Chapter 4 explored the window between LFACb and LFAC activation (LFACa). The window between the two states was describes by LFAC amplitude and LFAC frequency in an in-vivo rat sciatic nerve and an in-silico model of a myelinated motor neuron, the McIntyre-Richardson-Grill (MRG) axon model. Geometrical effects were also observed by varying the bipolar pair of contacts used to deliver the LFACb waveform from an asymmetrical tripolar cuff electrode. Plantar flexor force measurements and electromyography (EMG) of the lateral gastrocnemius (LG) and soleus (Sol) were used to quantify the effects of the LFAC waveform. Convergence between in-silico modeling and in-vivo results showed promise that modeling efforts could be used with confidence to explore the LFAC block-activation more completly. LFACa was found to be highly dependent on frequency with increasing frequency lowering the threshold of activation. LFACb was shown to be mostly invariant to frequency. The final chapter takes the information found in this dissertation and summarizes it. Future work on LFAC is also proposed and the hypothesized results presented with the findings from this dissertation and available literature.