The standard electrical stimulation waveform used for electrical activation of nerve is a rectangular pulse or a charge balanced rectangular pulse, where the pulse width is typically in the range of ∼100 µsec through ∼1000 µsec. In this work, we explore the effects of a continuous sinusoidal waveform with a frequency ranging from 5 through 20 Hz, which was named the Low Frequency Alternating Current (LFAC) waveform. The LFAC waveform was explored in the Bioelectronics Laboratory as a novel means to evoke nerve block. However, in an attempt to evoke complete nerve block on a somatic motor nerve, increasing the amplitude of the LFAC waveform unexpectedly produced nerve activation, and elicited a strong non-fatiguing muscle contraction in the anesthetized rabbit model (unpublished observation). The present thesis aimed to further explore the phenomenon to measure the effect of LFAC waveform frequency and amplitude on nerve activation.<div><br></div><div>In freshly excised canine cervical vagus nerve (n=3), it was found that the LFAC waveform at 5, 10, and 20 Hz produced burst modulated activity. Compound action potentials (CAP) synchronous to the stimuli was absent from the electroneurogram (ENG) recordings. When applied <i>in-vivo</i>, LFAC was capable of activating the cervical vagus nerve fibers in anaesthetized swine (n=5) and induced the Hering-Breuer reflex. Additionally, when applied <i>in-vivo</i> to anesthetized Sprague Dawley rats (n=4), the LFAC waveform was able to activate the left sciatic nerve fibers and induced muscle contractions.</div><div><br></div><div>The results demonstrate that LFAC activation was stochastic, and asynchronous to the stimuli unlike conventional pulse stimulation where nerve and muscle response simultaneously and synchronously to stimulus. The activation thresholds were found to be frequency dependent. As the waveform frequency increases the required current amplitude decreases. These experiments also implied that the LFAC phenomenon was most likely to be fiber type-size dependent but that more sophisticated exploration should be addressed before reaching clinical applications. In all settings, the LFAC amplitude was within the water window preventing irreversible electrochemical reactions and damages to the cuff electrodes or nerve tissues. This thesis also reconfirms the preliminary LFAC activation discovery and explores multiple methods to evaluate the experimental observations, which suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic and somatic nerve fibers. LFAC appears to be a promising new technique to activate peripheral nerve fibers.</div>

Indiana University-Purdue University Indianapolis (IUPUI) / The standard electrical stimulation waveform used for electrical activation of nerve is a rectangular pulse or a charge balanced rectangular pulse, where the pulse width is typically in the range of ∼100 µsec through ∼1000 µsec. In this work, we explore the effects of a continuous sinusoidal waveform with a frequency ranging from 5 through 20 Hz, which was named the Low Frequency Alternating Current (LFAC) waveform. The LFAC waveform was explored in the Bioelectronics Laboratory as a novel means to evoke nerve block. However, in an attempt to evoke complete nerve block on a somatic motor nerve, increasing the amplitude of the LFAC waveform unexpectedly produced nerve activation, and elicited a strong non-fatiguing muscle contraction in the anesthetized rabbit model (unpublished observation). The present thesis aimed to further explore the phenomenon to measure the effect of LFAC waveform frequency and amplitude on nerve activation. In freshly excised canine cervical vagus nerve (n=3), it was found that the LFAC waveform at 5, 10, and 20 Hz produced burst modulated activity. Compound action potentials (CAP) synchronous to the stimuli was absent from the electroneurogram (ENG) recordings. When applied in-vivo, LFAC was capable of activating the cervical vagus nerve fibers in anaesthetized swine (n=5) and induced the Hering-Breuer reflex. Additionally, when applied in-vivo to anesthetized Sprague Dawley rats (n=4), the LFAC waveform was able to activate the left sciatic nerve fibers and induced muscle contractions. The results demonstrate that LFAC activation was stochastic, and asynchronous to the stimuli unlike conventional pulse stimulation where nerve and muscle response simultaneously and synchronously to stimulus. The activation thresholds were found to be frequency dependent. As the waveform frequency increases the required current amplitude decreases. These experiments also implied that the LFAC phenomenon was most likely to be fiber type-size dependent but that more sophisticated exploration should be addressed before reaching clinical applications. In all settings, the LFAC amplitude was within the water window preventing irreversible electrochemical reactions and damages to the cuff electrodes or nerve tissues. This thesis also reconfirms the preliminary LFAC activation discovery and explores multiple methods to evaluate the experimental observations, which suggest the feasibility of the LFAC waveform at 5, 10, and 20 Hz to activate autonomic and somatic nerve fibers. LFAC appears to be a promising new technique to activate peripheral nerve fibers.