Abstract
<jats:p>Extracellular sinusoidal low frequency alternating current (LFAC) stimulation of peripheral motor nerves has been observed to induce size wise activation of nerve fibers, unlike the inverse recruitment order typically seen in extracellular pulsed stimulation. This study aims to explore potential biophysical mechanisms responsible for this phenomenon using computational modeling. Volume conductor model was utilized with a bipolar cuff electrode encasing a single rat-sized fascicle. The extracellular potentials generated by LFAC and pulse stimulation were projected onto the McIntyre--Richardson--Grill models of myelinated motor nerve fibers to examine the activation of fibers ranging from 5.7 to 16μm in diameter. Intracellular and extracellular stimulation were compared for strength-frequency relationships with LFAC (1-20Hz) and strength-duration curves for pulse stimulation. The threshold tracking technique was used to study membrane electrotonus and threshold electrotonus of different fibers to examine subthreshold accommodation in response to LFAC and prolonged pulse stimulation. The simulations revealed that the inverse order of fiber recruitment is an inherent characteristic of extracellular stimulation and is theoretically independent of the stimulation waveform. LFAC showed an inverse strength-frequency relationship (higher frequency, lower threshold current), similar to the inverse strength-duration relationship for pulsed stimulation. Analysis of subthreshold accommodation showed that larger fibers exhibit greater accommodation than smaller fibers, leading to increased activation thresholds as fast Na+ activation factor m3h decreases while slow K+ activation increases, supporting accommodation as a contributor to orderly recruitment. With increasing LFAC frequency (up to 20Hz), these accommodation characteristics were reduced and large-fiber state dynamics shifted toward those of smaller fibers. LFAC was also found to induce subthreshold oscillations that promoted spike initiation during slow depolarization. These findings suggest that LFAC provides a controlled and optimized method for achieving orderly recruitment without the need for complex selective blocking protocols. By leveraging intrinsic membrane properties, LFAC offers a neuromodulation strategy that preserves physiological recruitment order, with direct implications for selective nerve stimulation in clinical and neuroprosthetic applications.</jats:p>