Modulating Peripheral Neural Activity: Prolonged Low-Intensity Ultrasound for Controlled Excitation and Suppression in Rat Sciatic Nerve

ObjectiveLow-intensity, low-frequency ultrasound has shown promise for neuromodulation, particularly for influencing peripheral neural activity. However, the precise parameters required to modulate neuronal activity consistently remain poorly understood, limiting its broader application. Here, we investigate the effects of varying sonication duration (SD) and duty cycle (DC) on motor neuronal responses in the rat sciatic nerve, focusing on understanding how cumulative energy exposure influences the activation, enhancement, or suppression of peripheral neural activity during ultrasound neuromodulation. ApproachWe apply low-intensity, low-frequency ultrasound to the rat sciatic nerve in vivo at different sonication durations (30s, 60s, 90s, and 120s) and duty cycles (30%, 50%, and 80%). The cumulative energy exposure is calculated as the product of spatial-peak pulse-average intensity, SD, and DC. Electromyographic (EMG) activity in the gastrocnemius muscle is measured, and the thermal effects are monitored to ensure a non-cavitational, non-thermal application. Main ResultsOur findings demonstrate that higher cumulative energy exposures suppress EMG activity in the gastrocnemius muscle (enervated by the sciatic nerve). However, lower cumulative energy exposures enhance EMG activity and motor stimulation. Notably, the ultrasound-induced EMG changes persisted for 5 minutes post-sonication - three to five times longer than the application duration -- underscoring the therapeutic potential of ultrasound for precise neural control. In vivo evaluations suggest the mechanical nature of the observed effects without any significant temperature increase or induction of cavitation. In vivo evaluations suggest the mechanical nature of the observed effects without any significant temperature increase or induction of cavitation. SignificanceInterestingly, our results show a switch from excitation to suppression of electrically evoked EMG activity following ultrasound sonication depending on the acquired cumulative energy. This study establishes a safe parameter space for prolonged neuromodulation, demonstrating its potential for therapeutic applications that can precisely modulate peripheral nervous system activity. These findings contribute to the development of ultrasound-based treatments for neurological conditions, offering a novel and controllable method for peripheral nerve stimulation.