Low-Intensity ultrasound for controlled excitation and suppression in rat sciatic nerve

Low-intensity, low-frequency ultrasound has shown promise for neuromodulation, particularly for influencing peripheral neural activity. However, the precise parameters required to modulate neuronal activity remain poorly understood, limiting its broader application. Here, we investigated the effects of varying the sonication duration (SD) and duty cycle (DC) on motor neuronal responses in the rat sciatic nerve, with a focus on understanding how cumulative energy exposure influences the activation or suppression of peripheral neural activity during ultrasound neuromodulation. We applied low-intensity, low-frequency ultrasound to the rat sciatic nerve in vivo at different sonication durations and duty cycles. The cumulative energy exposure is calculated as the product of the spatial-peak pulse-average intensity, SD, and DC. Electromyographic (EMG) activity in the gastrocnemius muscle was measured, and the thermal effects were monitored to ensure a non-thermal application. Our findings demonstrate that higher cumulative energy exposure suppresses EMG activity in the gastrocnemius muscle (innervated by the sciatic nerve). However, lower cumulative energy exposure enhances motor stimulation. Notably, the ultrasound-induced EMG changes persisted for 5 min post-sonication - three to five times longer than the application duration - emphasizing the therapeutic potential of ultrasound for precise neural control. Interestingly, 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 for treating neuropathies and chronic pain. These findings contribute to the development of ultrasound-based treatments, offering a novel and controllable method for peripheral nerve stimulation.