Low-Intensity ultrasound for controlled excitation and suppression in rat sciatic nerve
Heba M. Badawe, Pierre D. Mourad, Massoud L. Khraiche
Scientific Reports 2025 · 10.1038/s41598-025-16407-5
Abstract
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.
Abstract via europepmc.
Exposures
Exposure 1: Sciatic nerve sonication with varied SD and DC
Target: sciatic nerve — “rat sciatic nerve”
Device: other named manufacturer · Mana Instruments · E0525-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.25 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | not reported | ⚑ |
| Duty cycle (%) | 30, 50, 80swept | ✓✓✓ |
| Sonication duration (s) | 30, 60, 90, 120swept | ✓✓✓ |
| Free-field pressure (kPa) | 460, 720swept | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | 1.4, 3.39swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | ⚑ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Pulses of 125 cycles (tone burst duration 250 microseconds) at 500 kHz; duty cycle varied by altering the burst period; sonication duration 30, 60, 90 or 120 s delivered concurrently with 2 Hz electrical stimulation, followed by 5 min of electrical stimulation alone; 15 min break between trials.
Flags from extraction
exposures[0].free_field.pressure_kpa— Peak negative pressures 0.46 and 0.72 MPa; measured with a hydrophone in degassed water at the cone tip, so placed in free_field.exposures[0].timing.pulse_repetition_frequency_hz— PRF not stated; duty cycle was varied by altering the burst period.exposures[0].timing.pulse_duration_ms— Tone burst duration of 250 microseconds converted to 0.25 ms.exposures[0].free_field.ispta_w_cm2— Only ISPPA stated; the text also gives a cumulative energy in J/cm2 and a thermal index.n_sessions_per_subject— Each rat underwent three trials per sonication duration; total sessions per rat not stated clearly.sham_type— Region A (electrical stimulation only) serves as within-animal baseline; no sham sonication described.