Badawe Heba M, Mourad Pierre D, Khraiche Massoud L
Biomedical Engineering Department, Neural Engineering and Nanobiosensors Group, American University of Beirut, Beirut, Lebanon.
Department of Neurological Surgery, University of Washington, Seattle, WA, USA.
Sci Rep. 2025 Oct 1;15(1):34260. doi: 10.1038/s41598-025-16407-5.
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.
低强度、低频超声已显示出神经调节的潜力，特别是在影响外周神经活动方面。然而，调节神经元活动所需的精确参数仍知之甚少，这限制了其更广泛的应用。在此，我们研究了改变超声处理持续时间（SD）和占空比（DC）对大鼠坐骨神经运动神经元反应的影响，重点是了解累积能量暴露如何在超声神经调节过程中影响外周神经活动的激活或抑制。我们在不同的超声处理持续时间和占空比下，对大鼠坐骨神经进行体内低强度、低频超声处理。累积能量暴露通过空间峰值脉冲平均强度、SD和DC的乘积来计算。测量腓肠肌的肌电图（EMG）活动，并监测热效应以确保非热应用。我们的研究结果表明，较高的累积能量暴露会抑制腓肠肌（由坐骨神经支配）的EMG活动。然而，较低的累积能量暴露会增强运动刺激。值得注意的是，超声诱导的EMG变化在超声处理后持续5分钟——比应用持续时间长三到五倍——强调了超声在精确神经控制方面的治疗潜力。有趣的是，我们的结果表明，根据获得的累积能量，超声处理后电诱发的EMG活动会从兴奋转变为抑制。这项研究建立了一个用于长期神经调节的安全参数空间，证明了其在治疗应用中的潜力，即可以精确调节外周神经系统活动来治疗神经病变和慢性疼痛。这些发现有助于基于超声的治疗方法的发展，为外周神经刺激提供了一种新颖且可控的方法。
