Alhawwash A, Horn M R, Lazorchak N, Yoshida K
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, United States of America.
Biomedical Technology Department, King Saud University, Riyadh 11451, Saudi Arabia.
J Neural Eng. 2025 Feb 11;22(1). doi: 10.1088/1741-2552/adafdc.
Direct electrical neurostimulation using continuous sinusoidal low frequency alternating currents (LFAC) is an emerging modality for neuromodulation. As opposed to the traditional rectangular pulse stimulation, there is limited background on the characteristics of peripheral nerves responses to sinusoidal LFAC stimulation; especially within the low frequency range (<50 Hz). In this study, we demonstrate LFAC activation as a means to activate motor nerves by direct bipolar nerve stimulation via cuff electrodes, and characterize the factors of activation. We study and quantify the effects of sinusoidal frequency and electrode geometry on the motor nerve activation thresholdand in computational models,.Acuteexperiments (= 34) were conducted on isoflurane-anaesthetized rats. A pure tone continuous sinusoidal current was applied to the rat sciatic nerve in bipolar configurations via bipolar or tripolar nerve cuff electrodes (different contact separations). LFAC activation thresholds were quantified by measuring the electromyogram (EMG) response of the triceps surae muscles and the induced twitch force to LFAC stimulation at six frequencies (1, 2, 3, 4, 8, and 20 Hz). Computationally, we utilized a volume conductor model of a bipolar cuff electrode around a single rat-size fascicle and projected the potentials to the McIntyre-Richardson-Grill models of myelinated motor nerve fibers. We compared theresponses of a range of fiber diameters (5.7 to 16m) to LFAC stimulation and their activation thresholds to thefindings.: Sinusoidal LFAC stimulation elicited motor nerve activityand, with a remarkable convergence of thepredictions to theobservations. The EMG activity showed that muscle responses to LFAC stimulation were phase-locked to the sinusoidal cycle but exhibited two distinct activation modes. These modes were classified as burst and unitary, indicating the presence of two distinct patterns of muscle activation during LFAC stimulation. The LFAC motor activation threshold was significantly dependent on frequency and influenced by the contact separation of the cuff electrode, with a greater extent of reduction at a higher frequency or wider separation. Moreover, the order of fiber recruitment was suggested to be normal-physiological (small-to-large caliber) given the nature of the induced EMG activity andpredictions.: These findings provide significant insights into the nature of sinusoidal LFAC stimulation, at the explored range of frequency, and the expected mammalian peripheral motor nerve responses to LFAC. The characteristics of sinusoidal LFAC stimulation would facilitate selectivity approaches in a broader range of therapeutic and rehabilitative neuromodulation applications.
使用连续正弦低频交流电（LFAC）进行直接电神经刺激是一种新兴的神经调节方式。与传统的矩形脉冲刺激不同，关于外周神经对正弦LFAC刺激反应特性的背景知识有限；特别是在低频范围（<50Hz）内。在本研究中，我们证明了通过袖带电极进行直接双极神经刺激，LFAC激活可作为激活运动神经的一种手段，并对激活因素进行了表征。我们研究并量化了正弦频率和电极几何形状对运动神经激活阈值的影响，并建立了计算模型。在异氟烷麻醉的大鼠上进行了急性实验（n = 34）。通过双极或三极神经袖带电极（不同的接触间距）以双极配置将纯音连续正弦电流施加到大鼠坐骨神经上。通过测量腓肠肌的肌电图（EMG）反应以及在六个频率（1、2、3、4、8和20Hz）下对LFAC刺激诱发的抽搐力来量化LFAC激活阈值。在计算方面，我们利用了围绕单个大鼠大小束状神经的双极袖带电极的容积导体模型，并将电位投影到有髓运动神经纤维的麦金太尔 -理查森 - 格里尔模型上。我们比较了一系列纤维直径（5.7至16μm）对LFAC刺激的反应及其激活阈值与实验结果。结果表明：正弦LFAC刺激引发了运动神经活动，并且预测结果与观察结果有显著的一致性。EMG活动表明，肌肉对LFAC刺激的反应与正弦周期锁相，但表现出两种不同的激活模式。这些模式被分类为爆发性和单一性，表明在LFAC刺激期间存在两种不同的肌肉激活模式。LFAC运动激活阈值显著依赖于频率，并受袖带电极接触间距的影响，在较高频率或较宽间距下降低程度更大。此外，鉴于诱发的EMG活动的性质和预测结果，纤维募集顺序被认为是正常生理顺序（从小口径到大口径）。这些发现为在探索的频率范围内正弦LFAC刺激的性质以及哺乳动物外周运动神经对LFAC的预期反应提供了重要见解。正弦LFAC刺激的特性将有助于在更广泛的治疗和康复神经调节应用中实现选择性方法。
