Vagus nerve stimulation (VNS) has rapidly gained interest as a treatment for a variety of disorders. A number of methods have been employed to stimulate the vagus nerve, but the most common relies on a cuff electrode implanted around the cervical branch of the nerve. Recently, two non-invasive methods have increased in popularity: transcutaneous cervical VNS (tcVNS) and transcutaneous auricular VNS (taVNS). Despite promising clinical results, there has been little direct comparison of these methods to stimulation delivered via an implanted device. In this study, we directly compared both non-invasive strategies to stimulation with an implanted cuff electrode on activation of the Hering-Breuer (HB) reflex, a non-invasive biomarker of A-fiber activation in the vagus. Stimulation was delivered across a wide range of parameters using tcVNS, taVNS, and an implanted cuff electrode in female rats. Activation of the HB reflex, changes in heart rate, and neck muscle twitch force were recorded. Consistent with low thresholds reported in previous studies, we found that the threshold to activate the HB reflex using an implanted cuff electrode was 0.406 ± 0.066 mA. tcVNS was capable of activating the HB reflex, but the threshold was 34.18 ± 1.86 mA, over 15 fold higher than the stimulation intensity that caused twitching of the neck muscles (2.09 ± 0.16 mA). No activation of the HB reflex was observed with taVNS at any parameters. These results describe activation of the HB reflex with each strategy and provide initial evidence regarding differences in the activation of the vagus nerve with invasive and non-invasive methods.

中文翻译：

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通过植入和非侵入性迷走神经刺激诱发的大鼠 Hering-Breuer 反射的参数表征。

迷走神经刺激（VNS）作为多种疾病的治疗方法迅速引起人们的兴趣。已经采用了多种方法来刺激迷走神经，但最常见的是依赖于神经颈支周围植入的袖带电极。最近，两种非侵入性方法越来越受欢迎：经皮颈部 VNS (tcVNS) 和经皮耳廓 VNS (taVNS)。尽管临床结果很有希望，但几乎没有将这些方法与通过植入设备提供的刺激进行直接比较。在这项研究中，我们直接比较了两种非侵入性策略与植入袖带电极刺激 Hering-Breuer (HB) 反射的激活情况，HB 反射是迷走神经中 A 纤维激活的非侵入性生物标志物。使用 tcVNS、taVNS 和植入的袖带电极对雌性大鼠进行多种参数的刺激。记录 HB 反射的激活、心率的变化和颈部肌肉抽搐力。与之前研究中报告的低阈值一致，我们发现使用植入式袖带电极激活 HB 反射的阈值是 0.406 ± 0.066 mA。tcVNS 能够激活 HB 反射，但阈值为 34.18 ± 1.86 mA，比引起颈部肌肉抽搐的刺激强度 (2.09 ± 0.16 mA) 高 15 倍以上。taVNS 在任何参数下均未观察到 HB 反射的激活。这些结果描述了每种策略对 HB 反射的激活，并提供了有关侵入性和非侵入性方法激活迷走神经差异的初步证据。