Closed-loop vagus nerve stimulation (VNS) paired with rehabilitative training has emerged as a strategy to enhance recovery after neurological injury. Previous studies demonstrate that brief bursts of closed-loop VNS paired with rehabilitative training substantially improve recovery of forelimb motor function in models of unilateral and bilateral contusive spinal cord injury (SCI) at spinal level C5/6. While these findings provide initial evidence of the utility of VNS for SCI, the injury model used in these studies spares the majority of alpha motor neurons originating in C7-T1 that innervate distal forelimb muscles. Because the clinical manifestation of SCI in many patients involves damage at these levels, it is important to define whether damage to the distal forelimb motor neuron pools limits VNS-dependent recovery. In this study, we assessed recovery of forelimb function in rats that received a bilateral incomplete contusive SCI at C7/8 and underwent extensive rehabilitative training with or without paired VNS. The study design, including planned sample size, assessments, and statistical comparisons, was preregistered prior to beginning data collection (https://osf.io/ysvgf/). VNS paired with rehabilitative training significantly improved recovery of volitional forelimb strength compared to equivalent rehabilitative training without VNS. Additionally, VNS-dependent enhancement of recovery generalized to 2 similar, but untrained, forelimb tasks. These findings indicate that damage to alpha motor neurons does not prevent VNS-dependent enhancement of recovery and provides additional evidence to support the evaluation of closed-loop VNS paired with rehabilitation in patients with incomplete cervical SCI.

中文翻译：

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迷走神经刺激与康复训练相结合可增强双侧脊髓损伤后颈前肢运动池的运动恢复

闭环迷走神经刺激 (VNS) 与康复训练相结合已成为促进神经损伤后恢复的一种策略。先前的研究表明，在 C5/6 脊髓水平的单侧和双侧挫伤性脊髓损伤 (SCI) 模型中，闭环 VNS 的短暂爆发与康复训练相结合，可显着改善前肢运动功能的恢复。虽然这些发现提供了 VNS 对 SCI 的效用的初步证据，但这些研究中使用的损伤模型保留了大部分源自 C7-T1 的 alpha 运动神经元，这些神经元支配远端前肢肌肉。由于许多患者 SCI 的临床表现涉及这些水平的损伤，因此重要的是要确定对远端前肢运动神经元池的损伤是否会限制 VNS 依赖性恢复。在这项研究中，我们评估了在 C7/8 处接受双侧不完全挫伤性 SCI 并在有或没有配对 VNS 的情况下接受广泛康复训练的大鼠的前肢功能恢复。研究设计，包括计划的样本量、评估和统计比较，在开始数据收集之前已预先注册 (https://osf.io/ysvgf/)。与没有 VNS 的等效康复训练相比，VNS 与康复训练相结合显着提高了意志力前肢力量的恢复。此外，依赖于 VNS 的恢复增强推广到 2 个类似但未经训练的前肢任务。