Department of Surgical Sciences, Section of Neurosurgery, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Department of Psychiatry and Psychotherapy, University of Regensburg, Regensburg, Germany.
Prog Brain Res. 2021;262:451-467. doi: 10.1016/bs.pbr.2020.08.011. Epub 2020 Oct 1.
Vagus nerve stimulation is a promising new tool in the treatment of chronic tinnitus. Current protocols involve pairing sounds, which exclude the tinnitus frequency, with simultaneous vagus nerve stimulation (VNS). This is based on extensive preclinical animal studies that demonstrate that pairing non-tinnitus sounds with VNS results in a tonotopic map plasticity. It is thought that by expanding the non-tinnitus sound representation, it is possible to overturn the expanded tonotopic map associated with the tinnitus frequency in these animal models. These findings have been translated into a clinical approach, where a clinically significant, but moderate improvement, in tinnitus distress and a modest benefit in tinnitus loudness perception has been shown. Yet, pairing tinnitus matched sound to VNS may produce tinnitus improvement by Pavlovian conditioning, in which the distressful tinnitus sound becomes associated with a relaxing "rest and digest" response from activation of the vagus nerve. If this hypothesis is correct, beneficial effects should be achieved with paired sounds that resemble the tinnitus sounds as much as possible. In conclusion, although the potential to use VNS to drive neural plasticity to reduce or eliminate the neural drivers of ongoing tinnitus is exciting, much work is needed to more completely understand the neural basis of tinnitus and to develop tailored therapies to address the suffering caused by this heterogeneous condition. Whether pairing of the vagus stimulation with non-tinnitus or tinnitus-matched sounds is essential is still to be determined.
迷走神经刺激是治疗慢性耳鸣的一种有前途的新方法。目前的方案涉及将排除耳鸣频率的声音与同时进行的迷走神经刺激（VNS）配对。这是基于广泛的临床前动物研究，这些研究表明，将非耳鸣声音与 VNS 配对会导致音调地图可塑性。人们认为，通过扩大非耳鸣声音的表示，可以扭转这些动物模型中与耳鸣频率相关的扩大音调图。这些发现已经转化为一种临床方法，其中在耳鸣困扰方面显示出临床显著但适度的改善，以及在耳鸣响度感知方面有适度的益处。然而，将耳鸣匹配的声音与 VNS 配对可能通过条件反射产生耳鸣改善，其中令人痛苦的耳鸣声音与迷走神经激活引起的放松的“休息和消化”反应相关联。如果这个假设是正确的，那么应该可以通过与耳鸣声音尽可能相似的配对声音来获得有益的效果。总之，虽然利用 VNS 驱动神经可塑性来减少或消除持续耳鸣的神经驱动因素具有很大的潜力，但仍需要做大量工作来更全面地了解耳鸣的神经基础，并开发针对这种异质状况引起的痛苦的定制疗法。与非耳鸣或耳鸣匹配声音的迷走神经刺激配对是否是必要的，仍有待确定。
