配对声音的迷走神经刺激治疗耳鸣：一项安全性和可行性试验

文献信息

中文摘要

目的： 耳鸣是在没有外部声源的情况下感知到声音，在耳鸣障碍中与不愉快感和痛苦相关。迷走神经刺激（VNS）与非耳鸣声音配对已显示出逆转耳鸣中所见音调拓扑图变化的希望。另一种方法是，将耳鸣声音的复制品与副交感VNS配对，可能通过巴甫洛夫式再条件化降低耳鸣显著性。我们评估了配对和非配对无创VNS与耳鸣匹配听觉刺激（AS）的安全性和可行性，并评估了对临床结局以及耳鸣相关网络内活动和功能连接的影响。
材料和方法： 患有慢性纯音耳鸣的参与者（N = 30，每组n = 10）被随机分配接受同步VNS和AS（交感）、VNS开始后延迟五秒的AS（副交感），或随机放置的VNS和AS（安慰剂）。参与者在三周内接受九次治疗。我们评估了安全性和可行性指标、耳鸣响度评分，以及心理困扰、睡眠和脑电图变化的指标。结局在基线、治疗结束后即刻以及一个月随访时收集。
结果： 未报告严重不良事件，配对刺激治疗可行。在耳鸣响度或耳鸣功能指数的变化方面，各组之间未发现显著差异。延迟AS组显示耳鸣不愉快感、焦虑和匹兹堡睡眠质量指数评分显著降低。在参与耳鸣和不愉快声音处理的区域发现了脑电图变化。
结论： VNS与耳鸣匹配声音配对是安全且可行的。探索性分析提示，延迟AS组可能在耳鸣声音不愉快感、睡眠功能障碍和焦虑方面有所降低。有必要开展一项具有预设疗效结局并适当校正多重比较的充分把握度试验，以确认这些发现、验证无创VNS引起的副交感激活，并研究该干预措施的长期效果。

英文摘要

OBJECTIVES: Tinnitus is the perception of sound in the absence of an external source, which is associated with unpleasantness and suffering in tinnitus disorder. Vagus nerve stimulation (VNS), paired with nontinnitus sounds, has shown promise in reversing tonotopic map changes seen in tinnitus. Alternatively, pairing a replica of the tinnitus sound with parasympathetic VNS could reduce tinnitus salience through Pavlovian reconditioning. We evaluated the safety and feasibility of paired and unpaired noninvasive VNS and tinnitus-matched auditory stimulation (AS) and assessed the effects on clinical outcomes, as well as activity and functional connectivity within tinnitus-related networks.
MATERIALS AND METHODS: Participants (N = 30, n = 10 in each group) with chronic, pure-tone tinnitus were randomized to receive simultaneous VNS and AS (sympathetic), AS delayed by five seconds after VNS onset (parasympathetic), or randomly placed VNS and AS (placebo). Participants received nine sessions of treatment over three weeks. We assessed safety and feasibility measures and tinnitus loudness ratings, as well as measures of psychologic distress, sleep, and electroencephalographic changes. Outcomes were collected at baseline, immediately post treatment, and at one-month follow-up.
RESULTS: No serious adverse events were reported, and the paired stimulation treatment was feasible. No significant differences were found between groups for changes in tinnitus loudness or tinnitus functional index. The delayed AS group showed significantly reduced tinnitus unpleasantness, anxiety, and Pittsburgh Sleep Quality Index scores. Electroencephalographic changes were identified in regions involved in tinnitus and unpleasant sound processing.
CONCLUSIONS: VNS paired with tinnitus-matched sound was safe and feasible. Exploratory analyses suggested possible reductions in tinnitus sound unpleasantness, sleep dysfunction, and anxiety in the delayed AS group. A fully powered trial with predefined efficacy outcomes and appropriate correction for multiple comparisons is warranted to confirm these findings, verify parasympathetic activation from noninvasive VNS, and investigate the longer-term effects of this intervention.