Spiral ganglion neuron (SGN) degeneration is a candidate factor for reduced hearing outcomes in cochlear implant (CI) users. However, there is no procedure available to identify CI contacts close to focal SGN degeneration in human patients. In an animal model, we assessed the impact of focal SGN degeneration on electrical responsiveness and derived an electrophysiological marker for the presence, location and size of such lesions.We introduced cochlear micro-lesions in 13 guinea pigs (6 female) and recorded electrically-evoked compound action potentials (eCAP) after 8-12 days. These were compared to recordings from controls (N=8) and acutely lesioned cochleae (N=12). We stimulated via 6-contact CIs in monopolar configuration with symmetric, biphasic pulses of alternating polarity. We histologically assessed the lesion and its relative position to the CI-contacts.The small lesions (230-850 µm) significantly elevated thresholds and reduced eCAP amplitudes. The effect was found at stimulation distances of 3.5 mm from the lesion. A novel eCAP marker, Failure Index (FI: maximal input/output ratio), was significantly elevated in the presence of degenerated SGN. It indicates the failure to efficiently transduce the stimulation current into neural activation (i.e., N1P1 amplitude). The FI showed classification accuracies of 80% and identified the contact closest to the lesion in ∼80% of cases within ±700 µm (∼electrode spacing) from the lesion-site and was correlated with the lesion-size.Thus, the FI is a clinically-relevant, non-invasive marker that is suitable for clinical data sets without any a priori knowledge on lesions, when combined with the statistical method of median-splitting.Significance Statement Spatially restricted degeneration of spiral ganglion neurons (i.e., focal lesions) in the inner ear significantly reduced responsiveness to electric stimulation via a cochlear implant (CI). An electrophysiological marker of these lesions, the Failure Index (FI), was specifically elevated in the presence of chronic degeneration, but not acute neural loss, and explained 60% of variance in lesion-size. With its potential for non-invasive assessment of focal lesions in human patients, the FI is considered highly relevant for clinical applications. If successfully transferred to the clinic, the identification of regions with reduced neural health via the FI may be used to adapt sound processor programming with the aim to improve speech intelligibility.

中文翻译：

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局部螺旋神经节神经元变性的电诱发化合物动作电位标志物：失败指数。


螺旋神经节神经元 （SGN） 变性是人工耳蜗 （CI） 用户听力结果降低的一个候选因素。然而，没有可用的程序来识别人类患者局灶性 SGN 变性附近的 CI 接触者。在动物模型中，我们评估了局灶性 SGN 变性对电反应性的影响，并得出了此类病变的存在、位置和大小的电生理标志物。我们在 13 只豚鼠 （6 只母猪） 中引入了人工耳蜗微病变，并在 8-12 天后记录了电诱发电位化合物动作电位 （eCAP）。将这些与对照组 （N=8） 和急性病变耳蜗 （N=12） 的记录进行了比较。我们通过单极配置的 6 触点 CI 刺激，具有交替极性的对称双相脉冲。我们组织学评估了病灶及其与 CI 接触的相对位置，小病灶 （230-850 μm） 显着提高了阈值并降低了 eCAP 振幅。在距病灶 3.5 mm 的刺激距离处发现效果。在退化 SGN 存在的情况下，一种新的 eCAP 标志物 Failure Index （FI： 最大输入/输出比） 显着升高。它表明未能有效地将刺激电流转导为神经激活（即 N1P1 振幅）。FI 显示 80% 的分类准确性，并在距病灶部位 ±700 μm（∼电极间距）范围内确定 ∼80% 病例最接近病灶的接触，并与病灶大小相关。因此，FI 是一种临床相关的非侵入性标志物，当与中位数分割的统计方法结合使用时，适用于没有任何病变先验知识的临床数据集。意义陈述 螺旋神经节神经元的空间限制性变性（即，局灶性病变）显着降低了通过人工耳蜗 （CI） 对电刺激的反应性。这些病变的电生理标志物，失败指数 （FI），在存在慢性变性的情况下特别升高，但没有急性神经丧失，并解释了病变大小 60% 的方差。FI 具有对人类患者局灶性病变进行无创评估的潜力，被认为与临床应用高度相关。如果成功转移到临床，通过 FI 识别神经健康下降的区域可用于调整声音处理器编程，以提高语音清晰度。