Konerding Wiebke, Arenberg Julie, Sznabel Dorota, Kral Andrej, Baumhoff Peter
Department of Experimental Otology, Hannover Medical School, Hannover 30625, Germany
Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114.
J Neurosci. 2025 Feb 12;45(7):e0954242024. doi: 10.1523/JNEUROSCI.0954-24.2024.
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 microlesions in 13 guinea pigs (six female) and recorded electrically evoked compound action potentials (eCAP) after 8-12 d. These were compared with recordings from controls ( = 8) and acutely lesioned cochleae ( = 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 lesions (230-850 µm) significantly elevated thresholds and reduced 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 (N1P1 amplitude). The FI showed classification accuracies of 80% and identified contacts 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, noninvasive marker that is suitable for clinical datasets without a priori knowledge on lesions, when combined with the statistical method of median splitting.
螺旋神经节神经元(SGN)变性是人工耳蜗(CI)使用者听力结果下降的一个潜在因素。然而,目前尚无方法可用于识别人类患者中靠近局灶性SGN变性的CI电极触点。在一个动物模型中,我们评估了局灶性SGN变性对电反应性的影响,并得出了一种电生理标志物,用于指示此类病变的存在、位置和大小。我们在13只豚鼠(6只雌性)中制造了耳蜗微损伤,并在8-12天后记录电诱发复合动作电位(eCAP)。将这些结果与对照组(n = 8)和急性损伤耳蜗(n = 12)的记录进行比较。我们通过6触点CI以单极配置,用交替极性的对称双相脉冲进行刺激。我们通过组织学评估了病变及其与CI电极触点的相对位置。病变(230-850μm)显著提高了阈值并降低了振幅。在距病变3.5mm的刺激距离处发现了这种效应。一种新的eCAP标志物,失败指数(FI:最大输入/输出比),在存在变性SGN时显著升高。它表明无法有效地将刺激电流转化为神经激活(N1P1振幅)。FI的分类准确率为80%,在距病变部位±700μm(约电极间距)范围内,约80%的病例中能识别出最靠近病变的电极触点,并且与病变大小相关。因此,当与中位数分割的统计方法相结合时,FI是一种适用于无病变先验知识的临床数据集的临床相关非侵入性标志物。