Konerding Wiebke, Arenberg Julie, Kral Andrej, Baumhoff Peter
Department of Experimental Otology, Hannover Medical School, Stadtfelddamm 34, 30625 Hannover, Germany.
Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA 02114, USA.
Hear Res. 2025 Sep;465:109341. doi: 10.1016/j.heares.2025.109341. Epub 2025 Jun 25.
While cochlear implants (CIs) historically use cathodic-leading pulses for stimulation, studies in humans found that anodic-leading pulses are perceived louder than cathodic-leading ones. Modeling studies proposed that cathodic pulses excite the spiral ganglion neurons (SGNs) more peripherally than anodic pulses. Thus, the anodic-benefit in human CI listeners is thought to reflect degenerated peripheral processes. We used an animal model to test the contributions of peripheral dendrites and central axons of SGNs to polarity-effectiveness in CI stimulation. We mechanically lesioned the SGN (∼400 µm diameter; n = 18 cochleae) and introduced a 9-day degeneration time (n = 13 cochleae) to mimic human SGN degeneration. These lesions were compared to 20 control ears. We stimulated via a guinea-pig adjusted CI with symmetric, biphasic pulses (monopolar mode) of alternating leading-phase polarity (50µs/phase). Electrically-evoked compound action potential recordings to anodic- and cathodic-leading pulses were separated in the analysis to calculate the polarity effect. We confirmed the cathodic-benefit for cochleae with healthy SGN (lower threshold, larger amplitudes, dynamic ranges, and steeper slopes). Longer latencies (50-70µs) to cathodic than anodic monophasic and biphasic pulses confirmed the proposed peripheral (cathodic) and central (anodic) spike-initiation sites. The cathodic benefit persisted after acute lesioning, which prolonged latencies for anodic- but not for cathodic-leading pulses - consistent with remaining structures being excited by both polarities. After chronic degeneration, the threshold showed polarity-specific changes, leading to an anodic-benefit. The observed decline in cathodic-effectiveness with reduced neural health confirmed theoretical considerations for human CI users with stimulus-polarity and degeneration-type dependent changes in spike-initiation site.
虽然从历史上看，人工耳蜗（CI）使用阴极领先脉冲进行刺激，但对人类的研究发现，阳极领先脉冲比阴极领先脉冲听起来更响亮。建模研究表明，阴极脉冲比阳极脉冲更能在外周激发螺旋神经节神经元（SGN）。因此，人类人工耳蜗使用者的阳极优势被认为反映了外周神经过程的退化。我们使用动物模型来测试SGN的外周树突和中枢轴突对人工耳蜗刺激中极性有效性的贡献。我们对SGN进行机械损伤（直径约400 µm；n = 18个耳蜗），并引入9天的退化时间（n = 13个耳蜗）以模拟人类SGN的退化。将这些损伤的耳蜗与20只对照耳进行比较。我们通过豚鼠适配的人工耳蜗，使用交替领先相极性（50µs/相）的对称双相脉冲（单极模式）进行刺激。在分析中，将阳极和阴极领先脉冲的电诱发复合动作电位记录分开，以计算极性效应。我们证实了健康SGN的耳蜗具有阴极优势（阈值更低、振幅更大、动态范围更大且斜率更陡）。与阳极单相和双相脉冲相比，阴极脉冲的潜伏期更长（50 - 70µs），这证实了所提出的外周（阴极）和中枢（阳极）的动作电位起始位点。急性损伤后，阴极优势仍然存在，这延长了阳极领先脉冲的潜伏期，但阴极领先脉冲的潜伏期未延长，这与剩余结构能被两种极性激发一致。慢性退化后，阈值出现了极性特异性变化，导致了阳极优势。随着神经健康状况下降，观察到的阴极有效性降低，证实了对于人工耳蜗使用者中刺激极性和退化类型依赖的动作电位起始位点变化的理论考虑。
