Hearing Technology @ WAVES, Department of Information Technology, Ghent University, Technologiepark 126, Zwijnaarde 9052, Belgium.
Medizinische Physik and Cluster of Excellence "Hearing4all", Department of Medical Physics and Acoustics, Carl von Ossietzky University of Oldenburg, Carl-von-Ossietzky-Straße 9-11, Oldenburg, 26129, Germany.
Hear Res. 2021 Feb;400:108132. doi: 10.1016/j.heares.2020.108132. Epub 2020 Dec 1.
Auditory de-afferentation, a permanent reduction in the number of inner-hair-cells and auditory-nerve synapses due to cochlear damage or synaptopathy, can reliably be quantified using temporal bone histology and immunostaining. However, there is an urgent need for non-invasive markers of synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) markers for synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or lack of measurement sensitivity. To render AEP-based markers of synaptopathy more sensitive and differential to the synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope to stimulate the available auditory-nerve population optimally and synchronously to generate strong envelope-following-responses (EFRs). We further used model simulations to explore which stimuli evoked a response that was sensitive to synaptopathy, while being maximally insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who had normal or impaired audiograms with suspected age-related synaptopathy in the older cohort. We conclude that optimal stimulation paradigms for EFR-based quantification of synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120-Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recordings, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth. Older listeners with normal or impaired audiometric thresholds showed significantly reduced EFRs, which were consistent with how (age-induced) synaptopathy affected these responses in the model.
听觉去传入，由于耳蜗损伤或突触病导致内毛细胞和听神经突触数量永久性减少，可以通过颞骨组织学和免疫染色可靠地定量。然而，迫切需要非侵入性的突触病标志物来研究其在活体人类中的感知后果，并开发有效的治疗干预措施。虽然动物研究已经确定了候选听觉诱发电位（AEP）标记物用于突触病，但由于与神经发生器差异、未知听力损伤组织病理学或测量灵敏度缺乏相关的翻译问题，其在人类中的解释受到了限制。为了使基于 AEP 的突触病标志物对突触病方面的感音神经性听力损失更敏感和有区别，我们采用了一种组合的计算和实验方法。从已知的听神经生理学特征开始，我们优化了刺激包络，以最佳和同步地刺激可用的听神经群体，从而产生强烈的包络跟随反应（EFR）。我们进一步使用模型模拟来探索哪些刺激产生了对突触病敏感的反应，同时对可能共存的外毛细胞病变最大程度不敏感。我们将模型预测的趋势与在年龄相关突触病疑似的年轻和老年听众（N=44，24f）中记录的 AEP 进行了比较。我们的结论是，基于 EFR 的突触病定量的最佳刺激方案应该具有急剧上升的包络形状，对于 120-Hz 调制率，最小平台持续时间为 1.7-2.1ms，并且包含近零幅度的峰间间隔。从我们的记录中，最佳的 EFR 激发刺激具有 25%占空比和 95%调制深度的矩形包络形状。具有正常或受损听力阈值的老年听众表现出明显降低的 EFR，这与（年龄诱导的）突触病如何影响模型中的这些反应一致。
