Walia Amit, Ortmann Amanda J, Lefler Shannon, Holden Timothy A, Puram Sidharth V, Herzog Jacques A, Buchman Craig A
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine in St. Louis, St Louis, Missouri, USA.
Ear Hear. 2025;46(1):253-264. doi: 10.1097/AUD.0000000000001579. Epub 2024 Sep 5.
Due to the challenges of direct in vivo measurements in humans, previous studies of cochlear tonotopy primarily utilized human cadavers and animal models. This study uses cochlear implant electrodes as a tool for intracochlear recordings of acoustically evoked responses to achieve two primary goals: (1) to map the in vivo tonotopy of the human cochlea, and (2) to assess the impact of sound intensity and the creation of an artificial "third window" on this tonotopic map.
Fifty patients with hearing loss received cochlear implant electrode arrays. Postimplantation, pure-tone acoustic stimuli (0.25 to 4 kHz) were delivered, and electrophysiological responses were recorded from all 22 electrode contacts. The analysis included fast Fourier transformation to determine the amplitude of the first harmonic, indicative of predominantly outer hair cell activity, and tuning curves to identify the best frequency (BF) electrode. These measures, coupled with postoperative imaging for precise electrode localization, facilitated the construction of an in vivo frequency-position function. The study included a specific examination of 2 patients with auditory neuropathy spectrum disorder (ANSD), with preserved cochlear function as assessed by present distortion-product otoacoustic emissions, to determine the impact of sound intensity on the frequency-position map. In addition, the electrophysiological map was recorded in a patient undergoing a translabyrinthine craniotomy for vestibular schwannoma removal, before and after creating an artificial third window, to explore whether an experimental artifact conducted in cadaveric experiments, as was performed in von Békésy landmark experiments, would produce a shift in the frequency-position map.
A significant deviation from the Greenwood model was observed in the electrophysiological frequency-position function, particularly at high-intensity stimulations. In subjects with hearing loss, frequency tuning, and BF location remained consistent across sound intensities. In contrast, ANSD patients exhibited Greenwood-like place coding at low intensities (40 dB SPL) and a basal shift in BF location at higher intensities (70 dB SPL or greater). Notably, creating an artificial "third-window" did not alter the frequency-position map.
This study successfully maps in vivo tonotopy of human cochleae with hearing loss, demonstrating a near-octave shift from traditional frequency-position maps. In patients with ANSD, representing more typical cochlear function, intermediate intensity levels (~70 to 80 dB SPL) produced results similar to high-intensity stimulation. These findings highlight the influence of stimulus intensity on the cochlear operational point in subjects with hearing loss. This knowledge could enhance cochlear implant programming and improve auditory rehabilitation by more accurately aligning electrode stimulation with natural cochlear responses.
由于人体直接体内测量存在挑战，以往关于耳蜗音调定位的研究主要利用人体尸体和动物模型。本研究使用人工耳蜗电极作为工具进行耳蜗内声学诱发反应的记录，以实现两个主要目标：（1）绘制人类耳蜗的体内音调定位图；（2）评估声音强度以及人工“第三窗”的创建对该音调定位图的影响。
50名听力损失患者接受了人工耳蜗电极阵列植入。植入后，给予纯音声学刺激（0.25至4kHz），并从所有22个电极触点记录电生理反应。分析包括快速傅里叶变换以确定基波的幅度，这主要指示外毛细胞的活动，以及调谐曲线以确定最佳频率（BF）电极。这些测量，再结合术后成像以进行精确的电极定位，有助于构建体内频率-位置函数。该研究特别检查了2名患有听觉神经病谱系障碍（ANSD）的患者，通过当前的畸变产物耳声发射评估其耳蜗功能保存情况，以确定声音强度对频率-位置图的影响。此外，在一名接受迷路后开颅手术以切除前庭神经鞘瘤的患者中，在创建人工第三窗之前和之后记录电生理图，以探索在尸体实验中进行的实验假象（如在冯·贝凯西标志性实验中所做的那样）是否会导致频率-位置图的偏移。
在电生理频率-位置函数中观察到与格林伍德模型存在显著偏差，特别是在高强度刺激时。在听力损失患者中，频率调谐和BF位置在不同声音强度下保持一致。相比之下，ANSD患者在低强度（约40dB SPL）时表现出类似格林伍德的位置编码，而在较高强度（约70dB SPL或更高）时BF位置出现基底移位。值得注意的是，创建人工“第三窗”并未改变频率-位置图。
本研究成功绘制了听力损失患者的人类耳蜗体内音调定位图，显示出与传统频率-位置图近一个倍频程的偏移。在代表更典型耳蜗功能的ANSD患者中，中等强度水平（约70至80dB SPL）产生的结果与高强度刺激相似。这些发现突出了刺激强度对听力损失患者耳蜗工作点的影响。这些知识可以通过更准确地使电极刺激与自然耳蜗反应相匹配来加强人工耳蜗编程并改善听觉康复。
