Xu J, Shepherd R K, Millard R E, Clark G M
Department of Otolaryngology, University of Melbourne, Parkville, Victoria, Australia.
Hear Res. 1997 Mar;105(1-2):1-29. doi: 10.1016/s0378-5955(96)00193-1.
A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 microseconds/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.
与近期人工耳蜗植入患者临床效果改善相关的一个主要因素是基于高刺激率的言语处理策略的发展。虽然这些处理策略显示出明显的临床优势，但我们对其长期安全性影响知之甚少。本研究旨在评估使用这些高刺激率进行长期鼓阶内电刺激的生理和组织病理学效应。13只听力正常的成年猫双侧植入鼓阶电极阵列，并使用两对双极或三个单极刺激电极单侧刺激长达2100小时。刺激由短持续时间（25 - 50微秒/相位）的电荷平衡双相电流脉冲组成，单极刺激时每个通道以每秒1000脉冲（pps）呈现，双极刺激时每个通道以2000 pps呈现。电流脉冲之间电极短路以最小化任何残余直流电，并且脉冲序列以50%的占空比（开500毫秒；关500毫秒）呈现以模拟言语。在慢性刺激程序期间定期记录听觉脑干反应的声学（ABR）和电（EABR）反应。所有耳蜗在植入手术后点击诱发的ABR阈值均升高；然而，大约一半受刺激的耳蜗在术后1个月恢复到接近正常水平。使用频率特异性刺激表明，最广泛的听力损失通常发生在与刺激电极相邻的耳蜗高频基底区域（12和24千赫）。然而，尽管长期电极植入和电刺激，较低频率（2、4和8千赫）的阈值仍接近正常水平。我们的纵向EABR结果显示，在评估的近40%的慢性刺激电极中，阈值有统计学上的显著增加；然而，在整个慢性刺激期间，EABR输入/输出（I/O）函数（诱发电位反应幅度与刺激电流）的斜率通常保持相当稳定。耳蜗的组织病理学检查显示，使用单极和双极电极配置的耳蜗之间神经节细胞密度没有统计学上的显著差异（P = 0.67），并且与对照耳蜗相比，没有高速电刺激导致耳蜗损伤的证据。事实上，螺旋神经节细胞密度与电刺激之间没有统计学上的显著关系（P = 0.459），内毛细胞（IHC，P = 0.86）或外毛细胞（OHC，P = 0.30）损失程度与电刺激之间也没有统计学上的显著关系。然而，螺旋神经节细胞损失受炎症程度（P = 0.016）和电极插入创伤的影响。这些组织病理学发现与生理数据一致。最后，在慢性刺激程序完成时测量的电极阻抗与电极阵列相邻组织反应的程度密切相关。这些结果表明，使用精心控制的电荷平衡双相电流脉冲，以高达2000 pps/通道的刺激率进行慢性鼓阶内电刺激，似乎不会对残余听神经元件或整个耳蜗产生不利影响。本研究为基于高速电刺激的改进言语处理策略的安全应用提供了重要依据。
