电刺激耳蜗记录下丘的空间调谐曲线

目的探索耳蜗电刺激的听觉中枢电活动机理，为多道人工耳蜗电刺激的部位代码提供生理依据。方法利用记录单单位和多单位电位反应的方法，分别描记１７只猫听觉下丘核团对耳蜗内单极电刺激，耳蜗内双极电刺激和纯音刺激反应的空间调谐曲线。结果耳蜗内双极电刺激能兴奋下丘中的特定区域，类似于对纯音刺激的反应；而耳蜗内单极电刺激使下丘细胞广泛地被兴奋，不能提供部位代码。结论使用双极电极时，刺激电流的局限范围是提高部位代码的关键；耳蜗内单极电刺激部位代码的电生理结果与心理物理学的结论以及人工耳蜗植入患者的临床效果相矛盾，对此的解释有待进一步研究。     

耳蜗内高速率电刺激对大鼠下丘神经元兴奋性的影响

目的 探讨耳蜗内不同强度下高速率电刺激对大鼠下丘神经元兴奋性的影响。方法在刺激强度分别为电刺激听性脑干反应（electrically evoked auditory brainstem responses，EABR）阈上6 dB和阈上12dB，用500pps和1000pps两种不同的电刺激速率急性刺激大鼠耳蜗，记录刺激2小时内及刺激停止后2小时内下丘神经元近场电位幅值。结果 刺激强度为EABR阈上6dB时，应用500 ppsg刺激速率，下丘神经元近场电位幅值在刺激过程中及刺激后2小时内都呈现上升趋势；应用1000pps刺激速率刺激2小时内，下丘神经元兴奋性有所下降，至刺激停止时为87％，但刺激停止后2小时内幅值不仅得到恢复，而且高于刺激前水平;予EABR阈上12dB强度电流刺激，在两种电刺激速率下，刺激后均可见下丘神经元反应幅值明显下降，速率越高下降越明显，恢复趋势越微弱。急性刺激停止时，500pps和1000pps刺激速率下丘神经元反应幅值分别下降52％、69％（P〈0．05），刺激停止后120分钟，分别下降10％、59％。结论在较低电流强度（EABR阈上6dB）刺激下，高速率电刺激（1000pps）会导致下丘神经元兴奋性下降，但刺激停止后可恢复甚至高于刺激前水平；高强度、高速率电刺激会导致下丘神经元兴奋性下降，且刺激停止后恢复较慢：与听觉神经纤维相比，下丘神经元兴奋性受耳蜗内高速率电刺激的影响更大。     

P物质抗体对豚鼠耳蜗核下丘核团内听觉诱发电位调谐曲线的影响

探索Ｐ物质在听觉脑干中枢中对声信号的频率分析作用。方法采用短音刺激，短纯音前掩蔽法和豚鼠耳蜗核、正丘、核团内电极，记录ＣＮ及ＩＣ核团内听觉诱发电位。观察核团内注射微量Ｐ物质抗体或对照注射等量兔血清后ＣＮ和ＩＣ核团内听觉诱发电位调谐曲线的变化。     

耳蜗急性纯音损伤后下丘及耳蜗核快速功能重组

实验比较高强度纯音损伤耳蜗局部区域前后，耳蜗背核及下丘接近损伤区边缘的神经元反应特性的改变。致损纯音的频率高于神经元的特征频率，且位于其兴奋区以外，所以不影响其兴奋性输入，结果发现此种纯音损伤在逾半数的神经元产生不同程度的去抑制效应，提示皮歧的功能重组可能部分地起源于低位中枢的功能改变，下丘和耳蜗背核的抑制性神经网络具有相当程度的侧抑制组分。     

外周听器损伤所致听觉中枢改变的研究进展

耳蜗核、上橄榄核复合体、外侧丘系、下丘共同组成听觉脑干中枢.下丘是耳蜗与大脑之间听觉信号传输的重要中转站,解剖位置恒定,易于定位和进行电生理记录,是研究皮层下听觉中枢功能的重点.本文拟就正常下丘神经元对纯音刺激的反应特点,以及外周听器损伤后下丘神经元的生理学改变和神经递质改变等研究进展进行综述.     

蜗轴骨化的人工耳蜗手术与术后神经电生理评价与主观检测

目的：探讨蜗轴骨化的人工耳蜗植入术和术后听觉神经电生理反应与听觉言语效果问题,为掌握人工耳蜗植入术的适应证提供参考。方法：在进行101例各种程度和类型的耳蜗骨化的人工耳蜗植入术中,涉及到耳蜗蜗轴骨化7例。耳蜗、蜗轴骨化的人工耳蜗植人术前均进行常规影像学检查。蜗轴骨化判断方法：按颞骨高分辨CT水平位和冠状位显示,正常耳蜗中央区的蜗轴结构呈中等密度,其CT值为400～630HU,骨化时蜗轴密度增高,CT值达900HU或以上,除外先天性等因素造成的蜗轴骨化或骨性闭锁等因素。进行术中和术后神经电生理与主观听觉言语检查。结果：7例耳蜗蜗轴骨化的人工耳蜗植入术中电极阻抗检查均正常。7例患者术后均进行EABR检查,1例术后无法引出可识别的EABR波形,其余6例均可以在中段或末端电极部位引出不典型的EABR波形。术后进行声场下的纯音检测：1例EABR无反应患者最大给声无反应;其余6例声场下纯音听力水平平均为75dB。术后听觉言语识别率：1例无听觉反应患者术后言语识别率为0,其余6例汉语普通话单韵母为100％、单声母为30％。结论：耳蜗完全骨化多数伴有蜗轴骨化,施行人工耳蜗植入的最佳方法是将多导电极环绕蜗轴旋转,其手术难度较大。蜗轴骨化的人工耳蜗植入术后听觉电生理反应呈现非典型表现,术后听觉言语效果很差,EABR无反应者存在无效的风险。     

耳蜗急性纯音损伤后下丘及耳蜗核快速功能重组

实验比较高强度纯音损伤耳蜗局部区域前后，耳蜗背核及下丘接近损伤区边缘的神经元反应特性的改变。致损纯音的频率高于神经元的特征频率，且位于其兴奋区以外，所以不影响其兴奋性输入。结果发现此种纯音损伤在逾半数的神经元产生不同程度的去抑制效应，提示皮层的功能重组可能部分地起源于低位中枢的功能改变，下丘和耳蜗背核的抑制性神经网络具有相当程度的侧抑制组分。     

人工听觉的过去现在和未来

电诱发人工听觉(简称人工听觉)通过电刺激听觉神经来恢复、提高或重建人的听觉功能。电刺激听神经包括早期使用的单电极及目前使用的多电极人工耳蜗植入，以及结合低频残存声听觉的短电极耳蜗植入。人工耳蜗植入的工作原理是绕过已损伤的毛细胞、直接电刺激残存的听神经纤维来达到恢复、重建听觉的目的。也可以将电刺激直接作用于听觉脑干和听觉皮层，适用于听神经发生病变的患者，例如听神经瘤患者。     

直流电脉冲刺激豚鼠耳蜗基底膜振动研究

为了在活体上研究哺乳类动物耳蜗基底膜的电－机械特性，将一对铂－铱电极分别置于３０只豚鼠耳蜗底回的前庭阶和鼓阶。用矩形直流脉冲电刺激蜗管，用激光多普勒测速仪测定电刺激诱发的耳蜗基底膜振动的幅度和速度。结果表明，在听敏度正常豚鼠的耳蜗，电刺激可诱发基底膜向正电极方向位移，其位移波形类似于电脉冲的矩形波。在矩形脉冲的起始沿和结束沿，由于外毛细胞的瞬态反应，可诱发与该部位特征频率一致的共振运动。据分析，这一共振运动是外毛细胞的主动耗能过程，并由耳蜗放大器参与。在听力受损的耳蜗，直流电刺激仍能引起基底膜的位移，但振铃运动明显减少或消失。这可能是受损毛细胞的能量代谢障碍所致。直流电刺激诱发的基底膜振动与声波一样，可通过行波沿基底膜向其它部位传输，这一特性奠定了电听觉和耳声发射的生理基础。     

人工耳蜗植入术中EABR监测的应用

目的探讨人工耳蜗植入术中进行EABR监测的方法，以了解耳蜗电刺激下听觉传导通路的神经反应情况。方法20例人工耳蜗植入患者，男14例，女6例，平均年龄13．6岁，语前聋患者14例，语后聋患者6例。全麻后安置体表记录电极，将PPS与听觉诱发电位仪触发端口连接，并选定听觉诱发电位仪的外触发模式。人工耳蜗电极植入后，先行常规NRT监测，然后将NRT刺激参数改为EABR模式，采用Basic双极刺激，脉宽50μs，强度由200CL起以10CL为步长递减至反应阈值。结果20例患者均记录到EABR，阈上20CL时Ⅲ波．Ⅴ波的平均潜伏期分别为2．04±0．20ms．3．96±0．41ms。相同刺激条件下的EABR反应平均阈值为148．46±11．63CL，NRT反应平均阈值为160．72±13．56CL。一例脑白质轻度发育异常患儿，术中NRT波形引出良好，EABRⅠ～Ⅳ波分化良好，Ⅴ波波形低钝，Ⅴ波／Ⅲ波振幅比〈1／2，考虑可能存在耳蜗核上性神经发育不良，现正在语言康复训练随访中。结论人工耳蜗植入术中进行EABR监测比NRT能提供更完整的．更接近听觉中枢的神经反应信息，能更进一步了解听觉传导通路的功能状态，以期对患者听力康复的效果提供更准确的预测。     

Spatial distribution of neural activity evoked by electrical stimulation of the cochlea

Activity in the central auditory system was mapped with 2-deoxyglucose (2-DG) autoradiography, using either pure tones or electrical stimulation of the normal cochlea. Electrical stimulation with both monopolar (distant reference electrode) and bipolar prostheses near threshold increased 2-DG uptake in auditory nuclei in a manner similar to that seen with a pure tone: increased 2-DG uptake was restricted to a small frequency region of brainstem and mid-brain auditory nuclei. The position of this area was related to the cochlear location of the prosthesis. At higher current amplitudes only the bipolar prosthesis retained spatial restriction of evoked neural activity, while stimulation through a monopolar prosthesis produced evoked activity in all frequency regions of auditory nuclei and in non-auditory nuclei. Activation of non-auditory structures was consistent with spread of current through the brainstem, rather than activation of peripheral nerves. At all current amplitudes, a monopolar prosthesis evoked higher levels of 2-DG uptake than a bipolar prosthesis.

The results suggest that while a bipolar prosthesis provides greater spatial restriction of evoked neural activity and a greater dynamic range, a monopolar prosthesis produces higher levels of evoked activity.     

Electrode configuration influences action potential initiation site and ensemble stochastic response properties

The configuration of intracochlear electrodes used to electrically stimulate the auditory nerve influences the ensemble fiber response. For example, monopolar stimulation produces lower thresholds and greater spread of excitation than does bipolar stimulation. We used two approaches to investigate how the ensemble of auditory-nerve fibers responds to stimulation delivered by different electrode configurations. As the electrically evoked compound action potential (ECAP) reflects the ensemble response of the nerve, we used its morphology and changes with stimulus level to assess issues related to site-of-excitation and fiber recruitment. In our first approach, feline ECAPs were obtained using a nucleus-style banded electrode array. ECAP latency functions indicated that bipolar stimulation can initiate action potentials at more peripheral sites than does monopolar stimulation. We observed double-peaked ECAPs with bipolar and tripolar stimulation, suggesting excitation of both peripheral and central neural processes. Finally, we observed in some cases a tendency for monopolar stimulation to produce wider ECAP potentials, consistent with the notion that monopolar stimulation excites a broader spatial extent of the fiber population. In our second approach, we applied a simple model to published surveys of single-fiber responses to provide insight into the stochastic properties of the ensemble response. Our results suggest that broader recruitment of fiber activity produced by monopolar stimulation results in a population response with more probabilistic response characteristics and ensemble spike jitter. These observations and our ECAP results are consistent with reports of perceptual advantages attributed to monopolar or other less-focused modes of stimulation.     

Cochleotopic selectivity of a multichannel scala tympani electrode array using the 2-deoxyglucose technique.

The 2-deoxyglucose (2-DG) technique was used to study the cochleotopic selectivity of a multichannel scala tympani electrode array in four cats with another acting as an unstimulated control. Each animal was unilaterally deafened and a multichannel electrode array inserted 6 mm into the scala tympani. Thresholds to electrical stimulation were determined by recording electrically evoked auditory brainstem responses (EABRs). Each animal was injected with 2-DG, and electrically stimulated using bipolar electrodes located either distal or proximal to the round window. The contralateral ear was stimulated with acoustic tone pips at frequencies that matched the electrode place. Stimulation of both distal and proximal bipolar electrodes at 3 x EABR threshold, evoked localized 2-DG labelling in both ipsilateral cochlear nucleus (CN) and the contralateral inferior colliculus (IC), which was very similar in orientation and breadth to labelling evoked by the contralateral tone pips. The cochleotopic position of labelling to proximal stimulation was located in the 24-26 kHz region of each structure, whereas the distal labelling was located around 12 kHz. Distal stimulation at 10 x EABR threshold produced very broad 2-DG labelling in IC centered around the 12 kHz place. The present 2-DG results clearly illustrate cochleotopic selectivity using multichannel bipolar scala tympani electrodes. The extent of this selectivity is dependent on electrical stimulus levels. The 2-DG technique has great potential in evaluating the efficacy of new electrode array designs.     

Monopolar Intracochlear Pulse Trains Selectively Activate the Inferior Colliculus

Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system—much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6–12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.     

Changes in cochlear electrical stimulation induced Fos expression in the rat inferior colliculus following deafness

Fos immunoreactive (IR) staining was used to examine changes in excitatory neuronal activity in the rat inferior colliculus (IC) between normal hearing and 21 day deaf rats evoked by basal or apical monopolar cochlear electrical stimulation. The location of evoked Fos IR neurons was consistent with expected tonotopic areas. The number of Fos IR cells increased as stimulation intensity increased in both normal and 21 day deaf animals. Stimulation at 1. 5x threshold evoked fewer Fos IR cells in 21 day deafened animals compared to normal hearing animals. At 5x and above, however, significantly increased numbers of Fos IR neurons (in a larger grouping) were evoked in 21 day deafened animals compared to normal hearing animals. Another group of animals had 7 days of deafness followed by 14 days of chronic basal cochlear electrical stimulation. In this group basal monopolar stimulation at 5x evoked not only a greater number of Fos IR neurons, compared to normal hearing animals, but the location of their grouping was slightly shifted to a more dorso-lateral region in the contralateral IC, compared to the normal hearing and 21 day deaf groups. These observations indicate that both deafness and chronic electrical stimulation may alter central auditory processing.     

The intensity-pitch relation revisited: monopolar versus bipolar cochlear stimulation

Objective/Hypothesis: The very high speech perception scores now being achieved with cochlear implants have led to demands for similar levels of achievement in music perception and perception in noisy environments. One of the crucial factors in these fields is pitch perception. The aim of the present study was to investigate the extent to which pitch perception is influenced by the intensity of the stimulus, through the use of different stimulation modes (monopolar, bipolar) and different electrodes (lateral and perimodiolar). Study Design: Sixteen postlingually deafened patients with an average implant use of 3.1 years were included in this study. All patients were using a Cochlear (CI24M, CI24R, CI24RE) cochlear implant. Methods: Subjects were asked to compare the pitch of an intensity-constant reference tone with the pitch of a test tone of varying intensity. The test was repeated for apical, mediocochlear, and basal channel locations, and also for monopolar and bipolar stimulation. Results: It was found that in monopolar stimulation 87.5% and in bipolar stimulation 85.7% of the patients perceived a clear pitch change with changing intensity of the stimulus (Spearman correlation coefficients r < −0.3 or r > 0.3, respectively). A total of 73.1% of these patients perceived lower pitches with increasing intensity, 26.9% reported the opposite effect. No statistically significant difference in the intensity–pitch correlation could be found between mono- and bipolar stimulation. Neither the mean dynamic range nor the type of electrode used was found to be related to the correlation coefficient. Conclusion: Although the majority of today's cochlear implant recipients perform well and the intensity–pitch relation in cochlear implant recipients is still poorly understood, rising demands on speech-coding strategies may soon make a compensation of the pitch shifts desirable. Although the results of our study tend to argue against a peripheral mechanism, the exact origin of this phenomenon remains unclear.     

Effects of Electrode Configuration and Place of Stimulation on Speech Perception with Cochlear Prostheses

Recent research and clinical experience with cochlear implants suggest that subjects' speech recognition with monopolar or broad bipolar stimulation might be equal to or better than that obtained with narrow bipolar stimulation or other spatially restricted electrode configurations. Furthermore, subjects often prefer the monopolar configurations. The mechanisms underlying these effects are not clear. Two hypotheses are (a) that broader configurations excite more neurons resulting in a more detailed and robust neural representation of the signal and (b) that broader configurations achieve a better spatial distribution of the excited neurons. In this study we compared the effects of electrode configuration and the effects of longitudinal placement and spacing of the active electrodes on speech recognition in human subjects. We used experimental processor maps consisting of 11 active electrodes in a 22-electrode scala tympani array. Narrow bipolar (BP), wide bipolar (BP + 6), and monopolar (MP2) configurations were tested with various locations of active electrodes. We tested basal, centered, and apical locations (with adjacent active electrodes) and spatially distributed locations (with every other electrode active) with electrode configuration held constant. Ten postlingually deafened adult human subjects with Nucleus prostheses were tested using the SPEAK processing strategy. The effects of electrode configuration and longitudinal place of stimulation on recognition of CNC phonemes and words in quiet and CUNY sentences in noise (+10 dB S/N) were similar. Both independent variables had large effects on speech recognition and there were interactions between these variables. These results suggest that the effects of electrode configuration on speech recognition might be due, in part, to differences among the various configurations in the spatial location of stimulation. Correlations of subjective judgments of sound quality with speech-recognition ability were moderate, suggesting that the mechanisms contributing to subjective quality and speech-recognition ability do not completely overlap.     

Behavioral thresholds for electrical stimulation applied to auditory brainstem nuclei in cat are altered by injurious and noninjurious sound

Each of three young-adult female cats with normal hearing received a total of eight permanent electrodes which were implanted bilaterally in cochlear nucleus (CN) and inferior colliculus (IC). Three experiments were performed using behaviorally measured thresholds for electrical stimulation of CN and IC. In Expt. 1, electrical stimulation thresholds (in dB re 1.0 μA) were obtained in the presence of a continuous tone of moderate intensity and in quiet. In comparison with quiet, electrical stimulation thresholds measured during tone were lower by as much as 15 dB (stimulation hypersensitivity). In Expt. 2, a brief exposure to an intense sound produced a temporary threshold shift (TTS) for acoustic stimuli but only produced small changes in electrical stimulation threshold. The acoustic stimuli used in Expts. 1 and 2 were termed noninjurious since no permanent hearing loss was produced. Expt. 3 employed an exposure to a white noise that resulted in a mean permanent threshold shift (PTS) of 34.1 dB for acoustic stimulation. The PTS was accompanied by a mean stimulation hypersensitivity of 9.6 dB. Comparing Expts. 1 and 3, it was shown that the transient hypersensitivity produced by the noninjurious continuous tone correlated strongly with the permanent hypersensitivity that was produced by the PTS. In regard to the origin of stimulation hypersensitivity, the suggestion is made that it is an indication of a physiological change localizable perhaps in the auditory nuclei of the upper brainstem.     

Post-stimulatory suppression, facilitation and tuning for delays shape responses of inferior colliculus neurons to sequential pure tones.

Temporal changes in the excitability of inferior colliculus (IC) neurons will shape their responses to complex stimuli. Single-unit responses of rat IC neurons to the second (probe) of a pair of tones exhibited suppression, facilitation and delay tuned effects. Responses to probe tones were markedly suppressed (by 76% for contralateral stimulation with equal intensity tone pairs) during contralateral and binaural stimulation in 60% of IC neurons. Suppression developed rapidly as a function of the duration of the initial tone, and approached maximum for tones of less than 200 ms. Suppression decreased as the interval between tones increased, and this recovery of responsiveness was often exponential (time constants: mean: 271.4 ms; median: 72.8 ms; n = 47), and independent of the duration and intensity of preceding stimulation. Facilitation of responses to probe tones was observed chiefly in neurons with 'pauser/buildup' response patterns, and decreased as the intertone interval increased. The greatest suppression of responses to probe tones occurred only after intertone intervals of 32 ms (delayed minimum; n = 8) in 11% of IC neurons. Other IC neurons exhibited an increased excitability to probe tones presented 128 ms after stimulation (delayed maximum; n = 7). The latencies of the later neurons' responses were longer (mean: 29.5 ms) than other IC neurons. The role of suppression in sound localization and echo suppression, and the relationship between 'delay tuning' effects and encoding of complex stimuli are discussed.