Age-related Alterations in the Auditory Brainstem Responses and the Compound Action Potentials in Guinea Pigs

The auditory brainstem response (ABR) and the eighth nerve compound action potential (CAP) were measured using click stimuli to investigate the agerelated alteration in the auditory function in 66 guinea pigs consisting of four age groups. With advancing age, a gradual elevation of the thresholds in both the ABR and CAP was clearly seen, together with the prolonged latencies for waves I, II, III, and IV to clicks at 95 dBpeSPL in the ABR. There were some individual differences in either threshold elevation or latency prolongation of both the ABR and CAP in aged guinea pigs. These findings suggest that the effect of individual differences on degenerative aging processes of the auditory system should be considered in selected aged animals, although a significant elevation of the neural auditory threshold is clearly found with advancing age as a whole.     

Human auditory nerve compound action potentials and long latency responses

CONCLUSION: The compound action potential (CAP) is followed by a long latency response (LLR), attributable to the post-auricular musculature. The LLR to one pulse may overlap with the CAP to a subsequent one, contributing to the clinically observed reduction in CAP at high pulse rates. OBJECTIVES: To measure refractory and other influences on CAPs in humans and guinea pigs. MATERIALS AND METHODS: CAPs were obtained from humans using trans-tympanic and extra-tympanic electrocochleography and from anaesthetized guinea pigs. Stimuli were single pulses presented at a slow rate, pairs of pulses, and 100 ms pulse trains where the inter-pulse interval alternated between 4 and 6 ms. RESULTS: For single pulses, the CAP shape was similar across species. For pairs of pulses, the CAP to the second pulse was smaller than that to the first, and decreased with increasing inter-pulse interval in a way that was similar across species. For pulse trains, CAPs were observed in response to each pulse in the train for the guinea pigs, but not for humans. For both filtered and unfiltered single pulses, there was a large LLR in humans, but not in guinea pigs, with peaks at latencies of 10-12 and 20-25 ms. Posture affected the LLR in a way consistent with the post-auricular response.     

Human auditory nerve compound action potentials and long latency responses

Conclusion. The compound action potential (CAP) is followed by a long latency response (LLR), attributable to the post-auricular musculature. The LLR to one pulse may overlap with the CAP to a subsequent one, contributing to the clinically observed reduction in CAP at high pulse rates. Objectives. To measure refractory and other influences on CAPs in humans and guinea pigs. Materials and methods. CAPs were obtained from humans using trans-tympanic and extra-tympanic electrocochleography and from anaesthetized guinea pigs. Stimuli were single pulses presented at a slow rate, pairs of pulses, and 100 ms pulse trains where the inter-pulse interval alternated between 4 and 6 ms. Results. For single pulses, the CAP shape was similar across species. For pairs of pulses, the CAP to the second pulse was smaller than that to the first, and decreased with increasing inter-pulse interval in a way that was similar across species. For pulse trains, CAPs were observed in response to each pulse in the train for the guinea pigs, but not for humans. For both filtered and unfiltered single pulses, there was a large LLR in humans, but not in guinea pigs, with peaks at latencies of 10–12 and 20–25 ms. Posture affected the LLR in a way consistent with the post-auricular response.     

Threshold elevation at high frequencies of the auditory nerve action potential in acute versus chronic recordings in guinea pigs

Thresholds of the auditory nerve compound action potential (CAP) responses to filtered clicks from 0.5 to 40 kHz, defining a CAP frequency threshold curve, have been determined in the same guinea pigs: (1) in acute conditions, the animal still anesthetized at the end of the operation for permanent implantation of a round-window electrode, and (2) several days later in the implanted awake and unrestrained animal. The results show higher CAP thresholds for high frequencies in acute conditions as compared to chronic recordings. This difference appears above about 12.5 kHz and increases progressively to around 40 dB at 40 kHz. Similar effects, although somewhat less pronounced, were observed during anesthesia alone in already implanted guinea pigs. These observations could explain the discrepancies which appear between electrophysiological thresholds, acutely recorded either from single fibers or whole-nerve responses, and behavioral audiograms. Moreover, in the accurate evaluation of the cochlea, slight impairments may be masked by this phenomenon as illustrated in guinea pigs treated with low doses of ototoxic antibiotic.     

Anesthesia and surgical traum: their influence on the guinea pig compound action potential

A chronic implant consisting of a fine thermocouple placed on the round window permitted measurement of temperature and of the compound action potential (CAP) of the cochlear nerve in guinea pigs. Thresholds and latencies of the CAP, in response to tone bursts (2–40 kHz), were measured when the animal was awake and unrestrained, and again after several hours of anesthesia. The CAP remained unchanged with a variety of common anesthetics when precise control of round window temperature was maintained. However, when anesthesia was accompanied by several hours of slight cochlear cooling, thresholds were elevated for CAPs evoked by frequencies above 24 kHz and latencies were increased for CAPs evoked by all frequencies tested.

The effects of surgery on CAP threshold and latency were also examined. Guinea pigs were tested while still anesthetized at the conclusion of the implantation procedure, and then again several days later while awake. Thresholds and latencies were unchanged. In two anesthetized guinea pigs already implanted with thermocouples, ventral and post-auricular surgery to expose the middle ear had no effect on the CAP, when low-speed drilling was used to open the auditory bulla. However, when small portions of the bulla were broken away with forceps, the CAP in response to high-frequency tone bursts immediately showed elevated thresholds. This alteration of the CAP was clearly different from that produced by lowered temperature, since the latencies at threshold were significantly decreased.     

Postnatal development of the auditory evoked brainstem potentials in the guinea pig

The postnatal development of lower stations in the auditory pathway was studied in the guinea pig by recording auditory brainstem potentials. At birth, the brainstem responses of young guinea pigs already have thresholds corresponding to those of adult animals. However, the latencies of the individual potentials are significantly longer than those in the control group. Within the 4 weeks of the study, the latency of each of the five potentials reached the adult value. Both the rate of latency normalization and the characteristic changes in potential amplitude indicate that maturation of the auditory pathway proceeds centripetally.     

Effect of interphase gap and pulse duration on electrically evoked potentials is correlated with auditory nerve survival

We investigated the effect of pulse duration (PD) and interphase-gap (IPG) on the electrically-evoked auditory brain stem response (EABR) and viiith nerve compound action potential (ECAP) of deafened guinea pigs in order to test the hypothesis that the extent of change in these neural responses is affected by the histological status of the auditory nerve. Fifteen guinea pigs were deafened by co-administration of kanamycin and furosemide. Animals were acutely implanted with an 8-band electrode array at 1, 4 or 12 weeks following deafening. EABR and ECAP input/output functions were recorded in response to charge balanced biphasic current pulses. We determined the change in current required to equalize; (i) the EABR amplitude when the duration of the current pulse was doubled (104-208 micros/phase); and (ii) the EABR and ECAP amplitudes when the IPG was increased from 8 to 58 micros using a 104 micros/phase current pulse. Following the completion of each experiment the cochleae were examined quantitatively for spiral ganglion neuron survival. As expected, the current level required to evoke an EABR with equal amplitude was lower when the animal was stimulated with current pulses of 208 compared with 104 micros/phase. Moreover, the current level required to evoke EABR/ECAPs with equal amplitude was lower when current pulses had an IPG of 58 versus 8 micros. Importantly, there was a reduction in the magnitude of this effect with greater neural loss; the reduced efficacy of changing both PD and IPG on these electrically-evoked potentials was statistically correlated with neural survival. These results may provide a tool for investigating the contribution of auditory nerve survival to clinical performance among cochlear implant subjects.     

Electrically evoked auditory steady-state responses in a guinea pig model: latency estimates and effects of stimulus parameters

Cochlear implant speech processors typically extract envelope information of speech signals for presentation to the auditory nerve as modulated trains of electric pulses. Recent studies showed the feasibility of recording, at the scalp, the electrically evoked auditory steady-state response using amplitude-modulated electric stimuli. Sinusoidally amplitude-modulated electric stimuli were used to elicit such responses from guinea pigs in order to characterize this response. Response latencies were derived to provide insight regarding neural generator sites. Two distinct sites, one cortical and another more peripheral, were indicated by latency estimates of 22 and 2 ms, respectively, with the former evoked by lower (13-49 Hz) and the latter by higher (55-320 Hz) modulation frequencies. Furthermore, response amplitudes declined with increasing carrier frequency, exhibited a compressive growth with increasing modulation depths, and were sensitive to modulation depths to as low as 5%.     

Age-related changes in the compound action potentials of the eighth nerve in guinea pigs

The eighth nerve compound action potential (CAP) in 95 guinea pigs was measured using click stimuli to investigate age-related changes in their neural auditory thresholds. The animals were separated into three groups: group A (n = 43, 86 ears; 2–4 months old); group B (n = 29; 58 ears, 13–15 months old); and group C (n = 23; 46 ears, 23–25 months old). With increasing age, a gradual elevation of CAP thresholds was clearly seen among the three groups. The negative peak (N1) latencies of the CAP were prolonged, and the N1 amplitudes of the CAP decreased. There were significant differences in N1 latencies among the three groups and in N1 amplitudes between groups A and B, and between groups A and C. However, the rate of decline of the thresholds as well as the input-output function curves of the CAP varied in some of the oldest animals, suggesting that there were some individual differences in degenerative aging processes of the auditory system.     

Single-unit response at the round window of the guinea pig

In guinea pigs the unit contribution (unit action potential, ap) to the response of the round window was computed following the method used by Kiang and co-workers (1976), i.e., fibre discharges registered by a microelectrode in the nerve were used as trigger pulses for the averaging process of the corresponding ap registered with a gross electrode at the round window. Normally the ap was independent of the fibre-CF, had a diphasic waveform, and its amplitude was about 0.1 microV. Small inter-animal differences were found in waveform and amplitude of the ap. In a pilot experiment exploring pathological influences on ap, the auditory nerve was stretched to mimic the effect of some acoustic nerve tumors. We found that the waveforms of both ap and compound action potential (CAP) changed. The results indicate that in normal guinea pig cochleas the existence of an elementary unit waveform can be used in the convolution of the CAP [Goldstein, M.H. Jr. and Kiang, N.Y.S. (1958) J. Acoust. Soc. Am. 30, 107-114]. In abnormal cochleas, however, deteriorated aps may disturb the simple convolution concept of the CAP.     

Age-related changes in the auditory evoked brainstem

Summary The auditory evoked brainstem responses of guinea pigs in two age groups were recorded and examined for evidence of age-dependent changes at peripheral stations in the auditory pathway. Because pigmented guinea pigs have been found to be less sensitive to sounds than albinos, both groups were included in this study. Old and young animals did not differ in response latency or in the conduction times associated with the individual potentials. By contrast, the amplitudes of the brainstem responses to high-frequency stimuli were distinctly reduced in old guinea pigs, with no difference in the dynamic of the amplitude between the two age groups. Within each age group, albino and pigmented animals resembled one another in all parameters studied. The effect of the aging process at the peripheral stations of the auditory pathway is discussed in the light of these results.Supported by the Deutsche Forschungsgemeinschaft (DFG)     

Prolonged electrode implantation in experimental studies. Critical evaluation of a technique

Stainless steel electrodes were chronically implanted through the right facial canal of 30 guinea pigs, close to the potential generator (VIII nerve). Compound action potential (CAP) thresholds, N1 latencies and input-output curves were recorded on day of implantation and 2, 4 and 8-12 weeks later. In the same sitting, auditory evoked brain stem response (ABR) thresholds, latencies and inter-peak-latencies were measured on both sides as a control. N1 thresholds and latencies at low and high intensities were stable. N1 amplitudes, however, showed some variation. Rate of infection was low and reimplantation was successful. Preserving the facial nerve as a land mark was found advantageous, particularly on reimplantation, and did not affect the CAP recording. The technique, originally described by Hildesheimer et al., proved to be reproducible. A few technical difficulties are pointed out and the implication of some interesting findings are discussed.     

豚鼠耳蜗顶部区域微循环障碍的实验研究

目的 研究豚鼠耳蜗顶部区域微循环障碍的听力损伤特点,建立以低上尖损伤为主的听力损伤模型,方法光化学法诱导豚鼠耳蜗顶部区域微循环障碍,常规火棉交切片观察耳蜗形态学变化,再用Madsen2250诱发电位系统记录各频率声刺激诱发的CAP和CM。结果 各频率CAP－N1潜伏期延长值、CAP阈移、CAP－N1和CM振幅下降示基听力损伤以低频较重,其血栓形成的 耳蜗顶回及第三回血管纹和螺旋韧带为主,结论 耳蜗顶部区域的局部微循环障碍可以导致低频范围为主的听力损伤。     

豚鼠耳蜗底回近末端局部微循环障碍的研究

目的 :探讨豚鼠耳蜗底回接近末端局部微循环障碍的听力损伤特点 ,建立以高频损伤为主的听力损伤模型。方法 :采用光化学法诱导豚鼠耳蜗底回接近末端 1/ 2段微循环障碍 ;常规火棉胶切片观察耳蜗形态学变化 ;Madsen2 2 5 0诱发电位系统记录各频率的耳蜗神经复合动作电位 (CAP)。结果 :各频率的 CAP N1 潜伏期、CAP阈移、CAP N1 振幅变化 ,提示其听力损伤以高频较重 ,组织病理学变化表明耳蜗形态学改变主要局限于耳蜗底回接近末端 1/ 2段。结论 :耳蜗底回接近末端局部微循环障碍可以导致高频范围为主的听力损伤。     

CAP amplitude after impulse noise exposure in guinea pigs

In this study, 21 guinea pigs were submitted to a single high energy impulse noise (gun shot with blank projectiles). The auditory function was evaluated over a 7-day recovery period by recording the compound action potential (CAP) from the round window. The threshold shift and input/output function (CAP amplitude and delay function of the stimulus intensity) were studied at different frequencies. CAP amplitude fell after the noise trauma, especially at the lower sound level, resulting in a threshold shift. Latency was significantly increased. During recovery, whereas latency returned to its initial value, CAP amplitude gradually increased and, in half the animals, exceeded the control value for the higher levels of stimulus. This could have been because of progressive disinhibition or recruitment, and may correspond clinically to hyperacusis. These results are discussed referring to those obtained by other authors using other methods.     

Discharge rate of the auditory nerve during noise revealed by electrocochlear stimulation

The purpose of this study was to evaluate the average discharge rate of all fibres in the whole auditory nerve (R(wn)) when a broad-band noise with steady-state effects is applied to the ear. We assessed the R(wn) parameter by detecting the state of refractoriness of the nerve during noise stimulation using an electric stimulus (ES) as a probe. The technique, applied in awake pre-implanted guinea pigs (Charlet de Sauvage et al., 1994), made it possible to obtain electro-acoustic responses (EARs), from which an estimate of the R(wn) parameter could be deduced. Negative current pulses of 100 micros duration, each followed by an identical pulse of positive polarity for charge balance, were applied between round window and indifferent vertex electrodes at intervals of 160 ms. The 120 ms wide-band noise masker started 92 ms before every other negative ES. The signal on the stimulating electrodes was averaged over a 5.12 ms window in synchrony with the negative pulse. EARs were obtained by alternately subtracting recordings during noise from those during silence. The R(wn) parameter was determined by comparing experimental and computed EAR patterns. For this purpose, a model of unit response incorporating changes in amplitude and conduction velocity during the relative refractory period was designed. The recovery function of the firing probability in response to ES was evaluated. Fibres were classified in different categories according to their background discharge rates. The probability of response of single fibres to ES in each category was calculated on the basis of their interval histograms during silence and noise. Individual spikes were combined accordingly to obtain the computed EAR waveform. R(wn) was determined by adjusting the EAR amplitude of the model in relation to that of the experimental EAR. R(wn) generally increases in a linear fashion with respect to noise intensity expressed in dB, thus following the increase in loudness perception estimated by Weber's law. At the highest noise levels, R(wn) tends to saturate. The estimated saturation rate was found to be about 380 spikes/s.     

Absence of tonic activity of the crossed olivocochlear bundle in determining compound action potential thresholds, amplitudes and masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities

In Nembutal- or Urethane-anaesthetised guinea pigs N1 audiograms and N1 input-output functions were measured as were compound action potential (CAP) tuning curves under forward masking and simultaneous masking conditions. Then the crossed olivocochlear bundle was lesioned at the floor of the fourth ventricle and the cochlear responses were re-measured. There were never any changes in the N1 audiograms, input-output functions, or the CAP tuning curves. Thus, the crossed efferent pathways do not appear to play any tonic role in determining cochlear threshold sensitivities, selectivities or masking phenomena in anaesthetised guinea pigs with normal hearing sensitivities.     

Electrovestibulogram: first results in the guinea pig

This paper describes a method of investigation of the peripheral vestibular system. Electrical stimulations (ES) are applied on the round window of chronically implanted guinea pigs, with and without vestibular stimulation (either per or post rotational accelerations). The whole nerve action potential recorded at the output of the internal auditory meatus, the difference between the two conditions, reveals the change in electrical excitability and thus presumably in discharge rate of vestibular fibres determined by rotational stimuli. This electrical vestibular action potential (EVAP) presents as a mainly monophasic potential with a peak latency to ES of about 0.3 ms. Right and left accelerations versus rest are shown to give responses with opposite polarity, reflecting the inhibitory and excitatory influences of these opposite accelerations, whereas the transfer function of EVAP versus acceleration amplitude appears roughly linear. These observations appear altogether coherent with published mechano-physiological data about individual discharge rates of canal fibres. Also relative amplitudes of acoustical and vestibular responses are in agreement with related number of fibres in the two systems. This EVAP could be the basis of a quantitative evaluation method for the vestibular system, the electrovestibulogram (EVG).     

自身免疫性听神经病动物模型的建立及听性脑干反应和畸变产物耳声发射的变化

目的建立自身免疫性听神经病动物模型，探讨其听性脑干反应（auditory brainstem response ABR）和畸变产物耳声发射（distortion product otoacoustic emission DPOAE）的变化特征。方法选取耳廓反射正常的白色豚鼠250只，分离、电泳与纯化豚鼠螺旋神经节及蜗轴内的耳蜗神经纤维抗原，然后与等量完全弗氏佐剂免疫同种豚鼠，其中正常组10只，对照组10只，试验组50只。观察ABR、DPOAE、血清IgG水平、螺旋神经节和耳蜗核团形态学的改变、听神经抗原蛋白在螺旋神经节和耳蜗神经的表达、听神经纤维超微结构的变化。结果免疫后16只动物（32／100耳）出现听性脑干反应阈提高10～25dB，Ⅰ、Ⅲ波潜伏期延长，到免疫后第3周最为明显，随后有逐渐恢复的趋势，其中Ⅲ波潜伏期到第6周恢复正常；该组豚鼠DPOAE没有变化，动物血清IgG显著性升高，与对照组相比差异有统计学意义（F=10．03，P〈0．05）；均有不同程度的螺旋神经节细胞变性、数目减少，螺旋神经节和小血管周围有淋巴细胞浸润；听神经纤维出现脱髓鞘、髓鞘断裂等现象。豚鼠耳蜗核各亚核团平均细胞密度和细胞平均面积各组差异比较没有统计学意义；听神经蛋白完全分布于耳蜗螺旋神经节和听神经纤维组织。免疫后34只动物（68／100耳）没有出现ABR反应阈升高，血清IgG没有升高，与对照组相比差异没有统计学意义，螺旋神经节、耳蜗核团、听神经纤维超微结构没有变化。结论建立了豚鼠自身免疫性听神经病动物模型，该动物模型的ABR反应阈轻中度提高，Ⅰ、Ⅲ波有自然恢复的趋势。DPOAE没有变化。