Time course of rate responses to two-tone stimuli in auditory nerve fibres in the guinea pig.

Peri-stimulus time histograms (PSTHs) were constructed from responses of auditory nerve fibres in anaesthetized guinea pigs. Acoustic stimuli consisted of pure tones, presented either as tone bursts, or in two-tone combinations in which a gated test tone was superimposed on a continuous excitatory tone at characteristic frequency (CF). The majority of the sample of fibres displayed two-tone rate suppression (2TRS). The suppression was either a monotonic or a non-monotonic function of the level of the superimposed test tone. Monotonic suppression of CF-driven rate occurred only for test tones at frequencies higher than CF, presented at levels up to the maximum available (approx. 100 dB SPL). For test tones below CF, 2TRS initially increased, then reverted towards excitation for higher levels of the test tone. Three levels were identified in non-monotonic, two-tone rate functions; (1) the threshold for rate suppression, (2) the maximally suppressing level and (3) the level (referred to as the balance point) at which average firing rate was restored to the background, CF-driven rate. PSTHs for two-tone responses obtained for test tone levels between the maximally-suppressing level and the balance point typically showed brief decrements (notches) in spike rate, at the onset and following the offset of the test tone. The latency, depth and duration of notches, however, depended on the level of the test tone, in a different manner for onset and offset. In some cases, without overt rate excitation above the probe-driven rate, the offset notch became more pronounced and of extended duration with increased level of the test tone, suggestive of adaptation to the test tone. Two-tone responses, in which rate exceeded the background, CF-driven rate, in general were preceded by a reduced onset notch and were followed by a longer-lasting depression of the background spike rate, typical of post-excitatory depression. Relative to responses obtained to the test tones presented alone, excitatory two-tone responses were of lower rate and were delayed by the onset notch. Onset notches sometimes preceded rate excitation in responses to single tones. Some features of the time course of rate suppression and excitation displayed in PSTHs for responses to one and two-tone stimuli seem inconsistent with current models of 2TRS.     

Diversity of characteristic frequency rate-intensity functions in guinea pig auditory nerve fibres

Rate-intensity functions at characteristic frequency (CF) were recorded from single fibres in the auditory nerve of anaesthetised guinea pigs. Within the same animal, CF rate-intensity functions, although probably forming a continuum, could be conveniently divided into three groups; (1) Saturating; reach maximum discharge rate within 30 dB of threshold, (2) Sloping-saturation; initially rapid growth in discharge rate leading to a slower growth in discharge rate but not saturating and (3) Straight; approximately constant increase in firing rate per decibel increase in sound pressure up to the maximum sound pressures used. Thresholds for individual fibres were plotted relative to compound action potential thresholds at the appropriate frequency. Fibres with straight CF rate-intensity functions had the highest thresholds. Fibres of the saturating CF sloping-saturation CF rate-intensity type had thresholds intermediate between saturating and straight. There was a close relationship between the type of CF rate-intensity function exhibited by a fibre and its spontaneous discharge rate. Fibres with saturating CF rate-intensity functions generally had high spontaneous discharge rates (greater than 18/s), whereas those with straight CF rate-intensity functions generally had low spontaneous discharge rates (less than 0.5/s). The majority of fibres with sloping-saturation CF rate-intensity functions had spontaneous rates between 0.5/s and 18/s. There was a negative correlation (r = -0.59) between the logarithm of the spontaneous discharge rate and relative threshold at CF with the lowest spontaneous rate fibres having the highest thresholds and vice-versa. This diversity of CF rate-intensity functions has functional implications for both frequency and intensity coding at high sound pressures in the mammalian auditory system.     

Representation of a low-frequency tone in the discharge rate of populations of auditory nerve fibers

Discharge rates for populations of single auditory nerve fibers in response to 1.5 kHz tone bursts were measured in anesthetized cats. Separate plots of average rate vs. best frequency (rate-place profiles) were made for high, medium and low spontaneous rate (SR) auditory nerve fibers. At the lowest sound levels studied (34 dB SPL), all three SR groups show a peak in the rate-place profile centered around 1.5 kHz. At the highest sound levels studied (87 dB SPL), the average rates of the high and medium SR fibers are saturated across a wide range of best frequencies, but a peak around 1.5 kHz is maintained in the rate-place representation of the low SR fibers. These results show that in addition to the temporal information present in the discharge patterns of auditory nerve fibers, a rate-place representation of a single low-frequency tone exists in the auditory nerve over a wide range of sound levels.     

Frequency threshold curves and simultaneous masking functions in single fibres of the guinea pig auditory nerve

Tuning curves for simultaneous masking were measured electrophysiologically, in single fibres of the guinea pig auditory nerve. The masking paradigm used was an analogy of that used in the determination of psychophysical tuning curves in man. The resulting tuning curves ran nearly parallel to the corresponding neural frequency threshold curve, over all except the high-frequency portion of the tuning curve. There, the masking functions had a shallower slope than the excitatory frequency threshold curve. The frequency at which the slope became shallower had a close and consistent dependence on fibre characteristic frequency, reaching a value of 1.2 times fibre characteristic frequency in high-frequency fibres. Analysis of firing rates during the threshold determination gave information about the mechanism of the masking, and the results were supported by theoretical analysis. The results give information useful for the interpretation of psychophysical tuning curves, determined by simultaneous masking, in man.     

Very rapid adaptation in the guinea pig auditory nerve

Guinea pig auditory ganglion cell responses to 100-ms duration tone bursts were recorded over a range of stimulus intensities. The responses, recorded in the form of peristimulus/poststimulus time histograms, were analysed by reduction into two phases. The first phase was a rapid exponential adaptation from an initial onset response; the second was a more gradual reduction in the firing rate which, over the 100 ms duration of the stimulus, appeared to be a linear function of time. The first, rapid, phase was nonlinear in its response to changes in stimulus intensity, exhibiting a change in amplitude and having a time constant which decreased with increasing intensity. Individual units were consistent in the magnitude and time course of this phase. The second phase was also nonlinear with intensity, and was far more variable from unit to unit. With the recording parameters employed it was not possible to determine whether the effect of intensity on the second phase was an effect on the magnitude or time course, or both. Stimulus termination responses were also analysed, and typically were of one of two forms. If, at any particular stimulus intensity, the unit under study showed little sign of the slower adaptation then the termination response was a simple depression of activity (perhaps to zero) which recovered with an exponential time constant of about 25 ms, independent of intensity. If, however, the peristimulus responses showed a significant amount of the slow adaptation then the termination responses also exhibited a second, slower, phase of recovery. This was modelled over the recording epoch as a linear function of time. The magnitude of the slow offset response also increased with intensity faster than did the average firing rate.     

Relationship between pure tone audiometry and tone burst auditory brainstem response at low frequencies gated with Blackman window

To assess the reliability of Blackman windowed tone burst auditory brainstem response (ABR) as a predictor of hearing threshold at low frequencies. Fifty-six subjects were divided in to three groups (normal hearing, conductive hearing loss, sensorineural hearing loss) after pure tone audiometry (PTA) testing. Then they underwent tone burst ABR using Blackman windowed stimuli at 0.5 kHz and 1 kHz. Results were compared with PTA threshold. Mean threshold differences between PTA and ABR ranged between 11 dB at 0.5 kHz and 14 dB at 1 kHz. ABR threshold was worse than PTA in each but 2 cases. Mean discrepancy between the two thresholds was about 20 dB in normal hearing, reducing in presence of hearing loss, without any differences in conductive and sensorineural cases. Tone burst ABR is a good predictor of hearing threshold at low frequencies, in case of suspected hearing loss. Further studies are recommended to evaluate an ipsilateral masking such as notched noise to ensure greater frequency specificity.     

Frequency threshold curves and simultaneous masking functions in high-threshold, broadly-tuned, fibres of the guinea pig auditory nerve

Tuning curves for simultaneous masking were measured electrophysiologically, in single fibres of the auditory nerve. The recordings were made in guinea pigs with cochlear hearing losses. The masking paradigm was an analogy of that used in the determination of psychophysical tuning curves in man. Below the probe frequency, the slope of the masking function was similar to that of the frequency-threshold curve. Here, changes in the slope of the frequency-threshold curve with hearing loss were closely mirrored by changes in the slope of the masking function. Above the probe frequency, however, the masking function for low-threshold fibres had a shallower slope than the frequency-threshold curve. When the high-frequency slope of the frequency-threshold curve became shallower with hearing loss, the changes were not mirrored in the masking function, until the threshold was raised to 70-80 dB SPL. The results are discussed in terms of the influence of cochlear nonlinearity on frequency resolution, and the vulnerability of the nonlinearity.     

Changes in cochlear sensitivity do not alter relative thresholds of different spontaneous rate categories of primary auditory nerve fibres

The CF thresholds of three different spontaneous firing rate categories of single auditory nerve fibres were measured in guinea pigs with widely differing cochlear sensitivities. The CF thresholds for all fibres were compared to the CAP thresholds at the same frequencies. The relationship between single fibre CF threshold and CAP thresholds for the three different fibre categories remained unchanged despite the very wide range of absolute CAP thresholds. The widely ranging CAP thresholds in these animals were probably due to varying degrees of outer hair cell pathology and these data therefore support the notion that in normal animals, the origin of differences in threshold between fibres with different spontaneous rates, lies in the properties of the inner hair cells and/or their synapses with afferent dendrites.     

Responses of gerbil and guinea pig auditory nerve fibers to low-frequency sinusoids

The characteristics of time-locked auditory nerve fiber responses to 50 Hz acoustic sinusoids were studied in gerbils and guinea pigs. Whereas the time-locked responses of all guinea pig fibers produced single-peaked period histograms, those of the gerbil produced distorted, multiple-peaked response histograms, especially fibers with characteristic frequencies (CFs) between 2 and 10 kHz. Although the shapes of the period histograms vary with stimulus intensity, the phases of the fundamental components are essentially invariant over the range of stimulus intensities used. In contrast to the phase of the cochlear microphonic produced by the 50 Hz stimulus, which was constant along the length of the cochlea in both species, the phase of the neural responses depends on the fiber CF in each of the two species. In guinea pigs, the phase of the neural responses relative to the acoustic stimulus decreases with the fiber CF from a phase lead of 90 degrees for fibers with CFs below 300 Hz to a phase lag of nearly 60 degrees for fibers with CFs greater than 3 kHz. In gerbils, the response phase also decreases with increasing CF below 2 kHz and above 10 kHz but undergoes an abrupt 160 degrees phase increase between those frequencies.     

Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons.

Recovery of neural thresholds following a forward masker was measured for auditory neurons in anesthetized chinchillas. We find that recovery of forward-masked thresholds is slower for low spontaneous-rate neurons compared to high spontaneous-rate neurons. In addition, we studied the dependence of the shape of PST histograms on the time between repetitions of a tone-burst. We find that for low spontaneous-rate neurons, peak onset responses increase in magnitude over a longer range of interstimulus intervals compared to high spontaneous-rate neurons. Both results are consistent with the conclusion that low spontaneous-rate neurons take longer to recover from prior stimulation compared to high spontaneous-rate neurons. We suggest applications of this finding in psychophysical experiments to investigate the role of low spontaneous-rate neurons in intensity coding.     

Two-tone suppression, excitation and the after effect in rate responses in auditory nerve fibres in the cat.

Responses were recorded from single, auditory nerve fibres in the anaesthetized cat. Acoustic stimuli consisted of two tones, one of which was at characteristic frequency (CF), the other (the suppressor) was at considerably lower frequency. Tones were presented in simultaneous and sequential configurations. For simultaneous presentations, well-known response properties were observed. The rising limb of the two-tone rate-intensity function closely matched that of the appropriately adapted response to the suppressor tone presented alone. Also, whether strongly suppressed relative to CF-driven rate, or equal to CF-driven rate, rate responses to the two-tone stimuli persisted unchanged when the CF tone was terminated and the suppressor tone continued alone. These results support the hypothesis that the suppressor tone has dual influences, suppressive and excitatory, that are distinct and additive. Peristimulus response histograms confirm in the cat that depression and slow recovery of sensitivity to CF may follow termination of the suppressor tone, as reported for the guinea pig [Hill, K.G. and Palmer, A.R. (1991) Hear. Res. 55, 167-176]. This delay in recovery of normal sensitivity to CF appeared to be directly related to the amount of excitation of the fibre that is attributable to the suppressor tone. A similar, delayed re-establishment of sensitivity also occurred in the response to a tone at CF, presented immediately following excitation by a suppressor tone. However, no delay occurred in the onset of response to the suppressor when preceded by the CF tone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Development of low-frequency tone burst versus the click auditory brainstem response

Often ABR threshold testing employs clicks to assess high-frequency hearing, and low-frequency tone bursts to assess low-frequency sensitivity. While a maturation effect has been shown for click stimuli, similar data are lacking for low-frequency toneburst stimuli. Thus, 305 infants ranging in conceptional age (CA) from 33 weeks to 74 weeks were tested. Absolute latencies were measured for wave V at 55, 35, and 25 dB nHL in response to a click and for wave V500 in response to a 500 Hz tone burst. Major wave latency in response to 500 Hz tone bursts decreases with age and do not stabilize by 70 weeks CA. Likewise, waves III and V latencies in response to clicks decrease with age, as has been reported by others, and do not stabilize by 70 weeks CA. Wave I latency produced by clicks did not decrease with age, being mature by 33 weeks CA.     

Eighth nerve auditory evoked responses recorded at the base of the vestibular nucleus in the guinea pig

Anatomical and physiological studies of brainstem acoustic nuclei involving the classical ascending auditory pathway or the cerebellar and reticular pathways imply that all afferents from the cochlea terminate in the cochlear nucleus. In the experimental pathology of complete and selective destruction of the cochlea in the guinea pig acoustic responses still evoked at mid and high intensities, demonstrated to come from the saccule, show a pattern of far field evoked brainstem potentials quite different from that of normal animals. Intracranial electrophysiological investigations of the brainstem were undertaken in such pathological animals and in normal guinea pigs for comparison. In both cases acoustic responses were recorded at the base of the vestibular nucleus, showing a first peak corresponding to an eighth nerve projection and after a synaptic delay a second peak of local activation. In normal animals acoustic responses from the vestibular nucleus showing normal threshold and tuning curves may represent a direct projection from the cochlea.     

Relationship between the auditory brainstem response and auditory nerve thresholds in cats with hearing loss

This study explored the relationship between the auditory brainstem response (ABR) and auditory nerve sensitivity in cats with normal hearing and with noise-induced permanent threshold shifts. A statistically significant linear correlation was found between each cat's ABR thresholds and the most sensitive single neuron thresholds at the same frequency. ABR thresholds were approximately 25 dB higher than the thresholds of the most sensitive neural responses in cats with normal hearing. The two measures produced equivalent thresholds at impaired frequencies in subjects with sensorineural hearing loss. Two factors may have contributed to this convergence of ABR and neural thresholds. First, our results suggest that the elevation of the most sensitive neural responses led to a compressed threshold distribution. Consequently, only a narrow range of sound levels separated stimulus conditions that activated relatively few fibers from those that were sufficient to evoke a robust population response. In addition, the threshold responses of impaired auditory nerve fibers may have been augmented by activity in the more sensitive 'off-frequency' regions that surrounded a discrete cochlear lesion. Across varying degrees of hearing loss, the ABR maintained a systematic relationship to auditory nerve fiber thresholds, and therefore has the potential to be used as a functional assay of cochlear pathology.     

外淋巴“枯竭“状态对听神经兴奋性影响

目的 通过记录电刺激诱发听觉脑干电位(EABR)阈值变化搞清楚内耳外淋巴“枯竭”状态对听神经兴奋性影响。方法 在手术显微镜帮助下,小心把标准刺激电极沿蜗轴插入鼓阶约4mm,用压碎的肌肉轻轻封住圆窗口。然后用波宽为50μs/phase、刺激速率为30次/秒电荷平衡双相脉冲电流刺激受试动物鼓阶内的靠近蜗尖的电极对(1/2),记录两次EABR阈值,取均值。然后把明胶海绵做成直径约为1mm,长约为4cm小的圆柱形,把一端放入前庭阶持续吸干外淋巴,直到显微镜下见鼓阶外淋巴消失,模拟外淋巴“枯竭”状,用以上电刺激参数再次记录电极对(1/2)的EABR阈值两次,取均值。比较前后两次EABR阈值的变化(t检验)。结果 耳蜗外淋巴“枯竭”状态时测试到的EABABR阈值0.63±0.11mA较充满外淋巴时0.27±0.08mA明显升高(P<0.001)。结论 EABR阈值升高说明耳蜗鼓阶外淋巴呈现“枯竭”状态时听神经兴奋性明显下降,临床上少数重聋或者全聋患者耳蜗外淋巴呈现“枯竭”状态,推测其电子耳蜗植入临床效果可能较耳蜗鼓阶内外淋巴正常患者差。     

Directional properties of the auditory periphery in the guinea pig

The directional sensitivity of the outer ear of the guinea pig was determined by recording changes in the amplitude of the cochlear microphonic to frequencies between 1 and 20 kHz as the location of the sound source was changed throughout 360 degrees of horizontal auditory space. The directional responses to frequencies below 3 kHz were almost omnidirectional. The directional responses for frequencies between 3 and 12 kHz were progressively more directional toward the anterior midline. The responses for frequencies above 12 kHz were highly directional along the ipsilateral interaural axis. In contrast, the directional responses to all frequencies in animals whose pinnae had been removed were orientated along the ipsilateral interaural axis. The observations suggest that the orientation and strength of the directional response of the auditory periphery in the guinea pig are dependent on frequency and that this dependence is attributable, at least in part, to the acoustic properties of the pinna. The observations also indicate that there is a substantial change in the interaural intensity difference at various frequencies and in the spectral transfer function of the ear according to the location of the sound source in the ipsilateral hemifield. The observation that these changes are asymmetrical about the interaural axis for a substantial part of the auditory range of the animal is consistent with the hypothesis that the frequency dependent directionality of the auditory periphery provides a spectral cue for the localization of broad band sounds in the free field.     

Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss

Increase in spontaneous neural activity after noise-induced hearing loss has frequently been associated with the phenomenon of tinnitus. Eighteen juvenile and adult cats were exposed for 2 h to a 6 kHz tone with an intensity of 115 dB SPL at the cat’s head. Seven non-exposed littermates and seven other normal hearing cats were used as age-matched controls. The trauma cats showed localized hearing losses, as assessed by ABR, ranging from less than 20 to 60 dB. The frequency representation in primary auditory cortex was mapped using an eight-electrode array. Single-unit spontaneous activity was recorded for 15 min. Peak cross-correlation coefficients (R) for unit cluster activity recorded on separate electrodes were calculated. We found elevated spontaneous firing rates in regions with reorganization of the tonotopic map compared to the neurons in the non-reorganized cortical regions in the same animals. A second finding was that in these regions the peak cross-correlation coefficients were also increased relative to the non-reorganized parts. A third finding was that exposed animals showed higher spontaneous activity compared to controls regardless of the presence of cortical reorganization. This may be a correlate of tinnitus in the presence of only minor hearing losses.     

Relationship between the nephrotoxicity and ototoxicity induced by gentamicin in the guinea pig

Guinea pigs were treated with daily single subcutaneous injections of 60 mg gentamicin per kg for 3 weeks. Renal, cochlear and vestibular functions were monitored before, during and after treatment. The degree and onset of gentamicin oto- and nephrotoxocity differed during the treatment period. Alterations to the kidney functions were observed from the first week while the onset of ototoxicity occurred later, at the third and fourth week for the cochlear and vestibular functions respectively. Moreover, when treatment ended, renal function demonstrated signs of recovery, while auditory and vestibular function continued to worsen. Deficits in cochlear function and structural changes (missing outer hair cells) correlated with gentamicin serum concentrations, while vestibular alterations (loss in nystagmic reactions) did not. No distinct relationship could be established between auditory and vestibular loss and the renal parameters monitored. The results suggest that gentamicin-induced nephro- and oto-toxicity are dissociated phenomena and that cochleotoxicity was dependent on aminoglycoside serum level.     

Frequency-dependence of early auditory evoked responses in the guinea pig

Summary Neural auditory responses in the guinea pig, monitored by surface electrodes (brain stem potentials and frequency-following responses) and by electrodes at the round window, were analyzed for evidence of frequency dependence in the range from 500 Hz to 15 kHz. The characteristics of the brain stem potentials and frequency-following responses with stimuli near threshold intensity for frequencies below 2 kHz indicate that this activity derives from the excitation of apical regions of the basilar membrane. The same interpretation applies to the potentials recorded at the round window. Comparison of the responses seen with surface electrodes and those appearing at the round window reveals that the broad potential P_I of the brain stem response to low-frequency stimuli corresponds to the compound action potential, while the frequency-following responses correspond to phase-locked responses in the acoustic nerve.