Treatment of age-related hearing loss in dogs with the vibrant soundbridge middle ear implant: short-term results in 3 dogs.

BACKGROUND: Age-related hearing loss (ARHL), or presbycusis, is the most common form of acquired hearing loss in dogs. Middle ear implants have been used successfully in people with ARHL who cannot benefit from conventional hearing aids. HYPOTHESIS: Audibility improves in dogs with ARHL after implantation of the Vibrant Soundbridge (VSB) middle ear implant. ANIMALS: Three Beagle dogs with ARHL, mean age 11.1 years. METHODS: The dogs were assessed pre- and postoperatively by brainstem-evoked response audiometry (BERA), otoscopy, and computed tomography scans of the ears. A VSB middle ear implant was implanted unilaterally. Three months later the functionality of the implants was assessed by auditory steady-state responses (ASSRs), after which the dogs were euthanized for histopathological examination. RESULTS: The VSB was implanted successfully in all dogs. Recovery from surgery was uneventful, except for transient facial nerve paralysis in 2 dogs. ASSRs showed that hearing improved after activation of the implants with a mean of 20.7, 13, and 16.3 dB at 1, 2, and 4 kHz, respectively. The implantation procedure did not affect residual hearing (with inactive implants) as measured by BERA. CONCLUSIONS AND CLINICAL IMPORTANCE: Implantation of the VSB resulted in lower ASSR thresholds, but only at the higher gain settings of the audioprocessor. As in humans, a more powerful audioprocessor is required to treat sensorineural hearing loss exceeding 20 dB in dogs. A substantial improvement in patient-owner communication will have to be demonstrated in future studies before the procedure can be recommended in clinical practice.

Effects of aging on inner ear morphology in dogs in relation to brainstem responses to toneburst auditory stimuli.

BACKGROUND: Age-related hearing loss (ARHL) is the most common form of hearing loss in humans and is increasingly recognized in dogs. HYPOTHESIS: Cochlear lesions in dogs with ARHL are similar to those in humans and the severity of the histological changes is reflected in tone audiograms. ANIMALS: Ten geriatric dogs (mean age: 12.7 years) and three 9-month-old dogs serving as controls for histological analysis. METHODS: Observational study. Auditory thresholds were determined by recording brainstem responses (BERA) to toneburst auditory stimuli (1, 2, 4, 8, 12, 16, 24, and 32 kHz). After euthanasia and perfusion fixation, the temporal bones were harvested and processed for histological examination of the cochleas. The numbers of outer hair cells (OHCs) and inner hair cells (IHCs) were counted and the spiral ganglion cell (SGC) packing density and stria vascularis cross-sectional area (SVCA) were determined. RESULTS: A combination of cochlear lesions was found in all geriatric dogs. There were significant reductions (P .001) in OHC (42%, 95% confidence interval [CI]; 24-64%) and IHC counts (21%, 95% CI; 62-90%) and SGC packing densities (323, 95% CI; 216-290) in the basal turn, SVCA was smaller in all turns. The greatest reduction in auditory sensitivity was at 8-32 kHz. CONCLUSIONS AND CLINICAL IMPORTANCE: ARHL in this specific population of geriatric dogs was comparable histologically to the mixed type of ARHL in humans. The predominance of histological changes in the basal cochlear turn was consistent with the large threshold shifts observed in the middle- to high-frequency region.

Effects of aging on brainstem responses to toneburst auditory stimuli: a cross-sectional and longitudinal study in dogs.

BACKGROUND: It is assumed that the hearing of dogs becomes impaired with advancing age, but little is known about the prevalence and electrophysiologic characteristics of presbycusis in this species. HYPOTHESIS: As in humans, hearing in dogs becomes impaired with aging across the entire frequency range, but primarily in the high-frequency area. This change can be assessed quantitatively by brainstem-evoked response audiometry (BERA). ANIMALS: Three groups of 10 mixed-breed dogs with similar body weights but different mean ages were used. At the start of the study, the mean age was 1.9 years (range, 0.9-3.4) in group I, 5.7 years (3.5-7) in group II, and 12.7 years (11-14) in group III. METHODS: In a cross-sectional study, the BERA audiograms obtained with toneburst stimuli were compared among the 3 groups. In a longitudinal study, changes in auditory thresholds of group II dogs were followed for 7 years. RESULTS: Thresholds were significantly higher in group III than in groups I and II at all frequencies tested, and higher in group II than in group I at 4 kHz. The audiograms in group II indicated a progressive increase in thresholds associated with aging starting around 8-10 years of age and most pronounced in the middle- to high-frequency region (8-32 kHz). CONCLUSIONS AND CLINICAL IMPORTANCE: Age-related hearing loss in these dogs started around 8-10 years of age and encompassed the entire frequency range, but started and progressed most rapidly in the middle- to high-frequency area. Its progression can be followed by BERA with frequency-specific stimulation.

Reduced expression of sialoglycoconjugates in the outer hair cell glycocalyx after systemic aminoglycoside administration.

In this study we investigated the effect of systemic aminoglycoside administration on the expression of sialoglycoconjugates in the outer hair cell (OHC) glycocalyx of the adult guinea pig. Sialoglycoconjugates were visualized by means of ultrastructural lectin cytochemistry, using Limax flavus agglutinin (LFA) and wheat germ agglutinin (WGA) as probes. Labelling densities were determined for the apical membranes (including the stereocilia and stereociliary cross-links) and basolateral membranes of OHCs in the respective (basal, middle and apical) cochlear turns from animals that had been treated with gentamicin or neomycin for 5 or 15 consecutive days. Our results indicate that: (1) sialoglycoconjugate expression in the OHC glycocalyx demonstrates an intracochlear gradient decreasing towards the apical turn; (2) OHCs demonstrate a polarity in sialoglycoconjugate expression, in that the basolateral membranes contain more sialoglycoconjugates per surface area than the apical membranes; (3) aminoglycoside administration results in reduced expression of sialoglycoconjugates in the OHC glycocalyx; in this respect, basal-turn OHCs are more susceptible than those in the middle and apical turns; (4) reduction in sialoglycoconjugate expression after aminoglycoside administration is more prominent in the basolateral membranes; and (5) the difference in ototoxic potencies between gentamicin and neomycin is not reflected at the level of sialoglycoconjugate expression. The present data support our earlier hypothesis that aminoglycosides, already at an early phase of intoxication, interfere with the function of the endoplasmic reticulum and/or the Golgi apparatus, implying that these organelles play a crucial role in the initial phase of aminoglycoside-induced OHC degeneration.

Ethyl benzene-induced ototoxicity in rats: a dose-dependent mid-frequency hearing loss.

Rats were exposed to ethyl benzene at 0, 300, 400 and 550 ppm for 8 hours/day for 5 consecutive days. Three to six weeks after the exposure, auditory function was tested by measuring compound action potentials (CAP) in the frequency range of 1-24 kHz and 2f1-f2 distortion product otoacoustic emissions (DPOAEs) in the frequency range of 4-22.6 kHz. In addition, outer hair cell (OHC) loss was quantified by histological examination. The lowest concentration ethyl benzene had no effect on any of the above measures. At 400 ppm, auditory thresholds were increased by 15 and 16 dB at 12 and 16 kHz, respectively, and at 550 ppm by 24, 31, and 22 dB at 8, 12, and 16 kHz, respectively. DPOAE amplitude growth with stimulus level was affected only after 550 ppm at 5.6, 8, and 11.3 kHz. OHC loss was found in two of the five examined locations in the cochlea. At 400 ppm, 25% OHC loss was found at the 11- and 21-kHz region. The highest concentration evoked 40% and 75% OHC loss at the 11- and 21-kHz location, respectively. Thus, the mid-frequency region of rats is affected after exposure to relatively low concentrations of ethyl benzene (400-550 ppm). These results indicate that ethyl benzene is one of the most potent ototoxic organic solvents known today.

Protection and spontaneous recovery from cisplatin-induced hearing loss.

Cisplatin [cis-diamminechloroplatinum(II)] has proved itself as a potent antineoplastic agent. However, nephrotoxicity, neurotoxicity, gastrointestinal toxicity, myelosuppression, and ototoxicity interfere with its therapeutical efficacy. Forced diuresis reduces nephrotoxicity, effectively leaving neurotoxicity and ototoxicity as the major side effects of concern, and gastrointestinal toxicity and myelosuppression as the secondary side effects. So far, attempts to reduce these side effects by developing equally potent platinum analogs have been unsuccessful. Some success has been achieved, however, by co-treatment with protective agents. Nearly all these agents are sulfur- or sulfhydryl-containing compounds (thio compounds), known as antioxidants and potent heavy metal chelators. These thio compounds may provide protection from cisplatin toxicity either (1) by direct interaction between the cisplatin and the thio moiety, (2) by displacing platinum from its site of toxic action, (3) by preventing platinum from interfering with superoxide dismutase, or (4) by scavenging of cisplatin-induced free radicals. In particular the first two protective mechanisms bear the risk of reducing the antineoplastic activity of cisplatin. Since nephrotoxicity can be controlled effectively by forced diuresis, a more specific approach of coping with ototoxicity by focusing on protection at the sensorineural level was chosen. Being familiar with the neuro-protective and neurotrophic properties of ACTH-related neuropeptides, specifically against cisplatin-induced peripheral neuropathies, it was judged expedient to test for a possible otoprotective action of these neuropeptides. The results were positive, although tainted with high interanimal variability. When testing for the possibility that the neuropeptides would merely delay cisplatin-induced ototoxicity rather than reduce it, it was discovered in control series without neuropeptide co-treatment that the ear can recover spontaneously from cisplatin-induced hearing loss. This was found both electrophysiologically and in outer hair cell (OHC) counts. Although these preliminary findings require further investigation, they strongly suggest that spontaneous recovery of cochlear injury can occur in the mature mammalian cochlea. Moreover, the otoprotective action of the ACTH-related neuropeptides suggests that it may be possible to stimulate recovery from acute hearing loss using neuropeptides.

Reversible cisplatin ototoxicity in the albino guinea pig.

Guinea pigs implanted with round window electrodes received daily doses (2.0 mg/kg) of cisplatin until a profound hearing loss occurred (> 40 dB at 8 kHz). Afterwards, pronounced recovery occurred. Recovery progressed over intervals up to 3 weeks before it saturated. Loss and recovery involved both the compound action potential and, less pronounced, the cochlear microphonics. Cochlear potentials evoked by lower frequencies recovered more fully than those evoked by higher frequencies. Loss and recovery was found also in the endocochlear potential. Outer hair cell counts did not change over the recovery period. These findings confirm our previously reported results on the reversibility of cisplatin damage. Further, they implicate the vascular stria as an important target for cisplatin in the cochlea.

Effects of temporary thershold shift on combination-tone generation and on two-tone suppression.

Two-tone suppression and combination tone generation (2f1 - f2) are two phenomena that can be described by a single cochlear nonlinearity. Both phenomena are affected by a permanent threshold shift, which supports the idea of a common origin. In the present experiment the effect of a temporary threshold shift (TTS) on both phenomena is investigated. A clear effect of TTS on combination tone level and phase was found, but no effect on two-tone suppression. Limited data and small TTS require caution when the results are interpreted. Tentatively, the results contradict the common-origin concept. The (reversible) effect of TTS on the combination tone demonstrates that the combination tone is not simply due to nonlinear basilar membrane mechanics, but that a sensorineural process is involved.

Cochlear potentials and their modulation by low-frequency sound in early endolymphatic hydrops.

Seventeen guinea pigs were unilaterally operated to produce endolymphatic hydrops. After 2 wk (9 animals) or 4 wk (8 animals), extracochlear electrophysiological responses to tone bursts of several frequencies were recorded in both the operated and non-operated ears. In addition, modulation by low-frequency (29 Hz sinusoidal bias) sound of the responses to 8 kHz tonebursts was measured. After the electrophysiological measurements, the animals were killed and examined histologically. Four weeks after the operation, cochlear microphonics in response to a 500 Hz tone burst and to the 29 Hz bias were significantly smaller in the operated ears. The summating potential showed a tendency to be larger in the operated ears. The compound action potential input-output curves for 2 kHz probes showed a small threshold shift accompanied by steep slopes, reminiscent of recruitment. Modulation of summating potentials by the low-frequency bias was smaller on the operated side. In most cochleae an endolymphatic hydrops was observed. Three cochleae showed a collapse of Reissner's membrane.

Modulation at the guinea pig round window of summating potentials and compound action potentials by low-frequency sound.

Low-frequency sound was used to modulate responses to short single-frequency tone bursts at the guinea pig round window. Summating potentials (SP) increase (reach higher positive values) during the negative half-cycle of the low-frequency cochlear microphonic (LFCM) and decrease during the positive half-cycle of the LFCM. The compound action potential (AP) amplitude decreases during the negative half-cycle of the LFCM. The negative half-cycle of the LFCM can be identified with scala tympani displacement. SP modulation depth is defined as the difference between the highest and the lowest SP value found for tone burst stimulation at different phases of the low-frequency sound while the sound levels of the tone burst and the low-frequency bias are kept constant. When normalized with respect to the SP amplitude found without bias, the SP modulation depth is independent of the sound level of the tone burst in the range from 48 to 68 dB SPL. The normalized AP suppression tends to increase with decreasing tone burst sound level. A dynamic nonlinear mechanism which might explain these results is discussed. This mechanism is based on voltage-sensitive changes.

Osmotically induced pressure difference in the cochlea and its effect on cochlear potentials.

The electrophysiological effects observed during scala tympani displacements in low-frequency biasing experiments, an increase of the summating potential (SP) together with a decrease of the compound action potential (CAP), correlate well with the effects found in guinea pigs with evoked endolymphatic hydrops. This contributes to the hypothesis that displacement of the basilar membrane underlies the changes found in endolymphatic hydrops. A major difference between both experimental situations is that in low-frequency biasing the basilar membrane is continuously moving, whereas in hydrops the hypothesized displacement would be static. To evaluate the importance of this difference, experiments were performed which attempted to evoke a static displacement of the basilar membrane by perfusing the perilymphatic spaces with perfusates of various osmolalities. Perfusion with hypotonic perfusate (183 mOsm/kg) increased the SP and decreased the CAP (4 kHz stimulation) whereas perfusion with a hypertonic perfusate (397 mOsm/kg) decreased both these potentials. The cochlear microphonics were hardly affected. These data demonstrate that both experimental situations (biasing, i.e. dynamic displacement and osmotic pressure, i.e. static displacement) cause similar changes in the SP and the CAP and the data support the hypothesis that basilar membrane displacement towards scala tympani is an important contributing factor to the electrophysiologic changes in endolymphatic hydrops.

Eighth-nerve action potentials evoked by tone bursts in cats before and after inducement of an acute noise trauma.

Properties of eighth-nerve action potentials (AP) evoked by single-frequency tone-bursts (test tone) were studied in cats. Curves representing AP threshold as a function of test-tone frequency have a shape similar to behavioral and single-fiber threshold curves. The absolute level of AP thresholds is higher than that of behavioral and single-fiber thresholds. Cats were exposed to broad-band noise (equal intensities per octave) halfway into the experiments. This exposure resulted in a long-term temporary threshold shift (TTS) which remained fairly steady during the measurements. APs were measured before and during an acute noise trauma in the same animal. After inducement of the trauma the greatest threshold shift is found between 2 and 6 kHz. Curves representing AP amplitude as a function of stimulus SPL are displaced to higher stimulus SPLs. Sometimes the slope of the curve is steeper after the noise exposure than before. AP latency at threshold did not change due to the excessive noise exposure. AP-latency values compared at equal sound pressure levels before and after inducement of the trauma showed higher values during the trauma than before.

Eighth-nerve action-potential tuning curves in cats before and after inducement of an acute noise trauma.

Potentials and limitations of eighth-nerve action-potential tuning curves (APTC) in providing us with a measure of frequency selectivity are studied in cats. APTCs are measured, using a forward-masking technique. They are essentially wider than auditory-nerve fiber tuning curves. Width of APTCs is dependent upon test-tone sound pressure level (SPL) and masking criterion. This can be explained by assuming that APs are formed by discharges of fiber with different CFs. Acoustic traumata are induced halfway into the experiments in order to measure APTCs before and during the trauma in the same animal. This broad-band noise exposure resulted in a long-lasting temporary threshold shift which remained fairly steady during the experiment. In the traumatized ear APTCs are wider than in the normal ear. This widening, also observed in auditory-nerve fibers, is not simply an SPL effect.

Masking of short probe sounds by tone bursts with a sweeping frequency.

The masked threshold of short (less than or equal to 40 ms) probe tone or a short one-third octave probe noise appears to increase if the frequency of a tonal masker is swept. Frequency sweeps were exponential (octave/s) and unidirectional. Probe sounds were presented in the time center of the masker at the center frequency of the masker. The sweep speed, S, appeared to be an important parameter; masker duration was much less important. For 10-ms tonal probes, in-phase with the masker in their common time center, 100-ms maskers, and upward sweeps, increase of the masked threshold appeared to be maximal at a sweep speed of 30 oct/s and the masked threshold was 21 dB higher than the masked threshold found for the stationary masker (S = 0 oct/s). Above 30 oct/s the masked threshold decreased. For downward sweeps masking was maximal at S = 20 oct/s and the threshold was 15 dB higher. Sweeping upward the increase in masking was 12 dB for both noise probes and tonal probes with phase differing by 90 degrees from the masker in their common time center. The results are inconsistent with current models of masking: sweeping the frequency the masked threshold increases whereas the energy within the critical band at the probe frequency decreases.

Responses from AVCN units in the cat before and after inducement of an acute noise trauma.

Acoustically evoked responses of single units in the anteroventral part of the cochlear nucleus (AVCN) in the cat were studied together with compound eighth-nerve action potentials (AP). Halfway through the experiments the cats were exposed for half an hour to pink noise at 105 dB SPL, producing an average threshold shift of 30 dB (maximum 50 dB) in the 2-6 kHz region. The effect of noise exposure was studied in two ways. On the one hand we compared the results for one population of units measured before the noise exposure with those found for another population measured afterwards. On the other hand we compared the results before and after the noise exposure for one unit that could be kept under observation during the noise exposure. After the noise exposure spontaneous activity and phase-locking of the responses of the units to the stimulus waveform were not significantly different from the pre-exposure findings. Response latency tended to increase. Therefore, the decrease of latency found for APs must be due to a shift to higher frequencies of the population of units contributing to the AP. The sharply tuned tip segments of tuning curves shift to higher levels whereas the low-frequency tails remain at about the same level. Q10 decreases by at most 50%, which was also found for AP tuning curves. Response spectra for clicks and noise (reverse correlation function) did not show a significant decrease of frequency selectivity. Units with CF less than 3 kHz may show a shift of CF to a lower frequency by 10-20%. After inducement of the noise trauma the sharply tuned tip segment of a tuning curve may not be found and CF may be assigned to a local minimum in the low-frequency tail of the tuning curve.

4-Aminopyridine effects on summating potentials in the guinea pig.

DC receptor potentials measured in hair cells, and the associated extracellular DC potential known as the summating potential (SP), originate with nonlinear elements in the mechanoelectric transduction chain. Nonlinear electric conductance has been demonstrated in the basolateral membrane of the hair cell, and is commonly attributed to the presence of voltage- and time-dependent K+ conductances in this part of the hair cell membrane. To study a possible contribution of these K+ channels to the SP we perfused the perilymphatic spaces of the guinea pig cochlea with the K+ channel blocker 4-aminopyridine (4-AP). Since 4-AP might also affect the afferent fibers and, thus, interfere with SP measurement, we added tetrodotoxin (TTX) to the perfusion solutions to block the neuronal discharges. Sound-evoked (2-12 kHz) intracochlear potentials were recorded from the basal turn of both scala vestibuli and scala tympani. The results showed a frequency- and level-dependent effect of 4-AP on the magnitude of the SP. At low and moderate levels of 8 and 12 kHz stimuli 4-AP mostly reduced the SP amplitude, while at high levels of these stimuli and at all levels of 2 and 4 kHz stimuli 4-AP enlarged the SP amplitude. These effects were reversible and occurred in both scala vestibuli and scala tympani. We attribute these bi-directional effects on the SP amplitude to a differential effect of 4-AP on inner hair cell (IHC) and outer hair cell (OHC) physiology. The decrease in SP was found for stimulus conditions where the SP presumably depends mainly on contributions from basal turn IHCs. Blocking the 4-AP-sensitive K+ channel in the IHC membrane should lead to a reduced contribution from the IHCs to the SP, because of an increase in basolateral membrane resistance. The increase in SP was found for stimulus conditions where the SP is assumed to depend mainly on contributions from basal turn OHCs. In this case the OHCs seemed to respond to blocking of the 4-AP-sensitive K+ channel in the basolateral membrane with an increased contribution to the nonlinearity of the transduction chain. Administration of 4-AP did not affect the endocochlear potential. Light microscopic examination revealed no apparent changes in morphology after 4-AP perfusion.

Tetraethylammonium effects on cochlear potentials in the guinea pig.

Voltage-dependent K+ channels in the basolateral membrane of hair cells in guinea-pig cochlea might contribute to the non-linear current-voltage relationships in these hair cells and, thereby, to generation of the extracellular summating potential (SP). To evaluate the role of K+ channels in the generation of the SP the perilymphatic perfusion technique was used to introduce the K(+)-channel blocker tetraethylammonium (TEA) into the cochlea. Sound-evoked cochlear potentials were measured subsequently. Without blocking nerve activity TEA induced reversible shifts of the SP in the negative direction, irrespective of whether we recorded from scala vestibuli or scala tympani. Shifts in the negative direction were probably due to TEA acting directly on the afferent fibres, since removal of nerve activity by the potent Na(+)-channel blocker tetrodotoxin (TTX) prevented TEA from shifting the SP in the negative direction. Once nerve activity had been removed by TTX, administration of TEA caused a small decrease in the magnitude of the SP, both in scala vestibuli and in scala tympani, irrespective of its polarity. The decrease was significant for the highest test frequencies only (8-12 kHz), and completely reversible. The rapidly activated K+ channel in the inner hair cell (IHC) is probably blocked by TEA and this blocking might be responsible for the small decrease in magnitude of the SP. The asymmetric contribution from this K+ channel to the IHC's current-voltage relationship seems to be only partly responsible for the generation of the SP, since blocking of this K+ channel with TEA caused relatively small decreases in the amplitude of the SP. TEA did not affect the endocochlear potential.

Identification of the nonlinearity governing even-order distortion products in cochlear potentials.

In order to characterize the cochlear transducer nonlinearities which are involved in the generation of the summating potential (SP), we investigated the effect of a change in the electrical operating point of the cochlear transducer on the SP. The electrical operating point of the cochlear transducer was affected by suppressing reversibly the endocochlear potential (EP). This was realized by intravenous injection of furosemide in guinea pig. A differential recording technique was used in the basal turn of the cochlea to measure locally generated even-order distortion products: the SP and the second harmonic component (2F0) of the cochlear microphonics (CM). These potentials were evoked by 2 and 8 kHz stimuli presented at 60 dB SPL. Following furosemide injection, the SP changed polarity twice over time. The zero crossings of the SP coincided with a minimum in the amplitude of 2F0. Concomitantly, the phase of 2F0 shifted about 120 degrees. The changes in the electrical even-order products were comparable to the changes that occurred in a mechanical even-order intermodulation distortion product (the difference tone F2-F1 otoacoustic emission) after furosemide application (Mills et al., J. Acoust. Soc. Am. 94 (1993) 2108-2122). The combined results suggest that only one sigmoidal transfer function may account for the SP, 2F0, and the emission of the difference tone F2-F1, and that shifts in the operating point of the transfer function would be the major cause behind the furosemide-induced changes in the even-order distortion products. The sigmoidal transfer function is likely associated with the mechano-electrical transducer channel at the apical pole of the outer hair cell.

The generation of DC potentials in a computational model of the organ of Corti: effects of voltage-dependent K+ channels in the basolateral membrane of the inner hair cell.

A computational model of the organ of Corti is described to assist in the interpretation of electrophysiological data concerning the role of the K+ channels residing in the basolateral membrane of cochlear hair cells. Recent in vivo data from Van Emst et al. (Hear. Res. 88, 27-35 (1995); Hear. Res. 102, 70-80 (1996)) about the effects of selective blocking of K+ channels indicate that these channels affect the magnitude of the summating potential. In order to understand the nature of this effect, the model of Dallos (Hear. Res. 14, 281-291 (1984)) was extended to account for the voltage- and time-dependent properties of the K+ channels in the basolateral membrane of the inner hair cell (IHC) (Kros and Crawford, J. Physiol. 421, 262-291 (1990)). The model shows that the K+ channels induce a shift in the mean IHC basolateral conductance when high-frequency stimuli are present. As a result, cochlear transduction shifts to a different electrical operating state and this is the source of a marked decrease in the stimulus-evoked DC response of the IHC. Extracellularly, in contrast, the magnitude of the DC response increases slightly. At low frequencies, the K+ channels respond to the stimulus waveform on a cycle-by-cycle basis. The waveform distortion associated with this dynamic basolateral impedance induces a further decrease in the intracellular stimulus-evoked DC response of the IHC. Thus, K+ channels in the IHC appear to be directly involved in the generation of the DC receptor potential at low frequencies, but at high frequencies they simply modify the size of the DC response.

Adaptation in the compound action potential response of the guinea pig VIIIth nerve to electric stimulation.

An experimental study, carried out in guinea pigs, was designed to investigate whether forward masking measured psychophysically in 3M-House cochlear implant users might have a correlate in VIIIth nerve activity. The study was based on electrically evoked VIIIth nerve compound action potentials (ECAPs), using a masking paradigm comparable to the one used in the psychophysical study. Trains of 50 maskers with inter-masker-intervals of 509 ms appeared to induce a long-term fatigue effect that could influence the recovery from adaptation measurements. Fatigue stabilized within about 1 to 3 min when masker trains were repeated with intervening silent intervals of 10.5 s. The change in amplitude of probe-evoked ECAPs with increasing masker-probe delays was determined within the steady fatigue state. The recovery-from-adaptation functions obtained from these measurements resembled the forward masking functions found in 3M-House cochlear implant users. No correlate of psychophysical backward masking was found at the VIIIth nerve level. To examine whether hair cells were involved in fatigue and recovery from adaptation, the measurements described above were carried out in intact cochleas and in cochleas without hair cells. Results were essentially the same in the different preparations. The results suggest that processes at the level of the VIIIth nerve could, at least partly, account for forward masking found in 3M-House cochlear implant users. Backward masking must be attributed to mechanisms located centrally to the VIIIth nerve.