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Effect of the middle ear reflex on sound transmission to the inner ear of rat.

The effect of the acoustic middle ear reflex (MER) was quantified using electrodes chronically implanted in the middle ears of rats. Cochlear microphonics (CM) and middle ear muscle EMG were measured under light Ketamin anesthesia after stimulation with tone pulses of 5-20 kHz ranging between 75 and 120 dB SPL. With increasing intensity, the CM measured before the onset of the MER increased to a maximum amplitude and then decreased with higher SPLs. At 10 kHz this maximum was reached at 95 dB SPL, for other stimulus frequencies at higher SPLs. After a latency of 10-20 ms, CM to 10 kHz stimuli of 80-95 dB SPL were decreased by the attenuating action of the MER. The lowest threshold of the MER was also measured at 10 kHz (77 dB SPL in the mean). To stimuli greater than 100 dB SPL after a latency of 6-10 ms, the CM amplitude was increased. That this CM increase to intense stimuli is caused by the action of the MER was confirmed by control experiments such as cutting the tendons of the middle ear muscles. The CM decrease to stimuli below 100 dB SPL, as well as the increase to very intense stimuli, can be explained by sound attenuation caused by the MER, together with the nonlinear dependence of CM amplitude on stimulus level. The observed shift of the maxima of the CM input-output function by the MER to higher stimulus levels probably indicates an increase of the dynamic range of the ear.

Acoustic Stimulation↗

Effects of selective inner hair cell loss on auditory nerve fiber threshold, tuning and spontaneous and driven discharge rate.

Current theories assume that the outer hair cells (OHC) are responsible for the sharp tuning and exquisite sensitivity of the ear whereas inner hair cells (IHC) are mainly responsible for transmitting acoustic information to the central nervous system. To further evaluate this model, we used a single (38 mg/kg) or double dose (38 mg/kg, 2 times) of carboplatin to produce a moderate (20-28%) or severe (60-95%) IHC loss while sparing a large proportion of the OHCs. The surviving OHCs were functionally intact as indicated by normal cochlear microphonic (CM) potentials and distortion product otoacoustic emissions (DPOAE). Single-unit responses were recorded from auditory nerve fibers to determine the effects of the moderate or severe IHC loss on the output of the surviving IHCs. Most neurons that responded to sound in the single-dose group had normal or near-normal thresholds and normal tuning. Relatively few neurons in the double-dose group responded to sound because of the severe IHC loss. The neurons that did respond to sound had narrow tuning curves. Some neurons in the double-dose group also had thresholds that were within the normal range, but most had thresholds that were elevated a mild-to-moderate degree. These results indicate that intact IHCs can retain relatively normal sensitivity and tuning despite massive IHC loss in surrounding regions of the cochlea. However, the spontaneous and driven discharge rates of neurons in the carboplatin-treated animals were significantly lower than normal. These changes could conceivably be due to sublethal damage to surviving IHCs or to postsynaptic dysfunction in the auditory nerve.

Action Potentials↗

The influence of the cochlear efferent system on chronic acoustic trauma.

The role of the olivocochlear bundle (OCB) in modulating noise-induced permanent injury to the auditory periphery was studied by completely sectioning the OCB fibers in chinchillas and exposing the animals while awake to a broad-band noise at 105 dB SPL for 6 h. Outer hair cell (OHC) function was assessed by measuring 2f1-f2 distortion product otoacoustic emissions (DPOAE) at frequencies from 1.2 to 9.6 kHz and cochlear microphonics (CM) at frequencies from 1 to 8 kHz. As a result of de-efferentation, the CM was decreased but the DPOAEs were unchanged in de-efferented ears as compared with efferented control and sham-operated ears. Following noise exposure, the ears that were de-efferented showed significantly more depression of DPOAE input/output functions and greater decrement of CM amplitude. The differences between de-efferented and efferent-innervated ears were evident across all the frequencies. The cochlear lesions of the OHCs reflected by traditional cytocochleograms, however, were minimal in both efferented and de-efferented ears. The results indicate that cochlear de-efferentation decreases the CM in chinchilla and increases the ear's susceptibility to noise-induced permanent hearing damage. More importantly, de-efferentation increases susceptibility at low frequencies as well as high frequencies.

Animals↗

Characteristics of DPOAE audiogram in tinnitus patients.

To investigate cochlear activity in tinnitus, the DPOAE (distortion product otoacoustic emission) audiograms (DP-gram) of tinnitus patients were measured. Nine tinnitus patients (15 ears) with normal hearing and 55 tinnitus patients (75 ears) with hearing impairment were included in this study. Significant decreases in DPOAE amplitude over a limited frequency range were observed in 93.3% of the normal hearing tinnitus group and in 96% of the hearing-impaired tinnitus group. The averaged DP-gram of the normal hearing tinnitus group was significantly different from that of the normal subject (repeated-measures ANOVA, P < 0.01). These results imply that tinnitus may be evaluated objectively by DPOAE.

Adult↗

Cochlear mechanisms of frequency and intensity coding. I. The place code for pitch.

In the past, several researchers have reported a substantial shift in the peak of the tone-evoked excitation pattern toward the base of the cochlea following an increase in the SPL of the stimulating tone. Evidence for such peak shifts has been found in the responses of auditory nerve fibers, cochlear microphonics, and the responses of outer hair cells and supporting cells in the cochlea, as well as in basilar membrane vibration measurements, and indirectly, in psychophysical data. However, direct evidence for such a peak shift in inner hair cell (IHC) responses has been relatively sparse. If the peak shift is preserved in the information conveyed to the auditory nerve fibers by the IHCs, the classical 'place theory' for frequency coding in the cochlea requires modification. In this study, the nature and extent of the SPL-dependent peak shift is examined with the help of recordings in the IHCs and other cells of the organ of Corti in the 0.5-2.5 kHz region of the Mongolian gerbil cochlea. It is demonstrated that the peak shift is a universal phenomenon in the diverse cell types in this region of the cochlea. Most importantly, a large SPL-dependent peak shift is demonstrated in IHC responses. On the other hand, the recordings indicate that the apical cutoff of the spatial excitation pattern is SPL-independent. We conclude, therefore, that the place theory of pitch perception must be abandoned or at least modified.

Acoustic Stimulation↗

Medial olivocochlear system stabilizes active cochlear micromechanical properties in humans.

To investigate the involvement of the medial olivocochlear system (MOCS) in outer hair cell (OHC) motility stabilization, evoked otoacoustic emissions (EOAEs) were recorded in 20 normal-hearing subjects and in eight vestibular-neurotomized subjects, successively in the presence and absence of low-intensity contralateral acoustic stimulation. Intrasubject EOAE amplitude variability was assessed as the standard deviation computed over several successive recordings. In normal-hearing subjects, a significantly lower EOAE amplitude variability with contralateral acoustic stimulation (CAS) was observed in subjects in whom the CAS induced the greatest EOAE amplitude reduction. This result could not be attributed to the EOAE amplitude reduction itself, since variability was otherwise found to increase when EOAE amplitude decreased. Moreover, statistically significant correlations between EOAE amplitude attenuation and EOAE amplitude variability under CAS were observed. In the eight subjects operated for vestibular neurotomy, no such effect was found. Being sectioned in vestibular-neurotomized subjects, the MOCS can no longer exert its effects. These results strongly support the notion that MOCS activity, as induced by CAS, elicits a reduction in EOAE amplitude variability in normal-hearing subjects. This finding and some of its possible implications for understanding the role of the MOCS in hearing in humans are discussed.

Acoustic Stimulation↗

A model of cochlear micromechanics.

A cochlear model is presented which has two degrees of freedom, the motion of the basilar membrane and that of the tectorial membrane (TM), in every cross section of the organ of Corti. It assumes that the reticular lamina is virtually rigid, so that the apical portion of the outer hair cells is firmly anchored to it, and also that the TM is directly driven by the BM through the marginal net of the TM, which anchor to the phalanges of the outermost row of Deiters' cells or Hensen's cells, or both. It is shown that the model can produce more than 40 dB of cochlear gain in the frequency-domain simulation and 30 dB in time-domain simulation. Transiently evoked otoacoustic emissions and cochlear microphonics are simulated in the time domain.

Acoustic Stimulation↗

Acoustical modulation of electrically evoked otoacoustic emission in intact gerbil cochlea.

In order to study the interaction between mechanical-electrical and electrical-mechanical transductions of outer hair cells (OHCs) in vivo, we observed the acoustically induced changes in the electrically evoked otoacoustic emission (EEOAE). One pole of a bipolar electrode was placed in the round window niche and the other pole on the surface of the first cochlear turn in the gerbil. A microphone and a speaker were used to monitor the EEOAE and to deliver an acoustical tone, respectively. It was found that a high sound level acoustical tone enhanced the EEOAE fine structure at frequencies below the acoustical frequency, and suppressed the overall level of the EEOAE at frequencies above the acoustical frequency. In addition, the EEOAE at frequencies approximately one half octave lower than the acoustical frequencies were relatively more enhanced or showed relatively less suppression than at other frequencies. The amplitudes of these changes had a positive relationship with acoustical tone levels. Furosemide eliminated the acoustically caused EEOAE change indicating that the acoustically caused change in the EEOAE is a phenomenon of the normal cochlea. One possible mechanism for the results is that the electrically and acoustically evoked basilar membrane (BM) vibrations interact at the EEOAE generation site and change the local mechanical and electrical properties. The second possible mechanism is that the acoustical stimulus creates an impedance discontinuity at its characteristic frequency location leading to a change in the reflected electrically evoked traveling wave, which may enhance or suppress the EEOAE by the vector summation of two waves.

Acoustic Stimulation↗

Effects of stimulus duration on responses of neurons in the chinchilla inferior colliculus.

The effects of the stimulus duration (10 to 300 ms) on the responses of chinchilla inferior colliculus neurons to pure tones were studied in 41 units. The responses of the majority of the neurons (90%) were classified as sustained, onset, pause with onset peak and pause without onset peak response patterns. Three neurons were found to have response to the stimulus offset (offset response pattern). One neuron responded to the sound with the decrease of the spontaneous discharge rate (inhibitory response pattern). The responses restricted within the stimulus duration could be simply predicted from the peristimulus time histogram (PSTH) to the longer duration. The leading part of the PSTH to the longer stimulus duration resembled that to the shorter stimulus duration. The function of the spike number versus duration was correlated with the PSTH patterns. The response following the stimulus offset (including inhibitory response) could vary with the stimulus duration nonmonotonically and show a band-pass or band-reject property. Overall, four (about 10%) of the neurons could be regarded as duration-tuned units. The duration selectivity could be understood by the interaction between the ongoing and the offset process of the neurons.

Acoustic Stimulation↗

Automatic monitoring of mechano-electrical transduction in the guinea pig cochlea.

We have estimated the transfer curve relating instantaneous sound pressure in the ear canal to instantaneous receptor current through the outer hair cells (OHCs) in the basal turn of the guinea pig cochlea using the cochlear microphonic (CM) elicited by continuous 200 Hz tones. The transfer curve is well approximated by a Boltzmann activation curve which has been automatically analysed using a custom-built electronic circuit which continuously derives the three parameters defining the curve with a time resolution of seconds. This technique offers a convenient method of monitoring changes in OHC mechano-electrical transduction due to cochlear disturbances, and allows the investigation of cochlear homeostasis over the course of hours. We present here details of the technique, evidence that the recordings are minimally contaminated by neural responses, and normative data on the changes in the parameters with sound level. As the level of the 200 Hz tone increases, the equivalent operating point on the transfer curve migrates in a way consistent with a movement of the organ of Corti towards scala tympani or a contraction of the outer hair cells. Surprisingly, the effective slope of the curve which represents the mechanical sensitivity of the transduction process decreases over an 8 to 1 range as the level of the 200 Hz tone is increased. The effect of this variation is that the amplitude of the equivalent mechanical displacement input to the mechano-electrical transduction process appears to increase by a mere 2 to 1 while the sound level increases by a factor of 20 to 1. These changes are not neurally mediated, since they also occur in the presence of tetrodotoxin and the blocker of afferent neurotransmission, kainate.

Acoustic Stimulation↗

A four-state kinetic model of the temporary threshold shift after loud sound based on inactivation of hair cell transduction channels.

A model of the temporary threshold shift (TTS) following loud sound is presented based on inactivation of the mechano-electrical transduction (MET) channels at the apex of the outer hair cells (OHCs). This inactivation is assumed to reduce temporarily the OHC receptor current with a consequent drop in the mechanical sensitivity of the organ of Corti. With acoustic over-stimulation some of the hair cells' MET channels are assumed to adopt one of three closed and non-transducing conformations or 'TTS states'. The sound-induced inactivation is assumed to occur because the sound makes the TTS states more energetically favourable when compared with the transducing states, and the distribution between these states is assumed to depend on the relative energies of the states and the time allowed for migration between them. By lumping the fast transducing states (one open and two closed) into a single transducing 'pseudo-state', the kinetics of the inactivation and re-activation processes (corresponding to the onset and recovery of TTS) can be described by a four-state kinetic model. The model allows an elegant description of the onset and recovery of TTS time-course in a human subject under a variety of continuous exposure conditions, and some features of intermittent exposure as well. The model also suggests that recovery of TTS may be accelerated by an intermittent tone during the recovery period which may explain some variability TTS in the literature. Other implications of the model are also discussed.

Acoustic Stimulation↗

Boltzmann analysis of CM waveforms using virtual instrument software.

We describe a modification to our technique for the rapid analysis of low-frequency cochlear microphonic (CM) waveforms in the basal turn of the guinea pig cochlea (Patuzzi and Moleirinho, 1998). The transfer curve relating instantaneous sound pressure in the ear canal to instantaneous receptor current through the outer hair cells (OHCs) is determined from the distorted microphonic waveform generated in the extracellular fluid near the hair cells, assuming a first-order Boltzmann activation curve. Previously, the analysis was done in real time using custom-built electronic circuitry. Here, the same task is performed numerically using virtual instrument software (National Instruments LabVIEW 4.1) running on a personal computer. The assumed theoretical function describing the CM waveform is Vcm = Voff + Vsat/[1 + exp[(Eo+Z.Po.sin(2pi f + phi(tot)))/kT]], where the six parameters are (i) a DC offset voltage (Voff); (ii) the frequency of the sinusoidal stimulus (f); (iii) the phase of the sinusoidal stimulus (phi(tot)); (iv) the maximal amplitude of the distorted microphonic signal (Vsat); (v) the sensitivity of the transduction process (Z); and (vi) the operating point on the sigmoidal transfer curve (Eo). The software obtains the least-squares fit to the CM waveforms by continuously deriving the six parameters at a speed of about one determination per second. The independent fitting of the frequency and phase allows the data to be analysed off-line from data previously recorded to tape (i.e. the frequency and phase of the microphonic response need not be known accurately beforehand). We present here an outline of the software we have used, and give an example of the changes which can be monitored using the technique (transient asphyxia). The method's advantages and limitations have been discussed in our previous paper. The virtual instrument described here is available from the authors on request.

Animals↗

Evidence for multiple DPOAE components based upon group delay of the 2f(1)-f(2) distortion in the gerbil.

The cochlear delay of the 2f(1)-f(2) distortion product otoacoustic emission (DPOAE) was measured using the phase gradient method. With a constant f(2) and swept f(1), the resulting phase change of 2f(1)-f(2) was used to calculate the group delay for f(2) frequencies from 1 to 60 kHz. For f(2) frequencies between 2 and 60 kHz, the group delays were between 2.2 and 0.11 ms and continuously decreased for increasing f(2) and for increasing primary stimulus levels. For f(2) frequencies below 2 kHz, the group delay decreased to around 1 ms and was largely independent of stimulus level. The ratio curves resulting from the f(1) sweeps for high frequencies (f(2)16 kHz) displayed the typical mammalian shape with a peak in the level of 2f(1)-f(2) for a larger primary frequency separation (f(2)/f(1)1.15) and decreasing 2f(1)-f(2) level for smaller primary separation. In addition to this typical level maximum, for f(2) frequencies from about 1.8 to 16 kHz, the ratio curves displayed a second component in the form of an increase in the level of 2f(1)-f(2) for small primary separation at higher primary levels (level of f(2)30 dB SPL). For f(2) frequencies below 1.8 kHz, only the second component and no typical ratio peak as for higher f(2) could be observed and the associated group delay was always close to 0.8 ms. Several possible causes for this behavior are discussed, including different modes of DPOAE generation and modulation as well as changes in the nature of mechanical processing from base to apex in the gerbil cochlea. To evaluate the relative sensitivity of non-linear cochlear mechanics, an iso-distortion threshold curve was constructed from acoustical growth functions of the 2f(1)-f(2) DPOAE at optimum primary separation, by plotting the level of f(2) sufficient to evoke a distortion of -10 dB SPL as a function of f(2)2.5 kHz but failed to reflect the sensitivity for lower frequencies. This may be a consequence of more linear frequency processing in the apex.

Acoustic Stimulation↗

Activation of medial olivocochlear efferent system in humans: influence of stimulus bandwidth.

The activity of the medial olivocochlear bundle (MOCB) can be studied in humans through variations in the level of evoked otoacoustic emissions (EOAEs) elicited by contralateral acoustic stimuli (CAS). The present study sought to investigate how the activity of the MOC system at a given frequency, as measured through the contralateral suppression of tone-pip EOAEs, depends on the bandwidth of the contralateral stimulus. EOAEs were recorded in 155 normal-hearing subjects, successively with and without contralateral stimuli whose bandwidth, center frequency and level were systematically varied. We showed a clear dependence of contralateral EOAE suppression on bandwidth demonstrating increased suppression with increased bandwidth over about two octaves around the center frequency of the noise. This effect was obtained irrespective of whether contralateral noise energy was kept constant independently of bandwidth or not, which indicates a role of bandwidth per se in contralateral EOAE suppression. Results are interpreted in terms of a simple model of MOCB activation mechanisms including peripheral bandpass filtering, within-channel compression and across-channel spatial summation by the afferent paths. Complementary experiments suggested a greater effectiveness of increases in bandwidth on the upper than on the lower side and of frequency components akin to or remote from the test frequency than of intermediate bands. Finally, these results were complemented by detailed spectrum analyses of the EOAE level variations induced by the different noises, which revealed that whilst noise components close to or remote from the center frequency generally attenuated EOAE level, intermediate components could in some cases lead to a relative increase in EOAE level. These results can further be explained by assuming different positive and negative weights on the inputs to the spatial summation process depending on their position relative to the center frequency.

Acoustic Impedance Tests↗

Cochlear microphonics and otoacoustic emissions in chronically de-efferented chinchilla.

The effects of eliminating the olivocochlear bundle (OCB) on cochlear electromechanical properties were examined by measuring cochlear microphonics (CM) and distortion product otoacoustic emissions (DPOAEs) in chronically de-efferented chinchillas. The OCB fibers to the right ears were successfully sectioned in six out of 15 adult chinchillas via a posterior paraflocular fossa approach. At the end of the experiment, these ears were histologically verified as being deprived of both lateral and medial OCB fibers. The opposite (left) ears from the animals served as controls. Following de-efferentation, changes of the inter-modulation distortion components (2f(1)-f(2), f(2)-f(1), 3f(1)-2f(2), 3f(2)-2f(1)) varied, depending on the frequencies and levels of the stimuli. DPOAE amplitudes to low-level stimuli were within the 95% confidence intervals around mean DPOAE amplitudes of the control ears at all the frequencies (1-8 kHz). At high stimulus levels, DPOAE amplitudes increased by 5-20 dB at 1 and 2 kHz while remaining in the normal range at 4 and 8 kHz. In contrast, the CM input/output functions to stimuli from 1 to 8 kHz were significantly reduced by approximately 40-50% at all input levels. The results suggest that the OCB may play a role in modulating electrical properties of the outer hair cells and in reducing the magnitude of cochlear distortion to high-level stimuli.

Acetylcholinesterase↗

Experimental labyrinthine disorders and direction of nystagmus.

The purpose of this paper is to demonstrate the variation of the direction of nystagmus which is elicited from the peripheral labyrinth. The direction of nystagmus depends, among other things, on the nature of the stimulus. Depending on the degree of pathophysiological conditions in the labyrinth, atypical nystagmus which does not comply with the rule is occasionally elicited even though the same stimulus is given. Hyperfunctional stimulation to the labyrinth, such as allergy, causes nystagmus which beats to the affected side and also shows hyperactivity of the whole nerve action potential and cochlear microphonics.

Animals↗

Interaction of polyanion against kanamycin ototoxicity.

We studied whether interference of the electron bindings between kanamycin (KM) and the outer plasma membranes of the hair cells with polyanion such as heparin can reduce ototoxicity. In a short course experiment, KM 200 mg/kg/day was injected intramuscularly 23 times with or without 1 U or 0.5 U of heparin/g/day differently to 22 guinea pigs. The reducing effect of heparin against KM ototoxicity was significant from a comparison of the N1 threshold obtained by the cochleogram. The number of surviving outer hair cells in the heparin groups was significantly greater in the third turn than in the group given KM alone. A long course experiment in which 50 injections of KM with or without 0.5 U of heparin were given intramuscularly to 16 guinea pigs revealed from the pinna reflex, cochlear microphonics and cell counting that heparin could reduce ototoxicity slightly at an early stage or before reaching crucial accumulation.

Animals↗

A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback.

alpha-tectorin is an extracellular matrix molecule of the inner ear. Mice homozygous for a targeted deletion in a-tectorin have tectorial membranes that are detached from the cochlear epithelium and lack all noncollagenous matrix, but the architecture of the organ of Corti is otherwise normal. The basilar membranes of wild-type and alpha-tectorin mutant mice are tuned, but the alpha-tectorin mutants are 35 dB less sensitive. Basilar membrane responses of wild-type mice exhibit a second resonance, indicating that the tectorial membrane provides an inertial mass against which outer hair cells can exert forces. Cochlear microphonics recorded in alpha-tectorin mutants differ in both phase and symmetry relative to those of wild-type mice. Thus, the tectorial membrane ensures that outer hair cells can effectively respond to basilar membrane motion and that feedback is delivered with the appropriate gain and timing required for amplification.

Acoustic Stimulation↗