Phase-Locked Responses to Tones of Chinchilla Auditory Nerve Fibers: Implications for Apical Cochlear Mechanics

Responses to tones with frequency ≤ 5 kHz were recorded from auditory nerve fibers (ANFs) of anesthetized chinchillas. With increasing stimulus level, discharge rate–frequency functions shift toward higher and lower frequencies, respectively, for ANFs with characteristic frequencies (CFs) lower and higher than ∼0.9 kHz. With increasing frequency separation from CF, rate–level functions are less steep and/or saturate at lower rates than at CF, indicating a CF-specific nonlinearity. The strength of phase locking has lower high-frequency cutoffs for CFs >4 kHz than for CFs < 3 kHz. Phase–frequency functions of ANFs with CFs lower and higher than ∼0.9 kHz have inflections, respectively, at frequencies higher and lower than CF. For CFs >2 kHz, the inflections coincide with the tip-tail transitions of threshold tuning curves. ANF responses to CF tones exhibit cumulative phase lags of 1.5 periods for CFs 0.7–3 kHz and lesser amounts for lower CFs. With increases of stimulus level, responses increasingly lag (lead) lower-level responses at frequencies lower (higher) than CF, so that group delays are maximal at, or slightly above, CF. The CF-specific magnitude and phase nonlinearities of ANFs with CFs < 2.5 kHz span their entire response bandwidths. Several properties of ANFs undergo sharp transitions in the cochlear region with CFs 2–5 kHz. Overall, the responses of chinchilla ANFs resemble those in other mammalian species but contrast with available measurements of apical cochlear vibrations in chinchilla, implying that either the latter are flawed or that a nonlinear “second filter” is interposed between vibrations and ANF excitation.     

Basilar Membrane Responses to Noise at a Basal Site of the Chinchilla Cochlea: Quasi-Linear Filtering

Basilar membrane responses to clicks and to white noise were recorded using laser velocimetry at basal sites of the chinchilla cochlea with characteristic frequencies near 10 kHz. Responses to noise grew at compressive rates and their instantaneous frequencies decreased with increasing stimulus level. First-order Wiener kernels were computed by cross-correlation of the noise stimuli and the responses. For linear systems, first-order Wiener kernels are identical to unit impulse responses. In the case of basilar membrane responses, first-order Wiener kernels and responses to clicks measured at the same sites were similar but not identical. Both consisted of transient oscillations with onset frequencies which increased rapidly, over about 0.5 ms, from 4–5 kHz to the characteristic frequency. Both first-order Wiener kernels and responses to clicks were more highly damped, exhibited slower frequency modulation, and grew at compressive rates with increasing stimulus levels. Responses to clicks had longer durations than the Wiener kernels. The statistical distribution of basilar membrane responses to Gaussian white noise is also Gaussian and the envelopes of the responses are Rayleigh distributed, as they should be for Gaussian noise passing through a linear band-pass filter. Accordingly, basilar membrane responses were accurately predicted by linear filters specified by the first-order Wiener kernels of responses to noise presented at the same level. Overall, the results indicate that cochlear nonlinearity is not instantaneous and resembles automatic gain control.     

Response Characteristics in the Apex of the Gerbil Cochlea Studied Through Auditory Nerve Recordings

In this study, we analyze the processing of low-frequency sounds in the cochlear apex through responses of auditory nerve fibers (ANFs) that innervate the apex. Single tones and irregularly spaced tone complexes were used to evoke ANF responses in Mongolian gerbil. The spike arrival times were analyzed in terms of phase locking, peripheral frequency selectivity, group delays, and the nonlinear effects of sound pressure level (SPL). Phase locking to single tones was similar to that in cat. Vector strength was maximal for stimulus frequencies around 500 Hz, decreased above 1 kHz, and became insignificant above 4 to 5 kHz. We used the responses to tone complexes to determine amplitude and phase curves of ANFs having a characteristic frequency (CF) below 5 kHz. With increasing CF, amplitude curves gradually changed from broadly tuned and asymmetric with a steep low-frequency flank to more sharply tuned and asymmetric with a steep high-frequency flank. Over the same CF range, phase curves gradually changed from a concave-upward shape to a concave-downward shape. Phase curves consisted of two or three approximately straight segments. Group delay was analyzed separately for these segments. Generally, the largest group delay was observed near CF. With increasing SPL, most amplitude curves broadened, sometimes accompanied by a downward shift of best frequency, and group delay changed along the entire range of stimulus frequencies. We observed considerable across-ANF variation in the effects of SPL on both amplitude and phase. Overall, our data suggest that mechanical responses in the apex of the cochlea are considerably nonlinear and that these nonlinearities are of a different character than those known from the base of the cochlea.     

Timing of neural excitation in relation to basilar membrane motion in the basal region of the guinea pig cochlea during the presentation of low-frequency acoustic stimulation

In spite of many studies concerning auditory nerve action potentials, the timing of neural excitation in relation to basilar membrane (BM) motion is still not well understood. In this study, therefore, BM vibrations in the basal region of the guinea pig cochlea were measured using a laser Doppler velocimeter, and action potentials in auditory nerve fibers were recorded by a conventional microelectrode technique. An attempt was then made to determine the relationship between BM motion and neural excitation in auditory nerve fibers. To obtain BM responses in the high-characteristic frequency (CF) region (18-22 kHz) and responses of auditory nerve fibers with high CFs (14-22 kHz), low-frequency stimuli (50-2000 Hz), frequencies of which were well below CFs, were presented at 60-100 dB SPL. The results indicated that neural excitation occurred when the BM was displaced toward the scala vestibuli. Moreover, the neural excitatory phase did not significantly vary with the fiber's CF between 14 and 22 kHz nor with the stimulus level between 60 and 100 dB SPL.     

Alterations of basilar membrane response phase and velocity after acoustic overstimulation

To investigate the physiology of noise-induced hearing loss, the sound-induced vibrations of the basilar membrane (BM) of the inner ear were measured in living anesthetized guinea pigs before and after intense sound exposure. The vibrations were measured using a laser Doppler velocimeter after placing reflective glass beads on the BM. Pseudo-random noise waveforms containing frequencies between 4 and 24 kHz were used to generate velocity tuning curves. Before overstimulation, sharp response peaks were seen at stimulus frequencies between 15 and 17 kHz, consistent with the expected best frequency of the recording location. The response to low level stimuli lagged the high level ones by up to 90 degrees at the characteristic frequency. Following exposure to loud sound, the BM vibrations showed a pronounced reduction in amplitude, primarily at low stimulus levels, and the best frequency moved to approximately 12 kHz. At higher levels, the reduction was either absent or much smaller. In addition to the amplitude changes, increased phase lags were seen at frequencies near the characteristic frequency. In animals with more severe exposures, response phases were altered also at frequencies showing no change of the amplitude. The phase was independent of stimulus level after severe exposures.     

Stapes Vibration in the Chinchilla Middle Ear: Relation to Behavioral and Auditory-Nerve Thresholds

The vibratory responses to tones of the stapes and incus were measured in the middle ears of deeply anesthetized chinchillas using a wide-band acoustic-stimulus system and a laser velocimeter coupled to a microscope. With the laser beam at an angle of about 40 ° relative to the axis of stapes piston-like motion, the sensitivity-vs.-frequency curves of vibrations at the head of the stapes and the incus lenticular process were very similar to each other but larger, in the range 15–30 kHz, than the vibrations of the incus just peripheral to the pedicle. With the laser beam aligned with the axis of piston-like stapes motion, vibrations of the incus just peripheral to its pedicle were very similar to the vibrations of the lenticular process or the stapes head measured at the 40 ° angle. Thus, the pedicle prevents transmission to the stapes of components of incus vibration not aligned with the axis of stapes piston-like motion. The mean magnitude curve of stapes velocities is fairly flat over a wide frequency range, with a mean value of about 0.19 mm^.(s Pa⁻¹), has a high-frequency cutoff of 25 kHz (measured at −3 dB re the mean value), and decreases with a slope of about −60 dB/octave at higher frequencies. According to our measurements, the chinchilla middle ear transmits acoustic signals into the cochlea at frequencies exceeding both the bandwidth of responses of auditory-nerve fibers and the upper cutoff of hearing. The phase lags of stapes velocity relative to ear-canal pressure increase approximately linearly, with slopes equivalent to pure delays of about 57–76 μs.     

Variation in the Phase of Response to Low-Frequency Pure Tones in the Guinea Pig Auditory Nerve as Functions of Stimulus Level and Frequency

The directionality of hair cell stimulation combined with the vibration of the basilar membrane causes the auditory nerve fiber action potentials, in response to low-frequency stimuli, to occur at a particular phase of the stimulus waveform. Because direct mechanical measurements at the cochlear apex are difficult, such phase locking has often been used to indirectly infer the basilar membrane motion. Here, we confirm and extend earlier data from mammals using sine wave stimulation over a wide range of sound levels (up to 90 dB sound pressure level). We recorded phase-locked responses to pure tones over a wide range of frequencies and sound levels of a large population of auditory nerve fibers in the anesthetized guinea pig. The results indicate that, for a constant frequency of stimulation, the phase lag decreases with increases in the characteristic frequency (CF) of the nerve fiber. The phase lag decreases up to a CF above the stimulation frequency, beyond which it decreases at a much slower rate. Such phase changes are consistent with known basal cochlear mechanics. Measurements from individual fibers showed smaller but systematic variations in phase with sound level, confirming previous reports. We found a “null” stimulation frequency at which little variation in phase occurred with sound level. This null frequency was often not at the CF. At stimulation frequencies below the null, there was a progressive lag with sound level and a progressive lead for stimulation frequencies above the null. This was maximally 0.2 cycles.     

Speech recognition in noise: estimating effects of compressive nonlinearities in the basilar-membrane response

OBJECTIVES: This experiment was designed to estimate effects of cochlear nonlinearities on tonal and speech masking for individuals with normal hearing who have a range of quiet thresholds. Physiological and psychophysical evidence indicates that for signals close to the characteristic frequency (CF) of a place on the basilar membrane, the normal growth of response of the basilar membrane is linear at lower stimulus levels and compressed at medium to higher stimulus levels. In contrast, at moderate to high CFs, the basilar membrane responds more linearly to stimuli at frequencies well below the CF regardless of input level. Thus, the hypothesis tested was that masker effectiveness would change as a function of stimulus level consistent with the underlying basilar membrane response. Specifically, with a fixed-level speech signal and a speech-shaped masker that ranges from low to higher levels, the resulting response of the basilar membrane to the masker would be linear at lower levels and compressed at medium to higher levels. This would result in relatively less effective masking at higher masker levels. It was further hypothesized that the transition from linear to compressed responses to both tones and maskers would occur at higher levels for listeners with higher quiet thresholds than for listeners with lower quiet thresholds. DESIGN: Tonal thresholds and speech recognition in noise were measured as a function of masker level. A 10-msec, 2.0-kHz tone was presented in a lower frequency masker ranging from 40 to 85 dB SPL. Moderate-level speech was presented in interrupted noise at six levels ranging from 47 to 77 dB SPL. To minimize differences in speech audibility that could arise during the "off" periods of the interrupted noise, a low-level steady-state "threshold-matching noise" was also present during measurement of speech recognition. Subjects were 30 adults with normal hearing with a 20-dB range of average quiet thresholds. RESULTS: Tonal breakpoints (i.e., the levels corresponding to the transitions from linear to nonlinear responses) were significantly correlated with quiet thresholds, whereas slopes measured above the breakpoints were not. Speech recognition in noise was consistent with the hypothesis that the response of the basilar membrane to the masker was linear at lower levels and compressed at medium to higher levels, resulting in less effective masking at higher masker levels. That is, at lower masker levels, as masker level increased, mean observed speech scores declined as predicted using the articulation index, an audibility-based model. With further increases in masker level, mean scores declined less than predicted. Moreover, for subjects with higher quiet thresholds, masker effectiveness remained constant for a wider range of masker levels than for subjects with lower quiet thresholds, consistent with the hypothesis that the transition from linear to compressed responses occurred at higher levels. Finally, significant negative correlations were obtained between individual subjects' tonal and speech measures. CONCLUSIONS: Results from tonal and speech tasks were consistent with basilar membrane nonlinearities and consistent with changes in nonlinearities with minor threshold elevations, providing support for their role in the understanding of speech in noise with increases in noise level.     

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.     

Simultaneous Measurements of Ossicular Velocity and Intracochlear Pressure Leading to the Cochlear Input Impedance in Gerbil

Recent measurements of three-dimensional stapes motion in gerbil indicated that the piston component of stapes motion was the primary contributor to intracochlear pressure. In order to make a detailed correlation between stapes piston motion and intracochlear pressure behind the stapes, simultaneous pressure and motion measurements were undertaken. We found that the scala vestibuli pressure followed the piston component of the stapes velocity with high fidelity, reinforcing our previous finding that the piston motion of the stapes was the main stimulus to the cochlea. The present data allowed us to calculate cochlear input impedance and power flow into the cochlea. Both the amplitude and phase of the impedance were quite flat with frequency from 3 kHz to at least 30 kHz, with a phase that was primarily resistive. With constant stimulus pressure in the ear canal the intracochlear pressure at the stapes has been previously shown to be approximately flat with frequency through a wide range, and coupling that result with the present findings indicates that the power that flows into the cochlea is quite flat from about 3 to 30 kHz. The observed wide-band intracochlear pressure and power flow are consistent with the wide-band audiogram of the gerbil.     

High-frequency sensitivity of the mature gerbil cochlea and its development

The thresholds of compound action potentials evoked by tone pips were measured in the cochleae of anesthetized gerbils, both in adults and in neonates aged 14, 16, 18, 20 and 30 days, using round-window electrodes. Stapes vibrations were also measured, using a laser velocimeter, in many of the same ears of adults and neonates aged 14, 16, 18 and 20 days to assess cochlear sensitivity in isolation from middle ear effects and to circumvent problems associated with calibration of acoustic stimuli at high frequencies. Whether referenced to sound pressure level in the ear canal or stapes vibration velocity, thresholds in adults were roughly uniform in the entire range of tested frequencies, 1.25-38.5 kHz. In neonates, thresholds decreased systematically as a function of age, with the largest reductions occurring at the highest frequencies. Thresholds remained slightly immature at all frequencies 30 days after birth. The results for adult gerbils are consistent with the recent finding that basilar-membrane responses to characteristic frequency tones normalized to stapes vibrations are as sensitive at sites near the round window as at more apical sites. The results for neonates confirm that the extreme basal region of the cochlea is the last to approach maturity, with substantial development occurring between 20 and 30 days after birth.     

Reverse Transmission along the Ossicular Chain in Gerbil

In a healthy cochlea stimulated with two tones f (1) and f (2), combination tones are generated by the cochlea's active process and its associated nonlinearity. These distortion tones travel "in reverse" through the middle ear. They can be detected with a sensitive microphone in the ear canal (EC) and are known as distortion product otoacoustic emissions. Comparisons of ossicular velocity and EC pressure responses at distortion product frequencies allowed us to evaluate the middle ear transmission in the reverse direction along the ossicular chain. In the current study, the gerbil ear was stimulated with two equal-intensity tones with fixed f (2)/f (1) ratio of 1.05 or 1.25. The middle ear ossicles were accessed through an opening of the pars flaccida, and their motion was measured in the direction in line with the stapes piston-like motion using a laser interferometer. When referencing the ossicular motion to EC pressure, an additional amplitude loss was found in reverse transmission compared to the gain in forward transmission, similar to previous findings relating intracochlear and EC pressure. In contrast, sound transmission along the ossicular chain was quite similar in forward and reverse directions. The difference in middle ear transmission in forward and reverse directions is most likely due to the different load impedances-the cochlea in forward transmission and the EC in reverse transmission.     

Effects of a perilymphatic fistula on the passive vibration response of the basilar membrane

In this study, a three-dimensional finite-element model of the passive human cochlea was created. Dynamic behavior of the basilar membrane caused by the vibration of the stapes footplate was analyzed considering a fluid-structure interaction with the cochlear fluid. Next, the effects of a perilymphatic fistula (PLF) on the vibration of the cochlea were examined by making a small hole on the wall of the cochlea model. Even if a PLF existed in the scala vestibuli, a traveling wave was generated on the basilar membrane. When a PLF existed at the basal end of the cochlea, the shape of the traveling wave envelope showed no remarkable change, but the maximum amplitude became smaller at the entire frequency range from 0.5 to 5kHz and decreased with decreasing frequency. In contrast, when a PLF existed at the second turn of the cochlea, the traveling wave envelope showed a notch at the position of the PLF and the maximum amplitude also became smaller. This model assists in elucidating the mechanisms of hearing loss due to a PLF from the view of dynamics.     

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.     

A short history of hearing research. IV: Physiology]

In 1863, Hensen concluded from measurements of the width of the basilar membrane that tones of high and low pitch were represented at the base and apex of the cochlea, respectively. According to his calculations on the tonotopic representation of sound stimuli in the cochlea Helmholtz proposed additional resonators that would transmit the amplified signal to the afferent nerve endings. He speculated that the pillar cells of the tunnel of Corti or strands of the basilar membrane might be these proposed resonators. The resonance theory was contradicted by Wien in 1905. However, further experiments by Held and Kleinknecht in 1927 and by Békésy in 1928 demonstrated that Helmholtz's ideas on the tonotopic dispersion of the vibration of the basilar membrane were correct. Békésy measured the vibration of the cochlear partition in human and animal cadavers and discovered the travelling-wave of the basilar membrane. At the turn of the century Ter Kuile noted that the vibration of the cochlear partition caused a deflection of the sensory hairs of the hair cells, the auditory receptor cells. Wever and Bray described in 1930 stimulus-evoked electrical currents near the cochlea with a wave form similar to that of the original sound stimulus. It was Adrian who later coined the term "cochlear microphonics" for this phenomenon. According to calculations of Gold (1948) and others active mechanical amplification would be required for such a sharp tuning in the cochlea. The first to measure action potentials of the afferent auditory nerve was Tasaki (1954).(ABSTRACT TRUNCATED AT 250 WORDS)     

Action Potentials in the Cochlea: Masking,Adaptation and Recruitment

Action potentials were picked up from the round window of guinea pigs. By averaging the cochlear responses to tone bursts, the sine wave polarity of which was reversed in half of the presentations, the CM was cancelled out. During steady tones of various frequencies and various intensities, the AP thresholds for short tone bursts of different frequencies were determined. In some experiments the short tone burst was presented shortly after a long tone burst: forward masking.

The masking curves of the steady pure tones are compared with the psycho-acoustic masking curves as given in the literature. Another curve is the frequency response curve of a certain location of the cochlea measured by de Boer with the method of reverse correlation. The frequency response curve gives the ability of the cochlea to initiate nerve impulses for various frequencies. The shapes of all these curves are similar and they point to a rather high frequency-selectivity in the cochlea. Tuning curves of single nerve fibers have the steepest slopes compared with the other curves.

The masking curves measured during forward masking have the same shape but the thresholds are less elevated for the same intensity of the masking tone.

Above threshold AP responses were measured with the method of forward masking. They are reduced when compared with the responses in the no-masking situation. The reduction has the highest value when the frequency of the test stimulus is near the frequency of the masking tone. At a constant level of the masking tone the reduction diminishes with increasing level of the test stimulus showing a kind of recruitment phenomenon. This is valid for all frequencies of the test stimulus and at high levels of the test stimulus the reduction has almost disappeared.     

On Cochlear Impedances and the Miscomputation of Power Gain

In their article, “Measurement of cochlear power gain in the sensitive gerbil ear,” Ren et al. (Nat Commun 2:216, 2011) claim to provide “the first direct experimental evidence of power amplification in the sensitive living cochlea.” While we recognize the technical challenges of the experiments and appreciate the beauty of the data, the authors’ analysis and interpretation of the measurements are invalid. We review the concept of impedance (i.e., the ratio of pressure to velocity) as it applies to cochlear mechanics and show that Ren et al. mistakenly equate the impedances near the basilar membrane and stapes with the impedance characteristic of an infinite, uniform tube of fluid. As a consequence of this error, Ren et al.’s measurements and analysis provide no evidence for power amplification in the cochlea. Compelling evidence for power amplification has, however, been previously provided by others.     

The vascular anatomy of the gerbil cochlea

The vascular pattern of the cochlea was studied in 12 adult gerbils (Meriones unguiculatus) using the Berlin blue (Prussian blue) contrast injection technique. The capillary areas of the gerbil cochlea are similar to those of other mammals studied. As in some other mammals, the vessel of the basilar membrane was inconsistently identified in the basal turn. It was usually replaced by a larger uninjected channel, supporting the suggestion that the vessel of the basilar membrane may be more functionally important in fetal life than in adulthood. The vascular pattern of the external cochlear wall is well maintained from base to apex, although a simplification of vasculature can be observed apically.     

Experimental look at cochlear mechanics.

The mechanisms by which the organ of Corti is stimulated by acoustic stimuli are discussed on the basis of experimental observations. This discussion refers to the resonance theory as well as to the traveling wave (TW) theory. The measurement of the basilar membrane displacements, of the cochlear microphonic (CM) responses to pure tones and impulses, and the recording of the intracochlear acoustic pressure seem to indicate that, at least in the basal part of the cochlea and for frequencies up to the characteristic frequency of a given location, the cochlear responses do not exhibit large phase lags and long delays which characterize the one-dimensional long-wave models (in which a TW transports the energy along the cochlear partition). These experimental observations suggest that the cochlear partition is excited simultaneously as a whole, more or less like a bank of resonators, as proposed a long time ago by Helmholtz.     

Predicting the effect of post-implant cochlear fibrosis on residual hearing

Intracochlear scarring is a well-described sequela of cochlear implantation. We developed a mathematical model of passive cochlear mechanics to predict the impact that this might have upon residual acoustical hearing after implantation. The cochlea was modeled using lumped impedance terms for scala vestibuli (SV), scala tympani (ST), and the cochlear partition (CP). The damping of ST and CP was increased in the basal one half of the cochlea to simulate the effect of scar tissue. We found that increasing the damping of the ST predominantly reduced basilar membrane vibrations in the apex of the cochlea while increasing the damping of the CP predominantly reduced basilar membrane vibrations in the base of the cochlea. As long as intracochlear scarring continues to occur with cochlear implantation, there will be limitations on hearing preservation. Newer surgical techniques and electrode technologies that do not result in as much scar tissue formation will permit improved hearing preservation.