Mammalian middle ear mechanics: A review.

The middle ear is part of the ear in all terrestrial vertebrates. It provides an interface between two media, air and fluid. How does it work? In mammals, the middle ear is traditionally described as increasing gain due to Helmholtz's hydraulic analogy and the lever action of the malleus-incus complex: in effect, an impedance transformer. The conical shape of the eardrum and a frequency-dependent synovial joint function for the ossicles suggest a greater complexity of function than the traditional view. Here we review acoustico-mechanical measurements of middle ear function and the development of middle ear models based on these measurements. We observe that an impedance-matching mechanism (reducing reflection) rather than an impedance transformer (providing gain) best explains experimental findings. We conclude by considering some outstanding questions about middle ear function, recognizing that we are still learning how the middle ear works.

Are suspensory ligaments important for middle ear reconstruction?

As the resolution of 3D printing techniques improves, the possibility of individualized, 3-ossicle constructions adds a new dimension to middle ear prostheses. In order to optimize these designs, it is essential to understand how the ossicles and ligaments work together to transmit sound, and thus how ligaments should be replicated in a middle ear reconstruction. The middle ear ligaments are thought to play a significant role in maintaining the position of the ossicles and constraining axis of rotation. Paradoxically, investigations of the role of ligaments to date have shown very little impact on middle ear sound transmission. We explored the role of the two attachments in the gerbil middle ear analogous to human ligaments, the posterior incudal ligament and the anterior mallear process, severing both attachments and measuring change in hearing sensitivity. The impact of severing the attachments on the position of the ossicular chain was visualized using synchrotron microtomography imaging of the middle ear. In contrast to previous studies, a threshold change on the order of 20 dB across a wide range of frequencies was found when both ligaments were severed. Concomitantly, a shift in position of the ossicles was observed from the x-ray imaging and 3D renderings of the ossicular chain. These findings contrast with previous studies, demonstrating that these ligaments play a significant role in the transmission of sound through the middle ear. It appears that both mallear and incudal ligaments must be severed in order to impair sound transmission. The results of this study have significance for middle ear reconstructive surgery and the design of 3D-printed three-ossicle biocompatible prostheses.

Examining the Factors that Contribute to Non-Monotonic Growth of the [Formula: see text] Otoacoustic Emission in Humans.

Cubic distortion product otoacoustic emission input-output functions in humans show a complex pattern of growth. To further investigate the growth of the [Formula: see text] otoacoustic emission, magnitude and phase input-output functions were obtained from human subjects using a range of stimulus levels, frequencies, and frequency ratios. Three factors related to cochlear nonlinearity may produce non-monotonic input-output functions: a two-component interaction, an operating point shift, and two-tone suppression. To complement data interpretation, a local model of distortion product otoacoustic emission generation was fit to the magnitude spectrum of the averaged ear canal sound pressure recording to quantify operating point shift. Results obtained are consistent with non-monotonic growth occurring primarily as a result of two-tone suppression and/or a two-component interaction. These two mechanisms are expected to operate at different stimulus levels, with different signature magnitude and phase patterns, and are unlikely to overlap in producing non-monotonic growth. An operating point shift was suggested in three cases. These results support multiple factors contributing to the complexity of growth of the [Formula: see text] otoacoustic emission in humans and highlight the importance of looking at phase in addition to magnitude when interpreting distortion product otoacoustic emission growth.

The endocochlear potential as an indicator of reticular lamina integrity after noise exposure in mice.

The endocochlear potential (EP) provides part of the electrochemical drive for sound-driven currents through cochlear hair cells. Intense noise exposure (110 dB SPL, 2 h) differentially affects the EP in three inbred mouse strains (C57BL/6 [B6], CBA/J [CBA], BALB/cJ [BALB]) (Ohlemiller and Gagnon, 2007, Hearing Research 224:34-50; Ohlemiller et al., 2011, JARO 12:45-58). At least for mice older than 3 mos, B6 mice are unaffected, CBA mice show temporary EP reduction, and BALB mice may show temporary or permanent EP reduction. EP reduction was well correlated with histological metrics for injury to stria vascularis and spiral ligament, and little evidence was found for holes or tears in the reticular lamina that might 'short out' the EP. Thus we suggested that the genes and processes that underlie the strain EP differences primarily impact cochlear lateral wall, not the organ of Corti. Our previous work did not test the range of noise exposure conditions over which strain differences apply. It therefore remained possible that the relation between exposure severity and acute EP reduction simply has a higher exposure threshold in B6 mice compared to CBA and BALB. We also did not test for age dependence. It is well established that young adult animals are especially vulnerable to noise-induced permanent threshold shifts (NIPTS). It is unknown, however, whether heightened vulnerability of the lateral wall contributes to this condition. The present study extends our previous work to multiple noise exposure levels and durations, and explicitly compares young adult (6-7 wks) and older mice (>4 mos). We find that the exposure level-versus-acute EP relation is dramatically strain-dependent, such that B6 mice widely diverge from both CBA and BALB. For all three strains, however, acute EP reduction is greater in young mice. Above 110 dB SPL, all mice exhibited rapid and severe EP reduction that is likely related to tearing of the reticular lamina. By contrast, EP-versus-noise duration examined at 104 dB suggested that different processes contribute to EP reduction in young and older mice. The average EP falls to a constant level after ∼7.5 min in older mice, but progressively decreases with further exposure in young mice. Confocal microscopy of organ of Corti surface preparations stained for phalloidin and zonula occludens-1 (ZO-1) indicated this corresponds to rapid loss of outer hair cells (OHCs) and formation of both holes and tears in the reticular lamina of young mice. In addition, when animals exposed at 119 dB were allowed to recover for 1 mo, only young B6 mice showed collapse of the EP to ≤5 mV. Confocal analysis suggested novel persistent loss of tight junctions in the lateral organ of Corti. This may allow paracellular leakage that permanently reduces the EP. From our other findings, we propose that noise-related lateral wall pathology in young CBA and BALB mice promotes hair cell loss and opening of the reticular lamina. The heightened vulnerability of young adult animals to noise exposure may in part reflect special sensitivity of the organ of Corti to acute lateral wall dysfunction at younger ages. This feature appears genetically modifiable.

A DPOAE assessment of outer hair cell integrity in ears with age-related hearing loss.

Distortion product otoacoustic emissions (DPOAEs) were used to assess outer hair cell (OHC) integrity in human ears with age-related hearing loss. Sound pressure measurements were made in the ear canal over the stimulus range 40-90 dB SPL (L2), with L1 = 0.45*L2 + 44 with F2 = 2 and 3 or 4 kHz. Model-generated DPOAE I/O functions were fit to DPOAE data to quantify the contribution of loss of nonlinearity (OHC loss) to the hearing loss. Results suggest OHC loss as a contributing cause of age-related hearing, regardless of audiogram configuration. It seems likely that OHC and strial pathology co-exist in ears with AHL.

The clinical utility of expressing hearing thresholds in terms of the forward-going sound pressure wave.

OBJECTIVE: To assess the clinical utility of quantifying pure-tone hearing thresholds in terms of the forward-going sound pressure wave. DESIGN: Sound pressure measurements in the ear canal were used to derive, with hearing threshold measurements, hearing thresholds expressed in terms of the forward-going sound pressure wave, hearing thresholds based on coupler-based calibration, and hearing thresholds expressed in terms of the sound pressure measured at the microphone. STUDY SAMPLE: Fifty-two adults, 18 to 34 years of age, served as the study group. RESULTS: Audiogram configurations were similar up to 2000 Hz for the three expressions of hearing threshold, consistent with the ear canal acting as a simple volume up to this frequency. Above 2000 Hz, notable differences in hearing threshold were found, consistent with the acoustic input impedance of the ear differing from a rigid, hard-walled cavity. Repeat testing showed all three expressions of hearing threshold to be repeatable. High density measurements of hearing threshold from 3000 to 6000 Hz provided qualified support for the derivation of the forward-going sound pressure wave. CONCLUSIONS: Hearing thresholds expressed in terms of the forward-going sound pressure wave are repeatable, and with in-situ calibration, may be superior to the current coupler-based method.

An analysis of the acoustic input impedance of the ear.

Ear canal acoustics was examined using a one-dimensional lossy transmission line with a distributed load impedance to model the ear. The acoustic input impedance of the ear was derived from sound pressure measurements in the ear canal of healthy human ears. A nonlinear least squares fit of the model to data generated estimates for ear canal radius, ear canal length, and quantified the resistance that would produce transmission losses. Derivation of ear canal radius has application to quantifying the impedance mismatch at the eardrum between the ear canal and the middle ear. The length of the ear canal was found, in general, to be longer than the length derived from the one-quarter wavelength standing wave frequency, consistent with the middle ear being mass-controlled at the standing wave frequency. Viscothermal losses in the ear canal, in some cases, may exceed that attributable to a smooth rigid wall. Resistance in the middle ear was found to contribute significantly to the total resistance. In effect, this analysis "reverse engineers" physical parameters of the ear from sound pressure measurements in the ear canal.

An in situ calibration for hearing thresholds.

Quantifying how the sound delivered to the ear canal relates to hearing threshold has historically relied on acoustic calibration in physical assemblies with an input impedance intended to match the human ear (e.g., a Zwislocki coupler). The variation in the input impedance of the human ear makes such a method of calibration questionable. It is preferable to calibrate the acoustic signal in each ear individually. By using a calibrated sound source and microphone, the acoustic input impedance of the ear can be determined, and the sound delivered to the ear calibrated in terms of either (i) the incident sound pressure wave or (ii) that portion of the incident sound pressure wave transmitted to the middle ear and cochlea. Hearing thresholds expressed in terms of these quantities are reported, these in situ calibrations not being confounded by ear canal standing waves. Either would serve as a suitable replacement for the current practice of hearing thresholds expressed in terms of sound pressure level calibrated in a 6cc or 2cc coupler.

Reconciling the origin of the transient evoked ototacoustic emission in humans.

A pervasive theme in the literature for the transient evoked otoacoustic emission (TEOAE) measured from the human ear canal has been one of the emission arising solely (or largely) from a single, place-fixed mechanism. Here TEOAEs are reported measured in the absence of significant stimulus contamination at stimulus onset, providing for the identification of a TEOAE response beginning within the time window that is typically removed by windowing. Contrary to previous studies, it was found that in humans, as has previously been found in guinea pig, the TEOAE appears to arise from two generation mechanisms, the relative contributions of these two mechanisms being time and stimulus-level dependent. The method of windowing the earliest part of the ear canal measurement to remove stimulus artifact removes part of the TEOAE i.e., much of the component arising from a nonlinear generation mechanism. This reconciliation of TEOAE origin is consistent with all OAEs in mammals arising in a stimulus-level dependent manner from two mechanisms of generation, one linear, one nonlinear, as suggested by Shera and Guinan [J. Acoust. Soc. Am. 105, 782-798 (1999)].

In search of basal distortion product generators.

The 2f1-f2 distortion product otoacoustic emission (DPOAE) is thought to arise primarily from the complex interaction of components that come from two different cochlear locations. Such distortion has its origin in the nonlinear interaction on the basilar membrane of the excitation patterns resulting from the two stimulus tones, f1 and f2. Here we examine the spatial extent of initial generation of the 2f1-f2 OAE by acoustically traumatizing the base of the cochlea and so eliminating the contribution of the basal region of the cochlea to the generation of 2f1-f2. Explicitly, amplitude-modulated, or continuously varying in level, stimulus tones with f2/f1= 1.2 and f2 =8000-8940 Hz were used to generate the 2f1-f2 DPOAE in guinea pig before and after acoustically traumatizing the basal region of the cochlea (the origin of any basal-to-f2 distortion product generators). It was found, based on correlation analysis, that there does not appear to be a basal-to-f2 distortion product generation mechanism contributing significantly to the guinea pig 2f1-f2 OAE up to L1 = 80 dB sound pressure level (SPL).

A comparison of OAEs arising from different generation mechanisms in guinea pig.

Otoacoustic emissions provide unambiguous evidence that the cochlea supports energy propagation both towards, and away from, the stapes. The standard wave model for energy transport and cochlear mechanical amplification provides for compressional and inertial waves to transport this energy, the compressional wave through the fluids and the inertial wave along the basilar membrane via fluid coupling. It is generally accepted that energy propagation away from the stapes is dominated by a traveling wave mechanism along the basilar membrane. The mechanism by which energy is predominantly transported back to the stapes remains controversial. Here, we compared signal onset delay measurements and rise/steady-state/fall times for SFOAEs and 2f1-f2 OAEs (f2/f1=1.2) obtained using a pulsed-tone paradigm in guinea pig. Comparison of 2f1-f2 OAE signal onset delay for the OAE arising from the f2 region with SFOAE signal onset delay (matched to the f2 stimulus frequency) based on signal onset occurring at 10% of the peak signal amplitude was suggestive of a bi-directional traveling wave mechanism. However, significant variability in signal onset delay and signal rise, steady-state duration, and fall times for both the 2f1-f2 OAE and SFOAE was found, qualifying this interpretation. Such variability requires explanation, awaiting further studies.

Delay dependence for the origin of the nonlinear derived transient evoked otoacoustic emission.

In the guinea pig it has been shown that the nonlinear derived transient evoked otoacoustic emission (TEOAEnl) is comprised of significant amounts of intermodulation distortion energy. It is expected that intermodulation distortion arising from a nonlinear distortion mechanism will contribute to the overall TEOAE in a stimulus-level-dependent manner, being greatest when basilar-membrane vibration in response to a click stimulus is greatest; with decay of vibration of the basilar membrane subsequent to stimulation by a click, nonlinear interaction along the cochlear partition should reduce and so provide for a linear mechanism to dominate TEOAEnl generation, i.e., the contributions of each of these mechanisms should be delay dependent. To examine this delay dependence, TEOAEnl evoked by acoustic clicks of varying bandwidth were time-domain windowed using a recursive exponential filter in an attempt to separate two components with amplitude and phase properties consistent with different mechanisms of OAE generation. It was found that the part of the TEOAEnl occurring first in time can have a relatively constant amplitude and shallow phase slope, consistent with a nonlinear distortion mechanism. The latter part of the TEOAEnl has an amplitude microstructure and a phase response more consistent with a place-fixed mechanism.

Cochlear delays measured with amplitude-modulated tone-burst-evoked OAEs.

Delay times in the mammalian cochlea, whether from measurement of basilar membrane (BM) vibration or otoacoustic emissions (OAEs) have, to date, been largely based on phase-gradient estimates from steady-state responses. Here we report cochlear delays measured directly in the time domain from OAEs evoked by amplitude-modulated tone-burst (AMTB) stimuli. Measurement using OAEs provides a non-invasive estimate of cochlear delay but is confounded by the complexity of generation of such OAEs. At low to moderate stimulus levels, and provided that the stimulus frequency range does not include a region of the cochlea where there is a large change in effective reflectance, AMTB stimuli evoke an OAE with an envelope shape that is similar to the stimulus and allow a direct calculation of cochlear group delay. Such delays are commensurate with BM estimates of delay, estimates of cochlear delay inferred from neural recordings, and previous OAE measures of delay in the guinea pig. However, a nonlinear distortion mechanism, variation in effective reflectance, and intermodulation distortion products generated by the nonlinear interaction in the cochlea of the carrier and sidebands of the AMTB stimulus, may all contribute to OAEs arising with envelope shapes that are not a scaled representation of the stimulus, confounding the estimation of cochlear group delay.

Sources and mechanisms of DPOAE generation: implications for the prediction of auditory sensitivity.

Otoacoustic emissions (OAEs) have become a commonly used clinical tool for assessing cochlear health status, in particular, the integrity of the cochlear amplifier or motor component of cochlear function. Predicting hearing thresholds from OAEs, however, remains a research challenge. Models and experimental data suggest that there are two mechanisms involved in the generation of OAEs. For distortion product, transient, and high-level stimulus frequency emissions, the interaction of multiple sources of emissions in the cochlea leads to amplitude variation in the composite ear canal signal. Multiple sources of emissions complicate simple correlations between audiometric test frequencies and otoacoustic emission frequencies. Current research offers new methods for estimating the individual components of OAE generation. Input-output functions and DP-grams of the nonlinear component of the 2f2-f2 DPOAE may ultimately show better correlations with hearing thresholds. This paper reviews models of OAE generation and methods for estimating the contribution of source components to the composite emission that is recorded in the ear canal. The clinical implications of multiple source components are discussed.

The origin of SFOAE microstructure in the guinea pig.

Human stimulus-frequency otoacoustic emissions (SFOAEs) evoked by low-level stimuli have previously been shown to have properties consistent with such emissions arising from a linear place-fixed reflection mechanism with SFOAE microstructure thought to be due to a variation in the effective reflectance with position along the cochlea [Zweig and Shera, J. Acoust. Soc. Am. 98 (1995) 2018-2047]. Here we report SFOAEs in the guinea pig obtained using a nonlinear extraction paradigm from the ear-canal recording that show amplitude and phase microstructure akin to that seen in human SFOAEs. Inverse Fourier analysis of the SFOAE spectrum indicates that SFOAEs in the guinea pig are a stimulus level-dependent mix of OAEs arising from linear-reflection and nonlinear-distortion mechanisms. Although the SFOAEs are dominated by OAE generated by a linear-reflection mechanism at low and moderate stimulus levels, nonlinear distortion can dominate some part of, or all of, the emission spectrum at high levels. Amplitude and phase microstructure in the guinea pig SFOAE is evidently a construct of (i). the complex addition of nonlinear-distortion and linear-reflection components; (ii). variation in the effective reflectance with position along the cochlea; and perhaps (iii). the complex addition of multiple intra-cochlear reflections.

Generation of DPOAEs in the guinea pig.

In humans, distortion product otoacoustic emissions (DPOAEs) at frequencies lower than the f(2) stimulus frequency are a composite of two separate sources, these two sources involving two distinctly different mechanisms for their production: non-linear distortion and linear coherent reflection [Talmadge et al., J. Acoust. Soc. Am. 104 (1998) 1517-1543; Talmadge et al., J. Acoust. Soc. Am. 105 (1999) 275-292; Shera and Guinan, J. Acoust. Soc. Am. 105 (1999) 332-348; Kalluri and Shera, J. Acoust. Soc. Am. 109 (2001) 662-637]. In rodents, DPOAEs are larger, consistent with broader filters; however the evidence for two separate mechanisms of DPOAE production as seen in humans is limited. In this study, we report DPOAE amplitude and phase fine structure from the guinea pig with f(2)/f(1) held constant at 1.2 and f(2) swept over a range of frequencies. Inverse Fast Fourier Transform analysis and time-domain windowing were used to separate the two components. Both the 2f(1)-f(2) DPOAE and the 2f(2)-f(1) DPOAE were examined. It was found that, commensurate with human data, the guinea pig DPOAE is a composite of two components arising from different mechanisms. It would appear that the 2f(1)-f(2) emission measured in the ear canal is usually dominated by non-linear distortion, at least for a stimulus frequency ratio of 1.2. The 2f(2)-f(1) DPOAE exhibits amplitude fine structure that, for the animals examined, is predominantly due to the variation in amplitude of the place-fixed component. Cochlear delay times appear consistent with a linear coherent reflection mechanism from the distortion product place for both the 2f(1)-f(2) and 2f(2)-f(1) place-fixed components.

What drives mechanical amplification in the mammalian cochlea?

The recent report by Peter Dallos and colleagues of the gene and protein responsible for outer hair cell somatic motility (Zheng, Shen, He, Long, Madison, & Dallos, 2000), and the work of James Hudspeth and colleagues demonstrating that vestibular stereocilia are capable of providing power that may boost the vibration of structures within the inner ear (Martin & Hudspeth, 1999), presents the tantalizing possibility that we may not be far away from answering the question what drives mechanical amplification in the mammalian cochlea? This article reviews the evidence for and against each of somatic motility as the motor, and a motor in the hair cell bundle, producing cochlear mechanical amplification. We consider three models based on somatic motility as the motor and two based on a motor in the hair cell bundle. Available evidence supports a hair cell bundle motor in nonmammals but the upper frequency limit of mammalian hearing in general exceeds that of nonmammals, in many cases by an order of magnitude or more. Only time will tell whether an evolutionary dichotomy exists (Manley, Kirk, Köppl, & Yates, 2001).