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The low-pass characteristic of the outer hair cell (OHC) voltage response to mechanical stimulation could be considered a serious problem for cochlear models aiming at explaining high-frequency active amplification by introducing instantaneous nonlinear terms because active gain would dramatically decrease at high frequency. Evidence from experimental studies by Nam and Fettiplace [(2012). PloS One 7, e50572] suggests that the local cutoff frequency significantly increases approaching the cochlear base, somehow mitigating this problem. In this study, low-pass filtering of an internal force term, derived from a physiologically plausible OHC schematization by Lu, Zhak, Dallos, and Sarpeshkar [(2006). Hear. Res. 214, 45–67] is included in a simple one-dimensional (1-D) two-degrees-of-freedom transmission-line model by Sisto, Shera, Altoè, and Moleti [(2019). J. Acoust. Soc. Am. 146, 1685–1695] The frequency dependence of the low-pass filter phase-shift naturally yields a transition from sharp tuning and wide dynamical gain range in the basal cochlea to low tuning and poor dynamical range in the apical region. On the other hand, the frequency-dependent attenuation of low-pass filtering makes it more difficult to obtain the high gain (40–50 dB) of the basal basilar membrane response that is experimentally measured in mammals at low stimulus levels. Pressure focusing in the short-wave resonant region, which is not accounted for in this 1-D model, may help in acquiring the additional gain necessary to match the experimental data. [ABSTRACT FROM AUTHOR]

A two-degrees-of-freedom nonlinear cochlear model [Sisto, Shera, Altoè, and Moleti (2019). J. Acoust. Soc. Am. 146, 1685–1695] correctly predicts that the reticular lamina response is nonlinear over a wide basal region. Numerical simulations of suppression tuning curves agree with a recent experiment [Dewey, Applegate, and Oghalai (2019). J. Neurosci. 39, 1805–1816], supporting the idea that the strong susceptibility of the reticular lamina response to suppression by high-frequency tones does not imply that the total traveling wave energy builds-up in correspondingly basal regions. This happens because the reticular lamina is the lightest element of a coupled-oscillators system, only indirectly coupled to the differential pressure. [ABSTRACT FROM AUTHOR]

Epidemiological studies have documented adverse associations between exposure to polychlorinated biphenyls (PCBs) and otological outcomes. Previously, we documented decreased distortion product otoacoustic emission (DPOAE) levels in children exposed to PCBs, up to the age of 45 months, amongst a cohort of children in eastern Slovakia. The objective of the present study is to evaluate cochlear dysfunction at 72 months of age in 214 children from this same cohort and to compare the otoacoustic test sensitivity to that of pure tone audiometry (PTA). The association between DPOAE, PTA, and PCBs was estimated by means of multivariate ANOVA (MANOVA) and linear regression models. ROC curves were computed to estimate the DPOAE-test power in children. The DPOAE level at 72 months was related to PCB-153 serum levels. The DPOAE Input/Output function test at mid-frequency (2 kHz) has shown instead nonmonotonic dependence on PCB exposure, for the left ears of children, over the whole growth curve. No significant association was found between PTA hearing levels and PCB-153 concentration. High diagnostic power of the DPOAE-test was found in children, similar to that found by the same authors in adults. In conclusions the DPOAE-PCB correlation obtained at 72 months is similar to that at 45 months suggesting a permanent and stable ototoxic effect of the PCB exposure. The lack of statistical significance of the PCB-PTA correlation suggests that DPOAEs are sensitive biomarkers of cochlear damage. [ABSTRACT FROM AUTHOR]

The study aim was to identify the timing of sensitive windows for ototoxicity related to perinatal exposure to PCBs. A total of 351 and 214 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 and 72 months, respectively, and distortion product otoacoustic emissions (DPOAEs) at 11 frequencies were recorded. Cord and child 6-, 16-, 45-, and 72- month blood samples were analyzed for PCB 153 concentration. The PCB 153 concentration-time profiles were approximated with a system model to calculate area under the PCB*time curves (AUCs) for specific time intervals (3 and 6 months for 45 and 72 months data, respectively). DPOAE amplitudes were correlated (Spearman) with cord serum PCB and AUCs, markers of prenatal and postnatal exposure, respectively. Two exposure critical windows were identified in infants, the first related to prenatal and early postnatal and the second to postnatal exposure to PCBs. Our data have shown tonotopicity, sexual dimorphism, and asymmetry in ototoxicity of PCBs. [ABSTRACT FROM AUTHOR]

An objective technique based on the time-frequency analysis of otoacoustic emissions is proposed to get fast and stable estimates of cochlear tuning. Time-frequency analysis allows one to get stable measurements of the delay/frequency function, which is theoretically expected to be a function of cochlear tuning. Theoretical considerations and numerical solutions of a nonlinear cochlear model suggest that the average phase-gradient delay of the otoacoustic emission single-reflection components, weighted, for each frequency, by the amplitude of the corresponding wavelet coefficients, approximately scales as the square root of the cochlear quality factor. The application of the method to human stimulus-frequency and transient-evoked otoacoustic emissions shows that tuning decreases approximately by a factor of 2, as the stimulus level increases by 30 dB in a moderate stimulus level range. The results also show a steady increase of tuning with increasing frequency, by a factor of 2 between 1 and 5 kHz. This last result is model-dependent, because it relies on the assumption that cochlear scale-invariance breaking is only due to the frequency dependence of tuning. The application of the method to the reflection component of distortion product otoacoustic emissions, separated using time-frequency filtering, is complicated by the necessity of effectively canceling the distortion component. [ABSTRACT FROM AUTHOR]

In animal experiments, the strong dependence on stimulus level of the basilar membrane gain and tuning is not matched by a corresponding change in the phase slope in the resonant region. Linear models, in which the gain dependence on the stimulus level has to be schematized by explicitly changing the tuning parameters of the resonant model, do not easily match this feature of the experimental data. Nonlinear models predict a phase slope that is relatively decoupled from tuning. In addition, delayed-stiffness and feed-forward models also show a significant intrinsic decoupling between gain and tuning, which helps in matching the experimental data. [ABSTRACT FROM AUTHOR]

The experimental observation of long- and short-latency components in both stimulus-frequency and transient-evoked otoacoustic emissions admits a comprehensive explanation within the coherent reflection mechanism, in a linear active transmission-line cochlear model. A local complex reflectivity function associated with roughness was defined and analyzed by varying the tuning factor of the model, systematically showing, for each frequency, a multiple-peak spatial structure, compatible with the observed multiple-latency structure of otoacoustic emissions. Although this spatial pattern and the peak relative intensity changes with the chosen random roughness function, the multiple-peak structure is a reproducible feature of different "digital ears," in good agreement with experimental data. If one computes the predicted transmission delays as a function of frequency and position for each source, one gets a good match to the latency-frequency patterns that are directly computed from synthesized otoacoustic spectra using time-frequency analysis. This result clarifies the role of the spatial distribution of the otoacoustic emission sources, further supporting the interpretation of different-latency otoacoustic components as due to reflection sources localized at different places along the basilar membrane. [ABSTRACT FROM AUTHOR]

Time-domain numerical solutions of a nonlinear active cochlear model forced by click stimuli are analyzed with a time-frequency wavelet technique to identify the components of the otoacoustic response associated with different generation mechanisms/places. Previous experimental studies have shown evidence for the presence of at least two components in the transient otoacoustic response: A long-latency response, growing compressively with increasing stimulus level, and a shorter-latency response, characterized by faster growth. The possible mechanisms for the generation of the two components are discussed using the results of the numerical simulations. The model is a one-dimensional (1-D) transmission line model with nonlinear and nonlocal active terms representing the anti-damping action of the 'cochlear amplifier.' The dependence on the stimulus level of latency and level was measured for the different components of the response. The generation mechanisms/places of the different components were identified by varying the stimulus level and by turning off the cochlear roughness in well-defined cochlear regions. The results suggest that reflections from roughness coming from basal regions of the cochlea may give a relevant contribution to the early otoacoustic response, whereas nonlinear mechanisms seem to produce a much smaller additional contribution. [ABSTRACT FROM AUTHOR]

Time-domain filtering is a standard analysis technique, which is used to disentangle the two main vector components of the distortion product otoacoustic emission response, exploiting their different phase-frequency relation. In this study, a time-frequency filtering technique based on the continuous wavelet transform is proposed to overcome the intrinsic limitations of the time-domain filtering technique and to extend it also to the analysis of stimulus-frequency and transient-evoked otoacoustic emissions. The advantages of the proposed technique are first discussed on a theoretical basis, then practically demonstrated by applying it to the analysis of synthesized and real otoacoustic data. The results show that the time-frequency approach can be empirically optimized to get effective separation of the components of the otoacoustic response associated with either different generation mechanisms or different generation places. Focusing on a single component of the otoacoustic response with a given time-frequency signature may also improve significantly the signal-to-noise ratio, because the random noise contribution tends to be uniformly distributed on the time-frequency plane. [ABSTRACT FROM AUTHOR]

This study focuses on the theoretical prediction and experimental evaluation of the latency of transient-evoked otoacoustic emissions. Response components with different delay have been identified in several studies. The main generator of the transient response is assumed to be coherent reflection from cochlear roughness near the resonant place. Additional components of different latency can be generated by different mechanisms. Experimental data are re-analyzed in this study to evaluate the dependence of the latency on stimulus level, for each component of the response, showing that previous estimates of the otoacoustic emission latency were affected by systematic errors. The latency of the emission from each generator changes very little with stimulus level, whereas their different growth rate causes sharp changes of the single-valued latency, estimated as the time of the absolute maximum of the bandpass filtered response. Results of passive linear models, in which gain and bandwidth of the cochlear amplifier are strictly related, are incompatible with the observations. Although active linear models including delayed stiffness terms do predict much slower dependence of latency on the stimulus level, a suitable nonlinear model should be designed, capable of decoupling more effectively the dependence on stimulus level of amplitude and phase of the otoacoustic response. [ABSTRACT FROM AUTHOR]

This study explores the phenomenology of distortion products in nonlinear cochlear models, predicting their amplitude and phase along the basilar membrane. The existence of a backward-traveling wave at the distortion-product frequency, which has been recently questioned by experiments measuring the phase of basilar-membrane vibration, is discussed. The effect of different modeling choices is analyzed, including feed-forward asymmetry, micromechanical roughness, and breaking of scaling symmetry. The experimentally observed negative slope of basilar-membrane phase is predicted by numerical simulations of nonlinear cochlear models under a wide range of parameters and modeling choices. In active models, positive phase slopes are predicted by the quasi-linear analytical computations and by the fully nonlinear numerical simulations only if the distortion-product sources are localized apical to the observation point and if the stapes reflectivity is unrealistically small. The results of this study predict a negative phase slope whenever the source is distributed over a reasonably wide cochlear region and/or a reasonably high stapes reflectivity is assumed. Therefore, the above-mentioned experiments do not contradict 'classical' models of cochlear mechanics and of distortion-product generation. [ABSTRACT FROM AUTHOR]

The state-space formalism [Elliott S. J., et al. (2007). J. Acoust. Soc. Am. 122, 2759–2771] allows one to discretize cochlear models in a straightforward matrix form and to modify the main physical properties of the cochlear model by changing the position and functional form of a few matrix elements. Feed-forward and feed-backward properties can be obtained by simply introducing off-diagonal terms in the matrixes expressing the coupling between the dynamical variables and the additional active pressure on the basilar membrane. Some theoretical issues related to different cochlear modeling choices, their implementation in a state-space scheme, and their physical consequences on the cochlear phenomenology, as predicted by numerical simulations, are discussed. Different schematizations of the active term describing the behavior of the outer hair cell’s feedback mechanism, including nonlinear and nonlocal dependences on either pressure or basilar membrane displacement, are also discussed, showing their effect on some measurable cochlear properties. [ABSTRACT FROM AUTHOR]

A nonlinear and non-local cochlear model has been efficiently solved in the time domain numerically, obtaining the evolution of the transverse displacement of the basilar membrane at each cochlear place. This information allows one to follow the forward and backward propagation of the traveling wave along the basilar membrane, and to evaluate the otoacoustic response from the time evolution of the stapes displacement. The phase/frequency relation of the response can be predicted, as well as the physical delay associated with the response onset time, to evaluate the relation between different cochlear characteristic times as a function of the stimulus level and of the physical parameters of the model. For a nonlinear cochlea, simplistic frequency-domain interpretations of the otoacoustic response phase behavior may give inconsistent results. Time-domain numerical solutions of the underlying nonlinear and non-local full cochlear model using a large number (thousands) of partitions in space and an adaptive mesh in time are rather time and memory consuming. Therefore, in order to be able to use standard personal computers for simulations reliably, the discretized model has been carefully designed to enforce sparsity of the matrices using a multi-iterative approach. Preliminary results concerning the cochlear characteristic delays are also presented. [ABSTRACT FROM AUTHOR]

The latency of transient evoked otoacoustic emissions has been evaluated in a sample of 58 ears from 34 preterm neonates, to understand if the estimates of cochlear tuning based on the otoacoustic emission latency show signs of developmental changes. A previous study on the same otoacoustic emissions analyzed here [Tognola et al. (2005). “Cochlear maturation and otoacoustic emissions in preterm infants: A time-frequency approach,” Hear. Res., 199, 71–80] reported indeed a significant change in the otoacoustic emission latency with postconception age. This last result, which would imply a significant decrease of tuning, was partially biased by the presence of spontaneous emissions. In this study, the same neonate data are reanalyzed using a novel time-frequency algorithm, less sensitive to spontaneous emissions. Asymmetry between right and left ears has been found, with the left ears showing no significant change, whereas in the right ears and in the 1.5–2.5 kHz frequency range only, a slow decrease of latency with postconception age (0.1–0.2 ms/week) was observed. The correspondent tuning estimates based on latency decrease by 0.4–0.5/week. Significant differences between neonate and adult latency were confirmed, which could be either cochlear or middle ear in nature. These findings are compared to previous studies on distortion product suppression tuning curves in preterm neonates. [ABSTRACT FROM AUTHOR]

The complex input/output function of transient evoked otoacoustic emissions is evaluated at different stimulus levels. The experimental response functions were best fitted to the reflectivity functions predicted by theoretical one-dimensional transmission-line models in the perturbative limit. Along with the otoacoustic emission sources usually considered, linear reflection from roughness (place-fixed) and nonlinear distortion (wave-fixed), a wave-fixed scattering potential is also considered, associated with the breaking of the scale-invariance symmetry, as a new additional mechanism for otoacoustic emission generation. A good fit was obtained, across stimulus level and frequency, for roughness, and not for nonlinear distortion, nor for scale-invariance violation. The phase-gradient delay of the same transient evoked otoacoustic emissions was consistent with the latency measured using a wavelet time-frequency technique, at all stimulus levels and frequencies. The results suggest that cochlear reflectivity is dominated by a component with a rapidly rotating phase, at all stimulus levels, in apparent contradiction with the usual assumption that, at high stimulus levels, a significant contribution to the transient evoked otoacoustic response should come from nonlinear distortion. Possible interpretations of this phenomenology are critically reviewed and discussed, considering the theoretical uncertainties and the limitations of the experimental technique. [ABSTRACT FROM AUTHOR]

Experimental measurements of the latency of transient evoked otoacoustic emission and auditory brainstem responses are compared, to discriminate between different cochlear models for the backward acoustic propagation of otoacoustic emissions. In most transmission-line cochlear models otoacoustic emissions propagate towards the base as a slow transverse traveling wave, whereas other models assume fast backward propagation via longitudinal compression waves in the fluid. Recently, sensitive measurements of the basilar membrane motion have cast serious doubts on the existence of slow backward traveling waves associated with distortion product otoacoustic emissions [He et al., Hear. Res. 228, 112–122 (2007)]. On the other hand, recent analyses of “Allen–Fahey” experiments suggest instead that the slow mechanism transports most of the otoacoustic energy [Shera et al., J. Acoust. Soc. Am. 122, 1564–1575 (2007)]. The two models can also be discriminated by comparing accurate estimates of the otoacoustic emission latency and of the auditory brainstem response latency. In this study, this comparison is done using human data, partly original, and partly from the literature. The results are inconsistent with fast otoacoustic propagation, and suggest that slow traveling waves on the basilar membrane are indeed the main mechanism for the backward propagation of the otoacoustic energy. [ABSTRACT FROM AUTHOR]

In transmission-line models of cochlear mechanics, predictions about otoacoustic-emission delays depend on the place- or wave-fixed nature of the emission generation mechanism. In this work, transient evoked otoacoustic emissions (TEOAEs), recorded at different stimulus levels in 10 young subjects, were analyzed using wavelet-based time-frequency analysis to determine the latency of each frequency component of the response. The same wave forms were Fourier analyzed to evaluate the phase-gradient delay as a function of frequency. Interpreting the relation between these two characteristic delays using cochlear models shows that most of the TEOAE response can be attributed to place-fixed reflection mechanisms. The causality principle explains observed correlations between fluctuations of the TEOAE amplitude and phase-gradient delay. [ABSTRACT FROM AUTHOR]

Cochlear latency has been evaluated in young adults by time-frequency analysis of transient evoked otoacoustic emissions recorded using the nonlinear acquisition mode at different levels of the click stimulus. Objective, even if model-dependent, estimates of cochlear tuning have been obtained from the otoacoustic latency estimates. Transmission-line cochlear models predict that the transient-evoked otoacoustic emission latency is dependent on the stimulus level, because the bandwidth of the cochlear filter (tuning) depends on the local cochlear excitation level due to nonlinear damping. The results of this study confirm the increase of tuning with increasing frequency and show clearly the decrease of latency and tuning with increasing stimulus level. This decrease is consistent with the expected relation between the slowing down of the traveling wave near the tonotopic place and the cochlear excitation amplitude predicted by cochlear models including nonlinear damping. More specifically, these results support the models in which nonlinear damping consists of a quadratic term and a constant positive term. [ABSTRACT FROM AUTHOR]

Transient evoked otoacoustic emissions of a large population of neonates (466 ears) are analyzed, with the aim of establishing if a significant latency difference can be observed between “pass” (333) and “fail” (133) ears, discriminated with a screening protocol based on band and global reproducibility. The ears that did not pass the test in at least one frequency band are named “fail,” for simplicity, but they should be more appropriately defined as “partial pass.” In a previous study, significantly different average latencies had been observed in adult subjects, comparing normal hearing and hearing impaired ears [J. Acoust. Soc. Am. 111, 297–308 (2002)], but no similar study has been conducted on neonates yet. An improved wavelet technique was applied to transient evoked otoacoustic emission data, to get accurate experimental measurements of the otoacoustic emission latency. The results show statistically significant differences between the latency distributions of the “pass” and “fail” populations, with the “fail” latencies longer. However, non-Gaussianity of the distributions and systematic errors associated with low reproducibility levels suggested using a conservative approach in the data analysis and interpretation. New otoacoustic estimates of cochlear tuning in neonates are also provided. [ABSTRACT FROM AUTHOR]

In this work, growth-rate curves of the 2 ƒ1-ƒ2 distortion product otoacoustic emission (DPOAE) are analyzed in a population of 30 noise exposed subjects, including both normal-hearing and hearing impaired subjects. A particular embedded limit-cycle oscillator equation is used to model the cochlear resonant response at the cochlear places of the primary and secondary tone frequencies (ƒ2 and 2ƒ1-ƒ2). The parameters of the oscillator equation can be directly interpreted in terms of effectiveness of the cochlear feedback mechanisms associated with the active filter amplification. A two-sources paradigm is included in the model, in agreement with experimental evidence and with the assumptions of more detailed full cochlear models based on the transmission line formalism. According to this paradigm, DPOAEs are nonlinearly generated at the cochlear place that is resonant at frequency ƒ2 , and coherently reflected at the 2ƒ1-ƒ2 place. The analysis shows that the model, which had been previously used to describe the relaxation dynamics of transient evoked otoacoustic emissions (TEOAEs), also correctly predicts the observed growth rate of the DPOAE response as a function of the primary tones amplitude. A significant difference is observed between normal and impaired ears. The comparison between the growth rate curves at different frequencies provides information about the dependence of cochlear tuning on frequency. [ABSTRACT FROM AUTHOR]

Different theoretical estimates of the sensitivity of gravitational wave resonant bar detectors, which have been published in the last decades, are reviewed and discussed. The "classical" cross-section estimate is obtained considering the bar as a classical or quantum oscillator, whose initial thermal state is that of a single oscillator driven by a single external stochastic force. Other theoretical studies computed a much larger cross-section, using a variety of quantum-mechanical arguments. The review of the existing literature shows that there is no well established model for the response of a resonant detector to gravitational waves. The resonant, yet random, nature of the Brownian thermal motion may justify considering the bar response at the fundamental longitudinal eigenfrequency as that of a large number of effective quantum mechanical oscillators. Assuming this hypothesis, quantum coherence effects, as first suggested by Weber, lead to a much larger cross-section than that "classically" predicted. The reduction of this amplification due to thermal noise itself is also computed. [ABSTRACT FROM AUTHOR]

A new method is presented for estimating cochlear tuning starting from measurements of either the transient evoked otoacoustic emission latency or the spontaneous otoacoustic emission minimal spacing. This method could be useful in obtaining indirect information about the tuning curve, particularly for subjects that, like neonates, cannot be studied with psycho-acoustical techniques. Theoretical models of the acoustic transmission along the cochlea based on the transmission line formalism predict a relation between the otoacoustic emission latency and the frequency. This relation depends on the tuning curve, i.e., the frequency dependence of the quality factor of the cochlear resonances. On the other hand, models for the generation of spontaneous emissions based on the concept of coherent scattering from cochlear random inhomogeneities imply an independent relation between the tuning curve and the minimal frequency spacing between spontaneous emissions. In this study, experimental measurements of the otoacoustic emission latency and of the minimal spacing between spontaneous emissions are presented. Theoretical relations are derived, which connect these two measured quantities and the tuning curve. The typically longer latency of neonates implies a higher degree of tuning at high levels of stimulation. [ABSTRACT FROM AUTHOR]

This paper discusses the role of two-dimensional (2-D)/three-dimensional (3-D) cochlear fluid hydrodynamics in the generation of the large nonlinear dynamical range of the basilar membrane (BM) and pressure response, in the decoupling between cochlear gain and tuning, and in the dynamic stabilization of the high-gain BM response in the peak region. The large and closely correlated dependence on stimulus level of the BM velocity and fluid pressure gain [Dong, W., and Olson, E. S. (2013). Biophys. J. 105(4), 1067–1078] is consistent with a physiologically oriented schematization of the outer hair cell (OHC) mechanism if two hydrodynamic effects are accounted for: amplification of the differential pressure associated with a focusing phenomenon, and viscous damping at the BM-fluid interface. The predictions of the analytical 2-D Wentzel-Kramers-Brillouin (WKB) approach are compared to solutions of a 3-D finite element model, showing that these hydrodynamic phenomena yield stable high-gain response in the peak region and a smooth transition among models with different effectiveness of the active mechanism, mimicking the cochlear nonlinear response over a wide stimulus level range. This study explains how an effectively anti-damping nonlinear outer hair cells (OHC) force may yield large BM and pressure dynamical ranges along with an almost level-independent admittance. [ABSTRACT FROM AUTHOR]

Long-delay components showing a symmetrical pattern with positive and negative delays can be observed in the time-frequency representation (or in the inverse Fourier transform) of distortion product otoacoustic emissions. Positive-only phase-gradient delays are predicted by place-fixed backscattering mechanisms, such as coherent reflection due to roughness, whereas the nonlinear distortion wave-fixed mechanism should generate an almost null-delay component. The symmetrical delay pattern arises whenever spectral amplitude fluctuations are not fully correlated to phase fluctuations. An interpretation of this phenomenon is proposed, involving place-fixed modulation of the spectral strength of the wave–fixed nonlinear generator. Experimental data are shown in which these negative-delay sources are particularly strong, and further amplified by contralateral stimulation, suggesting that this effect could be dynamically enhanced. Analytical solutions of a linear 1-d transmission line model, in which cubic nonlinearity and roughness were added as small perturbations, have been used to test this hypothesis. [ABSTRACT FROM AUTHOR]

This study uses a 3-D representation of the cochlear fluid to extend the results of a recent paper [Sisto, Belardinelli, and Moleti (2021b). J. Acoust. Soc. Am. 150, 4283–4296] in which two hydrodynamic effects, pressure focusing and viscous damping of the BM motion, both associated with the sharp increase in the wavenumber in the peak region, were analyzed for a 2-D fluid, coupled to a standard 1-D transmission-line WKB approach to cochlear modeling. The propagation equation is obtained from a 3-D fluid volume conservation equation, yielding the focusing effect, and the effect of viscosity is represented as a correction to the local 1-D admittance. In particular, pressure focusing amplifies the BM response without modifying the peak admittance, and viscous damping determines the position of the response peak counteracting focusing, as sharp gradients of the velocity field develop. The full 3-D WKB formalism is necessary to represent satisfactorily the behavior of the fluid velocity field near the BM-fluid interface, strictly related to viscous losses. As in finite element models, a thin layer of fluid is effectively attached to the BM due to viscosity, and the viscous force associated with the vertical gradient of the fluid vertical velocity acts on the BM through this layer. [ABSTRACT FROM AUTHOR]

Objective To investigate the peripheral auditory pathway in Parkinson's disease (PD) by using objective, quantitative and non-invasive audiological techniques, transient-evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions, in order to detect subclinical alterations of cochlear functioning and possible changes after dopaminergic stimulation. Methods We enrolled 11 untreated de-novo PD patients and 11 age and sex-matched healthy controls. Subjects underwent a routine audiological evaluation and otoacoustic emission recordings. The patients were then slowly-titrated to a stable dose of 100 mg levodopa four times in a day. A post-treatment assessment was made in order to detect significant changes in audiological responses. Finally, possible associations between clinical data and hearing results were also evaluated. Results At pure-tone audiometry, higher auditory threshold levels were observed in PD when compared to the controls. Moreover, DPOAE responses in PD patients were found low at almost all tested frequencies, suggesting subclinical cochlear damage. Interestingly, after dopaminergic treatment, a significant increase in DPOAE responses was detected. Notably, DPOAE dysfunction correlated with clinical severity, whereas high hearing thresholds appeared positively related with more prolonged disease duration. Conclusions Our findings demonstrate that otoacoustic emission recording and pure-tone audiometry reveal levodopa-sensitive cochlear dysfunction and hearing loss in PD. A parallel improvement in subjective motor symptoms and DPOAE objective responses could help clinicians in monitoring therapeutic responses and dynamic changes during the course of the disease. [ABSTRACT FROM AUTHOR]

Background: Sensorial non-motor symptoms (NMSs) in Parkinson’s disease (PD) still lack appropriate investigation in clinical practice.This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient’s quality of life (QoL).We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson’s Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis.60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS.This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.Methods: Sensorial non-motor symptoms (NMSs) in Parkinson’s disease (PD) still lack appropriate investigation in clinical practice.This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient’s quality of life (QoL).We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson’s Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis.60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS.This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.Results: Sensorial non-motor symptoms (NMSs) in Parkinson’s disease (PD) still lack appropriate investigation in clinical practice.This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient’s quality of life (QoL).We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson’s Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis.60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS.This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL.Conclusion: Sensorial non-motor symptoms (NMSs) in Parkinson’s disease (PD) still lack appropriate investigation in clinical practice.This study aimed to assess if and to what extent auditory dysfunction is associated with other NMSs in PD and its impact on patient’s quality of life (QoL).We selected patients with idiopathic PD, without other concomitant neurological diseases, dementia, or diagnosis of any audiological/vestibular disease. Demographic and clinical data were collected. Patients underwent otoscopic examination, audiological testing with pure tone audiometry (PTA) and distortion product otoacoustic emissions (DPOAEs) and completed Non-Motor Symptoms Scale (NMSS) and Parkinson’s Disease Questionnaires-39 (PDQ-39). ANCOVA and partial correlation analysis have been used for statistical analysis.60 patients were enrolled and completed PTA and DPOAEs. 32 patients with hearing impairment (HI), assessed by PTA, (hearing threshold ≥ 25 dB) showed similar disease duration, motor impairment, and staging, compared to patients without HI, but higher scores both in NMSS and in PDQ-39, except for cardiovascular (CV), gastrointestinal (GI), urogenital (U) and sexual function (SF) of NMSS. In addition, DPOAEs showed a significant correlation with higher scores both in NMSS and PDQ-39, except for CV, SF, GI, U and perceptual problem subdomains of NMSS.This study demonstrated that PD patients with HI have a greater burden of NMS and lower related QoL and functioning. Our results highlight the importance to reconsider HI as a NMS, in parallel with the others. HI evaluation, even in asymptomatic patients, may reveal a wider pathology with a worse QoL. [ABSTRACT FROM AUTHOR]

Objective: Distortion product otoacoustic emission (DPOAE) levels plotted as a function of stimulus frequency ratio demonstrate a bandpass shape. This bandpass shape is narrower at higher frequencies compared to lower frequencies and thus has been thought to be related to cochlear mechanical tuning. Design: However, the frequency- and level-dependence of these functions above 8 kHz is largely unknown. Furthermore, how tuning estimates from these functions are related to behavioural tuning is not fully understood. Study Sample: From experiment 1, we report DPOAE level ratio functions (LRF) from seven normal-hearing, young-adults for f2 = 0.75–16 kHz and two stimulus levels of 62/52 and 52/37 dB FPL. We found that LRFs became narrower as a function of increasing frequency and decreasing level. Results: Tuning estimates from these functions increased as expected from 1-8 kHz. In experiment 2, we compared tuning estimates from DPOAE LRF to behavioural tuning in 24 normal-hearing, young adults for 1 and 4 kHz and found that behavioural tuning generally predicted DPOAE LRF estimated tuning. Conclusions: Our findings suggest that DPOAE LRFs generally reflect the tuning profile consistent with basilar membrane, neural, and behavioural tuning. However, further investigations are warranted to fully determine the use of DPOAE LRF as a clinical measure of cochlear tuning. [ABSTRACT FROM AUTHOR]

The input/output functions of the different-latency components of human transient-evoked and stimulus-frequency otoacoustic emissions are analyzed, with the goal of relating them to the underlying nonlinear dynamical properties of the basilar membrane response. Several cochlear models predict a cubic nonlinearity that would yield a correspondent compressive response. The otoacoustic response comes from different generation mechanisms, each characterized by a particular relation between local basilar membrane displacement and otoacoustic level. For the same mechanism (e.g., reflection from cochlear roughness), different generation places would imply differently compressive regimes of the local basilar membrane dynamics. Therefore, this kind of study requires disentangling these contributions, using suitable data acquisition and time-frequency analysis techniques. Fortunately, different generation mechanisms/places also imply different phase-gradient delays, knowledge of which can be used to perform this task. In this study, the different-latency otoacoustic components systematically show differently compressive response, consistent with two simple hypotheses: (1) all emissions come from the reflection mechanism and (2) the basilar membrane response is strongly compressive in the resonance region and closer to linear in more basal regions. It is not clear if such a compressive behavior also extends to arbitrarily low stimulus levels. [ABSTRACT FROM AUTHOR]

Different time–frequency techniques may be used to investigate the relation between latency and frequency of transient-evoked otoacoustic emissions. In this work, the optimization of these techniques and the interpretation of the experimental result are discussed. Time–frequency analysis of click-evoked otoacoustic emissions of 42 normal-hearing young subjects has been performed, using both wavelet and matching pursuit algorithms. Wavelet techniques are very effective to provide fast and reliable evaluation of the average latency of large samples of subjects. A major advantage of the matching pursuit technique, as observed by Jedrzejczak et al. [J. Acoust. Soc. Am. 115, 2148–2158 (2004)], is to provide detailed information about the time evolution of the response of single ears at selected frequencies. A hybrid matching pursuit algorithm that includes Fourier spectral information was developed, capable of speeding-up computation times and of identifying “spurious” atoms, whose latency-frequency relation is apparently anomalous. These atoms could be associated with several known phenomena, either intrinsic, such as intermodulation distortion, spontaneous emissions and multiple internal reflections, or extrinsic, such as instrumental noise, linear ringing and the acquisition window onset. A correct interpretation of these phenomena is important to get accurate estimates of the otoacoustic emission latency. [ABSTRACT FROM AUTHOR]

Although styrene is an established ototoxic agent at occupational exposure levels, the mechanisms of styrene toxicity in the auditory system are still unclear. The aim of this study was to identify the consequences of styrene chronic exposure in cochlear structures, looking for the mechanisms of ototoxicity of this organic compound and focusing on cell targets and oxidative stress/inflammatory processes. Male adult Wistar rats were exposed to styrene (400 mg/kg by gavage for 5 days/week, 3 consecutive weeks). Hearing loss was evaluated by measuring auditory brainstem responses (ABR), morphological analysis were performed to evaluate hair cell and spiral ganglion neuron survival, as well as synaptic damage. Analysis of apoptotic (p53) and inflammatory (NF-κB, TNF-α, IL-1β and IL-10) mediators were performed by immunofluorescence analysis and western blot. Styrene ototoxic effects induced a hearing loss of about 35–40 dB. Immunofluorescence and western blotting analyses demonstrated that styrene administration induced redox imbalance and activated inflammatory processes, targeting sensory hair cell and neural dysfunction by a cross-talk between oxidative and inflammatory mediators. Major findings connect styrene ototoxicity to an interplay between redox imbalance and inflammation, leading to the intriguing assumption of a mixed sensory and neural styrene-induced ototoxicity. Thus, in a clinical perspective, data reported here have important implications for styrene risk assessment in humans. Image 1 • Styrene ototoxicity involves an interplay between redox unbalance and inflammation. • Styrene induces a sensory and neural damage in the cochlea. • Oxidative stress and inflammation are mediators of synaptopathy induced by styrene. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the ototoxic effect of the exposure to different organic solvents and noise using distortion product otoacoustic emissions (DPOAEs). Design: The exposure to different solvents was evaluated by measuring, before and at the end of the work-shift, the urinary concentrations of solvent metabolites used as dose biomarkers. The urinary concentrations of DNA and RNA oxidation products were also measured as biomarkers of oxidative damage. The simultaneous exposure to noise was also evaluated. DPOAEs and pure tone audiometry (PTA) were used as outcome variables, and were correlated to the exposure variables using mixed effect linear regression models. Study sample: Seventeen industrial painters exposed to a solvent mixture in a naval industry. A sample size of 15 was estimated from previous studies as sufficient for discriminating small hearing level and DPOAE level differences (5 dB and 2 dB, respectively) at a 95% confidence level. Results: Statistically significant associations were found between the DPOAE level and the urinary dose biomarkers and the oxidative damage biomarkers. DPOAE level and the logarithm of the metabolite concentration showed a significant negative correlation. Conclusions: DPOAE are sensitive biomarkers of exposure to ototoxic substances and can be effectively used for the early detection of hearing dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: The phase delay of stimulus frequency otoacoustic emissions (SFOAEs) has been proposed as a noninvasive, objective, and fast source for estimating cochlear mechanical tuning. However, the implementation of SFOAEs clinically has been thwarted by the gaps in understanding of the stability of SFOAE delay-based tuning estimates and their relationship to behavioral measures of tuning. Therefore, the goals of this study were (a) to investigate the relationship between delay-based tuning estimates from SFOAEs and simultaneously masked psychophysical tuning curves (PTCs) and (b) to assess the across- and within-session repeatability of tuning estimates from behavioral and OAE measures. Method: Three sets of behavioral and OAE measurements were collected in 24 normal-hearing, young adults for two probe frequencies, 1 and 4 kHz. For each participant, delay-based tuning estimates were derived from the phase gradient of SFOAEs. SFOAE-based and behavioral estimates of tuning obtained using the fast-swept PTC paradigm were compared within and across sessions. Results: In general, tuning estimates were sharper at 4 kHz compared to 1 kHz for both PTCs and SFOAEs. Statistical analyses revealed a significant correlation between SFOAE delay-based tuning and PTCs at 4 kHz, but not 1 kHz. Lastly, SFOAE delay-based tuning estimates showed better intra- and intersession repeatability compared to PTCs. Conclusions: SFOAE phase-gradient delays reflect aspects of cochlear mechanical tuning, in that a frequency dependence similar to that of basilar membrane tuning was observed. Furthermore, the significant correlation with PTCs at 4 kHz and the high repeatability of SFOAE-based tuning measures offer promise of an objective, nonbehavioral assay of tuning in human ears. [ABSTRACT FROM AUTHOR]

The zero crossings of basilar-membrane (BM) responses to clicks are nearly independent of stimulus intensity. This work explores the constraints that this invariance imposes on one-dimensional nonlinear cochlear models with two degrees of freedom (2DoF). The locations of the poles and zeros of the BM admittance, calculated for a set of linear models in which the strength of the active force is progressively decreased, provides a playground for evaluating the behavior of a corresponding nonlinear model at increasing stimulus levels. Mathematical constraints on the model parameters are derived by requiring that the poles of the admittance move horizontally in the s-plane as the active force is varied. These constraints ensure approximate zero-crossing invariance over a wide stimulus level range in a nonlinear model in which the active force varies as a function of the local instantaneous BM displacement and velocity. Two different 2DoF models are explored, each capable of reproducing the main qualitative characteristics of the BM response to tones (i.e., the tall and broad activity pattern at low stimulus levels, the large gain dynamics, and the partial decoupling between gain and phase). In each model, the motions of the two masses are compared with response data from animal experiments. [ABSTRACT FROM AUTHOR]

Abstract Hearing loss is an injury that can develop over time, and people may not even be aware of it until it becomes a severe disability. Ototoxicants are substances that may damage the inner ear by either affecting the structures in the ear itself or by affecting the nervous system. We have examined the possibility that ototoxicants may present a health hazard in association with environmental exposures, adding to existing knowledge of their proven hazards under medical therapeutic conditions or occupational activities. In addition to the already described human environmental ototoxicants, mainly organochlorines such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), hexachlorocyclohexane (HCH) and hexachlorobenzene (HCB), we have examined the ubiquitous chemical stressors phthalates, bisphenol A/S/F/, PFCs, flame retardants (FRs) and cadmium for potential ototoxic properties, both as single substances or as chemical mixtures. Our literature review confirmed that these chemicals may disturb thyroid hormones homeostasis, activate aryl hydrocarbon receptor (AhR), and induce oxidative stress, which in turn may initiate a chain of events resulting in impairment of cochlea and hearing loss. With regard to auditory plasticity, diagnostics of a mixture of effects of ototoxicants, potential interactions of chemical and physical agents with effects on hearing, parallel deterioration of hearing due to chemical exposures and ageing, metabolic diseases or obesity, even using specific methods as brainstem auditory evoked potentials (BAEP) or otoacoustic emissions (OAEs) registration, may be difficult, and establishment of concentration-response relationships problematic. This paper suggests the establishment of a class of environmental oxotoxicants next to the established classes of occupational and drug ototoxicants. This will help to properly manage risks associated with human exposure to chemical stressors with ototoxic properties and adequate regulatory measures. Highlights • We suggest environmental ototoxicants as a potential new class of chemical stressors. • These chemicals contribute to the prevalence of disabling hearing loss in this study population. • The literature search identified established and potentially new environmental ototoxicants. • Environmental exposures to organochlorines associate with cochlear deficits in humans. [ABSTRACT FROM AUTHOR]

Distortion product otoacoustic emissions (DPOAEs) have been accurately measured with an intensimetric technique, involving simultaneous measure of pressure and velocity in the ear canal, which allows one to correctly calibrate both the input stimuli and the otoacoustic emission (OAE) level. Suitable combinations of standard intensimetric quantities, active intensity and power density [Stanzial, Shiffrer, and Sacchi, J. Acoust. Soc. Am. 131, 269–280 (2012)], are used to equalize the stimuli transmitted to the middle ear, and to estimate the DPOAE level emitted by the eardrum. The DPOAE intensimetric spectra are consistent with those recorded with a high-quality conventional otoacoustic probe with state-of-the-art calibration of both stimulus and OAE response [Charaziak and Shera, J. Acoust. Soc. Am. 141, 515–525 (2017)], demonstrating the applicability of the intensimetric method to OAE measurements. [ABSTRACT FROM AUTHOR]

In this study, a systematic analysis of the dependence on stimulus level and primary frequency ratio r of the different components of human distortion product otoacoustic emissions has been performed, to check the validity of theoretical models of their generation, as regards the localization of the sources and the relative weight of distortion and reflection generation mechanisms. 2f1 - f2 and 2f2 - f1 distortion product otoacoustic emissions of 12 normal hearing ears from six human subjects have been measured at four different levels, in the range [35, 65] dB sound pressure level, at eight different ratios, in the range [1.1, 1.45]. Time-frequency filtering was used to separate distortion and reflection components. Numerical simulations have also been performed using an active nonlinear cochlear model. Both in the experiment and in the simulations, the behavior of the 2f1 - f2 distortion and reflection components was in agreement with previous measurements and with the predictions of the two-source model. The 2f2 - f1 response showed a rotating-phase component only, whose behavior was in general agreement with that predicted for a component generated and reflected within a region basal to the characteristic place of frequency 2f2 - f1, although alternative interpretations, which are also discussed, cannot be ruled out. [ABSTRACT FROM AUTHOR]

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. Objectives: Our aim was to evaluate the association between pre- and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. Results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6‑dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: –2.6, –0.5; p = 0.003). Conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months. [ABSTRACT FROM AUTHOR]

With the aim of investigating the capability of otoacoustic emission (OAE) in the detection of low levels of noise-induced hearing loss, audiometric and otoacoustic data of young workers (age: 18–35) exposed to different levels of industrial noise have been recorded. These subjects are participating in a long-term longitudinal study, in which audiometric, exposure (both professional and extra-professional), and OAE data (transient evoked and distortion product) will be collected for a period of several years. All measurements have been performed, during routine occupational health surveillance, with a standard clinical apparatus and acquisition procedure, which can be easily used in the occupational safety practice. The first study was focused on the correlation between transient evoked OAE signal-to-noise ratio and distortion product (DPOAE) OAE level and the audiometric threshold, investigating the causes of the rather large intersubject variability of the OAE levels. The data analysis has shown that, if both OAE data and audiometric data are averaged over a sufficiently large bandwidth, the correlation between DPOAE levels and audiometric hearing threshold is sufficient to design OAE-based diagnostic tests with good sensitivity and specificity also in a very mild hearing loss range, between 10 and 20 dB. [ABSTRACT FROM AUTHOR]