How 'hidden hearing loss' noise exposure affects neural coding in the inferior colliculus of rats.

Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.

The Relative Contribution of Cochlear Synaptopathy and Reduced Inhibition to Age-Related Hearing Impairment for People With Normal Audiograms.

Older people often show auditory temporal processing deficits and speech-in-noise intelligibility difficulties even when their audiogram is clinically normal. The causes of such problems remain unclear. Some studies have suggested that for people with normal audiograms, age-related hearing impairments may be due to a cognitive decline, while others have suggested that they may be caused by cochlear synaptopathy. Here, we explore an alternative hypothesis, namely that age-related hearing deficits are associated with decreased inhibition. For human adults (N = 30) selected to cover a reasonably wide age range (25-59 years), with normal audiograms and normal cognitive function, we measured speech reception thresholds in noise (SRTNs) for disyllabic words, gap detection thresholds (GDTs), and frequency modulation detection thresholds (FMDTs). We also measured the rate of growth (slope) of auditory brainstem response wave-I amplitude with increasing level as an indirect indicator of cochlear synaptopathy, and the interference inhibition score in the Stroop color and word test (SCWT) as a proxy for inhibition. As expected, performance in the auditory tasks worsened (SRTNs, GDTs, and FMDTs increased), and wave-I slope and SCWT inhibition scores decreased with ageing. Importantly, SRTNs, GDTs, and FMDTs were not related to wave-I slope but worsened with decreasing SCWT inhibition. Furthermore, after partialling out the effect of SCWT inhibition, age was no longer related to SRTNs or GDTs and became less strongly related to FMDTs. Altogether, results suggest that for people with normal audiograms, age-related deficits in auditory temporal processing and speech-in-noise intelligibility are mediated by decreased inhibition rather than cochlear synaptopathy.

A computational modelling framework for assessing information transmission with cochlear implants.

Computational models are useful tools to investigate scientific questions that would be complicated to address using an experimental approach. In the context of cochlear-implants (CIs), being able to simulate the neural activity evoked by these devices could help in understanding their limitations to provide natural hearing. Here, we present a computational modelling framework to quantify the transmission of information from sound to spikes in the auditory nerve of a CI user. The framework includes a model to simulate the electrical current waveform sensed by each auditory nerve fiber (electrode-neuron interface), followed by a model to simulate the timing at which a nerve fiber spikes in response to a current waveform (auditory nerve fiber model). Information theory is then applied to determine the amount of information transmitted from a suitable reference signal (e.g., the acoustic stimulus) to a simulated population of auditory nerve fibers. As a use case example, the framework is applied to simulate published data on modulation detection by CI users obtained using direct stimulation via a single electrode. Current spread as well as the number of fibers were varied independently to illustrate the framework capabilities. Simulations reasonably matched experimental data and suggested that the encoded modulation information is proportional to the total neural response. They also suggested that amplitude modulation is well encoded in the auditory nerve for modulation rates up to 1000 Hz and that the variability in modulation sensitivity across CI users is partly because different CI users use different references for detecting modulation.

Modeling temporal information encoding by the population of fibers in the healthy and synaptopathic auditory nerve.

We report a theoretical study aimed at investigating the impact of cochlear synapse loss (synaptopathy) on the encoding of the envelope (ENV) and temporal fine structure (TFS) of sounds by the population of auditory nerve fibers. A computational model was used to simulate auditory-nerve spike trains evoked by sinusoidally amplitude-modulated (AM) tones at 10 Hz with various carrier frequencies and levels. The model included 16 cochlear channels with characteristic frequencies (CFs) from 250 Hz to 8 kHz. Each channel was innervated by 3, 4 and 10 fibers with low (LSR), medium (MSR), and high spontaneous rates (HSR), respectively. For each channel, spike trains were collapsed into three separate 'population' post-stimulus time histograms (PSTHs), one per fiber type. Information theory was applied to reconstruct the stimulus waveform, ENV, and TFS from one or more PSTHs in a mathematically optimal way. The quality of the reconstruction was regarded as an estimate of the information present in the used PSTHs. Various synaptopathy scenarios were simulated by removing fibers of specific types and/or cochlear regions before stimulus reconstruction. We found that the TFS was predominantly encoded by HSR fibers at all stimulus carrier frequencies and levels. The encoding of the ENV was more complex. At lower levels, the ENV was predominantly encoded by HSR fibers with CFs near the stimulus carrier frequency. At higher levels, the ENV was equally well or better encoded by HSR fibers with CFs different from the AM carrier frequency as by LSR fibers with CFs at the carrier frequency. Altogether, findings suggest that a healthy population of HSR fibers (i.e., including fibers with CFs around and remote from the AM carrier frequency) might be sufficient to encode the ENV and TFS over a wide range of stimulus levels. Findings are discussed regarding their relevance for diagnosing synaptopathy using non-invasive ENV- and TFS-based measures.

Age-related central gain compensation for reduced auditory nerve output for people with normal audiograms, with and without tinnitus.

Central gain compensation for reduced auditory nerve output has been hypothesized as a mechanism for tinnitus with a normal audiogram. Here, we investigate if gain compensation occurs with aging. For 94 people (aged 12-68 years, 64 women, 7 tinnitus) with normal or close-to-normal audiograms, the amplitude of wave I of the auditory brainstem response decreased with increasing age but was not correlated with wave V amplitude after accounting for age-related subclinical hearing loss and cochlear damage, a result indicative of age-related gain compensation. The correlations between age and wave I/III or III/V amplitude ratios suggested that compensation occurs at the wave III generator site. For each one of the seven participants with non-pulsatile tinnitus, the amplitude of wave I, wave V, and the wave I/V amplitude ratio were well within the confidence limits of the non-tinnitus participants. We conclude that increased central gain occurs with aging and is not specific to tinnitus.

Correlation and Reliability of Behavioral and Otoacoustic-Emission Estimates of Contralateral Medial Olivocochlear Reflex Strength in Humans.

The roles of the medial olivocochlear reflex (MOCR) in human hearing have been widely investigated but remain controversial. We reason that this may be because the effects of MOCR activation on cochlear mechanical responses can be assessed only indirectly in healthy humans, and the different methods used to assess those effects possibly yield different and/or unreliable estimates. One aim of this study was to investigate the correlation between three methods often employed to assess the strength of MOCR activation by contralateral acoustic stimulation (CAS). We measured tone detection thresholds (N = 28), click-evoked otoacoustic emission (CEOAE) input/output (I/O) curves (N = 18), and distortion-product otoacoustic emission (DPOAE) I/O curves (N = 18) for various test frequencies in the presence and the absence of CAS (broadband noise of 60 dB SPL). As expected, CAS worsened tone detection thresholds, suppressed CEOAEs and DPOAEs, and horizontally shifted CEOAE and DPOAE I/O curves to higher levels. However, the CAS effect on tone detection thresholds was not correlated with the horizontal shift of CEOAE or DPOAE I/O curves, and the CAS-induced CEOAE suppression was not correlated with DPOAE suppression. Only the horizontal shifts of CEOAE and DPOAE I/O functions were correlated with each other at 1.5, 2, and 3 kHz. A second aim was to investigate which of the methods is more reliable. The test-retest variability of the CAS effect was high overall but smallest for tone detection thresholds and CEOAEs, suggesting that their use should be prioritized over the use of DPOAEs. Many factors not related with the MOCR, including the limited parametric space studied, the low resolution of the I/O curves, and the reduced numbers of observations due to data exclusion likely contributed to the weak correlations and the large test-retest variability noted. These findings can help us understand the inconsistencies among past studies and improve our understanding of the functional significance of the MOCR.

Evidence for age-related cochlear synaptopathy in humans unconnected to speech-in-noise intelligibility deficits.

Cochlear synaptopathy (or the loss of primary auditory synapses) remains a subclinical condition of uncertain prevalence. Here, we investigate whether it affects humans and whether it contributes to suprathreshold speech-in-noise intelligibility deficits. For 94 human listeners with normal audiometry (aged 12-68 years; 64 women), we measured click-evoked auditory brainstem responses (ABRs), self-reported lifetime noise exposure, and speech reception thresholds for sentences (at 65 dB SPL) and words (at 50, 65 and 80 dB SPL) in steady-state and fluctuating maskers. Based on animal research, we assumed that the shallower the rate of growth of ABR wave-I amplitude versus level function, the higher the risk of suffering from synaptopathy. We found that wave-I growth rates decreased with increasing age but not with increasing noise exposure. Speech reception thresholds in noise were not correlated with wave-I growth rates and mean speech reception thresholds were not statistically different for two subgroups of participants (N = 14) with matched audiograms (up to 12 kHz) but different wave-I growth rates. Altogether, the data are consistent with the existence of age-related but not noise-related synaptopathy. In addition, the data dispute the notion that synaptopathy contributes to suprathreshold speech-in-noise intelligibility deficits.

Predictors of Hearing-Aid Outcomes.

Over 360 million people worldwide suffer from disabling hearing loss. Most of them can be treated with hearing aids. Unfortunately, performance with hearing aids and the benefit obtained from using them vary widely across users. Here, we investigate the reasons for such variability. Sixty-eight hearing-aid users or candidates were fitted bilaterally with nonlinear hearing aids using standard procedures. Treatment outcome was assessed by measuring aided speech intelligibility in a time-reversed two-talker background and self-reported improvement in hearing ability. Statistical predictive models of these outcomes were obtained using linear combinations of 19 predictors, including demographic and audiological data, indicators of cochlear mechanical dysfunction and auditory temporal processing skills, hearing-aid settings, working memory capacity, and pretreatment self-perceived hearing ability. Aided intelligibility tended to be better for younger hearing-aid users with good unaided intelligibility in quiet and with good temporal processing abilities. Intelligibility tended to improve by increasing amplification for low-intensity sounds and by using more linear amplification for high-intensity sounds. Self-reported improvement in hearing ability was hard to predict but tended to be smaller for users with better working memory capacity. Indicators of cochlear mechanical dysfunction, alone or in combination with hearing settings, did not affect outcome predictions. The results may be useful for improving hearing aids and setting patients' expectations.

The Influence of Cochlear Mechanical Dysfunction, Temporal Processing Deficits, and Age on the Intelligibility of Audible Speech in Noise for Hearing-Impaired Listeners.

The aim of this study was to assess the relative importance of cochlear mechanical dysfunction, temporal processing deficits, and age on the ability of hearing-impaired listeners to understand speech in noisy backgrounds. Sixty-eight listeners took part in the study. They were provided with linear, frequency-specific amplification to compensate for their audiometric losses, and intelligibility was assessed for speech-shaped noise (SSN) and a time-reversed two-talker masker (R2TM). Behavioral estimates of cochlear gain loss and residual compression were available from a previous study and were used as indicators of cochlear mechanical dysfunction. Temporal processing abilities were assessed using frequency modulation detection thresholds. Age, audiometric thresholds, and the difference between audiometric threshold and cochlear gain loss were also included in the analyses. Stepwise multiple linear regression models were used to assess the relative importance of the various factors for intelligibility. Results showed that (a) cochlear gain loss was unrelated to intelligibility, (b) residual cochlear compression was related to intelligibility in SSN but not in a R2TM, (c) temporal processing was strongly related to intelligibility in a R2TM and much less so in SSN, and (d) age per se impaired intelligibility. In summary, all factors affected intelligibility, but their relative importance varied across maskers.

Forward-masking recovery and the assumptions of the temporal masking curve method of inferring cochlear compression.

The temporal masking curve (TMC) method is a behavioral technique for inferring human cochlear compression. The method relies on the assumptions that in the absence of compression, forward-masking recovery is independent of masker level and probe frequency. The present study aimed at testing the validity of these assumptions. Masking recovery was investigated for eight listeners with sensorineural hearing loss carefully selected to have absent or nearly absent distortion product otoacoustic emissions. It is assumed that for these listeners basilar membrane responses are linear, hence that masking recovery is independent of basilar membrane compression. TMCs for probe frequencies of 0.5, 1, 2, 4, and 6 kHz were available for these listeners from a previous study. The dataset included TMCs for masker frequencies equal to the probe frequencies plus reference TMCs measured using a high-frequency probe and a low, off-frequency masker. All of the TMCs were fitted using linear regression, and the resulting slope and intercept values were taken as indicative of masking recovery and masker level, respectively. Results for on-frequency TMCs suggest that forward-masking recovery is generally independent of probe frequency and of masker level and hence that it would be reasonable to use a reference TMC for a high-frequency probe to infer cochlear compression at lower frequencies. Results further show, however, that reference TMCs were sometimes shallower than corresponding on-frequency TMCs for identical probe frequencies, hence that compression could be overestimated in these cases. We discuss possible reasons for this result and the conditions when it might occur.

Across-frequency behavioral estimates of the contribution of inner and outer hair cell dysfunction to individualized audiometric loss.

Identifying the multiple contributors to the audiometric loss of a hearing impaired (HI) listener at a particular frequency is becoming gradually more useful as new treatments are developed. Here, we infer the contribution of inner (IHC) and outer hair cell (OHC) dysfunction to the total audiometric loss in a sample of 68 hearing aid candidates with mild-to-severe sensorineural hearing loss, and for test frequencies of 0.5, 1, 2, 4, and 6 kHz. It was assumed that the audiometric loss (HLTOTAL) at each test frequency was due to a combination of cochlear gain loss, or OHC dysfunction (HLOHC), and inefficient IHC processes (HLIHC), all of them in decibels. HLOHC and HLIHC were estimated from cochlear I/O curves inferred psychoacoustically using the temporal masking curve (TMC) method. 325 I/O curves were measured and 59% of them showed a compression threshold (CT). The analysis of these I/O curves suggests that (1) HLOHC and HLIHC account on average for 60-70 and 30-40% of HLTOTAL, respectively; (2) these percentages are roughly constant across frequencies; (3) across-listener variability is large; (4) residual cochlear gain is negatively correlated with hearing loss while residual compression is not correlated with hearing loss. Altogether, the present results support the conclusions from earlier studies and extend them to a wider range of test frequencies and hearing-loss ranges. Twenty-four percent of I/O curves were linear and suggested total cochlear gain loss. The number of linear I/O curves increased gradually with increasing frequency. The remaining 17% I/O curves suggested audiometric losses due mostly to IHC dysfunction and were more frequent at low (≤1 kHz) than at high frequencies. It is argued that in a majority of listeners, hearing loss is due to a common mechanism that concomitantly alters IHC and OHC function and that IHC processes may be more labile in the apex than in the base.

Contralateral efferent suppression of human hearing sensitivity.

The present study aimed at characterizing the suppressing effect of contralateral medial olivocochlear (MOC) efferents on human auditory sensitivity and mechanical cochlear responses at sound levels near behavioral thresholds. Absolute thresholds for pure tones of 500 and 4000 Hz with durations between 10-500 ms were measured in the presence and in the absence of a contralateral broadband noise. The intensity of the noise was fixed at 60 dB SPL to evoke the contralateral MOC reflex without evoking the middle-ear muscle reflex. In agreement with previously reported findings, thresholds measured without the contralateral noise decreased with increasing tone duration, and the rate of decrease was faster at 500 than at 4000 Hz. Contralateral stimulation increased thresholds by 1.07 and 1.72 dB at 500 and 4000 Hz, respectively. The mean increase (1.4 dB) just missed statistical significance (p = 0.08). Importantly, the across-frequency mean threshold increase was significantly greater for long than for short probes. This effect was more obvious at 4000 Hz than at 500 Hz. Assuming that thresholds depend on the MOC-dependent cochlear mechanical response followed by an MOC-independent, post-mechanical detection mechanism, the present results at 4000 Hz suggest that MOC efferent activation suppresses cochlear mechanical responses more at lower than at higher intensities across the range of intensities near threshold, while the results at 500 Hz suggest comparable mechanical suppression across the threshold intensity range. The results are discussed in the context of central masking and of auditory models of efferent suppression of cochlear mechanical responses.

Contralateral efferent regulation of human cochlear tuning: behavioural observations and computer model simulations.

In binaural listening, the two cochleae do not act as independent sound receptors; their functioning is linked via the contralateral medial olivo-cochlear reflex (MOCR), which can be activated by contralateral sounds. The present study aimed at characterizing the effect of a contralateral white noise (CWN) on psychophysical tuning curves (PTCs). PTCs were measured in forward masking for probe frequencies of 500 Hz and 4 kHz, with and without CWN. The sound pressure level of the probe was fixed across conditions. PTCs for different response criteria were measured by using various masker-probe time gaps. The CWN had no significant effects on PTCs at 4 kHz. At 500 Hz, by contrast, PTCs measured with CWN appeared broader, particularly for short gaps, and they showed a decrease in the masker level. This decrease was greater the longer the masker-probe time gap. A computer model of forward masking with efferent control of cochlear gain was used to explain the data. The model accounted for the data based on the assumption that the sole effect of the CWN was to reduce the cochlear gain by ∼6.5 dB at 500 Hz for low and moderate levels. It also suggested that the pattern of data at 500 Hz is the result of combined broad bandwidth of compression and off-frequency listening. Results are discussed in relation with other physiological and psychoacoustical studies on the effect of activation of MOCR on cochlear function.

Predictive value of serum human chorionic gonadotropin ratio, progesterone and inhibin A for expectant management of early pregnancies of unknown location.

OBJECTIVE: To evaluate serum human chorionic gonadotropin (hCG) ratio, progesterone and inhibin A as single parameters and in combination for the prediction of spontaneous resolution of pregnancies of unknown location (PUL). STUDY DESIGN: Prospective observational study of 105 consecutive patients with a diagnosis of PUL. Serum levels of hCG, progesterone and inhibin A were determined at the first visit and after 2 days. Patients were followed clinically until a final diagnosis of spontaneously resolving PUL, viable or non-viable intrauterine pregnancy, or ectopic pregnancy with need of laparoscopic intervention had been reached. Different combinations of hCG ratio (hCG at 48 h/hCG at 0 h), s-progesterone and s-inhibin A were investigated to find the best predictor for successful expectant management. RESULTS: The final pregnancy outcomes were: 52 spontaneously resolving PUL (49.5%), 37 viable intrauterine pregnancies (35.2%), 8 non-viable intrauterine pregnancies (7.6%), 7 ectopic pregnancies (6.7%), and one molar pregnancy (1.0%). An hCG ratio<0.80 predicted spontaneously resolving PUL with positive and negative predictive values (PPV and NPV), sensitivity, and specificity of 0.98, 0.78, 0.72, and 0.99, respectively. In patients with hCG ratio ≥ 0.80, a combination of s-progesterone < 20 nmol/l and s-inhibin A < 30 pg/ml predicted spontaneously resolving PUL with PPV, NPV, sensitivity and specificity of 0.92, 0.96, 0.85, and 0.98 respectively. CONCLUSION: Our results suggest that patients with PUL and hCG ratio < 0.80 display a high probability of spontaneously resolving PUL with minimum need of follow-up. In cases of hCG ratio ≥ 0.80, a combination of s-progesterone < 20 nmol/l and s-inhibin A < 30 pg/ml, may be a reliable predictor of spontaneously resolving PUL. The safety of this approach should be tested in large prospective studies.

Behavioral estimates of the contribution of inner and outer hair cell dysfunction to individualized audiometric loss.

Differentiating the relative importance of the various contributors to the audiometric loss (HL(TOTAL)) of a given hearing impaired listener and frequency region is becoming critical as more specific treatments are being developed. The aim of the present study was to assess the relative contribution of inner (IHC) and outer hair cell (OHC) dysfunction (HL(IHC) and HL(OHC), respectively) to the audiometric loss of patients with mild to moderate cochlear hearing loss. It was assumed that HL(TOTAL) = HL(OHC) + HL(IHC) (all in decibels) and that HL(OHC) may be estimated as the reduction in maximum cochlear gain. It is argued that the latter may be safely estimated from compression threshold shifts of cochlear input/output (I/O) curves relative to normal hearing references. I/O curves were inferred behaviorally using forward masking for 26 test frequencies in 18 hearing impaired listeners. Data suggested that the audiometric loss for six of these 26 test frequencies was consistent with pure OHC dysfunction, one was probably consistent with pure IHC dysfunction, 13 were indicative of mixed IHC and OHC dysfunction, and five were uncertain (one more was excluded from the analysis). HL(OHC) and HL(IHC) contributed on average 60 and 40 %, respectively, to the audiometric loss, but variability was large across cases. Indeed, in some cases, HL(IHC) was up to 63 % of HL(TOTAL), even for moderate losses. The repeatability of the results is assessed using Monte Carlo simulations and potential sources of bias are discussed.

Correspondence between behavioral and individually "optimized" otoacoustic emission estimates of human cochlear input/output curves.

Previous studies have shown a high within-subject correspondence between distortion product otoacoustic emission (DPOAE) input/output (I/O) curves and behaviorally inferred basilar membrane (BM) I/O curves for frequencies above approximately 2 kHz. For lower frequencies, DPOAE I/O curves contained notches and plateaus that did not have a counterpart in corresponding behavioral curves. It was hypothesized that this might improve by using individualized optimal DPOAE primary levels. Here, data from previous studies are re-analyzed to test this hypothesis by comparing behaviorally inferred BM I/O curves and DPOAE I/O curves measured with well-established group-average primary levels and two individualized primary level rules: one optimized to maximize DPOAE levels and one intended for primaries to evoke comparable BM responses at the f(2) cochlear region. Test frequencies were 0.5, 1, and 4 kHz. Behavioral I/O curves were obtained from temporal (forward) masking curves. Results showed high within-subject correspondence between behavioral and DPOAE I/O curves at 4 kHz only, regardless of the primary level rule. Plateaus and notches were equally common in low-frequency DPOAE I/O curves for individualized and group-average DPOAE primary levels at 0.5 and 1 kHz. Results are discussed in terms of the adequacy of DPOAE I/O curves for inferring individual cochlear nonlinearity characteristics.

Otoacoustic emission theories and behavioral estimates of human basilar membrane motion are mutually consistent.

When two pure tones (or primaries) of slightly different frequencies (f (1) and f (2)) are presented to the ear, new frequency components are generated by nonlinear interaction of the primaries within the cochlea. These new components can be recorded in the ear canal as otoacoustic emissions (OAE). The level of the 2f (1)-f (2) OAE component is known as the distortion product otoacoustic emission (DPOAE) and is regarded as an indicator of the physiological state of the cochlea. The current view is that maximal level DPOAEs occur for primaries that produce equal excitation at the f (2) cochlear region, but this notion cannot be directly tested in living humans because it is impossible to record their cochlear responses while monitoring their ear canal DPOAE levels. On the other hand, it has been claimed that the temporal masking curve (TMC) method of inferring human basilar membrane responses allows measurement of the levels of equally effective pure tones at any given cochlear site. The assumptions of this behavioral method, however, lack firm physiological support in humans. Here, the TMC method was applied to test the current notion on the conditions that maximize DPOAE levels in humans. DPOAE and TMC results were mutually consistent for frequencies of 1 and 4 kHz and for levels below around 65 dB sound pressure level. This match supports the current view on the generation of maximal level DPOAEs as well as the assumptions of the behavioral TMC method.

Cochlear nonlinearity in normal-hearing subjects as inferred psychophysically and from distortion-product otoacoustic emissions.

The aim was to investigate the correlation between compression exponent, compression threshold, and cochlear gain for normal-hearing subjects as inferred from temporal masking curves (TMCs) and distortion-product otoacoustic emission (DPOAEs) input-output (I/O) curves. Care was given to reduce the influence of DPOAE fine structure on the DPOAE I/O curves. A high correlation between compression exponent estimates obtained with the two methods was found at 4 kHz but not at 0.5 and 1 kHz. One reason is that the DPOAE I/O curves show plateaus or notches that result in unexpectedly high compression estimates. Moderately high correlation was found between compression threshold estimates obtained with the two methods, although DPOAE-based values were around 7 dB lower than those based on TMCs. Both methods show that compression exponent and threshold are approximately constant across the frequency range from 0.5 to 4 kHz. Cochlear gain as estimated from TMCs was found to be approximately 16 dB greater at 4 than at 0.5 kHz. In conclusion, DPOAEs and TMCs may be used interchangeably to infer precise individual nonlinear cochlear characteristics at 4 kHz, but it remains unclear that the same applies to lower frequencies.