Envelope following responses for hearing diagnosis: Robustness and methodological considerations.

Recent studies have found that envelope following responses (EFRs) are a marker of age-related and noise- or ototoxic-induced cochlear synaptopathy (CS) in research animals. Whereas the cochlear injury can be well controlled in animal research studies, humans may have an unknown mixture of sensorineural hearing loss [SNHL; e.g., inner- or outer-hair-cell (OHC) damage or CS] that cannot be teased apart in a standard hearing evaluation. Hence, a direct translation of EFR markers of CS to a differential CS diagnosis in humans might be compromised by the influence of SNHL subtypes and differences in recording modalities between research animals and humans. To quantify the robustness of EFR markers for use in human studies, this study investigates the impact of methodological considerations related to electrode montage, stimulus characteristics, and presentation, as well as analysis method on human-recorded EFR markers. The main focus is on rectangularly modulated pure-tone stimuli to evoke the EFR based on a recent auditory modelling study that showed that the EFR was least affected by OHC damage and most sensitive to CS in this stimulus configuration. The outcomes of this study can help guide future clinical implementations of electroencephalography-based SNHL diagnostic tests.

Predicting synapse counts in living humans by combining computational models with auditory physiology.

Aging, noise exposure, and ototoxic medications lead to cochlear synapse loss in animal models. As cochlear function is highly conserved across mammalian species, synaptopathy likely occurs in humans as well. Synaptopathy is predicted to result in perceptual deficits including tinnitus, hyperacusis, and difficulty understanding speech-in-noise. The lack of a method for diagnosing synaptopathy in living humans hinders studies designed to determine if noise-induced synaptopathy occurs in humans, identify the perceptual consequences of synaptopathy, or test potential drug treatments. Several physiological measures are sensitive to synaptopathy in animal models including auditory brainstem response (ABR) wave I amplitude. However, it is unclear how to translate these measures to synaptopathy diagnosis in humans. This work demonstrates how a human computational model of the auditory periphery, which can predict ABR waveforms and distortion product otoacoustic emissions (DPOAEs), can be used to predict synaptic loss in individual human participants based on their measured DPOAE levels and ABR wave I amplitudes. Lower predicted synapse numbers were associated with advancing age, higher noise exposure history, increased likelihood of tinnitus, and poorer speech-in-noise perception. These findings demonstrate the utility of this modeling approach in predicting synapse counts from physiological data in individual human subjects.

The role of hidden hearing loss in tinnitus: Insights from early markers of peripheral hearing damage.

Since the presence of tinnitus is not always associated with audiometric hearing loss, it has been hypothesized that hidden hearing loss may act as a potential trigger for increased central gain along the neural pathway leading to tinnitus perception. In recent years, the study of hidden hearing loss has improved with the discovery of cochlear synaptopathy and several objective diagnostic markers. This study investigated three potential markers of peripheral hidden hearing loss in subjects with tinnitus: extended high-frequency audiometric thresholds, the auditory brainstem response, and the envelope following response. In addition, speech intelligibility was measured as a functional outcome measurement of hidden hearing loss. To account for age-related hidden hearing loss, participants were grouped according to age, presence of tinnitus, and audiometric thresholds. Group comparisons were conducted to differentiate between age- and tinnitus-related effects of hidden hearing loss. All three markers revealed age-related differences, whereas no differences were observed between the tinnitus and non-tinnitus groups. However, the older tinnitus group showed improved performance on low-pass filtered speech in noise tests compared to the older non-tinnitus group. These low-pass speech in noise scores were significantly correlated with tinnitus distress, as indicated using questionnaires, and could be related to the presence of hyperacusis. Based on our observations, cochlear synaptopathy does not appear to be the underlying cause of tinnitus. The improvement in low-pass speech-in-noise could be explained by enhanced temporal fine structure encoding or hyperacusis. Therefore, we recommend that future tinnitus research takes into account age-related factors, explores low-frequency encoding, and thoroughly assesses hyperacusis.

Evaluation of Lifetime Noise Exposure History Reporting.

PURPOSE: The purpose of this study is to critically evaluate lifetime noise exposure history (LNEH) reporting. First, two different approaches to evaluate the cumulative LNEH were compared. Second, individual LNEH was associated with the subjects' hearing status. Third, loudness estimates of exposure activities, by means of Jokitulppo- and Ferguson-based exposure levels, were compared with dosimeter sound-level measurements. METHOD: One hundred one young adults completed the questionnaires, and a subgroup of 30 subjects underwent audiological assessment. Pure-tone audiometry, speech-in-noise intelligibility, distortion product otoacoustic emissions, auditory brainstem responses, and envelope following responses were included. Fifteen out of the 30 subjects took part in a noisy activity while wearing a dosimeter. RESULTS: First, results demonstrate that the structured questionnaire yielded a greater amount of information pertaining to the diverse activities, surpassing the insights obtained from an open-ended questionnaire. Second, no significant correlations between audiological assessment and LNEH were found. Lastly, the results indicate that Ferguson-based exposure levels offer a more precise estimation of the actual exposure levels, in contrast to Jokitulppo-based estimates. CONCLUSIONS: We propose several recommendations for determining the LNEH. First, it is vital to define accurate loudness categories and corresponding allocated levels, with a preference for the loudness levels proposed by Ferguson et al. (2019), as identified in this study. Second, a structured questionnaire regarding LNEH is recommended, discouraging open-ended questioning. Third, it is essential to include a separate category exclusively addressing work-related activities, encompassing various activities for more accurate surveying.

Individualized Cochlear Models Based on Distortion Product Otoacoustic Emissions.

Auditory models have been adopted for years to simulate characteristics of the human auditory processing for normal and hearing-impaired listeners. However, individual differences due to varying degrees of frequency-dependent hearing damage hinders the simulation of auditory processing on an individualized basis. Here, with a view on precise auditory profiling, recorded distortion product otoacoustic emission (DPOAE) metrics are used to determine individual parameters of cochlear non-linearity to yield individualized human cochlear models, which can be used as pre-processors for hearing-aid and machine-hearing applications. We test whether individualized cochlear models based on DPOAE measurements can simulate the measured DPOAEs and audiograms of normal-hearing and hearing-impaired listeners. Results showed that cochlear models individualized based on DPOAE-grams measured at low stimulus levels or DPOAE thresholds, yield the smallest simulation errors.

Towards Personalized Auditory Models: Predicting Individual Sensorineural Hearing-Loss Profiles From Recorded Human Auditory Physiology.

Over the past decades, different types of auditory models have been developed to study the functioning of normal and impaired auditory processing. Several models can simulate frequency-dependent sensorineural hearing loss (SNHL) and can in this way be used to develop personalized audio-signal processing for hearing aids. However, to determine individualized SNHL profiles, we rely on indirect and noninvasive markers of cochlear and auditory-nerve (AN) damage. Our progressive knowledge of the functional aspects of different SNHL subtypes stresses the importance of incorporating them into the simulated SNHL profile, but has at the same time complicated the task of accomplishing this on the basis of noninvasive markers. In particular, different auditory-evoked potential (AEP) types can show a different sensitivity to outer-hair-cell (OHC), inner-hair-cell (IHC), or AN damage, but it is not clear which AEP-derived metric is best suited to develop personalized auditory models. This study investigates how simulated and recorded AEPs can be used to derive individual AN- or OHC-damage patterns and personalize auditory processing models. First, we individualized the cochlear model parameters using common methods of frequency-specific OHC-damage quantification, after which we simulated AEPs for different degrees of AN damage. Using a classification technique, we determined the recorded AEP metric that best predicted the simulated individualized cochlear synaptopathy profiles. We cross-validated our method using the data set at hand, but also applied the trained classifier to recorded AEPs from a new cohort to illustrate the generalizability of the method.

The Variability in Potential Biomarkers for Cochlear Synaptopathy After Recreational Noise Exposure.

PURPOSE: Speech-in-noise tests and suprathreshold auditory evoked potentials are promising biomarkers to diagnose cochlear synaptopathy (CS) in humans. This study investigated whether these biomarkers changed after recreational noise exposure. METHOD: The baseline auditory status of 19 normal-hearing young adults was analyzed using questionnaires, pure-tone audiometry, speech audiometry, and auditory evoked potentials. Nineteen subjects attended a music festival and completed the same tests again at Day 1, Day 3, and Day 5 after the music festival. RESULTS: No significant relations were found between lifetime noise-exposure history and the hearing tests. Changes in biomarkers from the first session to the follow-up sessions were nonsignificant, except for speech audiometry, which showed a significant learning effect (performance improvement). CONCLUSIONS: Despite the individual variability in prefestival biomarkers, we did not observe changes related to the noise-exposure dose caused by the attended event. This can indicate the absence of noise exposure-driven CS in the study cohort, or reflect that biomarkers were not sensitive enough to detect mild CS. Future research should include a more diverse study cohort, dosimetry, and results from test-retest reliability studies to provide more insight into the relationship between recreational noise exposure and CS. Supplemental Material https://doi.org/10.23641/asha.16821283.

The derived-band envelope following response and its sensitivity to sensorineural hearing deficits.

The envelope following response (EFR) has been proposed as a non-invasive marker of synaptopathy in animal models. However, its amplitude is affected by the spread of basilar-membrane excitation and other coexisting sensorineural hearing deficits. This study aims to (i) improve frequency specificity of the EFR by introducing a derived-band EFR (DBEFR) technique and (ii) investigate the effect of lifetime noise exposure, age and outer-hair-cell (OHC) damage on DBEFR magnitudes. Additionally, we adopt a modelling approach to validate the frequency-specificity of the DBEFR and test how different aspects of sensorineural hearing loss affect peripheral generators. The combined analysis of simulations and experimental data proposes that the DBEFRs extracted from the [2-6]-kHz frequency band is a sensitive and frequency-specific measure of synaptopathy in humans. Individual variability in DBEFR magnitudes among listeners with normal audiograms was explained by their self-reported amount of experienced lifetime noise-exposure and corresponded to amplitude variability predicted by synaptopathy. Older listeners consistently had reduced DBEFR magnitudes in comparison to young normal-hearing listeners, in correspondence to how age-induced synaptopathy affects EFRs and compromises temporal envelope encoding. To a lesser degree, OHC damage was also seen to affect the DBEFR magnitude, hence the DBEFR metric should ideally be combined with a sensitive marker of OHC damage to offer a differential diagnosis of synaptopathy in listeners with impaired audiograms.