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.

Neural Adaptation at Stimulus Onset and Speed of Neural Processing as Critical Contributors to Speech Comprehension Independent of Hearing Threshold or Age.

Background: It is assumed that speech comprehension deficits in background noise are caused by age-related or acquired hearing loss. Methods: We examined young, middle-aged, and older individuals with and without hearing threshold loss using pure-tone (PT) audiometry, short-pulsed distortion-product otoacoustic emissions (pDPOAEs), auditory brainstem responses (ABRs), auditory steady-state responses (ASSRs), speech comprehension (OLSA), and syllable discrimination in quiet and noise. Results: A noticeable decline of hearing sensitivity in extended high-frequency regions and its influence on low-frequency-induced ABRs was striking. When testing for differences in OLSA thresholds normalized for PT thresholds (PTTs), marked differences in speech comprehension ability exist not only in noise, but also in quiet, and they exist throughout the whole age range investigated. Listeners with poor speech comprehension in quiet exhibited a relatively lower pDPOAE and, thus, cochlear amplifier performance independent of PTT, smaller and delayed ABRs, and lower performance in vowel-phoneme discrimination below phase-locking limits (/o/-/u/). When OLSA was tested in noise, listeners with poor speech comprehension independent of PTT had larger pDPOAEs and, thus, cochlear amplifier performance, larger ASSR amplitudes, and higher uncomfortable loudness levels, all linked with lower performance of vowel-phoneme discrimination above the phase-locking limit (/i/-/y/). Conslusions: This study indicates that listening in noise in humans has a sizable disadvantage in envelope coding when basilar-membrane compression is compromised. Clearly, and in contrast to previous assumptions, both good and poor speech comprehension can exist independently of differences in PTTs and age, a phenomenon that urgently requires improved techniques to diagnose sound processing at stimulus onset in the clinical routine.

Wireless and Wearable Auditory EEG Acquisition Hardware Using Around-The-Ear cEEGrid Electrodes.

Aside from a clinical interest in electroencephalography (EEG) measurements of real-time data with a high temporal resolution, there is a demand for acquisition systems that are operable outside the laboratory environment. In this study, we designed a wearable and low-power EEG system for multichannel EEG acquisition beyond the lab doors. Around-the-ear cEEGrid electrodes are used to capture 8 biopotential channels which are amplified by low-power precision instrumentation amplifiers and passed on to an analog-to-digital converter (ADC). An ESP32 micro-controller captures the data from the ADC and stores it on an external SD card. The proposed system is compared to a state-of-the-art EEG acquisition system (BioSemi) to assess its diagnostic power for auditory brainstem responses (ABRs). The recordings with our portable system match, and even outperform, the baseline method's specifications. Our hardware opens up new avenues for fast sampling-rate auditory EEG recordings that can be used in hearing diagnostics, damage prevention and treatment follow up.

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.

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.

A comparative study of eight human auditory models of monaural processing.

A number of auditory models have been developed using diverging approaches, either physiological or perceptual, but they share comparable stages of signal processing, as they are inspired by the same constitutive parts of the auditory system. We compare eight monaural models that are openly accessible in the Auditory Modelling Toolbox. We discuss the considerations required to make the model outputs comparable to each other, as well as the results for the following model processing stages or their equivalents: Outer and middle ear, cochlear filter bank, inner hair cell, auditory nerve synapse, cochlear nucleus, and inferior colliculus. The discussion includes a list of recommendations for future applications of auditory models.

Model-based hearing-enhancement strategies for cochlear synaptopathy pathologies.

It is well known that ageing and noise exposure are important causes of sensorineural hearing loss, and can result in damage of the outer hair cells or other structures of the inner ear, including synaptic damage to the auditory nerve (AN), i.e., cochlear synaptopathy (CS). Despite the suspected high prevalence of CS among people with self-reported hearing difficulties but seemingly normal hearing, conventional hearing-aid algorithms do not compensate for the functional deficits associated with CS. Here, we present and evaluate a number of auditory signal-processing strategies designed to maximally restore AN coding for listeners with CS pathologies. We evaluated our algorithms in subjects with and without suspected age-related CS to assess whether physiological and behavioural markers associated with CS can be improved. Our data show that after applying our algorithms, envelope-following responses and perceptual amplitude-modulation sensitivity were consistently enhanced in both young and older listeners. Speech-in-noise intelligibility showed small improvements after processing but mostly for young normal-hearing participants, with median improvements of up to 8.3%. Since our hearing-enhancement strategies were designed to optimally drive the AN fibres, they were able to improve temporal-envelope processing for listeners both with and without suspected CS. Our proposed algorithms can be rapidly executed and can thus extend the application range of current hearing aids and hearables, while leaving sound amplification unaffected.

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.

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.

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.

A convolutional neural-network framework for modelling auditory sensory cells and synapses.

In classical computational neuroscience, analytical model descriptions are derived from neuronal recordings to mimic the underlying biological system. These neuronal models are typically slow to compute and cannot be integrated within large-scale neuronal simulation frameworks. We present a hybrid, machine-learning and computational-neuroscience approach that transforms analytical models of sensory neurons and synapses into deep-neural-network (DNN) neuronal units with the same biophysical properties. Our DNN-model architecture comprises parallel and differentiable equations that can be used for backpropagation in neuro-engineering applications, and offers a simulation run-time improvement factor of 70 and 280 on CPU or GPU systems respectively. We focussed our development on auditory neurons and synapses, and show that our DNN-model architecture can be extended to a variety of existing analytical models. We describe how our approach for auditory models can be applied to other neuron and synapse types to help accelerate the development of large-scale brain networks and DNN-based treatments of the pathological system.

Envelope following responses predict speech-in-noise performance in normal-hearing listeners.

Permanent threshold elevation after noise exposure or aging is caused by loss of sensory cells; however, animal studies show that hair cell loss is often preceded by degeneration of the synapses between sensory cells and auditory nerve fibers. Silencing these neurons is likely to degrade auditory processing and may contribute to difficulties understanding speech in noisy backgrounds. Reduction of suprathreshold ABR amplitudes can be used to quantify synaptopathy in inbred mice. However, ABR amplitudes are highly variable in humans, and thus more challenging to use. Since noise-induced neuropathy preferentially targets fibers with high thresholds and low spontaneous rate and because phase locking to temporal envelopes is particularly strong in these fibers, measuring envelope following responses (EFRs) might be a more robust measure of cochlear synaptopathy. A recent auditory model further suggests that modulation of carrier tones with rectangular envelopes should be less sensitive to cochlear amplifier dysfunction and, therefore, a better metric of cochlear neural damage than sinusoidal amplitude modulation. In this study, we measure performance scores on a variety of difficult word-recognition tasks among listeners with normal audiograms and assess correlations with EFR magnitudes to rectangular versus sinusoidal modulation. Higher harmonics of EFR magnitudes evoked by a rectangular-envelope stimulus were significantly correlated with word scores, whereas those evoked by sinusoidally modulated tones did not. These results support previous reports that individual differences in synaptopathy may be a source of speech recognition variability despite the presence of normal thresholds at standard audiometric frequencies.NEW & NOTEWORTHY Recent studies suggest that millions of people may be at risk of permanent impairment from cochlear synaptopathy, the age-related and noise-induced degeneration of neural connections in the inner ear. This study examines electrophysiological responses to stimuli designed to improve detection of neural damage in subjects with normal hearing sensitivity. The resultant correlations with word recognition performance are consistent with a contribution of cochlear neural damage to deficits in hearing in noise abilities.

A convolutional neural-network model of human cochlear mechanics and filter tuning for real-time applications.

Auditory models are commonly used as feature extractors for automatic speech-recognition systems or as front-ends for robotics, machine-hearing and hearing-aid applications. Although auditory models can capture the biophysical and nonlinear properties of human hearing in great detail, these biophysical models are computationally expensive and cannot be used in real-time applications. We present a hybrid approach where convolutional neural networks are combined with computational neuroscience to yield a real-time end-to-end model for human cochlear mechanics, including level-dependent filter tuning (CoNNear). The CoNNear model was trained on acoustic speech material and its performance and applicability were evaluated using (unseen) sound stimuli commonly employed in cochlear mechanics research. The CoNNear model accurately simulates human cochlear frequency selectivity and its dependence on sound intensity, an essential quality for robust speech intelligibility at negative speech-to-background-noise ratios. The CoNNear architecture is based on parallel and differentiable computations and has the power to achieve real-time human performance. These unique CoNNear features will enable the next generation of human-like machine-hearing applications.

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.

Enhancing the sensitivity of the envelope-following response for cochlear synaptopathy screening in humans: The role of stimulus envelope.

Auditory de-afferentation, a permanent reduction in the number of inner-hair-cells and auditory-nerve synapses due to cochlear damage or synaptopathy, can reliably be quantified using temporal bone histology and immunostaining. However, there is an urgent need for non-invasive markers of synaptopathy to study its perceptual consequences in live humans and to develop effective therapeutic interventions. While animal studies have identified candidate auditory-evoked-potential (AEP) markers for synaptopathy, their interpretation in humans has suffered from translational issues related to neural generator differences, unknown hearing-damage histopathologies or lack of measurement sensitivity. To render AEP-based markers of synaptopathy more sensitive and differential to the synaptopathy aspect of sensorineural hearing loss, we followed a combined computational and experimental approach. Starting from the known characteristics of auditory-nerve physiology, we optimized the stimulus envelope to stimulate the available auditory-nerve population optimally and synchronously to generate strong envelope-following-responses (EFRs). We further used model simulations to explore which stimuli evoked a response that was sensitive to synaptopathy, while being maximally insensitive to possible co-existing outer-hair-cell pathologies. We compared the model-predicted trends to AEPs recorded in younger and older listeners (N=44, 24f) who had normal or impaired audiograms with suspected age-related synaptopathy in the older cohort. We conclude that optimal stimulation paradigms for EFR-based quantification of synaptopathy should have sharply rising envelope shapes, a minimal plateau duration of 1.7-2.1 ms for a 120-Hz modulation rate, and inter-peak intervals which contain near-zero amplitudes. From our recordings, the optimal EFR-evoking stimulus had a rectangular envelope shape with a 25% duty cycle and a 95% modulation depth. Older listeners with normal or impaired audiometric thresholds showed significantly reduced EFRs, which were consistent with how (age-induced) synaptopathy affected these responses in the model.

Optimized Tuning of Auditory Inner Hair Cells to Encode Complex Sound through Synergistic Activity of Six Independent K+ Current Entities.

Auditory inner hair cells (IHCs) convert sound vibrations into receptor potentials that drive synaptic transmission. For the precise encoding of sound qualities, receptor potentials are shaped by K+ conductances tuning the properties of the IHC membrane. Using patch-clamp and computational modeling, we unravel this membrane specialization showing that IHCs express an exclusive repertoire of six voltage-dependent K+ conductances mediated by Kv1.8, Kv7.4, Kv11.1, Kv12.1, and BKCa channels. All channels are active at rest but are triggered differentially during sound stimulation. This enables non-saturating tuning over a far larger potential range than in IHCs expressing fewer current entities. Each conductance contributes to optimizing responses, but the combined activity of all channels synergistically improves phase locking and the dynamic range of intensities that IHCs can encode. Conversely, hypothetical simpler IHCs appear limited to encode only certain aspects (frequency or intensity). The exclusive channel repertoire of IHCs thus constitutes an evolutionary adaptation to encode complex sound through multifaceted receptor potentials.

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.

Acquisition of Subcortical Auditory Potentials With Around-the-Ear cEEGrid Technology in Normal and Hearing Impaired Listeners.

Even though the principles of recording brain electrical activity remain unchanged since their discovery, their acquisition has seen major improvements. The cEEGrid, a recently developed flex-printed multi-channel sensory array, can be placed around the ear and successfully record well-known cortical electrophysiological potentials such as late auditory evoked potentials (AEPs) or the P300. Due to its fast and easy application as well as its long-lasting signal recording window, the cEEGrid technology offers great potential as a flexible and 'wearable' solution for the acquisition of neural correlates of hearing. Early potentials of auditory processing such as the auditory brainstem response (ABR) are already used in clinical assessment of sensorineural hearing disorders and envelope following responses (EFR) have shown promising results in the diagnosis of suprathreshold hearing deficits. This study evaluates the suitability of the cEEGrid electrode configuration to capture these AEPs. cEEGrid potentials were recorded and compared to cap-EEG potentials for young normal-hearing listeners and older listeners with high-frequency sloping audiograms to assess whether the recordings are adequately sensitive for hearing diagnostics. ABRs were elicited by presenting clicks (70 and 100-dB peSPL) and stimulation for the EFRs consisted of 120 Hz amplitude-modulated white noise carriers presented at 70-dB SPL. Data from nine bipolar cEEGrid channels and one classical cap-EEG montage (earlobes to vertex) were analysed and outcome measures were compared. Results show that the cEEGrid is able to record ABRs and EFRs with comparable shape to those recorded using a conventional cap-EEG recording montage and the same amplifier. Signal strength is lower but can still produce responses above the individual neural electrophysiological noise floor. This study shows that the application of the cEEGrid can be extended to the acquisition of early auditory evoked potentials.

Applicability of subcortical EEG metrics of synaptopathy to older listeners with impaired audiograms.

Emerging evidence suggests that cochlear synaptopathy is a common feature of sensorineural hearing loss, but it is not known to what extent electrophysiological metrics targeting synaptopathy in animals can be applied to people, such as those with impaired audiograms. This study investigates the applicability of subcortical electrophysiological measures associated with synaptopathy, i.e., auditory brainstem responses (ABRs) and envelope following responses (EFRs), to older participants with high-frequency sloping audiograms. The outcomes of this study are important for the development of reliable and sensitive synaptopathy diagnostics in people with normal or impaired outer-hair-cell function. Click-ABRs at different sound pressure levels and EFRs to amplitude-modulated stimuli were recorded, as well as relative EFR and ABR metrics which reduce the influence of individual factors such as head size and noise floor level on the measures. Most tested metrics showed significant differences between the groups and did not always follow the trends expected from synaptopathy. Age was not a reliable predictor for the electrophysiological metrics in the older hearing-impaired group or young normal-hearing control group. This study contributes to a better understanding of how electrophysiological synaptopathy metrics differ in ears with healthy and impaired audiograms, which is an important first step towards unravelling the perceptual consequences of synaptopathy.

The search for noise-induced cochlear synaptopathy in humans: Mission impossible?

Animal studies demonstrate that noise exposure can permanently damage the synapses between inner hair cells and auditory nerve fibers, even when outer hair cells are intact and there is no clinically relevant permanent threshold shift. Synaptopathy disrupts the afferent connection between the cochlea and the central auditory system and is predicted to impair speech understanding in noisy environments and potentially result in tinnitus and/or hyperacusis. While cochlear synaptopathy has been demonstrated in numerous experimental animal models, synaptopathy can only be confirmed through post-mortem temporal bone analysis, making it difficult to study in living humans. A variety of non-invasive measures have been used to determine whether noise-induced synaptopathy occurs in humans, but the results are conflicting. The overall objective of this article is to synthesize the existing data on the functional impact of noise-induced synaptopathy in the human auditory system. The first section of the article summarizes the studies that provide evidence for and against noise-induced synaptopathy in humans. The second section offers potential explanations for the differing results between studies. The final section outlines suggested methodologies for diagnosing synaptopathy in humans with the aim of improving consistency across studies.