A Systematic Review: State of the Science on Diagnostics of Hidden Hearing Loss

Hearing loss is a major public health issue with diverse etiologies and substantial comorbidities. Despite normal pure-tone audiograms, many individuals report difficulty understanding speech in noisy environments—termed hidden hearing loss (HHL). Its pathophysiologic correlate, cochlear synaptopathy, involves loss of synapses between inner hair cells and auditory nerve fibers and may precede or occur without hair cell loss. Risk factors include noise exposure, ototoxic drugs, neuropathies, and aging, and comorbidities include tinnitus and hyperacusis. Because HHL evades traditional screening, the study aims to identify and compare diagnostic tools capable of detecting HHL through objective physiological measures, provide context for their relationship to synaptopathy, and suggest directions toward standardization and clinical implementation.

The review outlines the pathophysiology of HHL as cochlear synaptopathy affecting afferent fibers and possibly myelination, leading to impaired auditory nerve responses with normal thresholds. It summarizes proposed diagnostic approaches: electrophysiological measures such as ABR (especially wave I amplitude and I/V ratio), MEMR (reliant on low-spontaneous-rate fibers), EcochG (SP and AP components, including SP/AP ratio), and FFR (EFR and TFS components). Behavioral measures like speech-in-noise tests, dichotic listening, and matrix tests are frequently used to assess perceptual impact but are not objective markers of synaptopathy. The literature indicates variable findings across methods and emphasizes the need for multimodal assessment and standardization.

A systematic review was conducted following PRISMA guidelines. Databases queried included PubMed, Cochrane Library, Google Scholar, and SCOPUS. Search terms combined MeSH and keywords related to hidden hearing loss, cochlear synaptopathy/neuropathy, and diagnostic measures. Inclusion criteria: original human studies published in or after 2019; adult subjects with normal audiograms (auditory thresholds ≤25 dB up to 8 kHz); objective physiological outcomes (e.g., neural activity, reflex measures); clear stratification into at-risk/symptomatic versus healthy/low-risk controls based on lifetime/occupational noise exposure, age-related risk, elevated high-frequency thresholds, or self-reported difficulty understanding speech in noise. Exclusion criteria: non-diagnostic frameworks; animal studies; subjects with abnormal audiograms or diagnosed SNHL/presbycusis; purely behavioral measures without physiological data; correlational designs lacking distinct groups; case reports, commentaries, reviews, and letters. The selection process (3–25 January 2025) identified 1756 records; 118 duplicates were removed; 671 were excluded by automated filters; 967 titles screened with 642 exclusions; 325 abstracts screened with 277 exclusions; 48 full texts assessed with 27 excluded; 21 studies included. Risk of bias was evaluated using the JBI critical appraisal checklist for diagnostic test accuracy studies. Data extracted included diagnostic method, subject population, behavioral correlates, and key findings.

Across 21 included studies, electrophysiological diagnostics predominated. ABR was assessed in 15 studies; 10 reported significant between-group differences, commonly reduced wave I amplitude and altered I/V ratios in at-risk groups, with occasional changes in wave V amplitude or latency. EcochG was used in 6 studies; 4 reported significant differences such as decreased AP amplitudes, inconsistent or increased SP amplitudes with paired clicks, and elevated SP/AP ratios in high-risk or symptomatic groups. MEMR was measured in 4 studies; 3 reported abnormalities (reduced strength or elevated/absent thresholds) in noise-exposed groups, consistent with damage to low-spontaneous-rate fibers; one study found an association with noise exposure without group differences. FFR was evaluated in 2 studies; findings were mixed, with age-related reductions in EFR/TFS reported in one study and no group differences (with potential musician-related confounds) in another. One fMRI study showed enhanced central auditory pathway responses to broadband noise in high-exposure participants, suggesting central hyperactivity compensating for peripheral synaptic loss. Behavioral measures—especially speech-in-noise tests—were frequently worse in high-risk groups, aligning perceptual deficits with physiological findings. Overall, ABR (wave I amplitude) emerged as the most common and potentially sensitive marker; EcochG (SP/AP metrics) and MEMR show promise but require further comparative validation; FFR evidence remains limited.

The review addresses the need for objective diagnostic tools for HHL by synthesizing evidence for electrophysiological proxies of cochlear synaptopathy. ABR, particularly wave I amplitude and I/V ratios, frequently differentiates at-risk from control groups, aligning with loss of auditory nerve synapses. EcochG measures (SP and AP, SP/AP ratios) also capture synaptic and neural dysfunction, with paired-click SP changes offering a novel approach. MEMR findings support sensitivity to low-SR fiber damage and may enable practical clinical screening, though threshold versus strength discrepancies require clarification. FFR results are less consistent and currently limited. Behavioral tests, notably speech-in-noise, consistently reflect functional impairment but lack specificity for synaptopathy; integrating behavioral and electrophysiological measures may improve diagnostic confidence and characterization of severity. The significance lies in guiding clinicians and researchers toward multimodal strategies and highlighting the need to standardize protocols for broader clinical implementation.

ABR, EcochG, and MEMR show promise as diagnostic tools for HHL/cochlear synaptopathy, with ABR wave I amplitude being the most commonly used and frequently sensitive measure. EcochG SP/AP metrics can complement ABR, while MEMR offers a practical screening option. Evidence for FFR remains mixed and limited. A multimodal, two-pronged diagnostic framework combining electrophysiological and behavioral measures is recommended to improve diagnostic confidence and capture gradations of impairment. Future work should focus on harmonizing methodologies, conducting head-to-head comparisons of ABR versus EcochG/MEMR, expanding evidence for FFR, and developing standardized diagnostic criteria to enable earlier identification and management of subclinical auditory deficits.

The review highlights the lack of standardization across studies as a major barrier to clinical implementation. Findings for MEMR vary between threshold and strength outcomes, indicating methodological discrepancies that need resolution. Evidence for FFR is limited to few studies with mixed results and potential confounds (e.g., musician vs. non-musician comparisons). The single fMRI study suggests central hyperactivity but is impractical for routine clinical diagnosis. Overall heterogeneity in study designs, stimuli, and outcome measures limits direct comparisons and definitive conclusions regarding the most sensitive diagnostic modality.