The hunt for hidden hearing loss in humans: From preclinical studies to effective interventions

Abstract

Many individuals experience hearing problems that are hidden under a normal audiogram. This not only impacts on individual sufferers, but also on clinicians who can offer little in the way of support. Animal studies using invasive methodologies have developed solid evidence for a range of pathologies underlying this hidden hearing loss (HHL), including cochlear synaptopathy, auditory nerve demyelination, elevated central gain, and neural mal-adaptation. Despite progress in pre-clinical models, evidence supporting the existence of HHL in humans remains inconclusive, and clinicians lack any non-invasive biomarkers sensitive to HHL, as well as a standardized protocol to manage hearing problems in the absence of elevated hearing thresholds. Here, we review animal models of HHL as well as the ongoing research for tools with which to diagnose and manage hearing difficulties associated with HHL. We also discuss new research opportunities facilitated by recent methodological tools that may overcome a series of barriers that have hampered meaningful progress in diagnosing and treating of HHL.

Keywords: central gain; cochlear synaptopathy; demyelination; hearables; hearing aids; noise exposure; noise-induced hearing loss; speech-in-noise hearing difficulties.

FIGURE 1

Effect of demyelination on the mice auditory brainstem response. Figure adapted from Wan and Corfas (2017).

FIGURE 2

Schematic presenting a model for elevated central gain—decreased auditory nerve activity resulting from cochlear synaptopathy leads to a lower wave I amplitude and to activation of central-gain mechanism that increase neural sensitivity and restore wave V amplitude at the level of the midbrain. Figure adapted from Schaette and McAlpine (2011).

FIGURE 3

Example of the full-range auditory evoked response, which provides a comprehensive representation of all the components of the auditory pathway—from the cochlea to the cortex (de la Torre et al., 2020).

FIGURE 4

Effect of elevated central gain and brainstem neural transmission time on speech-in-noise intelligibility (Valderrama et al., 2018). This figure shows that when central gain at the level of the midbrain is elevated (high gain), individuals with longer brainstem neural transmission time (measured via the ABR waves I-V interpeak latency) presented worse speech-in-noise hearing performance.

FIGURE 5

Figure adapted from Monaghan et al. (2020) presenting a model for synaptopathy and central gain activation. (A) The loss of high-threshold auditory nerve fibers in cochlear synaptopathy saturates the spiking probability of neurons in the inferior colliculus at supra-threshold level. (B) Central gain activation presents a multiplicative increase of the neurons sensitivity to restore the maximum (non-synaptopathic) spike probability. (C,D) As a consequence, the slope of the spike probability function increases in mid-levels, which leads to better discriminability from the HHL model (squares) than from the control model (circles) at 60 dB SPL, but reduced discriminability at 75 dB SPL.