The hunt for hidden hearing loss in humans: From preclinical studies to effective interventions Valderrama Valenzuela, Joaquín Tomás Torre Vega, Ángel De La Speech-in-noise hearing difficulties Cochlear synaptopathy Central gain Demyelination Noise-induced hearing loss Noise exposure Hearing aids Hearables 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. 2022-10-19T08:31:03Z 2022-10-19T08:31:03Z 2022-09-15 journal article Valderrama JT, de la Torre A and McAlpine D (2022) The hunt for hidden hearing loss in humans: From preclinical studies to effective interventions. Front. Neurosci. 16:1000304. doi: [10.3389/fnins.2022.1000304] https://hdl.handle.net/10481/77390 10.3389/fnins.2022.1000304 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Frontiers