Not-So-Hidden Hearing Loss

38 The Hearing Journal May 2016 SG Kujawa and MC Liberman published a paper that instantly became a modern classic (Kujawa. J Neurosci 2009;29[45]: 14077-14085). They exposed mice to a single, moderate-level noise for two hours— enough to cause a temporary threshold shift. Indeed, they documented this shift through distortion product otoacoustic emissions (DPOAEs), auditory brainstem responses (ABRs), and compound action potentials (CAPs). Shortly thereafter, DPOAEs thresholds returned to normal, but the ABRs and CAPs remained affected. Careful histological analyses of the noise-exposed cochleae showed the hair cells were left intact, but even after thresholds returned to normal there was an acute loss of afferent nerve terminals. The ear was healthy, but the connections from the ear to the brain were lost forever. Subsequent work has shown a similar effect following a life of moderate noise exposure (Sergeyenko. J Neurosci 2013; 33[34]:13686-13694), and that this neural degeneration targets the high threshold, low spontaneous rate nerve fibers that fire in noise (Furman. J Neurophysiol 2013;110[3]: 577-586). Thus, an animal can have a normal audiogram and normal hair cell function despite a profound loss of the neural infrastructure thought to be critical for auditory processing in noise (although this remains to be shown empirically). This so-called or “hidden hearing loss” (or “cochlear neuropathy”) has captivated auditory scientists, and provides an elegant hypothesis for the cause of age-related hearing difficulties (Ruggles. Curr Biol 2012;22[15]:1417-1422; Plack. Trends Hear 2014;18), auditory processing disorder (Bharadwaj. J Neurosci 2015;35[5]:2161-2172), tinnitus (Schaette. J Neurosci 2011;31[38]:13452-13457), and hyperacusis (Hickox. J Neurophysiol 2014;111[3]:552-564). Additionally, understanding this pathophysiology can point to a clinical strategy for pharmacological interventions if ever a drug be discovered to regenerate synapses. Several researchers have argued that hidden hearing loss is a widespread phenomenon in humans and are working to discover a diagnosis, and have argued that this work has important clinical implications—including in The Hearing Journal (Zeng. Hear J 2015;68[1]:6). While this work points to a compelling hypothesis about everyday communication, we believe several fundamental questions remain, many of which pose a bottleneck to clinical translation (Zeng. Hear J 2015;68[1]:6):  It has been posited hidden hearing loss explains age-related hearing difficulty, auditory processing disorder, tinnitus, and hyperacusis. How does a single injury manifest (at a minimum) as four distinct pathologies? What are the factors that lead two people to suffer the same acute injury, but develop different phenotypes? How does this peripheral injury interact with predispositions, lifestyle factors, and cognitive factors such as attention or working memory in contributing to patient outcomes?  An analogy has been drawn between hidden hearing loss and auditory neuropathy, the latter of which is characterized by normal hair cell function with an absent ABR. Many authors have suggested that hidden hearing loss is akin to a mild form or auditory neuropathy, especially given the presumed behavioral consequences of the peripheral deafferentation. This analogy fails to consider a competing hypothesis for neuropathy, however, which suggests these listeners have plenty of afferent synapses that simply fire dyssynchronously (Starr. Brain 2003;126[Pt 7]:1604-1619). The dyssynchyrony hypothesis is supported by computational modeling of neuropathy. Additionally, the protein otoferlin has been implicated in neuropathy because it regulates synaptic vesicle release at the afferent connections to inner hair cells (Roux. Cell 2006;127[2]:277-289), but is not necessary for ribbon synapse formation. Finally, we note an extremely rare but fascinating syndrome, temperature-dependent auditory neuropathy. These listeners exhibit transient auditory neuropathy when they have a fever, but their auditory function is otherwise essentially normal (Starr. Ear Hear 1998;19[3]:169-179). We highly doubt they undergo an immediate deafferentation when febrile and reafferentation when their temperature returns to normal. Together, this evidence questions the extent to which hidden hearing loss is similar to auditory neuropathy. Not-So-Hidden Hearing Loss