Resolving the Paradox of Hearing Complaints with a Normal Audiogram: Differential Diagnosis and Perceptual Impacts of Cochlear Deafferentation

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Approximately 10% of Veterans with hearing complaints have clinically normal audiograms. Unfortunately, treatment options for these patients are limited and the outcomes are variable, resulting in a lack of consensus on how to manage these patients. Loss of the cochlear synapses between inner hair cells and afferent auditory nerve fibers can co-occur with normal hearing thresholds and may account for these perceptual complaints. However, subclinical outer hair cell (OHC) damage or central auditory deficits, such as those arising from traumatic brain injury, could lead to similar problems. The variability in treatment outcomes may be due to the heterogeneous nature of the underlying damage, which cannot be determined using existing clinical tests. The best treatment approach may depend on the specific type of damage. Although OHC function can be assessed with otoacoustic emissions (OAEs), current audiological testing cannot differentiate between peripheral deafferentation and damage to the central auditory system. However, several physiological measures are sensitive to deafferentation in animal models. These include the auditory brainstem response (ABR), the envelope following response (EFR), and the middle ear muscle reflex (MEMR). Our published and preliminary data show that ABR, EFR, and MEMR measurements are reduced in magnitude among young Veterans who report high levels of noise exposure during their military service compared to non-Veterans with limited noise exposure, consistent with animal models of noise-induced deafferentation. In addition, our data indicates that reductions in these measurements are associated with auditory perceptual deficits such as tinnitus and increased cognitive load (i.e., listening effort) during complex speech perception. The overall objective of this proposal is to develop a clinical test for deafferentation and determine the perceptual impacts of this condition. Our central hypothesis is that patients with deafferentation can be identified by comparing their physiological measurements to those from a normative sample with a low risk of deafferentation and that patients with abnormal measurements will have auditory perceptual deficits (tinnitus, hyperacusis, and difficulty with complex speech perception, including increased listening effort). We plan to test our hypothesis by pursuing three specific aims: 1) Identify normative ranges for ABR, EFR, and MEMR measurements, statistically adjusted for sex and OHC function, that can be used to identify patients likely to have significant cochlear deafferentation; 2) Compare ABR, EFR, and MEMR measurements in terms of their ability to differentiate between groups with low vs. high deafferentation risk; and 3) Characterize the relationship between abnormal physiological measurements and auditory perceptual deficits. This approach is innovative because it 1) allows for identification of deafferentation in individual patients; 2) incorporates OHC function, through OAE measurements, into the normative ranges; 3) investigates the best combination of test measures/stimuli for identifying deafferentation, including the use of new EFR and MEMR measurements; and 4) assesses increased listening effort during complex speech perception as a possible consequence of deafferentation. The proposed research is significant because there is currently no clinical test for deafferentation and the perceptual consequences of deafferentation are unclear, preventing the development of treatment options. This study is expected to result in 1) identification of physiological test measures and stimulus parameters, with normative ranges, that we can recommend for clinical assessment of cochlear deafferentation and 2) clarification of the perceptual impacts of deafferentation. Clinical recommendations for diagnosing deafferentation will have immediate impacts on clinical practice by allowing audiologists to test for deafferentation. A clinical test for deafferentation in combination with measurement of OHC function using OAEs will allow for differential diagnosis of peripheral auditory damage. Future research can then focus on treatments for specific peripheral sites of lesion (e.g., individualized hearing aid algorithms based on the degree of OHC damage and deafferentation or drug treatments for synapse repair or regeneration).