Toward a Diagnostic Test for Hidden Hearing Loss.

Cochlear synaptopathy (or hidden hearing loss), due to noise exposure or aging, has been demonstrated in animal models using histological techniques. However, diagnosis of the condition in individual humans is problematic because of (a) test reliability and (b) lack of a gold standard validation measure. Wave I of the transient-evoked auditory brainstem response is a noninvasive electrophysiological measure of auditory nerve function and has been validated in the animal models. However, in humans, Wave I amplitude shows high variability both between and within individuals. The frequency-following response, a sustained evoked potential reflecting synchronous neural activity in the rostral brainstem, is potentially more robust than auditory brainstem response Wave I. However, the frequency-following response is a measure of central activity and may be dependent on individual differences in central processing. Psychophysical measures are also affected by intersubject variability in central processing. Differential measures may help to reduce intersubject variability due to unrelated factors. A measure can be compared, within an individual, between conditions that are affected differently by cochlear synaptopathy. Validation of the metrics is also an issue. Comparisons with animal models, computational modeling, auditory nerve imaging, and human temporal bone histology are all potential options for validation, but there are technical and practical hurdles and difficulties in interpretation. Despite the obstacles, a diagnostic test for hidden hearing loss is a worthwhile goal, with important implications for clinical practice and health surveillance.