Developing evidence-based objective tools for managing children with auditory neuropathy spectrum disorder

PROJECT SUMMARY/ABSTRACT Auditory Neuropathy Spectrum Disorder (ANSD) is a clinical diagnosis that is characterized by abnormal cochlear nerve (CN) function as indicated by absent or abnormal auditory brainstem responses in conjunction with some normal hair cell function as evidenced by the presence of cochlear microphonics and/or otoacoustic emissions. Current intervention options for ANSD include the use of hearing aids (HAs) and cochlear implants (CIs). Auditory abilities among patients with ANSD are extremely diverse and cannot be predicted based on the severity of hearing loss. Overall, ANSD remains a mystery despite decades of research. The current clinical paradigm for managing ANSD solely depends on reliable behavioral responses from patients, which is impossible in infants and many children with ANSD due to their young age and/or comorbidities. As a result, even though early identification of ANSD through effective newborn hearing screening programs is possible, implementing appropriate interventions for individual patients is delayed, which can have lasting detrimental effects on communication skills development. The proposed study aims to translate scientific findings in objective measures into clinical tools to address the following unmet, urgent clinical needs for managing patients with ASND: 1) how to determine whether the CN responds to acoustic stimulation in clinical settings, 2) how to determine the degree of hearing loss, 3) how to determine appropriate CI programming settings, and 4) how to accurately assess whether individual patients are making appropriate progress with HAs or CIs in a timely manner. In Aim 1, we propose to establish the electrocochleography recorded at the tympanic membrane as a noninvasive, clinical tool to evaluate frequency-specific CN function in patients, including children with ANSD. In Aim 2, we propose to establish the onset cortical auditory evoked potential (CAEP) as a clinical tool to objectively assess ear- and frequency-specific, audiometric thresholds in children with ANSD and children with conventional sensorineural hearing loss, as well as to validate the degree of cortical neural synchrony as an early identifier of the patients with ANSD who need to transition from HAs to CIs. In Aim 3, we propose to establish the clinical applications of the electrically evoked onset CAEP and the stapedial reflex threshold to assist in the CI programming process and to establish the degree of peripheral neural synchrony as a robust indicator to predict CI benefit for individual children with ANSD. This study has tremendous clinical significance because 1) it will shift the clinical paradigm for ANSD management from solely relying on behavioral response to a synergistic approach that includes both objective and behavioral measures, and 2) it will improve clinical care of children with SNHL who cannot provide reliable behavioral responses.