PROJECT SUMMARY/ABSTRACT
Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing loss, visual impairment,
and in some cases, vestibular dysfunction. It is the leading cause of hereditary deaf-blindness in humans. USH
causes extensive degeneration in the cochlear nerve (CN), especially in CN fibers innervating the base of the
cochlea. Whereas there is no treatment for arresting this degenerative process or for restoring visual loss, the
restoration of auditory input is possible with cochlear implantation. Due to the progressive deterioration in vision,
using visual cues for communication will eventually become impossible. Therefore, the importance of optimizing
auditory inputs through cochlear implants (CIs) for patients with USH is paramount. However, patients with USH
have much higher rates of neurological, mental, or behavioral disorders than the general CI patient population,
which limits their ability to provide reliable behavioral responses or sufficient verbal descriptions of their auditory
perception, especially for pediatric patients. In addition, optimal programming parameters for CI users with CN
damage differ from those used in typical CI users due to declined CN responsiveness to electrical stimulation.
As a result, the clinical programming process in implanted patients with USH can be extremely challenging. To
date, auditory neural encoding of electrical stimulation in patients with USH has not been systematically
evaluated. Consequently, the field lacks evidence-based practice guidelines for managing implanted patients
with USH. For patients who cannot provide reliable feedback, clinicians rely on a “trial-and-error” approach for
adjusting CI programming settings, which ultimately may not result in appropriate programming maps for
individual patients. Therefore, there is an urgent need to develop objective clinical tools for optimizing CI settings
for these patients. As the first step toward developing evidence-based practice for managing patients with USH,
this study evaluates local neural health, as well as the neural encoding of temporal and spectral cues at the CN
in implanted patients with USH. Aim 1 will determine local CN health in patients with USH by assessing the
sensitivity of the electrically evoked compound action potential to changes in interphase gap and pulse polarity.
Aim 2 will determine group differences in neural encoding of temporal and spectral cues at the CN between
patients with USH and patients with idiopathic hearing loss. Aim 3 will use supervised machine learning
techniques to develop an objective tool for assessing the electrode-neuron interface at individual electrode
locations. Results of this study have high scientific significance because they will establish how CN degeneration
affects neural encoding and processing of electrical stimulation, and identify tests that distinguish the loss of
spiral ganglion neurons from the loss of peripheral axons. Results of this study also have high clinical significance
because they will 1) lay the groundwork for developing effective, evidence-based clinical practice guidelines for
managing patients with USH, and 2) yield an objective tool for assessing the site-specific electrode-neuron
interface in all CI users, which is foundational for creating optimal programming maps for individual patients.