Characterization of the Responses to Electrical and Optical Stimulation of the Cochlear Nucleus in a Mouse Model of the Auditory Brainstem Implant.

Abstract

The auditory brainstem implant (ABI) is an auditory neuroprosthesis that provides a sense of hearing by stimulating the cochlear nucleus (CN), the first auditory nucleus in the brainstem. Currently, the performance of most ABI patients, as measured by speech comprehension, is poor. Variability in the placement of the ABI's electrode array may be one reason for these poor outcomes (Barber et al., 2017), however, whether the optimal placement is on the CN’s dorsal (D) or ventral (V) subdivision remains unknown. In this dissertation, Chapter 1 characterizes and compares the evoked responses to stimulation of the DCN vs. VCN in a mouse model of the ABI. DCN stimulation evoked responses in the inferior colliculus with a unimodal pattern and short latencies (early responses) at low stimulus levels. The pattern became bimodal with both early responses and an emerging group of late responses at higher stimulus levels. VCN stimulation evoked unimodal late responses at all stimulus levels. Chapter 2 characterizes the temporal characteristics of responses to electrical pulse trains of different rates and to those that are amplitude modulated. Chapter 3 explores the spatial characteristics of responses and explores whether optogenetic stimulation of the CN may provide better spatial selectivity. Here, two optogenetic mouse lines that express opsins in the CN are used to compare optical responses to the responses evoked by acoustic and electrical stimulation. Overall, this dissertation provides a more complete foundation toward understanding how the ABI may be used to more effectively provide better hearing to human subjects who use this device. The hope is that the information presented here will provide guidance on how to improve ABI patient outcomes and the next generation of ABIs.