Electrophysiological Investigation of Brain Stimulation Strategies to Improve Hearing Restoration via Auditory Neural Prostheses

Abstract

The auditory lemniscal system, the core pathway thought to be responsible for conducting high-fidelity auditory information, is yet to be well-understood, particularly at the level of the midbrain. The lack of understanding of the auditory lemniscal system resulted in limited performance of a central auditory neuroprosthesis called the auditory midbrain implant (AMI). The AMI is a linear array of 20 sites designed to stimulate the auditory lemniscal nucleus in the midbrain, the central nucleus of the inferior colliculus (ICC). In the first clinical trial, five patients were implanted with the AMI, which gave users improved lip reading abilities and environmental awareness. However, the AMI was unable to deliver sufficient temporal information, which is likely associated with suboptimal placement and stimulation strategies within the ICC. This doctoral thesis project investigated the central lemniscal system in order to improve results for future AMI patients. First, the organization of responses to auditory stimuli was investigated within the auditory lemniscal midbrain. This study found different response properties within a rostral-lateral verses caudal medial ICC region, corresponding to subregions with differential input and output projection patterns. Next, we investigated various stimulation strategies that would allow the AMI to deliver sufficient temporal information. Repeated stimulation of a single site in the ICC, which was the initial strategy of the AMI, resulted in refractory effects in the auditory cortex that could only be overcome by co-activating neurons along a lamina of the ICC. This co-activation resulted in cortical activity that was enhanced beyond the sum of individual neural activation, with the greatest enhancement occurring in supragranular cortical layers. Moreover, this enhancement was largest when stimulating the rostral-lateral rather than the caudal-medial ICC region. These ICC locations with different electrical stimulation properties matched the two subregions with different acoustic-driven response properties. Together, these studies found consistent differences in physiological properties within two subregions of the ICC, confirming the presence of dual lemniscal pathways from the midbrain to the cortex. In addition, these studies identified a potential stimulation strategy and implantation location for improving AMI performance: co-activating rostral-lateral neurons along the isofrequency laminae of the ICC.