[Show abstract][Hide abstract] ABSTRACT: Although the cochlear implant is already the world's most successful neural prosthesis, opportunities for further improvement abound. Promising areas of current research include work on improving the biological infrastructure in the implanted cochlea to optimize reception of cochlear implant stimulation and on designing the pattern of electrical stimulation to take maximal advantage of conditions in the implanted cochlea. In this review we summarize what is currently known about conditions in the cochlea of deaf, implanted humans and then review recent work from our animal laboratory investigating the effects of preserving or reinnervating tissues on psychophysical and electrophysiological measures of implant function. Additionally we review work from our human laboratory on optimizing the pattern of electrical stimulation to better utilize strengths in the cochlear infrastructure. Histological studies of human temporal bones from implant users and from people who would have been candidates for implants show a range of pathologic conditions including spiral ganglion cell counts ranging from approximately 2% to 92% of normal and partial hair cell survival in some cases. To duplicate these conditions in a guinea pig model, we use a variety of deafening and implantation procedures as well as post-deafening therapies designed to protect neurons and/or regenerate neurites. Across populations of human patients, relationships between nerve survival and functional measures such as speech have been difficult to demonstrate, possibly due to the numerous subject variables that can affect implant function and the elapsed time between functional measures and postmortem histology. However, psychophysical studies across stimulation sites within individual human subjects suggest that biological conditions near the implanted electrodes contribute significantly to implant function, and this is supported by studies in animal models comparing histological findings to psychophysical and electrophysiological data. Results of these studies support the efforts to improve the biological infrastructure in the implanted ear and guide strategies which optimize stimulation patterns to match patient-specific conditions in the cochlea.
[Show abstract][Hide abstract] ABSTRACT: Following the onset of sensorineural hearing loss, degeneration of mechanosensitive hair cells and spiral ganglion cells (SGCs) in humans and animals occurs to variable degrees, with a trend for greater neural degeneration with greater duration of deafness. Emergence of the cochlear implant prosthesis has provided much needed aid to many hearing impaired patients and has become a well-recognized therapy worldwide. However, ongoing peripheral nerve fiber regression and subsequent degeneration of SGC bodies can reduce the neural targets of cochlear implant stimulation and diminish its function. There is increasing interest in bio-engineering approaches that aim to enhance cochlear implant efficacy by preventing SGC body degeneration and/or regenerating peripheral nerve fibers into the deaf sensory epithelium. We review the advancements in maintaining and regenerating nerves in damaged animal cochleae, with an emphasis on the therapeutic capacity of neurotrophic factors delivered to the inner ear after an insult. Additionally, we summarize the histological process of neuronal degeneration in the inner ear and describe different animal models that have been employed to study this mechanism. Research on enhancing the biological infrastructure of the deafened cochlea in order to improve cochlear implant efficacy is of immediate clinical importance.