National Institute of Health
Contract HHS-N-263-2007-00053-C
The Effects of Intracochlear Electrical Stimulation on Neural Survival and Connectivity

The overall objectives of this contract are to develop techniques that employ intracochlear electrical stimulation (ICES) and drug administration which can support neural survival and function in order to improve the quality of auditory perception from a multichannel cochlear implant. Our goals are threefold; to study the effects of ICES on the developing auditory system for subjects implanted at a young age in order to minimize any delay in auditory stimulation; to examine the effects of ICES on the auditory system over a lifetime of use; and to evaluate the response of the auditory system in adult onset deafness to ICES, and the effect of duration of deafness, using functional, anatomical and behavioural measures.

To achieve these goals we will use a systems approach across a number of sub‑disciplines of neurobiology including electrophysiological, behavioural and neuroanatomical / molecular biological techniques in order to maximize data collection from each animal. We have divided our approach into two broad areas of research:

a)     Chronic stimulation studies investigating the trophic and plastic response of the deafened auditory pathway to chronic ICES. Studies in this area focus on the role of ICES in shaping both the developing and the mature auditory system. Key outcomes will be a deeper understanding of the effects of ICES on both the spatial and temporal processing ability of the auditory system, and the interaction of these effects with the preceding state of the auditory pathway (i.e. the duration of deafness and developmental state of the auditory pathway).

b)     Neurotrophin (NT) studies investigating the trophic and plastic response of the deafened auditory pathway to spiral ganglion neuron (SGN) rescue via ICES and exogenous neurotrophin delivery. The role of exogenous NTs in the rescue of SGN has been well established; therefore, studies in this area focus on developing and using delivery techniques we consider to have potential clinical application. Additionally, we will determine the effects of NT delivery and SGN rescue on the spatial and temporal processing ability of the central auditory system.

A major objective of this work is to apply our findings to the clinical environment. Therefore, while these studies are designed to provide insight into the effects of ICES on neural survival and connectivity across a range of etiologies and animal species, we will be using techniques that are clinically relevant whenever possible.