Protective Effects of Patterned Electrical Stimulation on the Deafened Auditory System

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Principal Investigator	Affiliation	Contract Number	Link
Pat Leake, Ph.D.	UCSF	N01-DC7-2105

Project Title: The Protective Effects of Patterned Electrical Stimulation on the Deafened Auditory System, August 1996

STATEMENT OF WORK

1. Background

The National Institute on Deafness and Other Communication Disorders (NIDCD) has supported research and development on essentially all aspects of auditory prostheses. The findings from the research that will result from this RFP will be applied to improve the function of such prostheses.

Investigations in deafened animals have shown that patterned electrical stimulation of the cochlea can provide auditory ganglion cells and their processes some protection from the degeneration that normally occurs with deafness from the loss of hair cells. The degree of this protection depends on the stimulus parameters used with recent results showing that higher frequencies (e.g., 80 or 300 pps) are more effective than lower frequencies (e.g., 30 pps). Other studies have revealed an increase in size of the soma and a reversal of the flattening of synapses in certain neurons in the cochlear nucleus as compared with the same types of neurons in non-stimulated deafened animals. In addition, it has been noted that certain regimens of chronic electrical stimulation can result in significant alterations in the spatial tuning curves of inferior colliculus auditory neurons and in the uptake of activity related markers such as 2-deoxyglucose.

One of the goals of this proposed study is to determine the mechanisms of these and similar effects. Another is to develop methods of optimizing the protective effects and expanding them to include protection of more central auditory structures while reducing or eliminating any adverse effects.

It is hoped that these animal studies will lead to methods of electrical stimulation in deaf humans that will protect the remaining structure and function of their auditory systems. This is especially appealing in the young deaf child and in the deafened adult who receive essentially no benefit from hearing aids, yet have significant portions of their auditory system central to damaged hair cells intact. It is also likely that methods of stimulation will be developed that alter the function of the remaining auditory system in a way that improves its ability to extract auditory information from cochlear implants. Another possibility is that this research will lead to methods for protecting portions of the auditory system in people who still have functional hearing but are losing hair cells due to aging or other causes. In this way, if and when they need an auditory prosthesis, an appropriate auditory substrate will still be available for stimulation.

This project represents a competitive renewal of a current research contract with the University of California, San Francisco (Contract # NO1-DC-4-2143). Progress reports from this contract and a bibliography of publications from previous and on-going studies supported by the NPP are available on the internet at:

www.ninds.nih.gov/npp

2. Objectives

The objective of this research is to develop methods of protecting the remaining portions of the auditory system from degeneration after loss of hair cells.

3. Work to be Performed

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment and facilities, not otherwise provided by the Government as needed to perform the statement of work. The Contractor shall exert its best efforts to evaluate the possibility that certain forms of chronic electrical stimulation of selected portions of the auditory system can maintain and possibly enhance the anatomical and physiological viability of the remaining auditory system following loss of hair cells in a manner compatible with preserving and possibly extending the function of an implanted auditory prosthesis.

I. Specifically the Contractor shall:

A. Select the following animal models.

1. A model of an approximately 1-2 year old human with acquired deafness from the loss of hair cells.

2. A model of an adult human with severe hearing loss from significant, but not total, loss of hair cells.

B. Obtain or fabricate implantable, multicontact, electrodes suitable for chronically stimulating selected portions of the auditory nerve.

C. Implant the above electrodes in the chosen models using a sufficient number of animals to give statistically significant answers to the questions raised in this RFP and chronically stimulate (except for control electrodes) for periods of at least 6 months duration at suprathreshold levels for evoking neural activity in auditory nerve fibers or auditory behavioral responses with spatio-temporal patterns of stimulation believed to be appropriate for maintaining and possibly enhancing the anatomical and physiological viability of the remaining auditory system.

D. In all but the control animals, periodically test the efficacy and the effects of neural stimulation by neurophysiological, and if appropriate, behavioral measures of auditory system activity. Try to determine the mechanisms of any measured alterations in auditory system function.

E. Upon completion of chronic stimulation, examine histopathologically the appropriate tissues including the cochleas, auditory nerves, and cochlear nuclei of both the stimulated and the control animals to determine:

1. Whether stimulation had any protective effects on neural structures, and if so which forms of stimulation were most effective.

2. Whether stimulation or implantation of non- stimulated control electrodes produced damage to the tissues.

3. Whether any functional changes observed are associated with neuroanatomical alterations in the auditory system.

F. Investigate the feasibility of developing a chronic, non- invasive, magnetic means of stimulating all or some of the auditory nerve fibers of the chosen adult model. If such a means of stimulation appears feasible, obtain or fabricate such a magnetic stimulator and evaluate it in some animals of the adult model in a manner appropriate to determine whether chronic magnetic stimulation might provide a protective effect for those auditory nerve fibers that are no longer synaptically connected to hair cells.

G. Upon completion of the animal studies and analysis of the results make recommendations in the final report as to appropriate types and patterns of stimulation that might be investigated in deaf humans to protect and possibly enhance the auditory system function with auditory prostheses.

H. In the performance of this contract, the Contractor shall coordinate its experimental program through the Project Officer with results of experimental findings developed by other collaborators in the Neural Prosthesis Program.

Last updated November 24, 2008