J Thomas Mortimer, BSEE, MS, PhD - US grants

The objective of this study is to develop a micturition assist device for the spinal cord injury patient with hyper-reflexic bladder paralysis. The device will be based on the technique of "collision block" of pudendal nerve activity for relaxation of the external urethral sphincter muscle and "sacral root stimulation" for activation of detrusor contraction. The focus of the study will be on research and development in animals of the collision block technique; sacral root stimulation techniques are under development elsewhere. The five phases of the study are concerned with: I the short-term development in animals of an effective method for eliciting relaxation of the external urethral sphincter and subsequent voiding using a pudendal nerve collision block; II the design and construction of an implantable electrode to induce the unidirectionally propagated action potentials required for collision block; III the development of a portable external stimulator to generate the collision block waveform; IV the development of a subsutaneous connector to permit percutaneous hardwiring the implant; and V the implantation and subsequent long-term evaluation of the efficacy and safety of the micturition assist device in animals. This research addresses a major health problem facing the majority of the estimated 200,000 spinal cord injury patients in the United States (to which 7,000 are added each year).

The research objective of this contract is to design, fabricate, and test, in an animal model, electrodes for use in functional neuromuscular stimulation (FNS) systems. This work shall be done in collaboration with a group actively involved in a clinical FNS investigation but this contract will not support the clinical program.

We propose to develop a multiple-contact nerve cuff electrode that can be used to activate and to control selectively force production in several muscles sharing a common peripheral nerve trunk. An electrode with these qualities will eliminate many of the problems that impede more wide spread use of neural prostheses for restoration of limb mobility. Although these electrodes are primarily intended for spinal cord injured patients the selective activation properties would make them suitable for other applications involving nerve trunks such as auditory and visual prostheses. The design approach will involve the development of two numerical models. The first model will be used to solve for the intraneural electric field generated by a cuff electrode housing an array of "dot" electrodes. A second model will be developed that stimulates the behavior of a mammalian myelinated axon when the axon is exposed to an extracellular electric field. In combination, these two models will be used to test the effectiveness of a given cuff design in activating motor axons located only in a small region of a large nerve trunk. This is the fundamental requirement for selective control of multiple muscles with a single cuff implant. Cuff electrode designs determined to be effective by this computer based development effort will be constructed and tested in both acute and chronic animal experiments. The emphasis of acute animal testing will be on evaluating prototype cuff designs. The chronic studies will characterize the long-term efficacy, performance, and reliability of the best cuff designs. Measured results will be compared with model predictions. Studies will be carried out to evaluate the electric field scattering effects of encapsulation layers, connective tissue boundaries, and the neural tissue itself; all of this information will be incorporated back into the models to further refine their usefulness for cuff design. The cuff electrodes to be produced by this grant will improve the reliability and capabilities of motor prostheses, greatly reduce the power requirements of implanted stimulators, and simplify the surgical procedures required to implant electrodes for the control of multiple muscles.

DESCRIPTION (Adapted from applicant's abstract): The purpose of this study is to establish limits for stimulus parameters to avoid tissue damage and electrode damage. We will establish safe limits for toxic products and minimize the charge injected into corrosive processes. Neural prostheses can be designed to effect controlled neurotransmitter release by selectively opening and closing voltage gated ion channels on select nerves, which opens numerous opportunities to restore or replace missing or impaired organ function. Selective control of these ion channels can be realized by precise positioning of electric fields and manipulation of the nonlinear properties of gates in these channels. Precise positioning of the electric fields involves reducing the physical size and area of the electrode. Manipulating the nonlinear properties of voltage gated ion channels involves stimulus pulse durations that are five to ten times longer than those used to simply create a propagated action potential. Small electrodes and long duration stimulation pulses both increase the likelihood of electrochemical reactions on the electrode surface that create toxic products and accelerate corrosion rates. Toxic reaction products kill the cells that are to be activated, and corrosion shortens the useful lifetime of the electrode. Both combine to shorten the useful life of a neural prosthesis. This study will test the hypothesis that electrochemical reaction products created at the electrode surface during the cathodic phase of stimulation can damage cells if generated at a sufficient rate. Limits will be established for the charge that can be safely injected into toxic reactions. A method will be developed to specify an imbalanced charge stimulation waveform, which is limited in the cathodic phase by charge injection into toxic electrochemical products, thus preventing tissue damage, and in the anodic phase by limiting the charge to levels required to return the electrode to the resting state, thus preventing corrosion. The results of these experiments will improve our understanding of tissue damage, and will improve our ability to deliver a safe neural prosthesis for clinical use, with fewer animal experiments. In addition to allowing design of a safe neural prosthesis by limiting reaction products, this work may lead to productive use of reaction products such as tumor destruction and intentionally induced ischemia. This work is expected to lead to the identification of the toxic product now believed to by an oxygen free radical created during oxygen reduction.