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|Principal Investigator||Affiliation||Contract Number||Link|
|Bill Agnew, Ph.D.||Huntington Medical Research Institutes||N01-NS8-2399|
Project Title: Microstimulation of the Lumbosacral Spinal Cord - Chronic Stimulation, November 1997
The Neural Prosthesis Program of the National Institute of Neurological Disorders and Stroke supports the development of aids for the neurologically handicapped. These aids, known as neural prostheses, replace or supplement neurological function by directly interfacing with the nervous system. One means of accomplishing this is by microstimulation with microelectrodes implanted directly into neural tissue. Animal and human studies have shown the potential value of microstimulation with respect to increased stimulus selectivity as compared to larger electrodes placed on the surface of neural tissue.
Recently efforts have been initiated by the Neural Prosthesis Program to explore the possibility of chronic microstimulation of the spinal cord. If successful, such a technique could be part of a prosthesis to restore genito-urinary, bowel and other motor functions to victims of spinal cord injury. Information from spinal cord microstimulation studies is especially needed by designers of neural prostheses for paraplegic individuals who have sustained injuries to their spinal cords above the lumbosacral region. In particular, it may be possible to selectively excite neurons innervating the bladder detrusor muscle while simultaneously stimulating interneurons which have inhibitory synaptic connections with neurons innervating the external urethral sphincter. Likewise, discrete control of penile erection, ejaculation, bowel evacuation and control of the somatic musculature of the limbs may be possible by selective spinal cord microstimulation below the level of spinal cord injury.
Before microstimulation of the spinal cord can be evaluated in humans, a suitable chronic stimulating microelectrode must be developed and its safety and effectiveness demonstrated in animals. The work requested in this request for proposals, Microstimulation of the Lumbosacral Spinal Cord - Chronic Stimulation, is a competitive renewal of an on-going contract (N01-NS-5-2333, Huntington Medical Research Institutes). Contract supported research over the past five years has demonstrated that it is possible to insert, stimulate and maintain discrete wire microelectodes in the sacral spinal cord on a chronic basis without undue tissue damage. However, the present design of the microelectrode/lead wire system causes excessive mechanical damage during movement of the spinal cord within the spinal canal and must be improved. The current work has not completed the establishment of safe ranges of stimulation parameters, nor has it investigated the use of thin film, integrated circuit microelectrodes, both of which are requested in this competitive renewal.
The research findings of this new contract will also complement research resulting from RFP-98-02, Microstimulation of the Lumbosacral Spinal Cord - Mapping, which is also a competitive renewal. Because their workscopes are related and their results will be complementary, they are being released simultaneously. Prospective offerors may bid on both RFP's, but each was written so that it is not required, nor necessarily advantageous, to bid on both.
A bibliography of publications from research supported by the NPP and copies of quarterly progress reports from the incumbent contract on microstimulation of the sacral spinal cord - chronic stimulation may be obtained free of charge from the Neural Prosthesis Program, N.I.H., Federal Building, Room 8A13, Bethesda, MD, 20892.
Note: A male animal model is specified in the following workscope because spinal cord injury is more common in the male human and also because electrical stimulation assisted voiding is more difficult to achieve in males.
b. Technical Specifications:
Independently, and not as an agent of the Government, the Contractor shall exert its best efforts to develop a method of chronic microstimulation of the lumbosacral spinal cord and to evaluate its effects on neural and surrounding tissue in non-human animals.
I. Specifically, the Contractor shall:
A. Select a non-human, male animal model taking into consideration factors that shall include:
1 similarities and differences of the animal and human motor systems innervated by lumbosacral motor neurons.
2 the size and mobility of the spinal cord within the vertebral canal.
3 the behavioral suitability of the animal species for tolerating a wearable spinal cord stimulator.
B. Obtain or develop a wearable, regulated current stimulator or tethered cable assembly and remote regulated current stimulator for chronic microstimulation of the animal's spinal cord. The stimulator should have the capability of at least two channel stimulation with both true simultaneous stimulation through each of the channels as well as sequential stimulation (interleaved stimuli). In this study chronic stimulation is defined as a total stimulation period of 24 hours.
C. Design a chronic microelectrode/lead system that eliminates or significantly reduces the mechanical trauma to the spinal cord and adjacent tissue as seen with current systems during normal movement of the spinal cord within the vertebral canal. A method of lead wire cabling shall be devised that does not contribute to mechanical instability of the microelectrodes.
D. Implant the above mentioned chronic microelectrodes as singles and as pairs into genito-urinary related nuclei and synaptically related populations of interneurons of the animal spinal cord and evaluate the effects of chronic implantation and stimulation by determining:
1 the absolute level and the stability of thresholds for physiologically evoked potential or muscular activity resulting from stimulation through a subset of the implanted microelectrodes as measured at least weekly over a three month period following implantation. In this series only the minimum duration of stimulation necessary for testing should be used. The animals should not be restrained except during the testing periods to allow normal movement of the spinal cord within the vertebral canal.
2 the effects of continuous stimulation using a different subset of microelectrodes with charge balanced, biphasic pulses at charge densities up to 1600 microcoulombs/sq cm for at least 24 hours. In different animals the effects of both true simultaneous stimulation and sequentially stimulated pairs of microelectrodes should be evaluated. The spacing of the microelectrodes in the pairs should be 500 microns or less.
3. the histopathological effects of implantation and continuous stimulation on the tissues surrounding implanted microelectrodes. This should include a determination of whether there is any microelectrode migration during the implantation period, the differences between tissue trauma produced by microelectrode insertion/movement and that due to stimulation, as well as the maximum "safe" level of stimulation as defined by the levels of both the charge density and the charge per phase at which no stimulation induced tissue damage is detected.
4. the effects of the microelectrode lead wire cabling and the tissue reaction to the cabling on microelectrode stability and on the tissues of the spinal cord. This should include histological examination of the cable anchoring that occurs at the pia-arachnoid and at the dura as well as any adhesions that might form between vertebrae, the meninges and the spinal cord.
E. Repeat (D.) above using dual tine, thin film silicon stimulating microelectrodes. (The silicon microelectrodes will be provided by the Project Officer at no charge unless the offeror prefers to furnish their own. If furnished by the Project Officer, the offeror will be responsible for attaching lead wires, and, for planning purposes, should anticipate 20 microelectrodes during the first two years of the contract. More microelectrodes will be furnished if desired.)
F. When studying tissue damage, identify and determine the role of possible mechanisms including mechanical trauma, mass activation of cortical neurons, changes in the composition of key constituents of the extracellular fluid surrounding the neurons, and generation of toxic substances by either the tissue or the microelectrodes.
II. 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. Adjustments and changes so indicated shall be approved in advance by the Project Officer and if necessary, by the Contracting Officer.
Last Modified November 24, 2008