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|Principal Investigator||Affiliation||Contract Number||Link|
|Jim Roppolo, Ph.D.||Univ. of Pittsburgh||N01-NS8-2301|
|Warren Grill, Ph.D.||CWRU||N01-NS8-2300|
Project Title: Microstimulation of the Lumbosacral Spinal Cord - Mapping, November 1998
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.
Efforts have been initiated by the Neural Prosthesis Program (NPP) to explore the possibility of 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, evidence from current studies indicate that is 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.
Current contract research has provided information about the locations of afferent and efferent neurons as well as interneurons controlling urinary function in the cat spinal cord using both normal and spinalized animals. Limited mapping has also been performed on the neurons that control erection in the male cat. The current contract research is also studying the possibility of controlling, by spinal cord microstimulation, the somatic musculature of individuals paralyzed as the result of spinal cord injuries. As an initial feasibility study, the locations of the neurons controlling the flexors and extensors of the knee are being mapped. Microstimulation of these mapped areas has demonstrated activation of both knee flexors and extensors. It is now necessary to provide more detailed maps, and to determine quantitatively, the degree of motor control of paralyzed muscles that can be produced by microstimulation of the lumbosacral spinal cord.
The work requested in this request for proposals, Microstimulation of the Lumbosacral Spinal Cord - Mapping, is a competitive renewal of two contracts (N01-NS-5-2331, Case Western Reserve University; N01-NS-5-2332, University of Pittsburgh. Results of the prior research are available, free of charge, as specified below.
The research findings of this new contract will also complement research resulting from RFP-98-03, Microstimulation of the Lumbosacral Spinal Cord - Chronic Stimulation, which is also a competitive renewal. Because the workscopes of both competitive RFP's 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 contracts on microstimulation of the sacral spinal cord 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 investigate the feasibility of microstimulation of the lumbosacral spinal cord as a method of controlling genito-urinary, bowel, and skeletal motor functions.
Chimpanzees should not be used in this study unless there are no other acceptable animal models.
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 motor systems innervated by lumbosacral motor neurons.
2. similarities and differences of the genito-urinary, bowel, and skeletal motor systems in chronic spinal cord lesioned animals to humans with spinal cord injuries.
3. the size and mobility of the spinal cord within the vertebral canal.
4. the suitability for tolerating a chronic, complete, spinal cord lesion and resulting lower body paralysis.
B. Obtain the following instrumentation:
1. a pressure monitoring system for use in the animal model capable of measuring pressures within the distal urethra, within the urethral sphincteric region, within the bladder, across the bladder wall, within the colon, and within the anal sphincter region while the animal is anesthetized. The system shall also be capable of recording urine flow in non-anesthetized animals.
2. a torque and position measuring system capable of measuring the isometric torque output at various joint angles and the isotonic positioning capabilities with various resistances of the knee or ankle flexors and extensors in the chosen animal model.
C. In both the normal and the chronic spinal animal model, using anatomical tracing techniques, determine the location and extent of the following populations of neurons in the lumbosacral spinal cord unless this information is already known for the animal model selected. (If possible by using different tracers, try to locate some of these different populations in the same animal):
1. detrusor motor neurons.
2. pudendal motor neurons innervating the external urethral sphincter, the pelvic floor muscles, and the muscles controlling erection and ejaculation.
3. excitatory and inhibitory afferent neurons from the bladder, urethra, and skin of the external genitalia.
4. excitatory and inhibitory interneurons which play a role in normal micturition and sexual function.
5. motor neurons innervating the flexors and extensors of the knee or ankle.
6. excitatory and inhibitory afferent neurons from the knee or ankle joint position sensors.
7. excitatory and inhibitory afferent neurons from the force sensors in and about the flexors and extensors of the knee or ankle.
D. In both normal and chronic spinal cord transected animals, using both single activated iridium microelectrodes and arrays of four or more activated iridium microelectrodes whose exposed surface areas are equal to or less than 400 square microns, determine the effectiveness and selectivity of microstimulation of the above mentioned neuronal populations in producing:
1. detrusor contraction.
2. urinary sphincter inhibition.
3. evacuation of bladder contents.
6. coordinated colonic contractions.
7. anal sphincter inhibition.
8. isometric torque output from flexors and extensors of the knee or ankle at various knee or ankle joint angles.
9. isotonic range of movement of the knee or ankle with various resistances to movement.
E. In the same animals used for microstimulation, attempt to develop a method of electrically mapping the surface of the lumbosacral spinal cord with a surface stimulating electrode to determine the approximate location of the neuronal populations mapped in 3. above to a degree of accuracy which would be useful in future human spinal cord implants where microscopic anatomical maps are not available.
F. Based on the results of these studies prepare a plan for further feasibility studies of genito-urinary prostheses and a skeletal lower limb muscle prosthesis for paralyzed humans.
Last Modified November 24, 2008