The overall goal of this project is to develop the use of intraspinal microstimulation (ISMS) for restoring lower extremity function after spinal cord injury (SCI). Intraspinal microstimulation is a new neuroprosthetic approach which entails implanting a few ultra fine wires, smaller than the human hair, in the spinal cord and delivering electrical stimuli through these wires to generate functional limb movements. All wires are implanted in a small region of the cord (only ~3 cm long) known to contain the neural circuits involved in controlling leg movements. Previous experiments demonstrated the effectiveness of ISMS in restoring standing and stepping after complete SCI in adult cats. Stimulation through some microwires (less than 0.3 mA) generated powerful leg contractions capable of carrying the weight of the hind quarters in animals with SCI, while ISMS through other wires generated upward, forward and backward movements of the legs. By coordinating ISMS through wires generating these movements weight-bearing and kinematically stable in-place stepping of the legs was achieved.
The aims of the present project are to advance the technical development of this miniature implant, obtain a better understanding of how ISMS interacts with the nerve cells in the spinal cord, and design """"""""smart"""""""" methods of controlling the stimulation paradigms to produce walking movements outside the lab environment. The effect of microwire implantation on spinal cord tissue will also be examined to determine the safety of this technique. Intraspinal microstimulation is expected to eliminate several of the difficulties associated with conventional peripheral nerve electrical stimulation systems used for augmenting limb movements in paralyzed individuals. If found to be safe and capable of generating walking movements reliably, the results from this project could lead to the first ISMS trials in human volunteers with SCI. Experiments will be conducted in adult cats. Arrays of microwires will be constructed for implantation in the lumbosacral cord using a standardized insertion technique. Dimensions of the cord will be obtained from high-resolution in vivo magnetic resonance imaging (MRI) scans to guide the fabrication of the arrays for each animal, and to track their location over time. The extent to which ISMS activates fibers-in-passage in the ventral horn of the spinal cord will be determined using extracellular recordings of local field potentials from single cells throughout the lumbosacral enlargement during ISMS, and activity-dependent immunohistochemical c-fos labeling techniques. The best control paradigms for restoring robust over-ground walking will be investigated in animals with complete SCI and a neuromorphic chip incorporating these control paradigms will be developed and tested. Electromyographic, kinematic and kinetic measures will be used to evaluate the ISMS-induced locomotor patterns in the paralyzed hind limbs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044225-09
Application #
8016680
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Ludwig, Kip A
Project Start
2002-09-01
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2014-01-31
Support Year
9
Fiscal Year
2011
Total Cost
$248,579
Indirect Cost
Name
University of Alberta
Department
Type
DUNS #
208095844
City
Edmonton
State
AB
Country
Canada
Zip Code
T6 2-E1
Ho, Chester H; Triolo, Ronald J; Elias, Anastasia L et al. (2014) Functional electrical stimulation and spinal cord injury. Phys Med Rehabil Clin N Am 25:631-54, ix
Khaled, Imad; Elmallah, Salma; Cheng, Cheng et al. (2013) A flexible base electrode array for intraspinal microstimulation. IEEE Trans Biomed Eng 60:2904-13
Holinski, B J; Everaert, D G; Mushahwar, V K et al. (2013) Real-time control of walking using recordings from dorsal root ganglia. J Neural Eng 10:056008
Cheng, Cheng; Kmech, Jonn; Mushahwar, Vivian K et al. (2013) Development of surrogate spinal cords for the evaluation of electrode arrays used in intraspinal implants. IEEE Trans Biomed Eng 60:1667-76
Troyk, Philip R; Mushahwar, Vivian K; Stein, Richard B et al. (2012) An implantable neural stimulator for intraspinal microstimulation. Conf Proc IEEE Eng Med Biol Soc 2012:900-3
Mazurek, K A; Holinski, B J; Everaert, D G et al. (2012) Feed forward and feedback control for over-ground locomotion in anaesthetized cats. J Neural Eng 9:026003
Holinski, Bradley J; Mazurek, Kevin A; Everaert, Dirk G et al. (2011) Restoring stepping after spinal cord injury using intraspinal microstimulation and novel control strategies. Conf Proc IEEE Eng Med Biol Soc 2011:5798-801
Bamford, Jeremy A; Putman, Charles T; Mushahwar, Vivian K (2011) Muscle plasticity in rat following spinal transection and chronic intraspinal microstimulation. IEEE Trans Neural Syst Rehabil Eng 19:79-83
Bamford, Jeremy A; Mushahwar, Vivian K (2011) Intraspinal microstimulation for the recovery of function following spinal cord injury. Prog Brain Res 194:227-39
Mukherjee, Dipti Prasad; Cheng, Irene; Ray, Nilanjan et al. (2010) Automatic segmentation of spinal cord MRI using symmetric boundary tracing. IEEE Trans Inf Technol Biomed 14:1275-8

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