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.
|Holinski, B J; Mazurek, K A; Everaert, D G et al. (2016) Intraspinal microstimulation produces over-ground walking in anesthetized cats. J Neural Eng 13:056016|
|Mazurek, Kevin A; Holinski, Bradley J; Everaert, Dirk G et al. (2016) A Mixed-Signal VLSI System for Producing Temporally Adapting Intraspinal Microstimulation Patterns for Locomotion. IEEE Trans Biomed Circuits Syst 10:902-11|
|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|
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