Restoration of limb movement following spinal cord injury (SCI) has been achieved using electrical stimulation of peripheral nerves and skeletal muscles. However, these stimulation techniques are limited by a rapid onset of muscle fatigue and by limited degrees of freedom that can be independently controlled using existing technology. Intraspinal microstimulation (ISMS) is an emerging technology that has shown significant potential for overcoming some of the limitations associated with electrical stimulation techniques. Specifically, intraspinal stimulation has been successful in evoking controlled limb movements in previously paralyzed limbs by directly activating motor neurons within the ventral gray matter of the spinal cord. State-of-the-art intraspinal microstimulation techniques rely on manual targeting of neuron populations and manual insertion of stimulating microelectrodes into the spinal cord. However, variance in neuroanatomy combined with differences in surgical strategy and skill can compromise clinical outcomes and prevent cross-study analysis. The goals of this proposal are to develop a targeting strategy for identifying motor neuron populations associated with specific target movements in a large animal model and demonstrate that targeted intraspinal stimulation can evoke controlled, reproducible, and sustained muscle contractions. In addition to evoking limb movements, the targeting and stimulation strategies proposed herein will allow characterization of spinal networks responsible for mediating motor function in a large animal. This in turn will allow optimization of stimulation paradigms for selective and coordinated recruitment of fatigue-resistant motor units. Moreover, it will allow ths technology to move closer to a clinical therapeutic system for human use.

Public Health Relevance

Spinal cord injury is a devastating condition that results in loss of motor function, significantly reducing independence and quality of life for affected individuals. Functional restoration of limb movement after spinal cord injury has been somewhat successful using electrical stimulation of peripheral nerves and muscles. Recently, direct stimulation of the spinal cord has shown promising results for improving functional movement in paralyzed limbs in small animal models of Spinal cord injury. The objective of this proposal is to improve targeting and microstimulation of spinal circuits responsible for controllin limb movement in a large animal model of spinal cord injury. In turn, these will facilitate translation of intraspinal microstimulation technology into a clinical setting for optimizing contrl of muscle action following spinal injury. These efforts represent the next step toward the development of a clinical system that will be capable of increasing independence and quality of life for individuals affected by spinal cord injury and other neurologic injuries and diseases.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Exploratory/Developmental Grants (R21)
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Ludwig, Kip A
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Mayo Clinic, Rochester
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Grahn, Peter J; Goerss, Stephan J; Lujan, J Luis et al. (2016) MRI-Guided Stereotactic System for Delivery of Intraspinal Microstimulation. Spine (Phila Pa 1976) 41:E806-13
Grahn, Peter J; Lee, Kendall H; Kasasbeh, Aimen et al. (2015) Wireless control of intraspinal microstimulation in a rodent model of paralysis. J Neurosurg 123:232-242
Mallory, Grant W; Grahn, Peter J; Hachmann, Jan T et al. (2015) Optical stimulation for restoration of motor function after spinal cord injury. Mayo Clin Proc 90:300-7
Grahn, Peter J; Mallory, Grant W; Berry, B Michael et al. (2014) Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: toward a next generation closed-loop neural prosthesis. Front Neurosci 8:296
Hachmann, Jan T; Jeong, Ju Ho; Grahn, Peter J et al. (2013) Large animal model for development of functional restoration paradigms using epidural and intraspinal stimulation. PLoS One 8:e81443