Spinal cord injury (SCI) disrupts the communication pathway between the brain and the nerves that control muscles to produce movement, typically leaving the planning, coordination and effector centers above and below the injury functional. One promising avenue of research is focused on creating new pathways for signal transmission between the brain and the rest of the body.
Researchers at Mayo Clinic's campus in Rochester, Minnesota, are exploring the use of electronic devices that can wirelessly transmit signals from the brain to the intact spinal cord circuitry below the injury. In this novel approach, injured nerves are bypassed with electronics. Although this field of research is in its early stages, the prospects are intriguing.
Worldwide, several different stimulation modalities for activating muscle have been tested in both animal models and humans, including transcutaneous stimulation, percutaneous stimulation, intramuscular stimulation and peripheral nerve stimulation; however, none of these techniques has experienced widespread clinical translation.
Mayo researchers are currently exploring the therapeutic use of electrical stimulation within the spinal cord, termed intraspinal microstimulation (ISMS), as a means to provide neuromuscular activation to restore function in paralyzed limbs. ISMS involves the implantation of stimulating electrodes within the ventral gray matter of the spinal cord to activate motor circuitry.
"Over the past 15 years, multiple studies have demonstrated that ISMS can successfully and safely evoke coordinated limb movement and weight bearing in rodent and feline models, while overcoming some of the limitations, such as the rapid onset of muscle fatigue during stimulation, that accompany conventional stimulation techniques," explains Mayo Clinic neurosurgeon Kendall H. Lee, M.D., Ph.D.
Dr. Lee is the director of the Mayo research team and co-author of a recent publication in the Journal of Neurosurgery outlining a study establishing proof of principle for wireless control of ISMS to evoke controlled motor function in a rodent model of complete spinal cord injury. Results from that study indicated that wireless ISMS was capable of evoking controlled and sustained activation of ankle, knee and hip muscles in 90 percent of spinalized rats.
But Dr. Lee and colleagues are careful to point out that a great deal more research must occur before ISMS technology can be used outside of a controlled laboratory environment to improve quality of life for people with SCI. Small animal models are not optimal for determining the clinical efficacy and safety of spinal stimulation techniques for functional restoration of movement.
Porcine model protocol
To address these and other issues, Mayo Clinic researchers recently created a protocol, published in PLOS One, using a large animal (porcine) model to allow standardized development, testing and optimization of novel clinical strategies for restoring motor function following SCI. Development of this larger animal model for testing ISMS technology will also help reduce variations in surgical procedure, targeting and electrode implantation techniques that could affect therapeutic outcomes and make it difficult to compare results derived from multiple studies.
"We tested this protocol using both epidural and intraspinal stimulation in a porcine model of spinal cord injury, but the protocol is suitable for the development of other novel therapeutic strategies," says Jose (Luis) L. Lujan, Ph.D., an assistant professor of biomedical engineering and neurosurgery and a member of Dr. Lee's team.
This protocol is helping to characterize spinal circuits vital for selective activation of motor neuron pools, which Mayo researchers hope will expedite the development and validation of high-precision therapeutic targeting strategies and stimulation technologies for optimal restoration of motor function in humans.
Continued refinement of the electronic devices used is another necessary advance required before ISMS or similar technologies can be used in the clinical setting. In a review article published in Frontiers in Neuroscience, Mayo researchers note that the next generation of neuroprosthetic systems must be fully implantable, multichannel stimulators capable of real-time processing and integration of both command signals from the brain and sensor-based feedback from the environment.
"Although clinical restoration of functional movement via ISMS remains a distant goal, we are hopeful that these recent advances will ultimately improve quality of life for people with SCI," says Peter J. Grahn, a Ph.D. candidate within Dr. Lee's laboratory.
For more information
Grahn, PJ, et al. Wireless control of intraspinal microstimulation in a rodent model of paralysis. Journal of Neurosurgery. In press.
Hachmann JT, et al. Large animal model for development of functional restoration paradigms using epidural and intraspinal stimulation. PLOS One. 2013;8:e81443.
Grahn PJ, et al. Restoration of motor function following spinal cord injury via optimal control of intraspinal microstimulation: Toward a next generation closed-loop neural prosthesis. Frontiers in Neuroscience. 2014;8:1.