overview: Neurostimulation therapy has shown promise for the treatment of spinal cord injury in animal models. Researchers hope the treatment can be used by people with spinal cord injuries to restore movement in their limbs.
sauce: Columbia University
In 1999, when Jason Carmel, MD, Ph.D. was a sophomore in medical school at Columbia University, his identical twin brother suffered a spinal cord injury that left him paralyzed from the chest down and limited use of his hands. I was.
That day also changed Jason Carmel’s life. His brother’s injuries eventually led Carmel to become a neurologist and neuroscientist, with the goal of developing new treatments to restore movement in people with paralysis.
Now, a neurostimulation therapy Carmel is developing in Columbia shows promise in animal studies and could eventually help people with spinal cord injuries restore arm function.
“This stimulation technique targets the connections in the nervous system that have been lost due to injury, allowing it to take over some of the lost function,” says Carmel, a neurologist at Columbia University and a New York Presbyterian. says.
In recent years, some high-profile studies on spinal cord stimulation have allowed a small number of people with incomplete paralysis to get up and start walking again.
Carmel’s approach targets the arms and hands, combines brain and spinal cord stimulation, and differs in that electrical stimulation of the brain is followed by spinal cord stimulation.
“When the two signals converge at the level of the spinal cord, they have the strongest effect within about 10 milliseconds of each other,” he says. ”
In his latest study, Carmel tested his technique, called spinal cord associative plasticity (SCAP), in rats with moderate spinal cord injuries. Ten days after he was injured, rats were randomized to receive his SCAP for 30 minutes or a sham stimulus for 10 days. At the end of the study period, rats that underwent arm-targeted SCAP exhibited significantly improved food handling and near-normal reflexes compared to rats in the control group.
“Both functional and physiological improvements were sustained for up to 50 days, as long as they were measured,” says Carmel.
Findings recently published in the journal brain, suggesting that SCAP induces sustained changes in synapses (connections between neurons) or neurons themselves. “A pair of signals essentially mimics the normal sensory-motor integration that needs to come together to perform a skilled movement,” Carmel says.
From mice to humans
If the same techniques work for people with spinal cord injuries, they can regain something else they lost with their injury: their independence. Much spinal cord stimulation research has focused on walking, but “when you ask the majority of people with cervical spinal cord injuries what kind of movement they want back, they say they want back hand and arm function,” says Carmel. says.
“Hand and arm functions allow people to become more independent, such as moving from bed to wheelchair, dressing and eating on their own.”
Carmel is currently testing SCAP in spinal cord injury patients from Columbia, Cornell, and VA Bronx Healthcare System in clinical trials sponsored by the National Institute of Neurological Disorders and Stroke.
Stimulation is performed during clinically necessary surgery or non-invasively using magnetic stimulation to the brain and stimulation of the skin on the front and back of the neck. Both techniques are routinely performed in clinical settings and are known to be safe.
In this trial, the researchers hope to learn more about how SCAP works and how signal timing and strength affect motor responses in fingers and hands. This will lay the groundwork for future trials to test the technology’s ability to meaningfully improve hand and arm function.
Looking further ahead, researchers believe this approach could be used to improve locomotion and sensation in paraplegic patients.
Meanwhile, the Jason Carmel twins are working, getting married, and raising twins of their own. I hope we can get the functionality back,” says Carmel.
About this spinal cord injury research news
author: press office
sauce: Columbia University
contact: Press Office – Columbia University
image: image is public domain
See also
Original research: closed access.
“Spinal connective plasticity improves forelimb sensorimotor function after neck injury’ Ajay Pal et al. brain
overview
Spinal connective plasticity improves forelimb sensorimotor function after neck injury
Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted the cortex and had variable and moderate effects. Additionally, the target circuit is inferred rather than directly tested. In contrast, we sought to target the strong convergence between the motor and sensory systems of the spinal cord.
To target this interaction, we developed spinal associative plasticity, a precise timing pairing of motor cortex and dorsal spinal cord stimulation. We tested the hypothesis that appropriately timed paired stimulation strengthens sensorimotor connectivity in the spinal cord and improves recovery after spinal cord injury. The physiological effects of paired stimulation, the pathways that mediate it, and its function were tested in preclinical studies.
Subthreshold spinal cord stimulation strongly enhanced motor cortex-evoked myopotentials when they paired, but only when they arrived at the spinal cord synchronously. It relied on both cortical descending movements and spinal proprioceptive afferents. Selective inactivation of either of these pathways completely abolishes the paired stimulatory effects. Spinal cord connective plasticity, 5 or 30 min of repeated pairing of these pathways in awake rats increased spinal cord excitability for hours after pairing ended.
To apply spinal associative plasticity as a therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was similarly strong in rats with cervical spinal cord injury as well as in intact rats, indicating that avoidance of connections after moderate spinal cord injury is sufficient to support plasticity. In a blinded study, rats received a moderate C4 contusive spinal cord injury. Ten days after injury, he was randomized to 30 minutes of spinal cord connective plasticity for 10 days or sham stimulation each day.
Rats with spinal connective plasticity had significantly improved function in the primary endpoint, a test of dexterity in manipulating food, 50 days after spinal cord injury. Furthermore, rats with spinal associative plasticity exhibited stronger sustained responses to cortical and spinal cord stimulation than sham rats, indicating a spinal trajectory of plasticity.
After spinal cord associative plasticity, H-reflex regulation in rats nearly normalized. The two groups did not differ on the pain scale, the Rat Grimace Scale.
We conclude that spinal associative plasticity strengthens sensorimotor connectivity within the spinal cord, resulting in partial recovery of reflex control and forelimb function after moderate spinal cord injury. Both motor cortex and spinal cord stimulation are routinely performed in humans, so this approach could be tried in people with spinal cord injuries or other disorders that impair sensorimotor connections and impair dexterity.
