Overview: Nerve stimulation therapy has shown promise in the treatment of spinal cord injuries in animal models. Researchers hope the treatment will be used in people with SCI to help restore limb movement.
Source: Columbia University
In 1999, when Jason Carmel, MD, Ph.D., was a sophomore medical student at Columbia, his identical twin brother suffered a spinal cord injury that left him paralyzed from the chest down and limited the use of his hands.
Jason Carmel’s life also changed that day. His brother’s injury eventually led Carmel to become a neurologist and neuroscientist, with the goal of developing new treatments to restore movement to people with paralysis.
Now, a nerve stimulation therapy that Carmel is developing at Columbia shows promise in animal studies and may eventually allow people with spinal cord injuries to regain the function of their arms.
“The stimulation technique targets the nervous system connections spared by injury,” says Carmel, a Columbia University and NewYork-Presbyterian neurologist, “allowing them to take over some of the lost function.”
In recent years, some high-profile studies of electrical stimulation of the spinal cord have allowed a few people with incomplete paralysis to stand and take steps again.
Carmel’s approach is different because it focuses on the arm and hand and because it combines stimulation of the brain and spinal cord with electrical stimulation of the brain followed by stimulation of the spinal cord.
“When the two signals converge at the spinal cord level, within about 10 milliseconds of each other, we get the strongest effect,” he says, “and the combination seems to cause the remaining connections in the spinal cord to take control.”
In his latest study, Carmel tested his technique, called spinal cord associative plasticity (SCAP), on rats with moderate spinal cord injuries. Ten days post-wounding, rats were randomized to receive SCAP or sham stimulation for 30 minutes for 10 days. At the end of the study period, rats that received SCAP on their arms were significantly better at handling food compared to those in the control group, and had almost normal reflexes.
“The improvements in both function and physiology lasted as long as they were measured, up to 50 days,” says Carmel.
The findings, recently published in the journal Brain, suggest that SCAP causes the synapses (connections between neurons) or the neurons themselves to undergo lasting change. “The paired signals essentially mimic the normal sensorimotor integration needed to perform skillful movements,” says Carmel.
From mice to humans
If the same technique works in people with spinal cord injuries, patients could regain something else they lost in the injury: independence. Many spinal cord stimulation studies focus on walking, but “if you ask people with cervical spinal cord injuries, which is the majority, what movement they want to regain, they say hand and arm function,” says Carmel.
“Hand and arm function allows people to be more independent, such as moving from a bed to a wheelchair or dressing and feeding themselves.”
Carmel is now testing SCAP on spinal cord injury patients at Columbia, Cornell and the VA Bronx Healthcare System in a clinical trial sponsored by the National Institute of Neurological Disorders and Stroke.
The stimulation is performed during clinically indicated surgery or non-invasively, using magnetic stimulation of 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 the trial, the researchers hope to learn more about how SCAP works and how the timing and strength of the signals affect motor responses in the fingers and hands. This would lay the groundwork for future trials to test the technique’s ability to meaningfully improve hand and arm function.
Looking further ahead, the researchers believe the approach could be used to improve movement and sensation in patients with lower body paralysis.
Meanwhile, Jason Carmel’s twin brother is working, getting married and raising twins of his own. “He has a full life, but I hope we can give him and other people with similar injuries more function,” says Carmel.
About this research news about spinal cord injury
Writer: Press Office
Source: Columbia University
Contact: Press Service – Columbia University
Image: The image is in the public domain
Original research: Closed access.
“Spinal cord associative plasticity improves sensorimotor function of the forelimbs after cervical injury” by Ajay Pal et al. Brain
Spinal cord associative plasticity improves sensorimotor function of the forelimbs after cervical injury
Associative plasticity occurs when two stimuli converge on a common neural target. Previous attempts to promote associative plasticity have focused on the cortex, with variable and moderate effects. In addition, the intended circuits are derived, rather than directly tested. In contrast, we sought to address the strong convergence between motor and sensory systems in the spinal cord.
We developed spinal cord associative plasticity, precisely timed coupling of motor cortex and dorsal spinal cord stimulations, to address this interaction. We tested the hypothesis that properly timed paired stimulation would strengthen sensorimotor connections in the spinal cord and improve recovery after spinal cord injury. We tested the physiological effects of paired stimulation, the pathways mediating them, and its function in a preclinical study.
Subthreshold stimulation of the spinal cord greatly increased motor cortex elicited muscle potentials at the time of pairing, but only when they arrived synchronously in the spinal cord. This paired stimulation effect depended on both cortical descending motor and spinal cord proprioceptive afferents; selective inactivation of any of these pathways completely negated the paired stimulation effect. Spinal cord associative plasticity, repeated coupling of these pathways for 5 or 30 minutes in awake rats, increased spinal excitability for hours after coupling ended.
To apply spinal cord associative plasticity as a therapy, we optimized the parameters to promote strong and long-lasting effects. This effect was just as strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that spared connections after moderate spinal cord injury were sufficient to support plasticity. In a blinded trial, rats suffered a moderate C4 spinal cord contusion. Ten days post-injury, they were randomized to 30 minutes of spinal cord associative plasticity every day for 10 days or sham stimulation.
Rats with spinal cord associative plasticity had significantly improved function on the primary outcome measure, a test of dexterity during food manipulation, 50 days after spinal cord injury. In addition, rats with spinal cord associative plasticity had persistently stronger responses to cortical and spinal stimulation than rats with sham stimulation, suggesting a spinal locus of plasticity.
After spinal cord associative plasticity, rats had near normalization of H-reflex modulation. The groups had no difference in the rat grimace scale, a measure of pain.
We conclude that spinal cord associative plasticity strengthens sensorimotor connections in the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Since stimulation of both the motor cortex and spinal cord is routinely performed in humans, this approach could be tried in people with spinal cord injury or other conditions that damage sensorimotor connections and impair dexterity.