Spinal cord injury: can brain and nerve stimulation restore movement?Thank you for reading this post, don't forget to subscribe!
Summary: Nerve stimulation therapy shows promise in the treatment of spinal cord injuries in animal models. The researchers hope the treatment will be used in people with SCI to help restore limb movement.
source: Columbia University
In 1999, when Jason Carmel, M.D., Ph.D., was a second-year medical student at Columbia, his identical twin brother suffered a spinal cord injury that paralyzed him from the chest down and limited the use of his arms.
Jason Carmel’s life also changed that day. His brother’s injury eventually led Carmel to become a neuroscientist with the goal of developing new treatments to restore movement to people living with paralysis.
Now, the nerve stimulation therapy Carmel is developing at Columbia is showing promise in animal studies and may eventually allow people with spinal cord injuries to regain hand function.
“The stimulation technique targets the connections of the nervous system spared from injury,” says Carmel, a neuroscientist at Columbia University and NewYork-Presbyterian, “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 several people with partial paralysis to start standing and taking steps again.
Carmel’s approach is different because it targets the hand and arm and because it combines brain and spinal cord stimulation, with electrical brain stimulation followed by spinal cord stimulation.
“When the two signals converge at the level of the spinal cord, within about 10 milliseconds of each other, we get the strongest effect,” he says, “and the combination seems to allow the rest of the connections in the spinal cord to take over. “
In his latest study, Carmel tested his technique — called spinal cord associative plasticity (SCAP) — on rats with moderate spinal cord injuries. Ten days post-injury, rats were randomized to receive 30 min of SCAP for 10 days or sham stimulation. At the end of the study period, rats that received SCAP directed at their arms were significantly better at handling food than those in the control group and had nearly normal reflexes.
“The improvements in function and physiology lasted as long as they were measured, up to 50 days,” Carmel says.
The findings, published recently in the journal brain, suggest that SCAP causes synapses (the connections between neurons) or the neurons themselves to undergo a permanent change. “The paired signals essentially mimic the normal sensory-motor integration that must come together to perform a skilled movement,” Carmel says.
From mice to humans
If the same technique works for people with spinal cord injuries, patients may 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 injury, which is the majority, what movement they want to regain, they say arm and hand function,” Carmel says.
“Hand and arm function allows people to be more independent, such as transferring 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.
Stimulation will be performed either during clinically indicated surgery or non-invasively using magnetic brain stimulation and skin stimulation on the front and back of the neck. Both techniques are routinely performed in clinical settings and are known to be safe.
In the process, 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 significantly improve hand and arm function.
Looking ahead, the researchers believe the approach could be used to improve movement and sensation in patients with lower-body paralysis.
Meanwhile, Jason’s twin Carmel is working, married and raising twins of his own. “He has a full life, but I hope we can bring back more function for him and others with similar injuries,” says Carmel.
About this news about spinal cord injury research
Original research: Closed access.
“Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury” by Ajay Pal et al. brain
Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury
Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted the cerebral cortex with variable and moderate effects. In addition, target circuits are assumed rather than directly tested. In contrast, we sought to target the strong convergence between motor and sensory systems in the spinal cord.
We developed spinal cord associative plasticity, a precisely synchronized pairing of motor cortex and dorsal spinal cord stimulations, to target 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 that mediate it, and its function in a preclinical trial.
Subthreshold spinal cord stimulation strongly potentiated motor cortex evoked muscle potentials at the time they were paired, but only when they arrived synchronously in the spinal cord. This effect of paired stimulation depends on both cortical descending motor and proprioceptive spinal cord afferents; selective inactivation of any of these pathways completely abolished the effect of paired stimulation. Spinal cord associative plasticity, repeated pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability for hours after pairing ends.
To implement spinal cord associative plasticity as a therapy, we optimized parameters to promote strong and long-lasting effects. This effect was as strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that preserved connections after moderate spinal cord injury are sufficient to maintain plasticity. In a blinded test, rats received a moderate C4 spinal cord contusion injury. Ten days after 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 food handling dexterity test, at day 50 after spinal cord injury. In addition, rats with spinal cord associative plasticity had consistently stronger responses to cortical and spinal stimulation than sham-stimulated rats, indicating a spinal locus of plasticity.
After associative spinal cord plasticity, rats have near-normalization of H-reflex modulation. Groups did not differ on the Rat Grimace Scale, a measure of pain.
We conclude that associative spinal cord plasticity strengthens sensorimotor connections in the spinal cord, leading to partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Because stimulation of both the motor cortex and the spinal cord is routinely performed in humans, this approach could be tried in people with spinal cord injury or other disorders that damage sensorimotor connections and impair dexterity.
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