Spinal cord injury: can brain and nerve stimulation restore movement?
Abstract: Nerve stimulation therapy has shown promise in the treatment of spinal cord injuries in animal models. The researchers hope that this treatment will be used in people with SCI to restore movement to the limbs.
Source: Columbia University
In 1999, when Jason Carmel, MD, Ph.D., was a second-year medical student at Columbia, his identical twin brother suffered a spinal cord injury, which paralyzed him from the chest down and limited the use of his arms.
That day, Jason Carmelo’s life also changed. His brother’s injury eventually led Carmelo to become a neurologist and neuroscientist, with the goal of developing new treatments to restore movement to people living with paralysis.
Now, the nerve stimulation therapy that Carmel is developing at Columbia is showing promise in animal studies and could eventually allow people with spinal cord injuries to regain function in their hands.
“The stimulation technique targets the connections of the nervous system spared by the injury,” says Carmel, a neurologist 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 a few people with partial paralysis to start standing and walking again.
Carmelo’s approach is different because it targets the arm and hand 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 appears to allow the remaining 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 minutes of SCAP for 10 days or sham stimulation. At the end of the study period, rats that received SCAP targeted to their hands were significantly better at handling food, compared to those in the control group, and had nearly 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 permanent changes to synapses (connections between neurons) or neurons themselves. “The paired signals essentially mimic the normal sensory-motor integration that needs to come together to perform a skilled movement,” says Carmel.
From mice to humans
If the same technique works for people with spinal cord injuries, patients could regain something else they lost in the injury: independence. Many studies of spinal cord stimulation focus on walking, but “if you ask people with cervical spinal cord injury, which is the majority, what movement they want to get back, they say it’s arms and hands that work,” 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 in 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 during clinically indicated surgery or non-invasively, by 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.
During the trial, the researchers hope to learn more about how SCAP works and how the timing and strength of the signal affect motor responses in the fingers and hands. This would set the stage for future trials to test the technique’s ability to meaningfully improve hand and arm function.
Looking further, the researchers think the approach could be used to improve movement and sensation in patients with lower-body paralysis.
Meanwhile, Jason Carmelo’s twin is working, married and raising his own twins. “He has a full life, but I hope we can restore more function for him and other people 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 focused on the cortex, with variable and moderate effects. Furthermore, the target circuits are assumed and not directly tested. In contrast, we sought to target a strong convergence between motor and sensory systems in the spinal cord.
We developed spinal cord associative plasticity, a precise temporal pairing of motor cortex and dorsal spinal cord stimulation, to target this interaction. We tested the hypothesis that properly selected paired stimulation would strengthen sensorimotor connections in the spinal cord and improve recovery after spinal cord injury. We examined the physiological effects of paired stimulation, the pathways mediating it and its function in a preclinical trial.
Subthreshold spinal cord stimulation strongly increased motor cortex evoked muscle potentials when they were paired, but only when they arrived synchronously in the spinal cord. This paired stimulation effect was dependent on cortical descending motor and proprioceptive spinal cord afferents; selective inactivation of either of these pathways completely abolished the effect of paired stimulation. Spinal cord associative plasticity, repetitive pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability hours after pairing ends.
To apply spinal cord associative plasticity as a therapy, we optimized parameters to promote strong and long-lasting effects. This effect was as strong in cervical spinal cord-injured rats as in uninjured rats, indicating that spared connections after moderate spinal cord injury were sufficient to support plasticity. In a blind experiment, rats received a moderate C4 contusion injury of the spinal cord. Ten days after the 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, the food manipulation dexterity test, 50 days after spinal cord injury. In addition, rats with spinal cord associative plasticity had persistently stronger responses to cortical and spinal stimulation than sham rats, indicating a spinal locus of plasticity.
After associative plasticity of the spinal cord, rats had almost normalization of H-reflex modulation. The groups had no differences in the rat grimace scale, a measure of pain.
We conclude that associative plasticity of the spinal cord strengthens sensorimotor connections within the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Because both motor cortex and spinal cord stimulation are routinely performed in humans, this approach can be tried in people with spinal cord injury or other disorders that damage sensorimotor connections and reduce dexterity.