Spinal cord injury: can brain and nerve stimulation restore movement?

Summary: Nerve stimulation therapy has shown promise in the treatment of spinal cord injury in animal models. Researchers hope the treatment will be used in humans with IBS to help restore limb movement.

Source: Colombia 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, crippling him from the chest down and limiting the use from his hands.

Jason Carmel’s life also changed that day. Her 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 is showing promise in animal studies and may eventually allow people with spinal cord injuries to regain function in their arms.

“The stimulation technique targets nervous system connections spared from injury,” says Carmel, a neurologist at Columbia University and NewYork-Presbyterian, “allowing them to regain some of the lost function.”

In recent years, some high-profile studies of electrical stimulation of the spinal cord have enabled a few people with incomplete paralysis to start standing and walking again.

Carmel’s approach is different because it targets the arm and hand and combines brain and spinal cord stimulation with electrical brain stimulation followed by spinal cord stimulation.

“When the two signals converge at the spinal cord, about 10 milliseconds apart, we get the strongest effect,” he says, “and the combination seems to allow the remaining connections of 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 damage. Ten days after injury, rats were randomized to receive 30 minutes of SCAP for 10 days or sham stimulation. At the end of the study period, the rats that received the targeted SCAP on their arms were significantly better at handling food, compared to those in the control group, and had nearly normal reflexes.

Credit: Columbia University

“The improvements in function and physiology persisted for as long as they were measured, up to 50 days,” says Carmel.

The results, recently published in the journal Brain, suggest that SCAP causes lasting changes in synapses (connections between neurons) or neurons themselves. “The paired cues essentially mimic the normal sensory-motor integration that must come together to perform a skilled movement,” 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 injury, which are the majority, what movement they want to recover, they say the function of hand and arm,” explains Carmel.

“The hand and arm function allows people to be more independent, such as moving from a bed to a wheelchair or dressing and feeding themselves.”

This shows a photo of a man holding a drawing of a spine
Now, a nerve stimulation therapy that Carmel is developing at Columbia is showing promise in animal studies and may eventually allow people with spinal cord injuries to regain function in their arms. Image is in public domain

Carmel is currently 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 done either during clinically indicated surgery or non-invasively, using magnetic brain stimulation and skin stimulation in the front and back of the neck. Both techniques are commonly practiced in clinical settings and are known to be safe.

As part of the trial, the researchers hope to learn more about how SCAP works and how the timing and strength of the signals affect the motor responses of 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.

In the longer term, the researchers believe the approach could be used to improve movement and sensation in patients with lower body paralysis.

In the meantime, Jason Carmel’s twin is working, getting married and raising his own twins. “He has a busy life, but hopefully we can return more duties to him and others with similar injuries,” says Carmel.

About this Spinal Cord Injury Research News

Author: Press office
Source: Colombia University
Contact: Press Office – Columbia University
Picture: Image is in public domain

See also

This shows an eye with the contact lens

Original research: Access closed.
“Associative spinal cord plasticity improves forelimb sensorimotor function after cervical injury” by Ajay Pal et al. Brain


Summary

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 cortex, with variable and moderate effects. Additionally, the targeted circuits are inferred rather than tested directly. 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 timed pairing of motor cortex and dorsal spinal cord stimulations, to target this interaction. We tested the hypothesis that correctly 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 increased motor cortex evoking muscle potentials as they were paired, but only when they arrived synchronously in the spinal cord. This paired stimulation effect was dependent on both cortical descending motor and spinal cord proprioceptive afferents; selective inactivation of either of these pathways completely abrogated the pairwise stimulation effect. Spinal cord associative plasticity, repetitive pairing of these pathways for 5 or 30 min in awake rats, increased spinal excitability for hours after pairing ceases.

To apply spinal cord associative plasticity as therapy, we optimized parameters to promote strong and long-lasting effects. This effect was equally strong in rats with cervical spinal cord injury as in uninjured rats, demonstrating that the connections spared after moderate spinal cord injury were sufficient to sustain plasticity. In a blinded trial, rats sustained moderate C4 spinal cord injury. Ten days after injury, they were randomized to 30 min of spinal cord associative plasticity daily for 10 days or sham stimulation.

Rats with spinal cord associative plasticity had significantly improved function on the primary outcome, a test of dexterity when handling food, 50 days after spinal cord injury. Moreover, rats with spinal cord associative plasticity had consistently stronger responses to cortical and spinal stimulation than rats with sham stimulation, indicating a spinal locus of plasticity.

After spinal cord associative plasticity, the 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 reinforces sensorimotor connections in the spinal cord, resulting in partial recovery of reflex modulation and forelimb function after moderate spinal cord injury. Since stimulation of the motor cortex and spinal cord is performed routinely in humans, this approach can be tested in people with spinal cord injury or other disorders that damage sensorimotor connections. and impair dexterity.

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