Innovative neurotechnology restores sensation after spinal cord injury in rodents

A nerve stimulation therapy developed at Columbia University’s Vagelos College of Physicians and Surgeons 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 Jason Carmel, MD, PhD, a neuroscientist at Columbia University and NewYork-Presbyterian, who led the study, “allowing them to take over some of the lost function.”

The findings were published in December in the journal brain.

A personal quest to develop treatments for people with paralysis

In 1999, when Carmel 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.

Carmel’s life also changed that day. His brother’s injury eventually led Carmel to become a neuroscientist and a neuroscientist with the goal of developing new treatments to restore movement to people living with paralysis.

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. “

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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 show 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, Weill 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.

Reference: Pal A, Park H, Ramamurthy A, et al. Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury. brain. 2022; 145 (12): 4531-4544. do: 10.1093/brain/awac235

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