People with debilitating spinal cord injuries are able to walk again with the help of medical devices that tap their nerves with electricity. But the designers of these new implants weren’t entirely sure how they restored motor function over time — now a new study offers clues.
The new study in humans and laboratory mice, published Nov. 9 in the journal Nature (opens in new tab), identifies a specific population of nerve cells that appears to be key to restoring walking ability after a debilitating spinal cord injury. With a surge of electricity, an implant can turn on these neurons, setting off a cascade of events in which the architecture of the nervous system changes. This cellular remodeling restores the lost pathways of communication between the Brain and the muscles needed to walk so that once paralyzed people can walk again, the researchers concluded.
Understanding how the nerve-wracking system, called epidural electrical stimulation (EES), “remodels spinal circuits could help researchers develop targeted walking-restoration techniques and potentially enable the recovery of more complex movements.” Eiman Azim (opens in new tab)a senior researcher at the Salk Institute for Biological Studies in La Jolla, California, and Kee Wu Huang (opens in new tab)a postdoctoral fellow in Azim’s lab, wrote in a comment (opens in new tab).
Nine people with debilitating spinal cord injuries took part in the new study. Six were mostly or completely unable to move their legs but retained some feeling in their limbs; The other three participants had no motor control or sensation from the waist down.
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The nine participants underwent surgery to have electrodes implanted on their lower spinal cord, below the muscles and bones but outside the membrane that encases the nervous system. Each participant then trained with their implant for five months. They began practicing standing, walking, and various indoor exercises in a weight-bearing harness, eventually transitioning to outdoor exercise in a walker for stability.
These exercises were performed with the EES implant turned on, but over time four of the nine participants were able to carry weight and walk with the device off, the researchers wrote in their report.
The team also found that as each participant regained the ability to walk, the overall activity of their spinal cords decreased in response to the EES — what at first appeared like a blazing fire of nerve cell activation dwindled to a smoldering fire. This suggested that the combination of rehab and electrical stimulation reorganized the nervous system, requiring fewer and fewer cells to perform the same action.
“If you think about it, it shouldn’t come as a surprise, because when you’re learning a task, that’s what you’re seeing in the brain — fewer and fewer neurons are being activated,” as you improve, co-senior author Gregory Courtine (opens in new tab)Neuroscientist and Professor at the Swiss Federal Institute of Technology in Lausanne (EPFL), said nature (opens in new tab).
The team used rodent-sized EES implants to study how this reorganization unfolds mice with debilitating spinal cord injuries. The mice underwent a rehabilitation course similar to the human participants, and during that time the researchers tracked which of their nerve cells responded to the treatment by altering which genes they turned on.
This analysis revealed a number of neurons in the lumbar spinal cord that consistently responded to therapy, even when other neurons became less active. Blocking the activity of these neurons in uninjured mice did not affect their ability to walk, but in injured mice with paralysis, shutting down the cells prevented them from walking again. This suggests that while other nerve cells may play their own roles in recovery, this particular group is particularly important, Courtine said Science (opens in new tab).
“The results are consistent with the idea that certain types of spinal neurons[s] Those who have lost their brain inputs after injury can be ‘revived’ or reused to restore movement when given the appropriate combination of stimulation and rehabilitation,” Azim and Huang wrote. Assuming the results of the mouse studies are transferrable to humans, the experiments could lay the groundwork for new and improved devices aimed at repairing the spinal cord after injury, they said.
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