In the study, published Wednesday, two wireless implants worked together as a "brain-spine interface" to communicate nerve signals between the brains and spines of the monkeys -- where each implant was positioned.
The implants communicated with each other through a computer and enabled brain signals to jump over the point of injury along the spine.
By resuming this once-broken path of communication, the signals can arrive in the spine, and the resulting nerve stimulation means specific muscles within the legs of the two monkeys could be activated as needed on the brain's command.
"What's key here is that we stimulate to induce the desired movement of the animal," said Grégoire Courtine
, professor of neural engineering at EPFL, who led the research. "Over the past decade, we've spent a lot of energy understanding how the spinal cord can be stimulated."
Similar research has been conducted in the past, with Courtine's team showing it could give paralyzed rats the ability to walk again, and even climb stairs, in previous studies. Other research groups have used electrodes and brain implants to restore movement in humans, both through their muscles as well as through prosthetic arms and legs.
But this new research in monkeys is the first to record brain activity and link this to nerves within the spinal cord itself. "The brain is in control," Courtine said.
It's also the first to go wireless.
The team now hopes the technology could one day be used in humans, but this will be no easy feat. "The idea is to go step-by-step," said Courtine.
How it works
Paraplegia is often caused by injury within someone's spinal cord or nerves, meaning nerve signals cannot be transmitted between the brain and the rest of the body, such as the legs. The location of the injury can determine the extent to which a person is paralyzed: The higher the injury, the worse the paralysis. Anything in the middle of the spine will cause paraplegia, or lower limb paralysis, and higher points of injury may result in quadriplegia, or paralysis in all four limbs.
This new interface involves two main implants -- one sensor in the brain and a nerve stimulator in the spine -- located on either side of the injury to bridge the line of communication.
The first implant, as small as a dime, is located in the motor cortex region of the brain -- where decisions are made about walking -- to pick up brain signals telling the muscles in the legs to walk. Though someone may be paralyzed, their brain continues to think about walking and creating the signals to command this action. "We extract the general intention of movement," Courtine said.
These brain signals would then typically travel down the bundles of nerves within an undamaged spinal cord to reach nerves in the leg muscles, but they are instead now transmitted wirelessly to a computer, which decodes the signal and sends a new message to the stimulator implanted in the spine, on the other side of the injury.
This second implant releases a few pulses of electricity, based on the commands from the brain and computer, to stimulate certain nerves that activate specific muscles within the legs to move and flex -- and therefore walk.
The nerve stimulator "releases specific amounts of electricity," Courtine said. "This reproduces the intended movement."
According to the team that oversaw the primates at Bordeaux University, the monkeys were able to walk almost immediately once the interface was activated, without the need for any training or physiotherapy. But achieving this level of movement in human legs will require some additional thinking.
To prove the functioning of the implants, Courtine's team created partial lesions in the spines of the two monkeys to paralyze them. The implants were inserted soon after.
To follow ethical protocol, small lesions were made in the monkeys' spines that would naturally heal and be overcome by nerve regeneration and reorganization. This was why the implants were tested soon after injury, as the monkeys would be paralyzed only in these initial weeks.
"We strive to minimize impact on the well-being of the animal," Courtine said. After three to six months, "the nerves grow and establish a natural bypass," he said.
The transition to humans
The goal for all researchers in this field is to apply these technologies to humans and improve the everyday lives of people with paraplegia, which the team plans to do. But applying the technology to humans will bring many more challenges than using it in monkeys.
"It's got a long way to go. ... Getting movement in the lower extremities is a much bigger challenge in humans," said Dr. Ali Rezai, director of the Neurological Institute
at Ohio State University, adding that the location of the brain area involved in leg movements (the motor cortex) "is a challenge to get to in humans."
Compared with monkeys, the leg-moving region of the motor cortex is much deeper inside the brain in humans. Enabling movement in the legs is also much more complicated. "The legs are more complex for meaningful movement," said Rezai, who was not involved in the trial.
Despite this, Rezai believes the team could do it. "This study shows we can take brain signals and leverage them and link them to leg movements, which has not been shown before," he said. "This technology accelerated the field."
Rezai has adopted similar approaches in humans, but to enable movement in arms rather than legs, using brain implants that send signals to a sleeve worn on a patient's arm that activate muscles to move from the outside. This year, he published results from a trial in which his team used this approach to restore movement and control in the right hand and fingers of a 24-year-old man, Ian Burkhart, who had been paralyzed from the chest down for six years.
"(Ian's) now performing much more sophisticated movement," Rezai said, adding a reminder that such refined movement within legs will require even more sophisticated technology. "It requires movement of multiple muscles, but it's a challenge this group is up for," he said.
Courtine is well aware of the road ahead, adding that "a small change in leg movement will not change your life a lot. You really need to change this a lot to improve function," he said.
To get there, Courtine's team has begun a trial testing the spinal implants in humans, with two people currently enrolled in the trial and a total of eight to receive the implants over the next two years. "It's a feasibility study ... (but) we're planning to bring this into clinical application step by step."
Professor Simone Di Giovanni
, who holds a chair in restorative neuroscience at Imperial College London, believes more work first needs to be done in animals: "The work in two non-human primates is solid, very promising and exciting; however, it will have to be tested in clinical settings and ideally in larger numbers of animals," he said in a statement. "The issue will be how much this approach will contribute to functional recovery that impacts on the quality of life. This is still very uncertain."
That is, after all, the end goal: to improve quality of life among people suffering from paralysis of their lower limbs.
"We need to be realistic. We're not going to cure people with this type of technology," Courtine said. "(But) this type of technology can improve their quality of life."