Wednesday, November 16, 2016

A brain-spine interface alleviating gait deficits after spinal cord injury

Capogrosso M, Milekovic T, Borton D, Wagner F, Moraud EM, Mignardot JB, Buse N, Gandar J, Barraud Q, Xing D, Rey E, Duis S, Jianzhong Y, Ko WK, Li Q, Detemple, P, Denison T, Micera S, Bezard E, Bloch J, Courtine G. A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature. 2016 Nov 9;539(7628):284-288.


Spinal cord injury disrupts the communication between the brain and the spinal circuits that orchestrate movement. To bypass the lesion, brain-computer interfaces have directly linked cortical activity to electrical stimulation of muscles, and have thus restored grasping abilities after hand paralysis. Theoretically, this strategy could also restore control over leg muscle activity for walking. However, replicating the complex sequence of individual muscle activation patterns underlying natural and adaptive locomotor movements poses formidable conceptual and technological challenges. Recently, it was shown in rats that epidural electrical stimulation of the lumbar spinal cord can reproduce the natural activation of synergistic muscle groups producing locomotion. Here we interface leg motor cortex activity with epidural electrical stimulation protocols to establish a brain-spine interface that alleviated gait deficits after a spinal cord injury in non-human primates. Rhesus monkeys (Macaca mulatta) were implanted with an intracortical microelectrode array in the leg area of the motor cortex and with a spinal cord stimulation system composed of a spatially selective epidural implant and a pulse generator with real-time triggering capabilities. We designed and implemented wireless control systems that linked online neural decoding of extension and flexion motor states with stimulation protocols promoting these movements. These systems allowed the monkeys to behave freely without any restrictions or constraining tethered electronics. After validation of the brain-spine interface in intact (uninjured) monkeys, we performed a unilateral corticospinal tract lesion at the thoracic level. As early as six days post-injury and without prior training of the monkeys, the brain-spine interface restored weight-bearing locomotion of the paralysed leg on a treadmill and overground. The implantable components integrated in the brain-spine interface have all been approved for investigational applications in similar human research, suggesting a practical translational pathway for proof-of-concept studies in people with spinal cord injury.

When a person becomes paralyzed, most – but not all – of the neurons that help signal muscles to move are broken. This keeps the brain from being able to send signals to certain muscle groups telling them to move. But if the body had a way of strengthening the few intact neurons, they might be able to do the heavy lifting themselves and restore the ability to move.

In the new study, researchers implanted tiny wireless devices into the brains of two monkeys that had been purposefully paralyzed -- each lost the use of a hind leg. The device recorded electrical signals from the brain’s motor cortex, which controls movement, and sent them to a computer. The computer then translated those signals into a language that electrodes -- connected to a group of neurons in the spinal cord -- could understand. Their work was published this week in the journal Nature…

As seen in the video [at link], the monkeys were able to move their paralyzed legs in conjunction with the other four as they walked. And unlike similar technologies that require a person (or monkey) to be somehow wired to a computer, this new technology is completely wireless. The monkeys wear a backpack which interprets and sends off the brain signals.

This success is just one of several achievements made in the last few years as scientists continue to better understand how electrical signals in the brain enable movement. But it's unique, and not just because it ditches the usual cords: In an accompanying commentary on the study, Newcastle University neuroscientist Andrew Jackson points out that the new device is a "closed-loop stimulation", which interprets brain signals in real time. The devices that are currently in use in humans with paralysis are open-looped, meaning they require repeated stimulation to excite or wake up the neurons that may have survived the patient's injury. That strengthens those neurons, but the closed-loop system strengthens the entire network connection of neurons between the brain and spinal cord.

But while this is a successful proof-of-concept experiment, work on creating a brain-computer interface suitable for humans is far from complete. The system used here is successful in allowing for broader muscle movements, like moving a leg to walk, but it would be less successful at allowing for more fine tuned movements like a small change in direction or enabling a person to balance. As research forges ahead, scientists will need both a better

1 comment:

  1. By implanting a wireless neural prosthetic into the spinal cord of paralyzed monkeys, a team led by Dr. Grégoire Courtine at the Swiss Federal institute of Technology (EPFL) in Lausanne, Switzerland achieved the seemingly impossible: the monkeys regained use of a paralyzed lower limb a mere six days after their initial injury without requiring any training.

    The close-looped system directly reads signals from the brain in real-time and works on the patients’ own limbs, which means it doesn’t require expensive exoskeletons or external stimulation of the patient’s leg muscles to induce the contractions necessary for walking. That’s huge: it means the system could be readily used by patients in their own homes without doctor supervision.

    “When we turned on the brain-spine interface for the very first time … and the animal was showing stepping movement using its paralyzed leg, I remember a lot of screaming in the room; it seemed incredible,” says Dr. Courtine in an interview with Nature.

    “The study represents a major step towards restoring lost motor function using neural interfaces,” agrees Jackson, who was not involved in the study...

    To get around the issue, Courtine and other brain-machine interface (BMI) experts are turning to neural interfaces to manually reconnect brain and muscle. And Courtine’s system is exceedingly clever.

    To start off, his team designed two implants: one to receive incoming signals from the brain and another to replace the damaged spinal cord.

    The first, a neural interface, is made up of arrays of 96 microelectrodes that hook into the parts of the brain that controls leg movement. Once implanted, it automatically captures signals coming from multiple neurons that usually work together to give out a certain command — for example, flexing your foot, bending your leg or stop walking altogether.

    The matchbox-sized device then sends the signal to an external computer, which uses an algorithm to figure out what movement the neural signals were encoding...

    Fine-tuning the input signal took a lot of effort. Figuring out how different sets of electrical signals represent different aspects of movement was just the first step. The scientists also had to map out how the signals cyclically changed with time as a monkey walked, to ensure they could reproduce the smooth, gliding gait when working with a paralyzed monkey.

    Once the neural signals were decoded, the computer used the information to wirelessly operate a second electrode array sitting over the lower part of the spinal cord of a paralyzed monkey, below the level of injury. This second implant, the “pulse generator,” acts as an electrical stimulator that takes in messages from the brain implant and delivers them to undamaged parts of the spinal cord that normally control leg muscle movement with a series of zaps.

    The results were astonishing.

    In two monkeys that each lost the use of a hind leg, the wireless brain-spine interface allowed them to walk normally within the first week after their injuries — without any training. As time went on, the quality and quantity of the steps improved, suggesting the system had triggered neuroplasticity in the brain and damaged spinal cord.