In November of 2016 Nature reported that the results of experiments in Beijing, in which a wireless brain implant — that stimulates electrodes in the leg by recreating signals recorded from the brain — has enabled monkeys with spinal-cord injuries to walk. “They have demonstrated that the animals can regain not only coordinated but also weight-bearing function, which is important for locomotion. This is great work,” says Gaurav Sharma, a neuroscientist who has worked on restoring arm movement in paralysed patients, at the non-profit research organization Battelle Memorial Institute in Columbus, Ohio.
Microelectrode arrays implanted in the brain of the paralysed monkeys picked up and decoded the signals that had earlier been associated with leg movement. Those signals were sent wirelessly to devices that generate electric pulses in the lower spine, which triggered muscles in the monkeys’ legs into motion.“This study helps to open exciting new pathways to clinical studies and new bioelectronic treatment options for patients living with paralysis,” says bioengineer Chad Bouton, who researches medical devices used to bypass spinal-cord injuries at the Feinstein Institute for Medical Research in Manhasset, New York.
However, according to Swiss neuroscientist Gregoire Courtine, replicating the same experiment on humans is more complex because human brains are more difficult to decode. The primate study, for example, used electrical activity recorded from the spinal cord before the injury and “played it back” to restore movement, notes Bouton. “That’s an approach that wouldn’t be practical after an actual spinal-cord injury,” he says.And Sharma says that further research will have to take into account other elements of walking. Rhythmic coordination of gait, for example — which the monkeys didn’t demonstrate — is controlled by a different group of neurons. Devices to enable human locomotion in paralysed patients would ideally include brain–computer interfaces, electrical stimulation for activating muscles, an exoskeleton-like device to help bear weight, and smarter electrical processing to enable gait control, he says.
In other developments the University of Louisville reported in 2018, “Two research participants living with traumatic, motor complete spinal cord injury are able to walk over ground thanks to epidural stimulation paired with daily locomotor training.” “This research demonstrates that some brain-to-spine connectivity may be restored years after a spinal cord injury as these participants living with motor complete paralysis were able to walk, stand, regain trunk mobility and recover a number of motor functions without physical assistance when using the epidural stimulator and maintaining focus to take steps,” said Susan Harkema, PhD.
DARPA has launched BG+ program to overcome these challenges and accelerate it’s applications to humans especially warfighters. Spinal cord injury disrupts the connection between brain and body, causing devastating loss of physiological function to the wounded warfighter. In addition to paralysis, service members living with these injuries exhibit increased long-term morbidity due to factors such as respiratory and cardiovascular complications. ridging the Gap Plus (BG+), a new DARPA program that combines neurotechnology, artificial intelligence, and biological sensors, opens the possibility of overcoming the worst effects of spinal cord injuries by promoting healing at the wound site and interfacing with the nervous system at points around the body to restore natural functions such as breathing, bowel and bladder control, movement, touch, and proprioception that can be lost when the spinal cord is damaged.
“In recent years, DARPA has made remarkable progress in demonstrating the potential of direct and indirect neural interfaces to help individuals with injuries and illness,” said Dr. Al Emondi, the DARPA program manager for BG+. “No two injuries are the same, however, and so we are embracing the opportunity provided by evolving technology to pursue new intelligent and adaptive interfaces that specifically address spinal cord injury. DARPA’s goal is to provide active warfighters and veterans with alternatives for overcoming one of war’s worst injuries.”
BG+ will encompass two research thrusts aimed at developing and integrating technologies for injury stabilization, regenerative therapy, and functional restoration to support patients during all phases of spinal cord injury — acute, sub-acute, and chronic. DARPA’s focus will be on improving healing outcomes during the acute and sub-acute phases of injury, and on restoring lost function in the chronic phase of injury. While the timeline for intervention varies from case to case, the acute phase of injury can generally be considered as the two days immediately following injury when hemorrhaging and inflammation are common. The sub-acute phase extends for approximately two weeks after injury and introduces scarring and axon dieback as damage extends into cells that are affected by the increasingly cytotoxic environment. The chronic phase of injury encompasses any time thereafter and may include limited functional improvements.
The first research thrust encompasses development of a range of novel regenerative medicine technologies that should be amenable to implantation in a stateside civilian trauma hospital as well as a down-range combat hospital. These devices should continuously measure biomarkers to track injury status and deliver therapeutic approaches to stabilize injuries and encourage neural regeneration. In recent years, researchers have demonstrated some progress in the laboratory using approaches such as electrical stimulation, pharmacology, cell therapy, and scaffolds to repair nerve projections in injured spines. However, the strategies currently being studied are typically limited to a single phase of injury or a single treatment modality. Additionally, apart from obtaining an anatomical scan of the surgical site, the clinician is often left effectively blind to the biological status of the injury, with minimal ability to monitor healing locally and provide local treatment to the site.
“Whereas with regular wounds, tissue heals in a relatively predictable manner, in spinal cord injuries the healing process is more complex,” said Emondi. “Physicians have very little information about what actually goes on in real time at the injury site. DARPA aims to change that using bioelectronic interfaces that measure biomarkers directly related to the injury. Once we know what’s taking place at the spinal cord from moment to moment, we think it will be possible to deliver intelligent interventions that optimize our ability to preserve and reinforce neural communications during the acute phase of spinal cord injury.”
The second research thrust includes development of networked interface devices that communicate with the nervous system or relevant end organs to restore physiological function. DARPA is especially interested in recovering voluntary and involuntary nervous system functions such as bladder control and respiration. In addition to restoring control functions, researchers will need to develop technologies to return sensory feedback to the users of BG+ systems to enable more natural function.
BG+ program manager Dr. Al Emondi said in a statement that “Physicians have very little information about what actually goes on in real time at the injury site. DARPA aims to change that using bioelectronic interfaces that measure biomarkers directly related to the injury.” “Once we know what’s taking place at the spinal cord from moment to moment, we think it will be possible to deliver intelligent interventions that optimize our ability to preserve and reinforce neural communications during the acute phase of spinal cord injury,” he added. Dr. Emondi also led DARPA’s Next-Generation Nonsurgical Neurotechnology (N3) program.
DARPA created BG+ as a five-year program, scheduled to conclude with clinical demonstrations in human patients.
“DARPA’s metrics for success for BG+ are mitigating the early effects of spinal cord injury, improving awareness and interactive therapies at the injury site to preserve neural function, and restoring multiple physiological functions,” said Emondi. “By the end of the program, we hope to deliver technologies that adapt to changes in the injury profile over time, inform new standards of care, minimize secondary complications, and address the long-term dysfunctions that can remain for years after spinal cord injury.”
In related research, DARPA recently began funding Brown University to develop a direct spinal cord interface that marries implanted electrodes with machine learning to potentially restore lower-limb motor and sensory control and proprioception to individuals living with paraplegia. The planned two-year study — led by Dr. David Borton and stemming from a proposal in response to BTO’s office-wide broad agency announcement — involves the development of high-density electrodes that wrap around the spinal cord and are capable of recording and stimulation. The team will also attempt to create novel algorithms that mimic natural processes in the spinal cord.
Whereas researchers proposing to BG+ can pursue interfaces anywhere in the human nervous system, the Brown-led team is focusing specifically on a direct, two-way interface with the spinal cord. The team must overcome two primary challenges. First, it will be necessary to sense and transduce the obscure, sparse, and dynamic data of the spinal cord into a viable motor control signal. Second, to restore sensation, the team must develop biomimetic stimulation models and identify appropriate parameters for shaping electrical fields.
DARPA has scheduled in-patient demonstrations at the end of each year of the Brown study to demonstrate proof of concept. At the end of the first year, the researchers will work with volunteers living with paraplegia to test a percutaneous interface system with the goal of restoring movement and sensation. By the end of the second year, the researchers plan to test a fully implanted system.