Paralyzed men move legs with new non-invasive spinal cord stimulation

After training, men move legs independently, without stimulation

Five men with complete motor paralysis were able to voluntarily generate step-like movements thanks to a new strategy that non-invasively delivers electrical stimulation to their spinal cords, according to a new study funded in part by the National Institutes of Health. The strategy, called transcutaneous stimulation, delivers electrical current to the spinal cord by way of electrodes strategically placed on the skin of the lower back. This expands to nine the number of completely paralyzed individuals who have achieved voluntary movement while receiving spinal stimulation, though this is the first time the stimulation was delivered non-invasively. Previously it was delivered via an electrical stimulation device surgically implanted on the spinal cord.

In the study, the men’s movements occurred while their legs were suspended in braces that hung from the ceiling, allowing them to move freely without resistance from gravity. Movement in this environment is not comparable to walking; nevertheless, the results signal significant progress towards the eventual goal of developing a therapy for a wide range of individuals with spinal cord injury.

“These encouraging results provide continued evidence that spinal cord injury may no longer mean a life-long sentence of paralysis and support the need for more research,” said Roderic Pettigrew, Ph.D., M.D., director of the National Institute of Biomedical Imaging and Bioengineering at NIH. “The potential to offer a life-changing therapy to patients without requiring surgery would be a major advance; it could greatly expand the number of individuals who might benefit from spinal stimulation. It’s a wonderful example of the power that comes from combining advances in basic biological research with technological innovation.”

The study was conducted by a team of researchers at the University of California, Los Angeles; University of California, San Francisco; and the Pavlov Institute, St. Petersburg, Russia. The team was led by V. Reggie Edgerton, Ph.D., a distinguished professor of integrative biology and physiology at UCLA and Yury Gerasimenko, Ph.D., director of the laboratory of movement physiology at Pavlov Institute and a researcher in UCLA’s Department of Integrative Biology and Physiology. They reported their results in the Journal of Neurotrauma.

Range of voluntary movement prior to receiving stimulation compared to movement after receiving stimulation, physical conditioning, and buspirone. The subject’s legs are supported so that they can move without resistance from gravity. The electrodes on the legs are used for recording muscle activity.

In a study published a little over a year ago, Edgerton — along with Susan Harkema, Ph.D., and Claudia Angeli, Ph.D., from the University of Louisville, Kentucky — reported that four men with complete motor paralysis were able to generate some voluntary movements while receiving electrical stimulation to their spinal cords. The stimulation came from a device called an epidural stimulator that was surgically implanted on the surface of the men’s spinal cords. On the heels of that success, Edgerton and colleagues began developing a strategy for delivering stimulation to the spinal cord non-invasively, believing it could greatly expand the number of paralyzed individuals who could potentially benefit from spinal stimulation.

“There are a lot of individuals with spinal cord injury that have already gone through many surgeries and some of them might not be up to or capable of going through another,” said Edgerton. “The other potentially high impact is that this intervention could be close to one-tenth the cost of an implanted stimulator.”

During this most recent study, five men — each paralyzed for more than two years — underwent a series of 45 minute sessions, once a week, for approximately 18 weeks, to determine the effects of non-invasive electrical stimulation on their ability to move their legs.

In addition to stimulation, the men received several minutes of conditioning each session, during which their legs were moved manually for them in a step-like pattern. The goal of the conditioning was to assess whether physical training combined with electrical stimulation could enhance efforts to move voluntarily. For the final four weeks of the study, the men were given the pharmacological drug buspirone, which mimics the action of serotonin and has been shown to induce locomotion in mice with spinal cord injuries. While receiving the stimulation, the men were instructed at different points to either try to move their legs or to remain passive.

At the initiation of the study, the men’s legs only moved when the stimulation was strong enough to generate involuntary step-like movements. However, when the men attempted to move their legs further while receiving stimulation, their range of movement significantly increased. After just four weeks of receiving stimulation and physical training, the men were able to double their range of motion when voluntarily moving their legs while receiving stimulation. The researchers suggest that this change was due to the ability of electrical stimulation to reawaken dormant connections that may exist between the brain and the spinal cord of patients with complete motor paralysis.

Surprisingly, by the end of the study, and following the addition of buspirone, the men were able to move their legs with no stimulation at all and their range of movement was — on average — the same as when they were moving while receiving stimulation.

“It’s as if we’ve reawakened some networks so that once the individuals learned how to use those networks, they become less dependent and even independent of the stimulation,” said Edgerton.

The researchers also made extensive recordings of electrical signals generated in the calf muscle and the muscle directly below the calf while the men attempted to flex their feet during stimulation. Over time, these signals increased with the same amount of stimulation, further supporting the hypothesis of re-established communication between the brain and spinal cord.

Edgerton has already initiated a new study to see whether these same men can be trained with non-invasive spinal stimulation to fully bear their weight, a feat that the four men with surgically implanted stimulators have already achieved. In addition, he is interested in determining whether, similar to epidural stimulation, non-invasive stimulation can help individuals regain some autonomic functions lost due to paralysis such as the ability to sweat, regulate blood pressure, and control bladder, bowel, and sexual function.

The hope is that further research can help determine whether non-invasive stimulation can restore function that will truly impact patient lives.

Edgerton also wants to test non-invasive stimulation on individuals who have partial paralysis. “We have focused on individuals with complete paralysis throughout this whole process because we knew that was going to be the toughest patient population to see changes in. We’ve always thought, and we have every reason to believe, that those individuals with partial injuries have even more room for improvement,” said Edgerton.

Though a non-invasive stimulation could offer advantages over a surgically implanted device, Edgerton says both need to continue to be developed. For example, a non-invasive stimulator might be useful in determining whether a patient will be receptive to neuromodulation, which could then help determine whether undergoing surgery to implant a stimulator is warranted. Alternatively, Edgerton speculates it may be possible early after an injury for non-invasive stimulation to help patients achieve a certain level of motor control that then allows them to continue to improve with physical rehabilitation and avoid surgery altogether.

“All patients are going to need something slightly different, and maybe non-invasive stimulation is going to be best in some cases and epidural stimulation in others,” said Edgerton. “What we need to do is maximize the clinical tool box that we have so that the physician and the patient can select a therapy that is best for them.”

Health News: Six firms selling pesticide tainted imported produce ♦ Predict amount of nicotine emitted from e-cigarettes ♦ Cheaper, high-performance prosthetic knee

Six firms selling pesticide tainted imported produce The California Department of Pesticide Regulation has fined six companies that ignored warnings and repeatedly sold imported fruits and vegetables with illegal pesticide residues to predominantly ethnic minority customers. According to an agency statement released July 28, the fines range from $10,000 to more than $20,000 for violating pesticide laws and potentially endangering consumers....

When surgeons listen to their preferred music, their stitches are better and faster From classical to rock, music can be heard in operating rooms across the world. When plastic surgeons listen to music they prefer, their surgical technique and efficiency when closing incisions is improved.

Novel model developed to predict amount of nicotine emitted from e-cigarettes Researchers have developed the first ever, evidence-based model that can predict with up to 90 percent accuracy the amount of nicotine emitted by an electronic cigarettes.

Paralyzed men move legs with new non-invasive spinal cord stimulation Five men with complete motor paralysis were able to voluntarily generate step-like movements thanks to a new strategy that non-invasively delivers electrical stimulation to their spinal cords. The strategy, called transcutaneous stimulation, delivers electrical current to the spinal cord by way of electrodes strategically placed on the skin of the lower back. This expands to nine the number of completely paralyzed individuals who have achieved voluntary movement while receiving spinal stimulation.

Cheaper, high-performance prosthetic knee Researchers report that they have designed a cheap prosthetic knee that mimics normal walking motion. They have calculated the ideal torque that a prosthetic knee should produce, given the mass of the leg segments, in order to induce able-bodied kinematics, or normal walking

Scientists Plug into a Learning Brain

Learning is easier when it only requires nerve cells to rearrange existing patterns of activity than when the nerve cells have to generate new patterns, a study of monkeys has found. The scientists explored the brain’s capacity to learn through recordings of electrical activity of brain cell networks. The study was partly funded by the National Institutes of Health.

“We looked into the brain and may have seen why it’s so hard to think outside the box,” said Aaron Batista, Ph.D., an assistant professor at the University of Pittsburgh and a senior author of the study published in Nature, with Byron Yu, Ph.D., assistant professor at Carnegie Mellon University, Pittsburgh.

Scientists mapped neural activity patterns (white dots) in a learning brain. They found that learning occurs faster when it only requires existing patterns of activity (red box) than when it needs to use patterns outside of the red box. Courtesy of Batista lab, University of Pittsburgh

The human brain contains nearly 86 billion neurons, which communicate through intricate networks of connections. Understanding how they work together during learning can be challenging. Dr. Batista and his colleagues combined two innovative technologies, brain-computer interfaces and machine learning, to study patterns of activity among neurons in monkey brains as the animals learned to use their thoughts to move a computer cursor.

“This is a fundamental advance in understanding the neurobiological patterns that underlie the learning process,” said Theresa Cruz, Ph.D., a program official at the National Center for Medical Rehabilitations Research at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “The findings may eventually lead to new treatments for stroke as well as other neurological disorders.”

Brain-computer interfaces seek to turn thoughts into action. With small surgically implanted electrodes, researchers can simultaneously monitor the electrical activity of hundreds of neurons. A computer converts the signals into commands to move an external device, such as a robotic arm or a computer cursor. Brain-computer interfaces are being developed to help paralyzed patients as well as to study the function of healthy brains.

“This evolving technology is a powerful tool for brain research,” said Daofen Chen, Ph.D., a program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of NIH. “It helps scientists study the dynamics of brain circuits that may explain the neural basis of learning.”

In this study, the research team used brain-computer interfaces in two animals to examine learning in the motor cortex, a part of the brain that controls movement. The firing patterns of the neurons they recorded were used to control a computer cursor. As the animals learned to move the cursor to a designated spot on the monitor, the computer used machine learning to map brain cell activity to cursor movement. Machine learning is a method of programming a computer to learn and constantly adjust its commands based on previous data or experience. In this case, it created a feedback loop between the animal and the computer, which improved the animal’s ability to use its thoughts to move the cursor.

“Just as Netflix uses machine learning to predict the movies we’d like to watch, we used it to characterize the activity patterns that the brain produced during learning,” said Dr. Yu.

At first, the scientists noticed that the ensemble of neurons recorded in each animal had a small set of natural, or favored, firing patterns that were used to move the cursor, which they called the “intrinsic manifold.” After determining the intrinsic manifold, the team reprogrammed the map between neural activity and cursor movement. For instance, if a firing pattern originally caused the cursor to move to the top of the screen, then the interface would move the cursor to the bottom. The team then observed whether the animals could learn to generate the appropriate neural activity patterns to compensate for the changes.

“It’s as if we turned a computer mouse upside down in a person’s hand and asked him to click on an icon, except the mouse is entirely within the subject’s brain,” said Patrick Sadtler, a Ph.D. candidate at the University of Pittsburgh, who is the lead author of the study.

The scientists discovered that the monkeys easily relearned how to move the cursor if they could use patterns within the intrinsic manifold in new ways.  In contrast, learning was more difficult when the interface required patterns of neural activity that were outside of the intrinsic manifold.

“It appears that the brain sets constraints on the speed with which we learn new things. Characterizing those constraints might enable us to predict which skills will be quicker to learn, and which might take longer,” said Dr. Batista. He and his colleagues speculated that, for humans, thinking outside the box requires more difficult changes in neural activity.