Posts tagged spinal cord injury
Articles and news from the latest research reports.
UC Davis team “spikes” stem cells to generate myelin
Findings hold promise for developing regenerative therapies for spinal cord injuries and diseases such as multiple sclerosis
Stem cell technology has long offered the hope of regenerating tissue to repair broken or damaged neural tissue. Findings from a team of UC Davis investigators have brought this dream a step closer by developing a method to generate functioning brain cells that produce myelin — a fatty, insulating sheath essential to normal neural conduction.
“Our findings represent an important conceptual advance in stem cell research,” said Wenbin Deng, principal investigator of the study and associate professor at the UC Davis Department of Biochemistry and Molecular Medicine. “We have bioengineered the first generation of myelin-producing cells with superior regenerative capacity.”
The brain is made up predominantly of two cell types: neurons and glial cells. Neurons are regarded as responsible for thought and sensation. Glial cells surround, support and communicate with neurons, helping neurons process and transmit information using electrical and chemical signals. One type of glial cell — the oligodendrocyte — produces a sheath called myelin that provides support and insulation to neurons. Myelin, which has been compared to insulation around electrical wires that helps to prevent short circuits, is essential for normal neural conduction and brain function; well-recognized conditions involving defective myelin development or myelin loss include multiple sclerosis and leukodystrophies.
In this study, the UC Davis team first developed a novel protocol to efficiently induce embryonic stem cells (ESCs) to differentiate into oligodendroglial progenitor cells (OPCs), early cells that normally develop into oligodendrocytes. Although this has been successfully done by other researchers, the UC Davis method results in a purer population of OPCs, according to Deng, with fewer other cell types arising from their technique.
They next compared electrophysiological properties of the derived OPCs to naturally occurring OPCs. They found that unlike natural OPCs, the ESC-derived OPCs lacked sodium ion channels in their cell membranes, making them unable to generate spikes when electrically stimulated. Using a technique called viral transduction, they then introduced DNA that codes for sodium channels into the ESC-derived OPCs. These OPCs then expressed ion channels in their cells and developed the ability to generate spikes.
According to Deng, this is the first time that scientists have successfully generated OPCs with so-called spiking properties. This achievement allowed them to compare the capabilities of spiking cells to non-spiking cells.
In cell culture, they found that only spiking OPCs received electrical input from neurons, and they showed superior capability to mature into oligodendrocytes.
They also transplanted spiking and non-spiking OPCs into the spinal cord and brains of mice that are genetically unable to produce myelin. Both types of OPCs had the capability to mature into oligo-dendrocytes and produce myelin, but those from spiking OPCs produced longer and thicker myelin sheaths around axons.
“We actually developed ‘super cells’ with an even greater capacity to spike than natural cells,” Deng said. “This appears to give them an edge for maturing into oligodendrocytes and producing better myelin.”
It is well known that adult human neural tissue has a poor capacity to regenerate naturally. Although early cells such as OPCs are present, they do not regenerate tissue very effectively when disease or injury strikes.
Deng believes that replacing glial cells with the enhanced spiking OPCs to treat neural injuries and diseases has the potential to be a better strategy than replacing neurons, which tend to be more problematic to work with. Providing the proper structure and environment for neurons to live may be the best approach to regenerate healthy neural tissue. He also notes that many diverse conditions that have not traditionally been considered to be myelin-related diseases – including schizophrenia, epilepsy and amyotrophic lateral sclerosis (ALS) – actually are now recognized to involve defective myelin.
Scientist discovers novel mechanism in spinal cord injury
More than 11,000 Americans suffer spinal cord injuries each year, and since over a quarter of those injuries are due to falls, the number is likely to rise as the population ages. The reason so many of those injuries are permanently disabling is that the human body lacks the capacity to regenerate nerve fibers. The best our bodies can do is route the surviving tissue around the injury site.
"It’s like a detour after an earthquake," says Kuo-Fen Lee, the Salk Institute’s Helen McLoraine Chair in Molecular Neurobiology. "If the freeway is down, but you can still take the side-streets, traffic can still move. So your strategy has to be to find a way to preserve as much tissue as possible, to give yourself a chance for that rerouting."
In a paper published in this week’s PLOS ONE, Lee and his colleagues describe how a protein named P45 may yield insight into a possible molecular mechanism to promote rerouting for spinal cord healing and functional recovery. Because injured mice can recover more fully than human beings, Lee sought the source of the difference. He discovered that P45 had a previously unknown neuroprotective effect.
"As a biochemist and neurobiologist, this discovery gives me hope that we can find a potential target molecule for drug treatments," says Lee. "Nevertheless, I must caution that this is only the first step in knowing what to look for."
In a human or a mouse, the success of an attempted rerouting after a spinal cord injury depends on how much healthy tissue is left. But wounds set off a cascade of reactions within cells, which if not stopped in time will result in more dead and dying tissue extending beyond the injury site. Nerve traction from the injury site leads to disconnection of the network required for normal sensory and motor functions. Lee found that P45 is the key factor determining whether the cascade continues on to its destructive end.
A complex of proteins, by sequentially interacting with each other, induces this cascade of cell death. Lee discovered that P45 is a natural antagonist to this process. Antagonists are molecules, some naturally occurring, some made in pharmaceutical laboratories, that work essentially like sticking gum in a lock. Because the antagonist is in place, no other molecule can get in. In this case, P45 prevents two other proteins in the death cascade from connecting, rendering their actions harmless and stopping cell death.
But there’s more to how P45 works that gives Lee hope that he may be on to a unique approach to finding new ways to treat spinal cord injuries. In other recent findings, which are being prepared for publication, his team saw P45 also yield positive effects, specifically the encouragement of healthy tissue growth. Thus, Lee concludes its real role may be as a sort of “see-saw” molecule that tips the balance in the cascade from negative to positive.
"The great thing about P45 is that it can both inhibit the negative by blocking the conformational change that would lead to more cell death, while promoting the positive-the survival and growth of tissue-thus making it easier to foster recovery following spinal cord injury," Lee explains.
"If you can understand where you could tilt the balance of positive/negative signal, it would give you less damage while helping to promote healing," says Lee. "It could be combinatorial-maybe one molecule can do both, or maybe it’s a combination of two molecules, one to negate, one to promote. The hope is if such a control switch could be found, more tissue could be preserved at the site of injury, thus increasing the chances that movement might someday be restored."
The next step for Lee’s laboratory will be to seek either a gene, or a process that works in a similar see-saw way in humans, or can be made to work with therapeutic intervention. Still, Lee cautions, this remains a proof of concept experiment in mice. Even if such a mechanism were found in humans, clinical applications would be years away.
Irreversible tissue loss seen within 40 days of spinal cord injury
The rate and extent of damage to the spinal cord and brain following spinal cord injury have long been a mystery. Now, a joint research effort between the University of Zurich, University Hospital Balgrist and colleagues from University College London have found evidence that patients already have irreversible tissue loss in the spinal cord within 40 days of injury. Using a new imaging measurement technique the impact of therapeutic treatments and rehabilitative interventions can be now determined more quickly and directly than before.
A spinal cord injury changes the functional state and structure of the spinal cord and the brain. For example, the patients’ ability to walk or move their hands can become restricted. How quickly such degenerative changes develop, however, has remained a mystery until now. The assumption was that it took years for patients with a spinal cord injury to also display anatomical changes in the spinal cord and brain above the injury site. For the first time, researchers from the University of Zurich and the Uniklinik Balgrist, along with English colleagues from University College London (UCL), now demonstrate that these changes already occur within 40 days of acute spinal cord injury.
Spinal cord depletes rapidly
The scientists studied 13 patients with acute spinal cord injuries every three months for a year using novel MRI (magnetic resonance imaging) protocols. They discovered that the diameter of the spinal cord had rapidly decreased and was already seven percent smaller after twelve months. A lesser volume decline was also evident in the corticospinal tract, a tract indispensable for motor control, and nerve cells in the sensorimotor cortex. The extent of the degenerative changes coincided with the clinical outcome. “Patients with a greater tissue loss above the injury site recovered less effectively than those with less changes,” explains Patrick Freund, the investigator responsible for the study at the Paraplegic Center Balgrist.
Gaining insights into effect of therapies
Treatments targeting the injured spinal cord have entered clinical trials. Gaining insights into mechanisms of repair and recovery within the first year are crucial. Thanks to the use of the new neuroimaging protocols, Freund says, we now have the possibility of displaying the effect of therapeutic treatments on the central nervous system and of rehabilitative measures more quickly. Consequently, the effect of new therapies can also be recorded more rapidly.
“This study is an excellent example of the value of combining the complementary expertise of the two universities,” says UCL’s Dean of Brain Sciences, Professor Alan Thompson, who is one of the senior authors of the study. “It provides exciting new insights into the complications of spinal cord trauma and gives us the possibility of identifying both imaging biomarkers and therapeutic targets.”
The findings are the result of a new three-year neuroscience partnership between the Neuroscience Centre Zurich (ZNZ) and UCL.
Literature:
Patrick Freund, Nikolaus Weiskopf, John Ashburner, Katharina Wolf, Reto Sutter, Daniel R Altmann, Karl Friston, Alan Thompson, Armin Curt. MRI investigation of the sensorimotor cortex and corticospinal tract after acute spinal cord injury: a prospective longitudinal study. The Lancet Neurology. July 2, 2013.
Restoring paretic hand function via an artificial neural connection bridging spinal cord injury
Functional loss of limb control in individuals with spinal cord injury or stroke can be caused by interruption of the neural pathways between brain and spinal cord, although the neural circuits located above and below the lesion remain functional. An artificial neural connection that bridges the lost pathway and connects brain to spinal circuits has potential to ameliorate the functional loss. Yukio Nishimura, Associate Professor of the National Institute for Physiological Sciences, Japan, and Eberhard Fetz, Professor and Steve Perlmuter, Research Associate Professor at the University of Washington, United States investigated the effects of introducing a novel artificial neural connection which bridged a spinal cord lesion in a paretic monkey. This allowed the monkey to electrically stimulate the spinal cord through volitionally controlled brain activity and thereby to restore volitional control of the paretic hand. This study demonstrates that artificial neural connections can compensate for interrupted descending pathways and promote volitional control of upper limb movement after damage of neural pathways such as spinal cord injury or stroke. The study will be published online in Frontiers in Neural Circuits on April 11.
"The important point is that individuals who are paralyzed want to be able to move their own bodies by their own will. This study was different from what other research groups have done up to now; we didn’t use any prosthetic limbs like robotic arms to replace the original arm. What’s new is that we have been able to use this artificial neuronal connection bypassing the lesion site to restore volitional control of the subject’s own paretic arm. I think that for lesions of the corticospinal pathway this might even have a better chance of becoming a real prosthetic treatment rather than the sort of robotic devices that have been developed recently", Associate professor Nishimura said.
Getting a grip on hand function: Discovering key spinal cord circuits
Professor and neurosurgeon Dr. Rob Brownstone and postdoctoral fellow Dr. Tuan Bui have identified the spinal cord circuit that controls the hands’ ability to grasp.
The world’s leading neuroscience journal, Neuron, published the breakthrough finding in its latest issue.
The researchers have found that a certain population of neurons in the spinal cord — called the dI3 interneurons — assess information from sensory neurons in the hands and then send the appropriate signals to motor neurons in the spinal cord, and hence to the muscles, to control the hands’ grip.
Importance of hand-grip control
“This circuit allows us to subtly and unconsciously adjust our grasp so we apply the right amount of force to whatever we’re holding,” says Dr. Brownstone, a professor in the Department of Medical Neurosciences and the Division of Neurosurgery. “This mechanism is disrupted in spinal cord injuries, which can completely eliminate the ability to grasp, and in neurodegenerative diseases like Alzheimer’s disease, which can lead to an uncontrollable reflexive grasp such that people grab and can’t let go of what they touch.”
Impaired hand function has a devastating effect on people’s independence and ability to function in daily life. As Dr. Brownstone points out, people with quadriplegia ranked hand function as their number-one priority, when asked in a 2004 survey which function they would most want to recover if they could. They rated hand function well above trunk stability, walking, sexual function, bladder and bowel control, and normal sensation.
An unexpected finding
Drs. Brownstone and Bui were testing a spinal cord circuit for its role in the rhythmic pattern of walking, when they found it controlled hand grip instead. “The mice with this circuit disrupted were walking just fine, but I found it was unusually easy to remove them from their cages,” recounts Dr. Bui. “Mice will usually grab onto the cage wires when you go take them out, so this really got us thinking.”
While Dr. Bui was pondering the meaning of this unexpected observation in the lab, Dr. Brownstone was in his neurosurgery clinic, assessing a patient who was unable to control her grasp. “When she took my hand, she was unable to let go,” he recalls. “I had to peel her fingers off one by one to release my hand.”
As they compared notes, Drs. Brownstone and Dr. Bui quickly realized they had come across the circuit that controls hand grasp. Struck by the implications of their observations, they embarked on a series of experiments — with collaborators, including Dr. Tom Jessell at Columbia University in New York City — which validated the finding.
A path to future treatments
Now that the researchers have identified the specific spinal cord circuit that controls hand grip, they can go on to find targets for potential treatments for impaired hand function. “It’s possible that a neurotransmitter or other agent could be delivered to the spinal cord to correct the faulty circuit,” notes Dr. Brownstone. “It could be a complex strategy, but understanding is always the first step.”
Dr. Brownstone is a Tier 1 Canada Research Chair in spinal cord circuits. His research is also supported through grants from the Canadian Institutes of Health Research. Dr. Bui is a key member of Dr. Brownstone’s research team in the Motor Control Lab at Dalhousie University, where they are identifying the neural circuits that control our ability to walk and move in coordinated ways. Their ultimate goal is to identify targets for therapies to restore lost motor function and control in people with spinal cord injuries and other neurological diseases.
New Hope for Reversing the Effects of Spinal Cord Injury
Walking is the obvious goal for individuals who have a chronic spinal cord injury, but it is not the only one. Regaining sensation and continence control also are important goals that can positively impact an individual’s quality of life. New hope for reversing the effects of spinal cord injury may be found in a combination of stem cell therapy and physical therapy as reported in Cell Transplantation by scientists at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.
“Our phase one/two clinical trial had one goal: to give patients who have no other treatment options some hope,” said Hatem E. Sabaawy, MD, PhD, an assistant professor of medicine in the molecular and regenerative medicine program at Robert Wood Johnson Medical School. “Early findings have concluded that we have met our goal and can improve the quality of life for individuals with spinal cord injuries by providing a safe treatment that restores some neurological function.”
Dr. Sabaawy led a clinical trial that included 70 patients who had cervical or thoracic spinal cord injuries and were previously treated for at least six months without response. The patients were randomized into two groups, both of which were given physical therapy treatment. One of the groups also received stem cells derived from their own bone marrow injected near the injury site. Using the American Spinal Injury Association Impairment (AIS) Scale, patients received neurological and physical evaluations monthly for 18 months to determine if sensory and motor functions improved.
“Of primary importance, there was a notable absence of side effects in patients treated with stem cells during the course of our investigation,” added Dr. Sabaawy, who also is a resident member of The Cancer Institute of New Jersey at Robert Wood Johnson Medical School.
None of the patients in the control group who received only physical therapy showed any improvement in sensory or motor function during the same time frame. Although the scale of injuries differed, all patients who were treated with a combination of bone-marrow derived stem cells and physical therapy responded to tactile and sensory stimuli as early as 4 weeks into the study. After 12 weeks, they experienced improvements in sensation and muscle strength, which was associated with enhanced potency and improved bladder and bowel control that eventually allowed patients to live catheter-free. Patients who showed improvement based on the AIS scale also were able to sit up and turn in their beds.
“Since the emergence of stem cells as a potential therapy for spinal cord injury, scientists have diligently sought the best application for using their regenerating properties to improve a patient’s mobility,” said Joseph R. Bertino, MD, University Professor of medicine and pharmacology, interim director, Stem Cell Institute of New Jersey and chief scientific officer at The Cancer Institute of New Jersey. “Dr. Sabaawy’s discovery that treatment is more successful when stem cell therapy is combined with physical therapy could provide a remarkable, and hopefully sustainable, improvement in the overall quality of life for patients with spinal cord injury.”
At the end of 18 months, 23 of the 50 patients who received both physical therapy and stem cell therapy showed a significant improvement of at least 10 points on the AIS scale. Several were able to walk with assistance. In addition, more gains were made in motor skill control by patients with thoracic spinal cord injuries, suggesting that patients with thoracic spinal cord injuries may respond better to the combined treatment.
Dr. Sabaawy however cautioned that more studies are needed with a larger number of patients to test different cell dose levels and intervals at which stem cell therapy should be delivered.
“Although a cure for spinal cord injury does not yet exist, it is clear that the regenerative and secretory properties of bone-marrow derived stem cells can improve symptoms of paralysis in some patients when coupled with the current standard of care that physical therapy provides,” said Dr. Sabaawy. “We will continue monitoring our patients for long-term safety effects of stem cell therapy and work to expand our research through a phase two clinical trial that can be conducted at multiple centers nationwide and internationally.”
(Image courtesy: University of Alberta, Faculty of Rehabilitation Medicine)
Mind-controlled exoskeleton to help disabled people walk again
Every year thousands of people in Europe are paralysed by a spinal cord injury. Many are young adults, facing the rest of their lives confined to a wheelchair. Although no medical cure currently exists, in the future they could be able to walk again thanks to a mind-controlled robotic exoskeleton being developed by EU-funded researchers.
The system, based on innovative ‘Brain-neural-computer interface’ (BNCI) technology - combined with a light-weight exoskeleton attached to users’ legs and a virtual reality environment for training - could also find applications in the rehabilitation of stroke victims and in assisting astronauts rebuild muscle mass after prolonged periods in space.
In the United Kingdom, every eight hours someone suffers a spinal cord injury, often leading to partial or full lower-body paralysis. In the United States, more than 250.000 people are living with paralysis as a result of damage to their spinal cord, usually because of a traffic accident, fall or sporting injury. Many are under the age of 50, and with no known medical cure or way of repairing damaged spinal nerves they face the rest of their lives in a wheelchair.
But by bypassing the spinal cord entirely and routing brain signals to a robotic exoskeleton, they should be able to get back on their feet. That is the ultimate goal of researchers working in the ‘Mind-controlled orthosis and VR-training environment for walk empowering' (Mindwalker) project, a three-year initiative supported by EUR 2.75 million in funding from the European Commission.
'Mindwalker was proposed as a very ambitious project intended to investigate promising approaches to exploit brain signals for the purpose of controlling advanced orthosis, and to design and implement a prototype system demonstrating the potential of related technologies,' explains Michel Ilzkovitz, the project coordinator at Space Applications Services in Belgium.
The team’s approach relies on an advanced BNCI system that converts electroencephalography (EEG) signals from the brain, or electromyography (EMG) signals from shoulder muscles, into electronic commands to control the exoskeleton.
The Laboratory of Neurophysiology and Movement Biomechanics at the Université Libre de Bruxelles (ULB) focused on the exploitation of EEG and EMG signals treated by an artificial neural network, while the Foundation Santa Lucia in Italy developed techniques based on EMG signals modelled by the coupling of neural and biomechanical oscillators.
One approach for controlling the exoskeleton uses so-called ‘steady-state visually evoked potential’, a method that reads flickering visual stimuli produced at different frequencies to induce correlated EEG signals. Detection of these EEG signals is used to trigger commands such as ‘stand’, ‘walk’, ‘faster’ or ‘slower’.
A second approach is based on processing EMG signals generated by the user’s shoulders and exploits the natural arm-leg coordination in human walking: arm-swing patterns can be perceived in this way and converted into control signals commanding the exoskeleton’s legs.
A third approach, ‘ideation’, is also based on EEG-signal processing. It uses the identification and exploitation of EEG Theta cortical signals produced by the natural mental process associated with walking. The approach was investigated by the Mindwalker team but had to be dropped due to the difficulty, and time needed, in turning the results of early experiments into a fully exploitable system.
Regardless of which method is used, the BNCI signals have to be filtered and processed before they can be used to control the exoskeleton. To achieve this, the Mindwalker researchers fed the signals into a ‘Dynamic recurrent neural network’ (DRNN), a processing technique capable of learning and exploiting the dynamic character of the BNCI signals.
'This is appealing for kinematic control and allows a much more natural and fluid way of controlling an exoskeleton,' Mr Ilzkovitz says.
The team adopted a similarly practical approach for collecting EEG signals from the user’s scalp. Most BNCI systems are either invasive, requiring electrodes to be placed directly into brain tissue, or require users to wear a ‘wet’ capon their head, necessitating lengthy fitting procedures and the use of special gels to reduce the electrical resistance at the interface between the skin and the electrodes. While such systems deliver signals of very good quality and signal-to-noise ratio, they are impractical for everyday use.
The Mindwalker team therefore turned to a ‘dry’ technology developed by Berlin-based eemagine Medical Imaging Solutions: a cap covered in electrodes that the user can fit themselves, and which uses innovative electronic components to amplify and optimise signals before sending them to the neural network.
'The dry EEG cap can be placed by the subject on their head by themselves in less than a minute, just like a swimming cap,' Mr Ilzkovitz says.
A new study by Kennedy Krieger Institute’s International Center for Spinal Cord Injury (Epub ahead of print) finds that long-term lower extremity functional electrical stimulation (FES) cycling, as part of a rehabilitation regimen, is associated with substantial improvements in individuals with chronic spinal cord injury (SCI). Improvements include neurological and functional gains, as well as enhanced physical health demonstrated by decreased fat, increased muscle mass and improved lipid profile. Prior to this study’s publication in the Journal of Spinal Cord Medicine, the benefits of activity-based restorative therapy (ABRT) programs, such as FES cycling, were largely anecdotal despite publicity in conjunction with the recovery of actor and activist Christopher Reeve.
In FES, small electrical pulses are applied to paralyzed muscles to stimulate movement. In the case of FES cycling, FES pulses prompt the legs of an individual with SCI to “cycle” on an adapted stationary recumbent bicycle. The repetitive activity offers cardiovascular exercise similar to that which an able-bodied individual achieves through walking, but this new research shows that the results go far beyond basic health benefits.
“Exercise has not been commonly advocated for individuals with paralysis because of the assumption that it is of little benefit and it is challenging to exercise limbs that an individual cannot voluntarily move,” said John W. McDonald, M.D., Ph.D., senior study author and director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute. “However, we found that FES cycling is a practical form of exercise that provides substantial benefits, including improved physical integrity, enhanced neurological and functional performance, increased muscle size and strength, reduced muscle spasticity and improved quality of life.”
Scientists find genes linked to human neurological disorders in sea lamprey genome
Scientists at the Marine Biological Laboratory (MBL) have identified several genes linked to human neurological disorders, including Alzheimer’s disease, Parkinson’s disease and spinal cord injury, in the sea lamprey, a vertebrate fish whose whole-genome sequence is reported this week in the journal Nature Genetics.
"This means that we can use the sea lamprey as a powerful model to drive forward our molecular understanding of human neurodegenerative disease and neurological disorders," says Jennifer Morgan of the MBL’s Eugene Bell Center for Regenerative Biology and Tissue Engineering. The ultimate goals are to determine what goes wrong with neurons after injury and during disease, and to determine how to correct these deficits in order to restore normal nervous system functions.
Unlike humans, the lamprey has an extraordinary capacity to regenerate its nervous system. If a lamprey’s spinal cord is severed, it can regenerate the damaged nerve cells and be swimming again in 10-12 weeks.
Morgan and her collaborators at MBL, Ona Bloom and Joseph Buxbaum, have been studying the lamprey’s recovery from spinal cord injury since 2009. The lamprey has large, identified neurons in its brain and spinal cord, making it an excellent model to study regeneration at the single cell-level. Now, the lamprey’s genomic information gives them a whole new “toolkit” for understanding its regenerative mechanisms, and for comparing aspects of its physiology, such as inflammation response, to that of humans.
The lamprey genome project was accomplished by a consortium of 59 researchers led by Weiming Li of Michigan State University and Jeramiah Smith of the University of Kentucky. The MBL scientists’ contribution focused on neural aspects of the genome, including one of the project’s most intriguing findings.
Lampreys, in contrast to humans, don’t have myelin, an insulating sheath around neurons that allows faster conduction of nerve impulses. Yet the consortium found genes expressed in the lamprey that are normally expressed in myelin. In humans, myelin-associated molecules inhibit nerves from regenerating if damaged. “A lot of the focus of the spinal cord injury field is on neutralizing those inhibitory molecules,” Morgan says.
"So there is an interesting conundrum," Morgan says. "What are these myelin-associated genes doing in an animal that doesn’t have myelin, and yet is good at regeneration? It opens up a new and interesting set of questions, " she says. Addressing them could bring insight to why humans lost the capacity for neural regeneration long ago, and how this might be restored.
At present, Morgan and her collaborators are focused on analyzing which genes are expressed and when, after spinal cord injury and regeneration. The whole-genome sequence gives them an invaluable reference for their work.
Researchers at the University of Pittsburgh School of Medicine and UPMC describe in PLoS ONE how an electrode array sitting on top of the brain enabled a 30-year-old paralyzed man to control the movement of a character on a computer screen in three dimensions with just his thoughts. It also enabled him to move a robot arm to touch a friend’s hand for the first time in the seven years since he was injured in a motorcycle accident.
With brain-computer interface (BCI) technology, the thoughts of Tim Hemmes, who sustained a spinal cord injury that left him unable to move his body below the shoulders, were interpreted by computer algorithms and translated into intended movement of a computer cursor and, later, a robot arm, explained lead investigator Wei Wang, Ph.D., assistant professor, Department of Physical Medicine and Rehabilitation, Pitt School of Medicine.
“When Tim reached out to high-five me with the robotic arm, we knew this technology had the potential to help people who cannot move their own arms achieve greater independence,” said Dr. Wang, reflecting on a memorable scene from September 2011 that was re-told in stories around the world. “It’s very important that we continue this effort to fulfill the promise we saw that day.”
Six weeks before the implantation surgery, the team conducted functional magnetic resonance imaging (fMRI) of Mr. Hemmes’ brain while he watched videos of arm movement. They used that information to place a postage stamp-size electrocortigraphy (ECoG) grid of 28 recording electrodes on the surface of the brain region that fMRI showed controlled right arm and hand movement. Wires from the device were tunneled under the skin of his neck to emerge from his chest where they could be connected to computer cables as necessary.
For 12 days at his home and nine days in the research lab, Mr. Hemmes began the testing protocol by watching a virtual arm move, which triggered neural signals that were sensed by the electrodes. Distinct signal patterns for particular observed movements were used to guide the up and down motion of a ball on a computer screen. Soon after mastering movement of the ball in two dimensions, namely up/down and right/left, he was able to also move it in/out with accuracy on a 3-dimensional display.
“During the learning process, the computer helped Tim hit his target smoothly by restricting how far off course the ball could wander,” Dr. Wang said. “We gradually took off the ‘training wheels,’ as we called it, and he was soon doing the tasks by himself with 100 percent brain control.”
The robot arm was developed by Johns Hopkins University’s Applied Physics Laboratory. Currently, Jan Scheuermann, of Whitehall, Pa., is testing another BCI technology at Pitt/UPMC.