In a Stanford-led research report, three participants with movement impairment controlled an onscreen cursor simply by imagining their own hand movements.
A clinical research publication led by Stanford University investigators has demonstrated that a brain-to-computer hookup can enable people with paralysis to type via direct brain control at the highest speeds and accuracy levels reported to date.
The report involved three study participants with severe limb weakness — two from amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, and one from a spinal cord injury. They each had one or two baby-aspirin-sized electrode arrays placed in their brains to record signals from the motor cortex, a region controlling muscle movement. These signals were transmitted to a computer via a cable and translated by algorithms into point-and-click commands guiding a cursor to characters on an onscreen keyboard.
Each participant, after minimal training, mastered the technique sufficiently to outperform the results of any previous test of brain-computer interfaces, or BCIs, for enhancing communication by people with similarly impaired movement. Notably, the study participants achieved these typing rates without the use of automatic word-completion assistance common in electronic keyboarding applications nowadays, which likely would have boosted their performance.
One participant, Dennis Degray of Menlo Park, California, was able to type 39 correct characters per minute, equivalent to about eight words per minute.
‘A major milestone’
This point-and-click approach could be applied to a variety of computing devices, including smartphones and tablets, without substantial modifications, the Stanford researchers said.
“Our study’s success marks a major milestone on the road to improving quality of life for people with paralysis,” said Jaimie Henderson, MD, professor of neurosurgery, who performed two of the three device-implantation procedures at Stanford Hospital. The third took place at Massachusetts General Hospital.
Henderson and Krishna Shenoy, PhD, professor of electrical engineering, are co-senior authors of the study, which was published online Feb. 21 in eLife. The lead authors are former postdoctoral scholar Chethan Pandarinath, PhD, and postdoctoral scholar Paul Nuyujukian, MD, PhD, both of whom spent well over two years working full time on the project at Stanford.
“This study reports the highest speed and accuracy, by a factor of three, over what’s been shown before,” said Shenoy, a Howard Hughes Medical Institute investigator who’s been pursuing BCI development for 15 years and working with Henderson since 2009. “We’re approaching the speed at which you can type text on your cellphone.”
“The performance is really exciting,” said Pandarinath, who now has a joint appointment at Emory University and the Georgia Institute of Technology as an assistant professor of biomedical engineering. “We’re achieving communication rates that many people with arm and hand paralysis would find useful. That’s a critical step for making devices that could be suitable for real-world use.”
Shenoy’s lab pioneered the algorithms used to decode the complex volleys of electrical signals fired by nerve cells in the motor cortex, the brain’s command center for movement, and convert them in real time into actions ordinarily executed by spinal cord and muscles.
“These high-performing BCI algorithms’ use in human clinical trials demonstrates the potential for this class of technology to restore communication to people with paralysis,” said Nuyujukian.
Millions of people with paralysis reside in the United States. Sometimes their paralysis comes gradually, as occurs in ALS. Sometimes it arrives suddenly, as in Degray’s case.
Now 64, Degray became quadriplegic on Oct. 10, 2007, when he fell and sustained a life-changing spinal-cord injury. “I was taking out the trash in the rain,” he said. Holding the garbage in one hand and the recycling in the other, he slipped on the grass and landed on his chin. The impact spared his brain but severely injured his spine, cutting off all communication between his brain and musculature from the head down.
“I’ve got nothing going on below the collarbones,” he said.
Degray received two device implants at Henderson’s hands in August 2016. In several ensuing research sessions, he and the other two study participants, who underwent similar surgeries, were encouraged to attempt or visualize patterns of desired arm, hand and finger movements. Resulting neural signals from the motor cortex were electronically extracted by the embedded recording devices, transmitted to a computer and translated by Shenoy’s algorithms into commands directing a cursor on an onscreen keyboard to participant-specified characters.
The researchers gauged the speeds at which the patients were able to correctly copy phrases and sentences — for example, “The quick brown fox jumped over the lazy dog.” Average rates were 7.8 words per minute for Degray and 6.3 and 2.7 words per minute, respectively, for the other two participants.
A tiny silicon chip
The investigational system used in the study, an intracortical brain-computer interface called the BrainGate Neural Interface System*, represents the newest generation of BCIs. Previous generations picked up signals first via electrical leads placed on the scalp, then by being surgically positioned at the brain’s surface beneath the skull.
An intracortical BCI uses a tiny silicon chip, just over one-sixth of an inch square, from which protrude 100 electrodes that penetrate the brain to about the thickness of a quarter and tap into the electrical activity of individual nerve cells in the motor cortex.
This is like one of the coolest video games I’ve ever gotten to play with.
Henderson likened the resulting improved resolution of neural sensing, compared with that of older-generation BCIs, to that of handing out applause meters to individual members of a studio audience rather than just stationing them on the ceiling, “so you can tell just how hard and how fast each person in the audience is clapping.”
Shenoy said the day will come — closer to five than 10 years from now, he predicted —when a self-calibrating, fully implanted wireless system can be used without caregiver assistance, has no cosmetic impact and can be used around the clock.
“I don’t see any insurmountable challenges.” he said. “We know the steps we have to take to get there.”
Degray, who continues to participate actively in the research, knew how to type before his accident but was no expert at it. He described his newly revealed prowess in the language of a video game aficionado.
“This is like one of the coolest video games I’ve ever gotten to play with,” he said. “And I don’t even have to put a quarter in it.”
The study’s results are the culmination of a long-running collaboration between Henderson and Shenoy and a multi-institutional consortium called BrainGate. Leigh Hochberg, MD, PhD, a neurologist and neuroscientist at Massachusetts General Hospital, Brown University and the VA Rehabilitation Research and Development Center for Neurorestoration and Neurotechnology in Providence, Rhode Island, directs the pilot clinical trial of the BrainGate system and is a study co-author.
“This incredible collaboration continues to break new ground in developing powerful, intuitive, flexible neural interfaces that we all hope will one day restore communication, mobility and independence for people with neurologic disease or injury,” said Hochberg.
It is located at Stanford University Medical Center in Stanford, California. It is the successor to the Medical Department of the University of the Pacific, founded in San Francisco in 1858 and later named Cooper Medical College; the medical school was acquired by Stanford in 1908. Due to this descent it ranks as the oldest medical school in the Western United States. The medical school moved to the Stanford campus near Palo Alto, California in 1959.
Clinical rotations occur at several hospital sites. In addition to the Stanford University Medical Center (Stanford Hospital and Clinics) and Lucile Packard Children’s Hospital, Stanford has formal affiliations with Kaiser Permanente, Santa Clara Valley Medical Center and the Palo Alto Veterans Administration. Stanford medical students also manage two free clinics: Arbor Free Clinic in Menlo Park and Pacific Free Clinic in San Jose. Stanford is a cutting-edge center for translational and biomedical research (both basic science and clinical) and emphasizes medical innovation, novel methods, discoveries, and interventions in its integrated curriculum.
The School of Medicine also has a Physician Assistant (PA) program that was added in 1971, called the Primary Care Associate Program. It was one of the first accredited physician assistant programs in California. It is offered in association with Foothill College. The program has graduated more than 1,300 physician assistants since its opening. Most graduates fulfill the program’s mission of serving underserved medical communities.
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Microfluidics, electronics and inkjet technology underlie a newly developed all-in-one biochip from Stanford that can analyze cells for research and clinical applications.
Researchers at the Stanford University School of Medicine have developed a way to produce a cheap and reusable diagnostic “lab on a chip” with the help of an ordinary inkjet printer.
At a production cost of as little as 1 cent per chip, the new technology could usher in a medical diagnostics revolution like the kind brought on by low-cost genome sequencing said Ron Davis, PhD, professor of biochemistry and of genetics and director of the Stanford Genome Technology Center.
A study describing the technology was published online Feb. 6 in the Proceedings of the National Academy of Sciences. Davis is the senior author. The lead author is Rahim Esfandyarpour, PhD, an engineering research associate at the genome center.
The inexpensive lab-on-a-chip technology has the potential to enhance diagnostic capabilities around the world, especially in developing countries. Due to inferior access to early diagnostics, the survival rate of breast cancer patients is only 40 percent in low-income nations — half the rate of such patients in developed nations. Other lethal diseases, such as malaria, tuberculosis and HIV, also have high incidence and bad patient outcomes in developing countries. Better access to cheap diagnostics could help turn this around, especially as most such equipment costs thousands of dollars.
“Enabling early detection of diseases is one of the greatest opportunities we have for developing effective treatments,” Esfandyarpour said. “Maybe $1 in the U.S. doesn’t count that much, but somewhere in the developing world, it’s a lot of money.”
A two-part system
A combination of microfluidics, electronics and inkjet printing technology, the lab on a chip is a two-part system. The first is a clear silicone microfluidic chamber for housing cells and a reusable electronic strip. The second part is a regular inkjet printer that can be used to print the electronic strip onto a flexible sheet of polyester using commercially available conductive nanoparticle ink.
“We designed it to eliminate the need for clean-room facilities and trained personnel to fabricate such a device,” said Esfandyarpour, an electrical engineer by training. One chip can be produced in about 20 minutes, he said.
Designed as a multifunctional platform, one of its applications is that it allows users to analyze different cell types without using fluorescent or magnetic labels that are typically required to track cells. Instead, the chip separates cells based on their intrinsic electrical properties: When an electric potential is applied across the inkjet-printed strip, cells loaded into the microfluidic chamber get pulled in different directions depending on their “polarizability” in a process called dielectrophoresis. This label-free method to analyze cells greatly improves precision and cuts lengthy labeling processes.
The tool is designed to handle small-volume samples for a variety of assays. The researchers showed the device can help capture single cells from a mix, isolate rare cells and count cells based on cell types. The cost of these multifunctional biochips is orders of magnitude lower than that of the individual technologies that perform each of those functions. A standalone flow cytometer machine, for example, which is used to sort and count cells, costs $100,000, without taking any operational costs into account.
Potential to democratize diagnostics
“The motivation was really how to export technology and how to decrease the cost of things,” Davis said.
The low cost of the chips could democratize diagnostics similar to how low-cost sequencing created a revolution in health care and personalized medicine, Davis said. Inexpensive sequencing technology allows clinicians to sequence tumor DNA to identify specific mutations and recommend personalized treatment plans. In the same way, the lab on a chip has the potential to diagnose cancer early by detecting tumor cells that circulate in the bloodstream. “The genome project has changed the way an awful lot of medicine is done, and we want to continue that with all sorts of other technology that are just really inexpensive and accessible,” Davis said.
The technology has the potential to not only advance health care, but also to accelerate basic and applied research. It would allow scientists and clinicians to potentially analyze more cells in shorter time periods, manipulate stem cells to achieve efficient gene transfer and develop cost-effective ways to diagnose diseases, Esfandyarpour said. The team hopes the chip will create a transformation in how people use instruments in the lab. “I’m pretty sure it will open a window for researchers because it makes life much easier for them — just print it and use it,” he said.
The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.
Researchers at the Stanford University School of Medicine have mapped out the sets of biological and chemical signals necessary to quickly and efficiently direct human embryonic stem cells to become pure populations of any of 12 cell types, including bone, heart muscle and cartilage. The ability to make pure populations of these cells within days rather than the weeks or months previously required is a key step toward clinically useful regenerative medicine — potentially allowing researchers to generate new beating heart cells to repair damage after a heart attack or to create cartilage or bone to reinvigorate creaky joints or heal from trauma.
The study also highlights key, but short-lived, patterns of gene expression that occur during human embryo segmentation and confirms that human development appears to rely on processes that are evolutionarily conserved among many animals.