Controlling movement through thought alone

Brown students steeped in neuroscience played key role in BrainGate

by Wendy Y. Lawton

The mind-to-movement system that allows a quadriplegic man to control a computer using only his thoughts is a scientific milestone. It was reached, in large part, through the smarts and sweat of Brown students.

The system, developed in the laboratory of John Donoghue, turns movement commands from the brain into action on a computer screen. Matthew Nagle, a 25-year-old taking part in a clinical trial of the system, called BrainGate, has opened e-mail, switched TV channels, turned on lights. He even moved a robotic hand from his wheelchair.

This marks the first time that neural movement signals have been recorded and decoded in a human with spinal cord injury. The system is also the first to allow a human to control his surrounding environment using his mind. This feat wouldn't have been possible without the work of Brown undergraduate and graduate students.

A dozen students played key roles in everything from basic animal research behind the system to creation of the startup company that developed it for human testing. A handful of alumni now work at the Foxborough, Mass., company, Cyberkinetics Neurotechnology Systems Inc., as it tests the system for safety and effectiveness in humans.

"The role of students has been essential - key, really - to this project," said Donoghue, Henry Merritt Wriston Professor and chair of the Department of Neuroscience as well as the chief scientific officer at Cyberkinetics.

"It's a testament to how good Brown students are. They are smart, excited, engaged," Donoghue said. "There is a tradition here that undergraduates are involved in research. A lot of institutions say that, but at Brown, it really happens."

When research proving that brain signals could be harnessed for use outside the body - in this case, monkeys playing a video game with thought alone - was published in 2002 in Nature, four of the five authors were current or former Brown students.

Liam Paninski, a '99 neuroscience graduate, used an existing algorithm to take raw data from the brain and decode it into movement commands. Matthew Fellows, now completing his Ph.D. in neuroscience, also worked on the mathematics behind the decoding and helped develop the surgical techniques used to implant the sensor in monkeys' brains.

Nicholas Hatsopolous, who earned his Ph.D. in cognitive science at Brown in 1992 and returned three years later to conduct neuroscience research and teach, worked with Donoghue to conduct the first recordings of monkeys' brain activity nearly a decade ago.

Mijail "Misha" Serruya, lead author of the Nature paper, was pursing an M.D.-Ph.D. degree at Brown Medical School when the research made an international splash. Serruya had a hand in all facets of the monkey experiments, right down to creating the simple Ping-Pong game the animals played.

"I lived in the lab - I actually slept there on a desk a few times," he recalls with a laugh. "But the experience, as a student, was incredible. I learned how to handle a complex project. I learned how to write a grant and submit a research paper. I also learned how to set objectives and meet them on time, or even ahead of time."

Serruya, who has completed requirements for his dual degree and will graduate this spring, was a co-founder of Cyberkinetics. He now works at the company as a junior clinical scientist, recruiting patients for the trial and working on product development.

Donoghue - with Hatsopolous, Serruya, and Brown neurosurgery professor Gerhard Friehs - founded Cyberkinetics in 2001. Even during the start-up phase, Brown students were involved. Undergrad Mikhail Shapiro, for example, acted as a de facto CEO, writing a business plan, interviewing lawyers, reading contracts and helping to pull in venture capital.

Now that the company is up and running - it went public last month - Brown grads still play a vital role. Dan Morris, a '00 neuroscience concentrator who worked for three years in the Donoghue lab, serves as a software engineering consultant while pursuing a Ph.D. in computer science from Stanford.

Abe Caplan and Maryam Saleh have a front-row seat as Cyberkinetics makes science history. The recent Brown grads, who earned bachelor of science degrees in computer engineering, work directly with Nagle, who is the only patient so far enrolled in the clinical trial.

Nagle is unable to move his arms and legs after he was stabbed in the neck three years ago. Now the Massachusetts resident and former football player can turn his TV on and off, play video games like Tetris, control room lights and open an e-mail program from his wheelchair. He can even clench and release a robotic hand using only his thoughts.

Caplan and Saleh are aces in both the hardware and the software behind the computer system that takes movement commands from Nagle's brain and turns them into action. They helped develop the tasks he performs during weekly test sessions - like a program that allows him to control a TV - in a small, spare hospital room. These exercises are critical to the trial, telling scientists how well the system is working.

Both troubleshoot the four-computer setup to optimize the brain signals used to control the computer cursor and develop new programs that Nagle can use. Both Caplan and Saleh are 25, the same age as Nagle.

"This is a very cool job," Caplan said. "I love what I do. This technology is going to improve people's lives. I always had faith that it would work. But to see it happen, and happen so quickly, has been amazing."

Morris said alumni involvement in Cyberkinetics helped speed the process from bench to trial. Because former students worked in Donoghue's lab and are steeped in the neuroscience underpinning BrainGate, Morris said, there was no need to find and train new employees. "There's also a research mentality that we bring," he said. "We can think critically about the system and I think ultimately that will make a better product."

Virtually all student involvement in this translational research breakthrough can be traced to Donoghue. Just about everyone worked in his lab. Some, like Selim Suner, even come back. As an undergrad, Suner conducted experiments 20 years ago in the Donoghue lab and returned three years ago to work on the BrainGate sensor that captures neural activity.

"A lot of this is a testament to John," said Suner, who works as an emergency room physician at Rhode Island Hospital. "He attracts great people - and has a way of making things very interesting."

Alumni say their involvement in the project is also a testament to Brown. Part of this is by default. Because graduate programs tend to be small, undergrads take on a lot of responsibility in labs. But alums say that student involvement is also a function of campus culture.

"At Brown, the curriculum allows, and sometimes requires, students to work in the lab," said Ammar Shaikhouni, an M.D.-Ph.D. student involved in the basic research. "The University encourages personal choices and independence, and that can lead to great things in research."

From bench to trial: Brown students and BrainGate

• Abe Caplan, '03 B.S. computer engineering, assisted in basic research, currently works as clinical engineer at Cyberkinetics, working directly with patient in clinical trial
• Matthew Fellows, Ph.D. candidate in neuroscience, assisted in several facets of basic animal research
• Nicholas Hatsopolous, '92 Ph.D. cognitive science and former assistant professor, worked on animals experiments, co-founder of Cyberkinetics
• Leigh Hochberg, '90 B.S. neuroscience and current investigator in neuroscience, unpaid adviser to Cyberkinetics, developing protocols for patients in the clinical trial
• Dan Morris, '00 B.S. neuroscience, helped conduct basic research in animals, currently works as software engineering consultant at Cyberkinetics
• Dan O'Connell, '92 B.A. history, provided Cyberkinetics start-up funds through his venture capital company, NeuroVentures, Inc.
• Liam Paninski, '99 B.S. neuroscience, helped in basic research by modifying an algorithm to translate brain signals into movement commands
• Ammar Shaikhouni, '00 B.S. engineering, '06 M.D.-Ph.D. candidate, conducted basic research on robotics in Donoghue lab
• Maryam Saleh, '01 B.S. computer engineering, worked in Donoghue lab after graduation on basic research, currently works as clinical research associate at Cyberkinetics
• Mijail "Misha" Serruya, '96 B.S. neuroscience, '03 Ph.D. neuroscience, '05 M.D., led basic research, co-founder of Cyberkinetics, works as junior clinical scientist at company
• Mikhail Shapiro, '04 B.S. neuroscience, wrote Cyberkinetics business plan, helped negotiate licensing agreement with Brown, and assisted in raising venture capital
• Selim Suner, '86 B.S. electrical engineering, '87 M.S. biomedical engineering, '92 M.D., conducted early neural research in rats in Donoghue lab 20 years ago, returned to assist in testing technology in monkeys