UNIVERSITY OF UTAH MEDIA RELEASE

***Embargoed by the journal Nature***for release at noon MDT Weds. Oct. 24, 2001

Contacts:-- Richard Normann, professor of bioengineering and ophthalmology (available beginning Oct. 22) - (801) 581-7645, [email protected]

-- Lee Siegel, science news specialist, University of Utah Public Relations - (801) 581-8993, cell (801) 244-5399, [email protected]

AN EARLY STEP TOWARD HELPING THE PARALYZED WALKDespite Paralysis, Brain Areas Controlling Movement Still Operate

Oct. 24, 2001 - Areas of the brain that control walking and other movements continue to work normally in patients paralyzed by spinal cord injuries, according to a University of Utah study in the Oct. 25 issue of the journal Nature.

The discovery represents an early step toward a long-term goal of implanting electrodes that would bypass damaged nerves and make it possible for paralyzed people to move and perhaps even walk again.

"This study suggests that many years from now, technologies being developed in the laboratory today might enable paralyzed individuals to stand up out of a wheelchair and walk," said Richard Normann, a professor of bioengineering and ophthalmology at the University of Utah.

Already, he noted, "a number of researchers are trying to develop brain-computer interfaces that can be used to control external devices - robotic arms, wheelchairs, computer terminals - using signals originating within a paralyzed person's brain."

Normal command signals from a paralyzed person's brain could be used initially "to control devices," Normann said. "But eventually these same signals perhaps could be used to directly control the muscles of a paraplegic person, ultimately allowing them to move their body just through the desire to do so. That's really long way away. This is not a problem I'm going to solve, but maybe my students will solve it."

A crucial first step is to show the brain's motor cortex does not degenerate significantly - and still can send command signals - in people paralyzed by a spinal injury.

That's exactly what Normann and colleagues did in the new study, which showed that appropriate areas of the brain "lit up" under functional magnetic resonance imaging (MRI) when five paralyzed patients were asked to move their extremities.

"They were asked to move their hands, purse their lips, move their ankles, rotate their elbows and extend their knees," Normann said.

All could purse their lips, because the head is above the injured part of the spine. Four of the five were quadriplegics - also known as tetraplegics - and could not move the other body parts when requested. The fifth had some ability to move his hands.

In each patient, MRI scans showed increased electrical activity in the corresponding part of the brain when the patient was asked to move a hand, elbow ankle or knee.

Five uninjured student volunteers also had their brains imaged by MRI while they were told to perform the same movements. That confirmed previous research showing which parts of the brain's motor cortex control movements of various body parts.

The study, published in the Oct. 25 issue of the journal Nature, was conducted under Normann's supervision by Shy Shoham, a former Utah bioengineering graduate student now doing postdoctoral research at Princeton University. Others who conducted the study were Utah bioengineer Edwin Maynard and Eric Halgren, a former Utah brain-imaging specialist now at Massachusetts General Hospital.

The patients in the study were young adults, mean age 28, paralyzed in motor vehicle crashes one to five years before the study. All had been patients at the University of Utah's University Hospital, and volunteered for the study after being asked to participate.

"They have an altruistic view of helping other people with the same problem," Normann said.

He said researchers had feared paralyzed people's brains might not retain the ability to send signals to muscles. That is because when portions of the brain are not used, they often undergo a certain amount of "reorganization" where other parts of the brain take over the computing power for other purposes. The new study showed such fears were unwarranted, at least up to five years after a paralyzing spinal injury.

The next step is to conduct lab experiments showing an electrode can be implanted to read brain signals on a long-term basis without harming the brain or implant, Normann said.

After such an initial safety demonstration, implants would require testing in human volunteers, perhaps brain-tumor patients who are undergoing brain surgery anyway, he added. Later, the devices would be tested in paraplegics and quadriplegics. Such experiments would determine if the electrodes could receive command signals from the brain's motor cortex.

In an even later stage, electrodes would be implanted just outside the spinal cord. Those electrodes would receive the command signals from the electrodes in the brain - via either wires or radio signals - and relay those signals to the appropriate muscles.

In previously published research, Normann and colleagues demonstrated that small electrodes implanted in the sciatic nerves of anesthetized laboratory animals receive external command signals and can be used to precisely control movements of the animals' ankles.

To restore movement to paralyzed people, it will not be enough to bypass the damaged spinal cord by sending brain signals through electrodes to the muscles, Normann said.

The brain also must be able to receive sensory feedback from those muscles, for example, so the brain "knows" the legs' physical location and can exert fine control as the legs move. So in addition to electrodes in the motor cortex and outside the spinal cord, other electrodes would have to be implanted in the sensory cortex and outside the spinal cord to carry sensory information from muscles back to the brain.

Normann noted research aimed at restoring movement in paralyzed people is advancing on two fronts. One is the "engineered" approach he is taking, aimed at brain-computer interfaces that would let paralyzed people control devices and eventually their own muscles. Other researchers, however, are looking for biological solutions in which gene therapy or stem cells might be used to regenerate damaged spinal tissue, he said.

Normann is well known for his research aimed at developing a scoreboard-like artificial vision system to help profoundly blind people regain some ability to see. Such a system would use a tiny eyeglass-mounted camera to collect visual information, and then relay it to electrodes in the brain's visual cortex. So far, such electrodes have been implanted in four people to make sure there are no adverse reactions, but Normann has not yet used the electrodes to produce artificial vision.

The Utah researcher also is working on an artificial hearing system to transmit nerve impulses from sounds to stimulate the auditory nerves of people with impaired hearing.

A copy this news release and downloadable photos of Richard Normann and of electrical activity in the brain of a paraplegic patient are available at:

http://www.utah.edu/unews/releases/01/oct/spinal.html

University of Utah Public Relations201 S Presidents Circle, Room 308Salt Lake City, Utah 84112-9017(801) 581-6773 fax: 585-3350

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CITATIONS

Nature, 25-Oct-2001 (25-Oct-2001)