Biomedicine

Regrowing the Damaged Brain

Electrically stimulating the cerebral cortex could help stroke recovery.

In recent years, scientists have discovered that the brain has a remarkable capacity for self-repair. Hoping to take advantage of this ability, researchers have developed a technology to deliver electrical stimulation directly to brain tissue. The therapy, now being tested in large clinical trials, could boost the brain’s repair mechanisms and improve recovery after stroke.

A flat, 1”x1” electrode placed over the brain’s outer membrane stimulates the cortical tissue below without the wearer feeling sensation. The device could help patients recover motor function after a stroke. (Courtesy of Northstar Neuroscience.)

Studies in both laboratory animals and humans have shown that after stroke, neurons near the damaged tissue begin to reorganize themselves in an attempt to compensate for the injured areas. However, this healing ability can be hit or miss – some patients regain the ability to walk or talk while others are left permanently disabled.

[Click here for illustrations of the brain’s areas and device’s functions.]

In many cases, patients can stimulate recovery through practice. Someone who has lost function in their left hand, for example, could practice various movements with that hand to boost the brain’s innate repair mechanisms. “But in most cases, that neuroplasticity doesn’t go far enough,” says Alan Levy, CEO of Northstar Neuroscience, a medical device company based in Seattle, WA.

So Levy and collaborators designed a way to stimulate specific parts of the cortex to try to further enhance the brain’s natural neuroplasticity. The technology has shown promise in preliminary human studies – researchers found that patients receiving both rehabilitation therapy and stimulation improved 15 to 30 percent on standard tests of hand and arm function; while controls, who underwent only physical therapy, improved just 0 to 12 percent. Northstar is now sponsoring a larger clinical trial at 18 rehabilitation centers across the United States.

Experts caution that it’s too soon to say how effective or broadly applicable the technology will be, though. “We need to see studies in larger groups to know if it’s effective,” says Douglas Katz, a neurologist at Boston University Medical School, “and under what circumstances it’s effective, such as the location of stroke, the time after stroke [that the treatment is used], and how much stimulation is necessary.” Adds Katz: “But I do think these techniques show a lot of promise.”

The benefits may also depend on the severity of stroke. It’s possible that this therapy will be effective only in patients with relatively mild impairments, says Randolph Nudo, director of the Landon Center on Aging at the University of Kansas Medical Center in Kansas City, who is studying the effects of the Northstar technology in animal models of stroke. People who have had a more severe stroke, and therefore have fewer neurons left to compensate for the damaged area, may not be able to benefit from stimulation.

Nudo and colleagues are running exhaustive animal studies to determine the most effective parameters for the cortical stimulation treatment, as well as if remote areas of the brain may be recruited to aid people with more severe stroke.

In the cortical stimulation procedure, doctors first map the extent of the damage using brain imaging. Movement of the hand, for example, is governed by a specific part of the motor cortex, a layer of the brain that governs movement. Physicians use functional magnetic resonance imaging, which measures blood flow in different parts of the brain, to locate the part of the cortex that is damaged, as well as the neighboring areas that are trying to take over control of the damaged hand. A neurosurgeon then drills a small hole in the skull over this area and places a flat electrode on top of the dura, a tough membrane covering the brain, to stimulate the cortical region below.

The stimulator is powered via a pacemaker-like device implanted in the chest and connected to the electrode by a cord threaded under the skin. A doctor or physical therapist can turn the stimulator on and off with a wireless controller. The stimulator is turned on only when patients are doing rehabilitation exercises; patients in the Northstar clinical trial will undergo an intensive six-week physical therapy program.

Scientists don’t yet know exactly how the electrical stimulation works, but research in animal models gives some clues. “We think we’re changing the excitability of neurons within the spared region of tissue,” says Nudo.

Neurons communicate by sending electrical messages to each other. When a person moves his or her hand to pick up a cup, for example, the neurons in the motor cortex fire to tell the arm muscles to move. If neurons in a recuperating brain area are electrically stimulated at the same time that a patient tries to move the cup, it may become easier for these neurons to fire. Scientists theorize that with repeated practice and electrical stimulation, these neurons develop new neural connections that strengthen the patient’s ability to pick up the cup, leading to a lasting change in motor ability.

In fact, experts say it is the pairing of stimulation and therapy that’s the key to this treatment. “The technology is enhancing the effectiveness of the patient’s own voluntary movement,” says Carolee J. Winstein, a biokinesiologist and physical therapist at the University of Southern California in Los Angeles. “The combination of techniques seems to be more effective than any technique by itself,” she says. Winstein is running a part of the current Northstar trial.

Northstar’s cortical stimulator isn’t the only treatment in development to boost neuroplasticity after stroke. Some neuroscientists are studying transcranial magnetic stimulation, a non-invasive method to stimulate specific brain areas. Others are developing drugs that boost neuroplasticity. But Nudo says that direct electrical stimulation may have some advantages. “We can control the location of the stimulation better, as well as other parameters, such as frequency,” he says. “You don’t have that control with a drug.”

Northstar eventually hopes to develop the technology for a wide range of disorders, including brain injury, auditory and pain disorders, movement disorders, and neuropsychiatric disorders. The company is currently sponsoring clinical trials of aphasia (loss of speech), tinnitus (ringing in the ears), and hemiparesis (weakness on one side of the body.)

Chris Ware, a former police officer, had a stroke nine years ago that left him partially paralyzed in his right side. He learned to walk and talk again after the stroke but was still seriously impaired. After participating in a clinical trial of the Northstar technology in 2004, he says was able to do a lot more on his own, like tying his shoes and driving.

“The concept of neural plasticity has breathed new life into potential for more recovery after brain injury,” says Winstein. “I think we will see the development of many new technologies and treatments that attempt to tap into this natural ability. It’s a very exciting time in rehab.”

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