May 2001

From Whitaker Foundation

An off switch for epilepsy?

ARLINGTON, Va., May 17, 2001 --- Biomedical engineers have used a mild electric field to control seizure-like activity in brain cells. The work hints at the possibility of controlling epilepsy in a similar way.

In a recent issue of The Journal of Neuroscience, the researchers described a feedback system that monitors brain cells for seizure-like firing. When the firing begins, the system responds by applying a mild electric field, fewer than 50 millivolts per millimeter. When the erratic firing stops, the electric field shuts off.

The applied field, whose strength is determined by the feedback loop, alters the electrical charge of the overactive nerve cells, making them less responsive to the firing of neighboring cells. Exactly how this works is still unclear and being investigated.

Bruce Gluckman, Ph.D., assistant professor of physics and astronomy, and Steven Schiff, M.D., Krasnow Professor of Neurobiology, both of George Mason University, led the research group. Collaborators included Hanh Nguyen, Ph.D., of George Mason and Steven Weinstein, M.D., of Children's National Medical Center of Washington.

Their feedback system makes it possible to control the seizure-like activity automatically and over long periods. This, combined with the low electrical field requirement, has the group thinking about the long-term possibility of medical applications.

The original experiments used brain tissue from rats. Live animal testing is now getting started and human clinical trials are under discussion. A big question will be whether brain cells in the living organism will respond to the electrical field in the same way that cells do in a laboratory culture.

The normal firing of brain cells is not well understood, but the chaotic firing characteristic of seizures can be described as a nonlinear system. "The dynamic that generates the burst is much simpler than what all of the individual actors are doing," Gluckman said.

Nonlinear dynamics have proved useful in other medical applications as well, such as defibrillators that correct irregular heartbeats. Medical scientists do not understand exactly how a jolt of electricity restores a normal heartbeat, but it does.

Gluckman's feedback system may be used to investigate some of these questions. The group can change the system's electrical settings to achieve a reverse effect, so it can be used with very precise control to initiate or aggravate seizure-like activity. It can also hold a network of brain cells on the threshold of a seizure.

"Control techniques such as those presented here, especially the ability to maintain the network so close to seizure initiation, may be useful tools to probe such basic mechanisms underlying seizure generation," the group reported.

There are about 2 million epileptics in the United States, most of whom benefit from drugs that control seizures. But about 200,000 do not respond to drug therapy and have few options, one being surgery to remove parts of the brain.

The Food and Drug Administration has approved an implant that works like a heart pacemaker by providing continuous electrical stimulation to control epileptic seizures. The device is implanted under the collarbone and stimulates the vagus nerve in the neck. A majority of patients show some improvement when using the device.

Gluckman and his colleagues, however, believe that direct stimulation of the brain may ultimately prove to be more effective. Their research was supported by The Whitaker Foundation and the National Institutes of Health.












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