January 30, 2001

A Dream of Fighting Epilepsy With a Flip of a Brain Switch

By JAMES GLANZ

From sublime poetry to serious malady, the brain is the focus of some of the
most complex phenomena in nature. But sometimes, it is just another
electrical circuit that can be controlled with the flip of a switch.

That, at least, is one possible conclusion to be drawn from a paper in the
Jan. 15 issue of The Journal of Neuroscience. The authors of the paper,
titled "Adaptive Electric Field Control of Epileptic Seizures," used slices
of rat brain as just another element of an electrical feedback circuit. The
circuit sensed when the specially treated brain slices were firing
spasmodically in a way that mimicked an epileptic seizure, and then shut
the seizure off by applying weak electric fields to the slices.

Researchers then reduced the electric field until the onset of the next
seizure — a loop that is the essence of a feedback circuit. While the
immediate impact of the work is likely to remain in the realm of basic
science, the researchers have a longer-term goal of testing the technique
as a therapy for human epilepsy.

The new experiments grew out of work by many scientists over the last
decade suggesting that in some respects, the electrical behavior of the
interconnected neurons in a brain are another example of the "nonlinear
dynamics" governing physical systems as varied as electronic circuitry,
multiplanetary systems and dripping faucets.

Although each of those systems is made of many parts that would be
difficult to understand in complete detail — the tiny eddies and molecular
dynamics of the water in a faucet, for example — physicists have used
nonlinear analysis to shed light on their overall workings. In particular,
the science of chaos has shown that these apparently disparate systems show
broadly similar rhythms that are neither completely random nor absolutely
regular.

Those rhythms might involve the irregular rate at which a faucet drips or a
faulty laser, connected to an ordinary circuit, sputters and shines.
Researchers in the past have shown that once they understand this behavior,
they can bring it under control and bring pure regularity out of the chaos.
For the laser, that might involve adding small but carefully timed
electrical pulses to the circuit.

The new paper, which describes research done at the Krasnow Institute for
Advanced Study at George Mason University in Fairfax, Va., and financed by
the National Institutes of Health and the Whitaker Foundation, took as its
starting point earlier work showing that electric fields could affect the
firing of individual neurons or slices of brain tissue containing many
neurons.

In the experiments, researchers used salt solutions to induce the tissue to
undergo the intense, spasmodic firing characteristic of epilepsy. They
sensed the onset of the firing with one set of electrical probes and
applied carefully tailored electric fields with another, shutting the
firing off and returning it to something like normal behavior.

The work was led by Dr. Bruce J. Gluckman of the physics and astronomy
department at George Mason and Dr. Steven J. Schiff of the psychology
department there. It also involved Hanh Nguyen at George Mason and Dr.
Steven Weinstein of the Children's National Medical Center of Washington.

"What's unique is the idea of getting feedback from the tissue," said Dr.
John G. R. Jefferys, a professor of neuroscience at the University of
Birmingham in England who is familiar with the work. "Epileptic activity
produces a big signal; when the seizure starts, the field goes on,"
returning the brain to normal firing.

The normal firing patterns of neurons in brain tissue are complicated and,
Dr. Gluckman acknowledged, difficult to understand. But when a seizure
begins, "a whole group of neurons all of a sudden do something together,"
firing in a kind of sporadic synchrony, he said. "The dynamic that
generates the burst is much simpler than what all of the individual actors
are doing."

That simplicity let the researchers control the brain's behavior once a
seizure started, if only to knock it back into the more complicated state,
Dr. Gluckman said. The ability to control the system without understanding
everything about its parts showed, once again, the usefulness of an
approach based on nonlinear dynamics, he said.

Dr. Schiff, who is also a neurosurgeon specializing in epilepsy, said the
long-term goal of the work was to develop alternative treatments for focal
epilepsy, a form of epilepsy that is often treated by removing parts of the
brain when drugs are ineffective. The procedure, called resection, is
usually performed in the hippocampus, an area involved in learning and memory.

Relying on weak electric fields "minimizes how invasive you have to be in
order to put a device in," Dr. Schiff said, adding that such a device would
involve small electrodes placed on the surface of the brain or its fluid
spaces and that engineering work to design such a device had already begun.
Dr. Schiff said he and collaborators planned to apply in the next year to
begin the first phase of clinical trials to test for safety. He and others
have also begun tests involving whole, live animals.

Electrodes are already placed temporarily on the brains of candidates for
resection, Dr. Schiff said. The electrodes are stimulated to identify
functional areas of the brain to be avoided in surgery.

Two million Americans have epilepsy, and 20 percent of those cases are so
intractable that the disease is hard to control with drugs.

Dr. Ray Dingledine, an epilepsy researcher who is chairman of the
pharmacology department at Emory University, said electrodes were used to
stimulate the brain as an alternative to drugs or surgery in the treatment
of Parkinson's disease. More specifically, he added that electrical
stimulation of nerves outside the brain was known to ward off epileptic
seizures in some cases.

As to the physics of stopping the seizures, Dr. Gluckman said the electric
fields slightly redistributed electrical charges inside individual neurons,
changing the likelihood that they would fire in response to stimulation by
the other neurons around them. Previous work in controlling the behavior of
brain slices was based more closely on the detailed theory of chaos, Dr.
Gluckman said. The precise reasons that the new approach was successful are
still being worked out, he said.

The fields applied in the experiment are weak enough to be generated by a
small battery. Although people commonly encounter fields of that strength
in urban settings, he said, the skull, skin and fluids surrounding the
brain largely shield it.


Copyright 2001 The New York Times Company
http://www.nytimes.com/2001/01/30/health/30PHYS.html?pagewanted=all

janet paterson, an akinetic rigid subtype parkie
53 now / 44 dx cd / 43 onset cd / 41 dx pd / 37 onset pd
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