From the magazine "Discover" (not related to discovery channel!!
webposted 22.10.2001
URL:
http://www.discover.com/nov_01/gthere.html?article=news_chemical.html
--Scott_Hill@...


DISCOVER Vol. 22 No. 11 (November 2001)


Brain Rx: Magnets
It seems like voodoo, but altering electrical
currents in the brain may help treat
depression, epilepsy, and Parkinson's disease
By Karen Wright
Photographs by Brian Finke

Electroconvulsive therapy, or shock therapy, is the most effective
treatment
known for severe depression. A strong electrical current applied to
the skull
triggers epilepticlike seizures that somehow jolt the mind free of
melancholy.
But shock treatment is a famously blunt instrument. It requires the
use of
general anesthesia, often causes memory loss and confusion, and can
bring on
a headache that rivals the worst hangover.

An ideal version of electroconvulsive
therapy would dispense with the seizure
and the side effects. It would target only
those areas of the brain involved in
depression. It would be easy to administer,
and it wouldn't hurt. In short, the
procedure would look a lot like
transcranial magnetic stimulation (TMS), a
kinder, gentler way of jolting the brain that
is winning the enthusiasm of clinicians and
basic researchers alike. Though still
unproven, TMS holds promise as an
alternative treatment for a number of
psychiatric disorders, as well as epilepsy,
Parkinson's disease, and even writer's
cramp. It's already helping to map the circuitry of the normal brain
and reveal
faulty wiring.

"TMS is an incredible tool because it has the potential to be both
diagnostic
and therapeutic," says Mark George of the Medical University of
South
Carolina, a neurologist and psychiatrist who is one of the
technique's pioneers.

Like shock therapy, TMS stimulates the brain with an electrical
current. But it
delivers the current indirectly rather than directly. When
electricity passes
through a wire coil, it generates a magnetic field that can, in
turn, induce an
electrical current in any nearby conducting material. The brain is
nothing if not
electrically conductive: Nerve impulses are essentially electrical
signals passing
along a network of neurons. So magnetic stimulation can create
electrical
fields in the brain.

Shock therapy requires powerful currents in order to penetrate the
relatively
nonconducting bone of the skull. But weaker currents can be used in
TMS
because the skull puts up no resistance to magnetic fields. A paddle
containing
a coiled wire is held close to the head, and an electrical current
passed
through the wire generates a magnetic field. Where the magnetic
field meets
brain tissue, it creates an electrical pulse that scrambles nerve
signals, causing
a kind of blackout in the region of the brain just beneath the
paddle. A single
pulse causes nearby nerve cells to fire; if the pulses are rapidly
repeated, a
kind of blackout ensues, scrambling neural activity for some time
after
treatment. These disruptions aren't evident to subjects.

"You feel a tapping on your head, caused by contractions of the
scalp
muscles," says psychiatrist Holly Lisanby, who, as director of
magnetic brain
stimulation at Columbia University College of Physicians and
Surgeons, has
administered TMS to hundreds of patients. "In some cases, you do get
some
scalp pain," she says. "But many subjects find it's not painful at
all." And
because the currents generated are not nearly as strong as those
used in
electroconvulsive therapy, she says, there's no seizure, no apparent
memory
loss, and no need for anesthesia. "I have people who go right back
to work
after TMS treatment. You're alert, you're awake, you're not groggy
or
disoriented."

The technology for TMS was introduced in
1985 for diagnosing injuries in peripheral
nerves that control body movement and
sensation. But the technique also offered
scientists the unparalleled ability to
stimulate specific brain regions and
observe the effects on fully conscious,
healthy human subjects. Zapping a spot a
few inches above the left ear, for example,
makes the right thumb twitch. Basic
researchers soon began tweaking other
nerve pathways involved in vision,
language, learning, hormone responses,
and drug reactions. "You can't study the brain as directly in humans
with any
other technique," says Eric Wassermann, who with George conducted
some
of the first studies on TMS and mood at the National Institutes of
Health. "It's
an excellent physiological probe."

But clinical practitioners are most excited by TMS's potential to
alter regions
of the brain affected by mental disorders. In the mid-1990s,
researchers
worldwide began testing the method's ability to alleviate the
symptoms of
depression, obsessive-compulsive disorder, mania, and schizophrenia.
Some
results are encouraging: In one study of depressed patients who
didn't
respond to medication, more than half showed marked improvement
after five
days of TMS treatment. In another depression trial, success rates
with TMS
rivaled those of electroconvulsive therapy. A study of
obsessive-compulsive
patients reported a decrease in compulsive urges lasting for eight
hours after a
single treatment. And in some schizophrenic patients, TMS relieved
their
auditory hallucinations for weeks.

But advocates of the technique have struggled to replicate these
results. They
often see profound improvements in some patients and no response in
others.
"There might be a lot of variation in the circuitry between
individuals," Lisanby
says. And different treatment protocols seem to produce profoundly
different
results. Despite earlier reports of success in patients with
Parkinson's disease,
for example, her own TMS studies showed that the treatment could
temporarily make symptoms worse.

Experts acknowledge that they have yet to determine the most
effective
procedures for magnetic stimulation. In a typical TMS treatment for
depression, for example, the coil is held just in front of and above
the left ear,
over a region of the brain called the prefrontal cortex, which has
been
implicated in mood disorders. The current cycles 10 times per second
and
lasts for eight seconds at a time. Each half-hour session consists
of 20 of these
pulses, and a full treatment course is made up of 10 daily sessions.
All of these
parameters--the placement of the coil; the frequency, intensity, and
duration of
stimulation; the number of treatments per day; and the length of the
treatment
period--are arbitrary. Other combinations might work better.

Researchers are hoping to refine TMS as a
clinical tool by identifying the kinds of
patients it helps most and finding the best
location for and pattern of stimulation for
each disease and each patient. Eventually,
TMS could have a number of possible
applications in treating a disease like
depression: Along with helping
medication-resistant patients, it might be
used as an adjunct for psychotherapy and
medication--either short term, before drug
effects kick in, or as a long-term
maintenance strategy. TMS is approved
for treating depression in Canada and Europe, but it is available in
the United
States only in experimental trials.

And TMS isn't likely to be rushed into clinics here for two reasons.
First, the
machine's manufacturers are small companies that can't compete with
the big
drug companies that develop antidepressants. Second, researchers are
still
trying to figure out how the technique works. In animals, magnetic
stimulation
can produce changes in the levels of neurotransmitters, the activity
of
nerve-cell receptors, and the expression of genes related to nerve
growth in
the brain. Lisanby has shown that TMS also alters the structure of
rat nerve
cells, hinting at long-term changes in brain activity. To explore
the treatment's
effects in humans, George is using MRI to chart brain blood flow in
real time
before, during, and after TMS.

"The scientist in me says we're just barely at the surface of this
technique,"
says George. "We need to do a lot of work and understand it before
we can
proceed effectively." On the other hand, he says, the modes of
action of some
of the most effective treatments for mental illness, including
lithium for manic
depression, serotonin enhancers for depression, antipsychotics, and
electroconvulsive therapy, are still a mystery too. "The clinician
in me says we
don't understand almost any of our treatments. Nevertheless, they
save lives."



RELATED WEB SITES:

For a comprehensive site about TMS, including links to news,
conferences,
and scientific articles, see the TMS resources page at
www.musc.edu/tmsmirror/TMSresrc.html.