Magnetic
stimulation of the brain: An update
(This article was first printed in the August
2005 issue of the Harvard Mental Health
Letter. For more information or to order,
please go to http://www.health.harvard.edu/mental.)
In recent decades, scientists have developed
electrical and magnetic devices for observing
the brain in action — remembering, deciding,
experiencing emotion — in ways that were
once unimaginable. Functional magnetic resonance
imaging (fMRI) and magnetic resonance spectroscopy
(MRS) are among the most revolutionary of these
techniques. Changing brain activity
in any meaningful or lasting way by electromagnetic
means has proved more difficult, but glimmers
of progress are appearing.
The chief established electromagnetic technique
used in psychiatry is electroconvulsive therapy
(ECT), in which a strong electrical current applied
to the scalp induces generalized seizures (spreading
to the whole brain) for the relief of severe
intractable depression and other psychiatric
disorders. The treatment is highly effective
but produces short-term confusion and occasionally
some memory loss. Patients often must be hospitalized
and always require general anesthesia and muscle
relaxants.
Less disruptive alternatives may now be provided
by a group of techniques involving magnetic stimulation
that are coming into wider use.
Repetitive TMS
A growing body of research suggests that the
best known of these techniques, transcranial
magnetic stimulation (TMS) may be a weapon against
depression, schizophrenia, and other psychiatric
disorders.
It works this way: An electrical generator operating
in very short on–off bursts produces a
series of strong magnetic fields in a wire coil,
generally in the shape of a figure 8, that is
mounted on a paddle and positioned on or near
a patient’s forehead or scalp. Unlike electrical
currents, magnetic fields are not absorbed and
scattered by the bone of the skull — the
reason high voltages are required for ECT. The
fluctuating magnetic force penetrates to a depth
of about an inch, producing an electrical current
that influences neurons in the area directly
under the coil. The signals do not reach subcortical
brain regions but may eventually be used to change
activity in some of these regions via connections
that are now being mapped. Researchers are also
experimenting with different types and numbers
of coils to achieve deeper penetration.
Stimulation by TMS is much milder and more localized
than ECT. The magnetic field can be applied to
fully conscious patients, who feel no pain; at
most, they notice a slight clicking or pinching
sensation. They can read or talk during the treatment
and drive themselves home afterward. Memory is
not affected. Single pulses have no reported
side effects; repetitive TMS can cause muscle
tension headaches, which are usually mild and
easily treated with aspirin. Accidental seizures,
a rare complication, have not been reported since
safety guidelines were clarified in the mid-1990s.
In animal studies, rats receiving TMS weekly
for as long as three months suffered no learning
or memory impairment.
With more powerful apparatus now available,
TMS can be administered at frequencies up to
60 cycles a second (60 Hz). Although there is
considerable individual variation, lower-frequency
signals apparently lower blood flow and suppress
activity in the cerebral cortex, while higher-frequency
signals, above 20 Hz, have the opposite effect.
By varying the frequency of the pulse and the
position of the coil, researchers can turn different
brain regions on and off and study how they are
involved in vision, motor control, memory, attention,
and language.
For example, by placing the coil over the motor
cortex, they can make a thumb twitch or a leg
jerk to learn more about how the brain controls
the body’s muscles. They can also temporarily
block or enhance some aspect of vision or speech.
Previously, the only way to stimulate small regions
of the brain directly was to apply electrodes
during surgery.
Treating mood disorders
The main psychiatric use of TMS is in the treatment
of depression. For this purpose, therapists usually
place the coil over the left prefrontal cortex,
just behind the forehead, where fMRI and other
brain scans suggest that activity is often low
in depressed persons. This area, a seat of planning
and decision-making, is linked to the emotional
centers in the limbic system. Typically, high-frequency
magnetic impulses are applied for a half-hour
a day five days a week for about two weeks — in
some cases, up to six weeks. Researchers have
also been experimenting with low-frequency TMS
directed at the right prefrontal cortex.
Although results are still inconsistent, the
news from what now amounts to a large number
of controlled studies is getting better. For
example, in one study, high-frequency TMS directed
at the left prefrontal cortex combined with low-frequency
TMS to the right prefrontal cortex improved depression
in patients who had not responded to drugs. Researchers
have also found TMS helpful as a weekly maintenance
treatment for adults with bipolar depression
who were taking lithium. And interestingly, high-frequency
TMS to the right prefrontal cortex may improve
symptoms of bipolar mania.
Results of direct comparisons with ECT have
been conflicting, but in one study, patients
not helped by antidepressant medications who
received five sessions a week of TMS for four
weeks did as well as those who received similar
ECT treatment.
Over all, about 40% of patients with medication-resistant
depression have shown some improvement after
TMS. In two small studies, TMS reduced depressive
symptoms by 28%; sham (placebo) treatments, in
which the paddle was angled to misdirect the
magnetic energy, reduced symptoms by only 7%.
Research also suggests that TMS may shorten the
time it takes drugs to begin working. Researchers
are collaborating on a large rigorous study in
which more than 200 patients at 14 sites will
receive either TMS or sham treatment, so we may
soon have a better idea of its safety and effectiveness.
Schizophrenia
Although ECT is an established treatment for
severe schizophrenic symptoms as well as depression,
there are few studies of TMS in schizophrenia.
Some trials have been disappointing, but there
are conflicting reports that TMS can banish hallucinatory
voices. In a small study, researchers found that
two out of three patients who received low-frequency
TMS directed at the auditory region of the cortex
stayed free of threatening and abusive voices
for more than two weeks — one of them for
two months. None responded to sham TMS.
These results were confirmed in another study.
Seven out of ten schizophrenic patients who received
low-frequency TMS responded, and five of them
maintained the improvement for at least two months.
In still another (uncontrolled) study, four weeks
of TMS produced an improvement in the negative
or deficit symptoms of schizophrenia — apathy,
emotional constriction, limited speech — that
lasted at least a month. But hallucinations and
delusions were not affected.
Other conditions
Findings are mixed. Some reports suggest that
TMS can relieve the symptoms of post-traumatic
stress disorder at least for short periods. In
a controlled study, TMS was no more effective
than sham treatment for patients with obsessive-compulsive
disorder. More than 30 studies are under way
in the United States testing the potential of
TMS in a variety of conditions including stroke,
Parkinson’s disease, and cerebral palsy.
Magnetic seizure therapy
Researchers are exploring new ways of using
the TMS apparatus — delivering magnetic
fields at a frequency high enough to cause seizures.
Magnetically induced seizures, unlike those produced
by ECT, are localized rather than general. In
theory, they could be directed where they would
do the most good and the least harm — avoiding
areas critical for memory, for example. But like
ECT, magnetic seizure therapy (MST) requires
general anesthesia, which increases risk and
expense. And because the frequency has to be
high, it also requires a more powerful machine
than TMS.
MST has been tested in both monkeys and humans,
and the preliminary results suggest that it might
be effective, with fewer side effects than ECT.
In a study under way in 2005, patients have been
assigned at random to receive first ECT and then
MST or the reverse, with follow-ups after two
and six months. Direct comparisons among MST,
ECT, and conventional TMS may incidentally help
determine whether the generalized seizures produced
by ECT are necessary for relieving intractable
depression or are only a byproduct of some other,
more specific change that supplies the therapeutic
effect.
Magnetic resonance spectroscopy
Transcranial magnetic stimulation is not the
only magnetic technique that has shown some promise
in the treatment of psychiatric disorders. Magnetic
resonance spectroscopy (MRS), which uses magnetic
fields to map brain chemistry, is best known
as a research tool that provides new information
about the structure and activity of living cells.
The magnetic field involved is weaker than the
field generated by TMS but penetrates the whole
brain uniformly. In a study reported in 2004,
researchers serendipitously found that a form
of MRS they were using to examine the brains
of depressed patients improved the symptoms of
depression, at least for a few days. A comparison
with sham treatment confirmed the result.
These findings from a single study with a brief
follow-up need confirmation, but there is further
evidence from animal experiments. The subjects
were rats forced to swim for hours with no possibility
of escape. This situation often leads to learned
helplessness, a state resembling human depression.
Rats given a form of magnetic resonance spectroscopy
before forced swimming took longer to give up
hope; antidepressant drugs have the same effect.
As of mid-2005, the FDA has not approved magnetic
stimulation of the brain for the treatment of
any psychiatric condition, and research is just
beginning. Many questions are open, and many
paths remain to be explored. In therapy, which
patients will respond best, and how do individual
brain structure and function affect the response?
(One early study found that depression in patients
with a preference for the left visual field,
controlled by the right hemisphere of the brain,
did not respond to TMS in the left hemisphere).
Do high-frequency and low-frequency TMS affect
different types of depression? What is the best
timing, how long should treatment continue (there
is some evidence that more than two weeks may
be better), and what is the best placement of
the magnetic coil? How long does the antidepressant
effect last?
Further research could also advance early diagnosis
of depression and other disorders, help to predict
their course, and possibly identify the best
medication or other treatment for a given patient.
And magnetic stimulation might be used in combination
with magnetic resonance imaging and other brain
scanning techniques to investigate how different
brain regions are coordinated and why coordination
fails.
(This article was first printed in the August
2005 issue of the Harvard Mental Health
Letter. For more information or to order,
please go to http://www.health.harvard.edu/mental.)
|
HOME
MY
CART
12
monthly issues
