CHARLES EPSTEIN, a neurologist from Emory University in Atlanta, Georgia, was
recently party to a remarkable experiment that quite literally left his
colleagues struggling for words. Epstein asked fellow researcher James Lah to
start counting out loud, while he held a small magnetic coil, roughly the size
of a mobile phone, against Lah鈥檚 forehead.
鈥淥ne, two, three,鈥� said Lah, quite happily. But when Epstein flicked on the
power to the coil, Lah rapidly lost the power of speech. All that he could
manage was 鈥渇o鈥�, fo鈥�, fo鈥︹��. When Epstein cut the power again, Lah
continued, 鈥渇our, five, six,鈥� as if nothing had happened.
鈥淭he sensation really was quite weird,鈥� says Lah. He claims that he could
think about the words he wanted to say, but just couldn鈥檛 get them out. He says
it was a frustrating feeling similar to when your arm or leg falls asleep,
except that this time it was the muscles of his face that failed to respond
properly. Of course, Epstein鈥檚 demonstration is more than just a neat party
trick. In fact, he had momentarily interrupted the workings of a part of Lah鈥檚
brain, by stimulating it with a magnetic pulse.
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The technique he used is called transcranial magnetic stimulation, or TMS.
While scientists have been trying to alter brain activity with magnetic and
electrical fields for more than a century, the modern age of TMS research began
only around 15 years ago. TMS was developed as a technique to stimulate the
brain鈥檚 motor circuits to test their integrity after damage to the brain or
spinal cord. But within the past ten years researchers have started using it to
look at how the brain controls other types of behaviour. TMS has also been tried
out as a potential treatment for depression. So it is now making a big
impression not just on Lah鈥檚 ability to count out loud, but in neuroscience labs
all around the world.
It is the ability of TMS to change the activity in small parts of the brain
for short periods of time that is so exciting cognitive scientists. Depending on
how it is used, TMS can slow down or even switch off parts of the brain
temporarily. With a tweak to the settings it can stimulate brain activity
instead. There are even some tantalising clues that TMS could enhance learning
and perception. And the technique is giving researchers the first real proof
that activity in particular parts of the brain gives rise to particular
sensations or behaviours鈥攁 vital step in their quest to understand how the
brain works and how it gives rise to the mind.
The basic idea behind TMS is simple. A short-lived electrical current in a
figure-of-8 stimulating coil, produces an intense magnetic field, about 200
times the strength of the average fridge magnet, within about one-thousandth of
a second. This rapid switch induces an electric field in a small region which
can extend a couple of centimetres down from the surface of the brain, making
the neurons there fire abnormally. Depending on the firing patterns, this can
boost activity, or effectively scramble or jam the signal from that area of the
brain. The field intensity, the shape of the stimulating coil and the rate of
the pulses (anything from a single pulse to 50 each second) determine how
widespread and how intense the effect is.
Brief interruption
Whereas prompting the brain into action might seem an exciting prospect,
remarkably neuroscientists are also keen to interrupt the workings of the brain.
This is because some of the most enlightening information about how the brain
works has come from patients with brain damage, caused by accidents, strokes or
surgical removal of brain tumours. By studying these patients, you can see what
abilities are lost along with a particular brain region, and get a reasonable
idea about where memories are stored, which areas of the brain are important for
vision, language, movement and so on. But such patients are in fairly short
supply, and no two patients are identical. Moreover, this type of brain damage
is rarely confined to small and functionally discrete areas of the brain, so
it鈥檚 not easy to pin down the functions of different brain locations very
precisely.
Brain scanning techniques have vastly improved our knowledge of the functions
of different brain regions, by showing which areas are active at a particular
time during a particular task. However, as Stephen Kosslyn, a psychologist at
Harvard University in Cambridge, Massachusetts, points out: 鈥淣euroimaging
techniques only establish a correlation. A given set of brain areas are
activated when someone performs a given task. But we all know that correlation
does not show causation.鈥� Kosslyn points out that TMS provides a stronger link
between cause and effect, by showing exactly what happens when you interrupt
brain activity in a particular area. Researchers no longer have to wait for a
patient to turn up in the clinic to verify their functional brain maps. With TMS
they can create 鈥渧irtual patients鈥�.
Kosslyn and his colleagues showed how this could work last year. He has a
long-standing interest in visual imagery, and was keen to know whether creating
a mental picture of an object uses the same brain circuitry as actually looking
at it. Brain scans and brain-damaged patients have shown that some areas of
cortex at the back of the brain would normally be active during both
activities鈥攂ut which are vital?
Kosslyn used TMS to block activity in a small area of the visual cortex,
called area 17, while he asked people to look at two images and compare
properties such as the relative lengths of stripes within the images.
Stimulating area 17 with TMS prevented people who were looking at the images
from making rapid comparisons. Interestingly, when Kosslyn asked his volunteers
to compare the stripes in their mind鈥檚 eye, again they had difficulty making the
comparisons when area 17 was stimulated. So area 17 seems to be crucial for both
seeing and imagining.
Vincent Walsh, a Royal Society Research Fellow working at the Experimental
Psychology Department at Oxford University, and his colleagues, have also used
TMS to study the visual system, but have concentrated on motion perception.
Clinical and experimental studies suggest that another visual area at the back
of the brain, V5, is involved in motion processing. When Walsh stimulated V5
using TMS he disrupted people鈥檚 ability to spot a small moving X in an array of
stationary Xs. But he also found a more interesting effect. By blocking motion
processing in V5, he could make it easier to spot a target defined by its shape
or colour, when motion of the target or the other stimuli in the array was
irrelevant and distracting. 鈥淭his may indicate that some areas of the brain
normally compete with each other for limited resources,鈥� says Walsh. 鈥淒isrupting
the function in one area may `free-up鈥� processing in another area, leading to
the improved performance.鈥�
No compensation
Similar effects are difficult to spot in patients with real brain injury,
perhaps because over time the brain reorganises a little to compensate for the
damage. For Walsh this reveals the true value of TMS. 鈥淭he key point here is
that the `virtual lesions鈥� induced by TMS last only a few milliseconds, and this
doesn鈥檛 give the brain time to reorganise.鈥�
There are other tantalising signs that TMS could improve brain function.
Alvaro Pascual-Leone and his colleagues from the Beth Israel Deaconess Medical
Center in Boston have tested the effect of TMS on learning, in this case
learning a simple sequence of key presses guided by the position of an asterisk
on a computer screen. In a series of trials the asterisk dances across the
screen and the subject taps out the corresponding sequence of key presses as
quickly as possible. 鈥淲e have known for a long time that subjects get faster if,
unbeknown to them, an ordered sequence is repeatedly presented,鈥� says
Pascual-Leone. But the researchers found that TMS could speed up reaction times
even more. 鈥淲hat is novel and potentially very exciting is that by stimulating
the motor cortex at particular frequencies we were able to speed up the learning
of this task,鈥� says Pascual-Leone.
And it鈥檚 not just motor learning that could benefit from a burst of magnetic
pulses. Ralph Topper from Aachen Technical University in Germany and his
colleagues seem to have enhanced peoples鈥� ability to name objects appearing as
line drawings on a computer screen. Volunteers named the objects faster if they
had been exposed to a pulse of TMS over the language area known as Wernicke鈥檚
area, on the left side of the brain, just before they saw each of the
pictures.
To Pascual-Leone, these findings suggest that TMS might one day enhance
standard rehabilitation techniques for stroke cases and brain damage. TMS could
potentially jump-start or 鈥渨arm up鈥� brain circuits to help them take over the
function of the damaged region. 鈥淭he adult brain is turning out to be more
flexible than we initially thought鈥攚e need to find ways to encourage and
control this flexibility,鈥� says Pascual-Leone. 鈥淭MS might just be such an
补辫辫谤辞补肠丑.鈥�
It looks as though TMS might help lift some people out of their depression by
reviving neural activity in underactive circuits (New 杏吧原创, 5
August 1995, p 24). Early tests showed promising improvements in the mood of a
small number of patients. And the most recent results suggest that TMS might
help patients who have not responded to standard drug treatments. In a large
trial of TMS for treating depression, under way in Boston, patients with major
depressive disorder have been given an intensive course of TMS for 30 minutes
every weekday for two weeks, then monitored for 3 months afterwards.
So far, the treatment has produced marked improvements in the standard
clinical rating scales for depression in more than half of the patients, after
stimulation of the left prefrontal cortex鈥攁n area at the front of the
brain, which seems to be underactive in depressed patients. This is a remarkable
number considering the severity of their condition and their lack of response to
three different classes of antidepressant drugs. Many of these patients had been
in hospital as a result of their depression and some had attempted suicide in
the past.
鈥淭he most striking finding is that the beneficial effects can last for up to
six months after TMS,鈥� says Pascual-Leone. In some patients, they have been able
to keep symptoms at bay simply by giving a further course of TMS every three
months, avoiding all other forms of medication. Preliminary results from a brain
scanning study suggest that this improvement may actually represent a return to
normal brain metabolism in this left prefrontal area, although Pascual-Leone and
Walsh are not yet convinced. Ray Dolan, a psychiatrist at the Functional Imaging
Laboratory in London points out that the difficulty with TMS, like
electro-convulsive therapy (ECT), is that there is no clear biological mechanism
to explain how it might provide an effective treatment for depression. We just
don鈥檛 know how stimulating these brain areas affects mood. 鈥淣obody seriously
thinks that the regions targeted by TMS in these studies are directly involved
in mood regulation,鈥� says Dolan. And even if they were, how do the benefits
persist for a matter of months?
But perhaps not surprisingly, researchers around the world are sufficiently
heartened by the potential of TMS to start trying it out on other
neuropsychiatric conditions such as obsessive-compulsive disorder, mania,
post-traumatic stress disorder and schizophrenia.
Walsh predicts that within 20 years, every psychology department will have
its own TMS machine. At 拢20 000 a set, it is a relatively cheap way of
studying the brain, considering that a functional MRI brain scanner costs
several million pounds. But before this happens, some feel that we should pause
and think. There are ethical and safety issues that need to be considered. After
all, TMS works by scrambling neural activity. Indeed, there were a handful of
early reports of epileptic seizures after TMS, but these were all in people who
had a previous history or family history of epilepsy or were the result of high
intensity TMS used in the early development of the technique.
The TMS community has tackled this issue head-on by devising a set of
guidelines for how TMS should be used. Walsh puts it like this: 鈥淥bviously one
has to be careful with any experimental technique, but the TMS community is very
aware of this and has published a set of ethical and safety guidelines that are
designed to prevent any problems. They appear to work very well and experiments
are now always carried out at the lowest possible intensities and are rightly
subject to local ethical committee approval.鈥�
Pascual-Leone thinks we should also consider the problems associated with the
possible recreational use of TMS. 鈥淕iven the non-invasive nature of this
technique and its apparent safety, together with the possibility of effects on
mood, there is a potential for unauthorised research or even recreational use,鈥�
he says. He notes that humans are prone to ridiculous extremes. But the last
thing we want is a Delgadoian vision of a psycho-civilised society, he says.
Delgado stimulated the brain to induce and block rage in experimental animals
around 30 years ago and speculated wildly about how this might be used to
control society. 鈥淲hile there is no evidence that TMS can be used in any of
these ways, society must ultimately have a stake in how this technique is
耻蝉别诲.鈥�