In June 1979, in a procedure that lasted nearly 10 hours, doctors created a
firebreak to contain Vicki's seizures by slicing through her corpus callosum,
the bundle of neuronal fibres connecting the two sides of her brain. This
drastic procedure, called a corpus callosotomy, disconnects the two sides of the
neocortex, the home of language, conscious thought and movement control. Vicki's
supermarket predicament was the consequence of a brain that behaved in some ways
as if it were two separate minds.
After about a year, Vicki's difficulties abated. “I could get things
together,” she says. For the most part she was herself: slicing vegetables,
tying her shoe laces, playing cards, even waterskiing.
But what Vicki could never have known was that her surgery would turn her
into an accidental superstar of neuroscience. She is one of fewer than a dozen
'split-brain' patients, whose brains and behaviours have been subject to
countless hours of experiments, hundreds of scientific papers, and references in
just about every psychology textbook of the past generation. And now their
numbers are dwindling.
Through studies of this group, neuroscientists now know that the healthy
brain can look like two markedly different machines, cabled together and
exchanging a torrent of data. But when the primary cable is severed, information
— a word, an object, a picture — presented to one hemisphere goes unnoticed in
the other. Michael Gazzaniga, a cognitive neuroscientist at the University of
California, Santa Barbara, and the godfather of modern split-brain science, says
that even after working with these patients for five decades, he still finds it
thrilling to observe the disconnection effects first-hand. “You see a
split-brain patient just doing a standard thing — you show him an image and he
can't say what it is. But he can pull that same object out of a grab-bag,”
Gazzaniga says. “Your heart just races!”
Nature Podcast
Michael Gazzaniga reflects on five decades of split-brain research [Podcast
on website]
Work with the patients has teased out differences between the two
hemispheres, revealing, for instance, that the left side usually leads the way
for speech and language computation, and the right specializes in visual-spatial
processing and facial recognition. “The split work really showed that the two
hemispheres are both very competent at most things, but provide us with two
different snapshots of the world,” says Richard Ivry, director of the Institute
of Cognitive and Brain Sciences at the University of California, Berkeley. The
idea of dichotomous consciousness captivated the public, and was greatly
exaggerated in the notion of the 'creative right brain'. But further testing
with split-brain patients gave a more-nuanced picture. The brain isn't like a
computer, with specific sections of hardware charged with specific tasks. It's
more like a network of computers connected by very big, busy broadband cables.
The connectivity between active brain regions is turning out to be just as
important, if not more so, than the operation of the distinct parts. “With
split-brain patients, you can see the impact of disconnecting a huge portion of
that network, but without damage to any particular modules,” says Michael
Miller, a psychologist at the University of California, Santa Barbara.
David Roberts, head of neurosurgery at Dartmouth-Hitchcock Medical Center in
Lebanon, New Hampshire, sees an important lesson in split-brain research. He
operated on some of the cohort members, and has worked closely with Gazzaniga.
“In medical school, and science in general, there is so much emphasis on large
numbers, labs, diagnostics and statistical significance,” Roberts says — all
crucial when, say, evaluating a new drug. But the split-brain cohort brought
home to him how much can be gleaned from a single case. “I came to learn that
one individual, studied well, and thoughtfully, might enable you to draw
conclusions that apply to the entire human species,” he says.
Today, the split-brain patients are getting on in years; a few have died, one
has had a stroke and age in general has made them all less fit for what can be
taxing research sessions of sitting, staring and concentrating. The surgery,
already quite rare, has been replaced by drug treatments and less drastic
surgical procedures. Meanwhile, imaging technologies have become the preferred
way to look at brain function, as scientists can simply watch which areas of the
brain are active during a task.
Michael Gazzaniga has worked with split-brain patients
for 50 years.
PHOTO BY MIKE MCGREG OR/CONTOUR BY GETTY
But to Miller, Ivry, Gazzaniga and others, split-brain patients remain an
invaluable resource. Imaging tools can confirm, for example, that the left
hemisphere is more active than the right when processing language. But this is
dramatically embodied in a split-brain patient, who may not be able to read
aloud a word such as 'pan' when it's presented to the right hemisphere, but can
point to the appropriate drawing. “That gives you a sense of the right
hemisphere's ability to read, even if it can't access the motor system to
produce speech,” Ivry says. “Imaging is very good for telling you where
something happens,” he adds, “whereas patient work can tell you how something
happens.”
A cable, cut
Severing the corpus callosum was first used as a treatment for severe
epilepsy in the 1940s, on a group of 26 people in Rochester, New York. The aim
was to limit the electrical storm of the seizure to one side of the brain. At
first, it didn't seem to work. But in 1962, one patient showed significant
improvement. Although the procedure never became a favoured treatment strategy —
it's invasive, risky, and drugs can ease symptoms in many people — in the
decades since it nevertheless became a technique of last resort for treating
intractable epilepsy.
To Roger Sperry, then a neurobiologist and neuropsychologist at the
California Institute of Technology, and Gazzaniga, a graduate student in
Sperry's lab, split-brain patients presented a unique opportunity to explore the
lateralized nature of the human brain. At the time, opinion on the matter was
itself divided. Researchers who studied the first split-brain patients in the
1940s had concluded that the separation didn't noticeably affect thought or
behaviour. (Gazzaniga and others suspect that these early sections were
incomplete, which might also explain why they didn't help the seizures.)
Conversely, studies conducted by Sperry and colleagues in the 1950s revealed
greatly altered brain function in animals that had undergone callosal sections.
Sperry and Gazzaniga became obsessed with this inconsistency, and saw in the
split-brain patients a way to find answers.
The duo's first patient was a man known as W. J., a former Second World War
paratrooper who had started having seizures after a German soldier clocked him
in the head with the butt of a rifle. In 1962, after W.J.'s operation, Gazzaniga
ran an experiment in which he asked W.J. to press a button whenever he saw an
image. Researchers would then flash images of letters, light bursts and other
stimuli to his left or right field of view. Because the left field of view is
processed by the right hemisphere and vice versa, flashing images quickly to one
side or the other delivers the information solely to the intended hemisphere
(see
'Of
two minds').
For
stimuli delivered to the left hemisphere, W.J. showed no hang-ups; he simply
pressed the button and told the scientists what he saw. With the right
hemisphere, W.J. said he saw nothing, yet his left hand kept pressing the button
every time an image appeared. “The left and right didn't know what the other was
doing,” says Gazzaniga. It was a paradigm-blasting discovery showing that the
brain is more divided than anyone had predicted
1.
Suddenly, the race was on to delve into the world of lateralized function.
But finding more patients to study proved difficult. Gazzaniga estimates that at
least 100 patients, and possibly many more, received a corpus callosotomy. But
individuals considered for the operation tend to have other significant
developmental or cognitive problems; only a few have super-clean cuts and are
neurologically healthy enough to be useful to researchers. For a while, Sperry,
Gazzaniga and their colleagues didn't know if there was ever going to be anyone
else like W.J..
But after contacting neurosurgeons, partnering with epilepsy centres and
assessing many potential patients, they were able to identify a few suitable
people in California, then a cluster from the eastern part of the United States,
including Vicki. Through the 1970s and the early 1980s, split-brain research
expanded, and neuroscientists became particularly interested in the capabilities
of the right hemisphere — the one conventionally believed to be incapable of
processing language and producing speech.
Gazzaniga can tick through the names of his “endlessly patient patients” with
the ease of a proud grandparent doing a roll call of grandchildren — W.J., A.A.,
R.Y., L.B., N.G.. For medical confidentiality, they are known in the literature
by initials only. (Vicki agreed to be identified in this article, provided that
her last name and hometown were not published.)
On stage last May, delivering a keynote address at the Society of
Neurological Surgeons' annual meeting in Portland, Oregon, Gazzaniga showed a
few grainy film clips from a 1976 experiment with patient P.S., who was only 13
or 14 at the time. The scientists wanted to see his response if only his right
hemisphere saw written words.
In Gazzaniga's video, the boy is asked: who is your favourite girlfriend,
with the word girlfriend flashed only to the right hemisphere. As predicted, the
boy can't respond verbally. He shrugs and shakes his head, indicating that he
doesn't see any word, as had been the case with W.J.. But then he giggles. It's
one of those tell-tale teen giggles — a soundtrack to a blush. His right
hemisphere has seen the message, but the verbal left-hemisphere remains unaware.
Then, using his left hand, the boy slowly selects three Scrabble tiles from the
assortment in front of him. He lines them up to spell L-I-Z: the name, we can
safely assume, of the cute girl in his class. “That told us that he was capable
of language comprehension in the right hemisphere,” Gazzaniga later told me. “He
was one of the first confirmation cases that you could get bilateral language —
he could answer queries using language from either side.”
The implications of these early observations were “huge”, says Miller. They
showed that “the right hemisphere is experiencing its own aspect of the world
that it can no longer express, except through gestures and control of the left
hand”. A few years later, the researchers found that Vicki also had a
right-hemisphere capacity for speech
2.
Full callosotomy, it turned out, resulted in some universal disconnections, but
also affected individuals very differently.
In 1981, Sperry was awarded a share of the Nobel Prize in Physiology or
Medicine for the split-brain discoveries. (“He deserved it,” Gazzaniga says.)
Sperry died in 1994, but by that point, Gazzaniga was leading the charge. By the
turn of the century, he and other split-brain investigators had turned their
attention to another mystery: despite the dramatic effects of callosotomy, W.J.
and later patients never reported feeling anything less than whole. As Gazzaniga
wrote many times: the hemispheres didn't miss each other.
The callosum tissue seen in a healthy brain (bright white
in top image) retracts after a corpus callosotomy, leaving just the ventricle
(black).
M. GAZZANIGA
Gazzaniga developed what he calls the interpreter theory to explain why
people — including split-brain patients — have a unified sense of self and
mental life
3.
It grew out of tasks in which he asked a split-brain person to explain in words,
which uses the left hemisphere, an action that had been directed to and carried
out only by the right one. “The left hemisphere made up a post hoc answer that
fit the situation.” In one of Gazzaniga's favourite examples, he flashed the
word 'smile' to a patient's right hemisphere and the word 'face' to the left
hemisphere, and asked the patient to draw what he'd seen. “His right hand drew a
smiling face,” Gazzaniga recalled. “'Why did you do that?' I asked. He said,
'What do you want, a sad face? Who wants a sad face around?'.” The left-brain
interpreter, Gazzaniga says, is what everyone uses to seek explanations for
events, triage the barrage of incoming information and construct narratives that
help to make sense of the world.
The split-brain studies constitute “an incredible body of work”, said Robert
Breeze, a neurosurgeon at the University of Colorado Hospital in Aurora, after
listening to Gazzaniga's lecture last year. But Breeze, like many other
neuroscientists, sees split-brain research as outdated. “Now we have
technologies that enable us to see these things” — tools such as functional
magnetic resonance imaging (fMRI) that show the whereabouts of brain function in
great detail.
Miller, however, disagrees. “These kinds of patients can tell us things that
fMRI can never tell us,” he says.
Subject of interest
Seated at a small, oval dining-room table, Vicki faces a laptop propped up on
a stand, and a console with a few large red and green buttons. David Turk, a
psychologist at the University of Aberdeen, UK, has flown in for the week to run
a series of experiments.
Vicki's grey-white hair is pulled back in a ponytail. She wears simple white
sneakers and, despite the autumn chill, shorts. She doesn't want to get too
warm: when that happens she can get drowsy and lose focus, which can wreck a
whole day of research.
During a break, Vicki fetches an old photo album. In one picture, taken soon
after her surgery, she is sitting up in the hospital bed. Her hair is starting
to grow back as black stubble and she and her daughter have wide smiles. Another
page of the album has a slightly faded printout of a 1981 paper from
The
Journal of Neuroscience glued into it: the first published report involving
data gleaned from Vicki, in which researchers describe how she, like P.S., had
some capacity for language in her right hemisphere
4.
When pressed to share the most difficult aspect of her life in science, the
perpetually upbeat Vicki says that it would have to be an apparatus called the
dual Purkinje eye tracker. This medieval-looking device requires the wearer to
bite down on a bar to help keep the head still so that researchers can present
an image to just the left or right field of view. It is quite possible that
Vicki has spent more of her waking hours biting down on one of those bars than
anyone else on the planet.
Soon, it is time to get back to work. Turk uses some two-sided tape to affix
a pair of three-dimensional glasses onto the front of Vicki's thin, gold-rimmed
bifocals. The experiment he is running aims to separate the role of the corpus
callosum in visual processing from that of deeper, 'subcortical' connections
unaffected by the callosotomy. Focusing on the centre of the screen, Vicki is
told to watch as the picture slowly switches between a house and different faces
— and to press the button every time she sees the image change. Adjusting her
seat, she looks down the bridge of her nose at the screen and tells Turk that
she's ready to begin.
Deep connections
Other researchers are studying the role of subcortical communication in the
coordinated movements of the hands. Split-brain patients have little difficulty
with 'bimanual' tasks, and Vicki and at least one other patient are able to
drive a car. In 2000, a team led by Liz Franz at the University of Otago in New
Zealand asked split-brain patients to carry out both familiar and new bimanual
tasks. A patient who was an experienced fisherman, they found, could pantomime
tying a fishing line, but not the unfamiliar task of threading a needle. Franz
concluded that well-practised bimanual skills are coordinated at the subcortical
level, so split-brain people are able to smoothly choreograph both
hands
5.
Miller and Gazzaniga have also started to study the right hemisphere's role
in moral reasoning. It is the kind of higher-level function for which the left
hemisphere was assumed to be king. But in the past few years, imaging studies
have shown that the right hemisphere is heavily involved in the processing of
others' emotions, intentions and beliefs — what many scientists have come to
understand as the 'theory of mind'
6. To Miller, the field of enquiry
perfectly illustrates the value of split-brain studies because answers can't be
found by way of imaging tools alone.
In work that began in 2009, the researchers presented two split-brain
patients with a series of stories, each of which involved either accidental or
intentional harm. The aim was to find out whether the patients felt that someone
who intends to poison his boss but fails because he mistakes sugar for rat
poison, is on equal moral ground with someone who accidentally kills his boss by
mistaking rat poison for sugar
7. (Most people conclude that the
former is more morally reprehensible.) The researchers read the stories aloud,
which meant that the input was directed to the left hemisphere, and asked for
verbal responses, so that the left hemisphere, guided by the interpreter
mechanism, would also create and deliver the response. So could the split-brain
patients make a conventional moral judgement using just that side of the
brain?
No. The patients reasoned that both scenarios were morally equal. The results
suggest that both sides of the cortex are necessary for this type of reasoning
task.
But this finding presents an additional puzzle, because relatives and friends
of split-brain patients do not notice unusual reasoning or theory-of-mind
deficits. Miller's team speculates that, in everyday life, other reasoning
mechanisms may compensate for disconnection effects that are exposed in the lab.
It's an idea that he plans to test in the future.
As the opportunities for split-brain research dwindle, Gazzaniga is busy
trying to digitize the archive of recordings of tests with cohort members, some
of which date back more than 50 years. “Each scene is so easy to remember for
me, and so moving,” he says. “We were observing so many astonishing things, and
others should have the same opportunity through these videos.” Perhaps, he says,
other researchers will even uncover something new.
Other split-brain patients may become available — there is a small cluster in
Italy, for instance. But with competition from imaging research and many of the
biggest discoveries about the split brain behind him, Gazzaniga admits that the
glory days of this field of science are probably gone. “It is winding down in
terms of patients commonly tested.” Still, he adds: “I have a hard time saying
it's all over.”
And maybe it's not — as long as there are scientists pushing to tackle new
questions about lateralized brain function, connectivity and communication, and
as long as Vicki and her fellow cohort members are still around and still
willing participants in science. Her involvement over the years, Vicki says, was
never really about her. “It was always about getting information from me that
might help others.”
This schematic shows the two virtual reality mazes used
in the study. As the mouse ran down the long corridor, it would see a cue on the
right or left side of the corridor indicating that it should turn right or left
when it gets to the T-intersection. At the "cue offset," the mouse would pass
the sign and no longer see it, so the animal must remember which sign it saw
until it reaches the T-intersection and makes the turn. (Image courtesy of
Nature, Christopher Harvey and David Tank)
The aging brain loses its ability to recognize when it is
time to move on to a new task, explaining why the elderly have difficulty
multi-tasking, Yale University researchers report.
“The aged brain seems to get lost in transition,” said Mark Laubach,
associate professor at the John B. Pierce Laboratory and the Yale School of
Medicine, and senior author of a study that appears in the March 14 issue of
The Journal of Neuroscience.
