[tt] New Yorker: Silent Minds

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Silent Minds: What scanning techniques are revealing about vegetative 
patients.
http://www.newyorker.com/reporting/2007/10/15/071015fa_fact_groopman
[Linked by Arts & Letters Daily.]
7.10.15

by Jerome Groopman

Ten years ago, Adrian Owen, a young British neuroscientist, was
working at a brain-imaging center at Addenbrooke's Hospital, at the
University of Cambridge. He had recently returned from the Montreal
Neurological Institute, where he used advanced scanning technology
to map areas of the brain, including those involved in recognizing
human faces, and he was eager to continue his research. The imaging
center was next to the hospital's neurological intensive-care unit,
and Owen heard about a patient there named Kate Bainbridge, a
twenty-six-year-old schoolteacher who had become comatose after a
flulike illness, and was eventually diagnosed as being in what
neurologists call a vegetative state. Owen decided to scan
Bainbridge's brain. "We were looking for interesting patients to
study," he told me. "She was the first vegetative patient I came
across."

For four months, Bainbridge had not spoken or responded to her
family or her doctors, although her eyes were often open and
roving. (A person in a coma appears to be asleep and is unaware of
even painful stimulation; a person in a vegetative state has
periods of wakefulness but shows no awareness of her environment
and does not make purposeful movements.) Owen placed Bainbridge in
a PET scanner, a machine that records changes in metabolism and
blood flow in the brain, and, on a screen in front of her,
projected photographs of faces belonging to members of her family,
as well as digitally distorted images, in which the faces were
unrecognizable. Whenever pictures of Bainbridge's family flashed on
the screen, an area of her brain called the fusiform gyrus, which
neuroscientists had identified as playing a central role in face
recognition, lit up on the scan. "We were stunned," Owen told me.
"The fusiform-gyrus activation in her brain was not simply similar
to normal; it was exactly the same as normal volunteers'."

Excited by this result, Owen resolved to try to conduct brain scans
of other vegetative patients in the Cambridge area. Since 1997, he
has studied several dozen people, though he decided to use speech
sounds rather than photographs to stimulate their brains. (Owen was
concerned that showing images of faces might not be a reliable way
to test recognition, since the eyes of vegetative patients often
wander. "We shifted to auditory responses because you can always
put a pair of headphones on the person and know that you are
transmitting sound," he said.) Three years ago, he began using a
functional MRI (fMRI) scanner, which is faster than a PET scanner,
capturing changes in blood flow in the brain almost as they occur.
The patients' brains were scanned while they listened to a
recording of simple sentences interspersed with meaningless "noise
sounds." The scans of some of the patients showed the same response
to the sentences as scans of healthy volunteers, but Owen wasn't
sure that the patients had understood the words. "So we went the
next step up the cognitive ladder, to look at comprehension," he
said.

Psycholinguists have shown that when we hear a noun at the
beginning of a sentence we tend to associate the word with its most
common meaning. For example, Owen said, most people hearing a
sentence that begins, "The shell was . . ." think of an object
typically found at the beach. But if the sentence is completed by
the phrase "fired at the tank," the listener quickly corrects
himself, a process that is evident on a brain scan. "You can
actually see it happening and image it on the scanner," Owen said.
"The beautiful thing about the psychological task is that we just
do it automatically. When you play ambiguous sentences, areas in
the inferior frontal lobe and in the posterior temporal lobe become
activated, and these areas are very important for speech
comprehension. They show that you understand the meaning of the
word: it's not just about perceiving speech; it's about decoding.
Your brain somehow appreciates that there are two meanings to a
word like `shell.' "

Owen eventually identified two vegetative patients whose brains
showed the same activity in response to ambiguous sentences as the
brains of healthy volunteers. He also took brain scans of healthy
physicians, who were presented with the ambiguous sentences while
under general anesthesia. Owen found that, as the effects of the
anesthesia increased, the physicians showed less activity in the
brain regions associated with comprehension. "That, of course, is
in keeping with our personal experience of consciousness, which is
that as you sort of drift into sleep you understand less and less
of what is around you," he said. (An article about this experiment
appears this week in PNAS, the journal of the National Academy of
Sciences.)

Owen's final experiment was the most ambitious: a test to determine
whether vegetative patients who seemed able to comprehend speech
could also perform a complex mental task on command. He decided to
ask them to imagine playing tennis. ("We chose sports, and tried to
find one that involved a lot of upper-body movements and not too
much running around," he said.) First, he took brain scans of
thirty-four healthy volunteers who were instructed to picture
themselves playing the game for at least thirty seconds. Their
brains showed activity in a region of the cerebrum that would be
stimulated in an actual match. "This was an extremely robust
activation, and it wasn't difficult to tell whether somebody was
imagining tennis or not," Owen said. He then repeated the
experiment using one of the vegetative patients, a woman who had
been severely injured in a car accident. The woman had to be able
to hear and understand Owen's instructions, retrieve a memory of
tennis--including a conception of forehand and backhand and how the
ball and the racquet meet--and focus her attention for at least
thirty seconds. To Owen's astonishment, she passed the test. "Lo
and behold, she produced a beautiful activation, indistinguishable
from those of the group of normal volunteers," he said. (Another
vegetative patient, a man in his twenties, also passed the test,
though Owen, having learned that the man was a soccer fan, asked
him to imagine playing that sport instead of tennis.)

In September, 2006, Owen, along with Martin Coleman, a
neuroscientist at Addenbrooke's, and four other researchers,
published an article about the tennis experiment in Science and
ignited a vigorous debate. In letters to the journal, some
neurologists argued that the woman must have been misdiagnosed--a
claim that Owen disputed. "She fulfilled all of the internationally
agreed-upon criteria, and there wasn't anything that she did that
would lead anybody to say she wasn't vegetative," he told me. "Now,
naturally, in hindsight she wasn't vegetative; she was actually
conscious. It's a very interesting issue, because it means that she
was in fact misdiagnosed, but not misdiagnosed in the sense that
somebody made an error. Clearly, she is consciously aware of things
around her. So something is missing in the diagnostic criteria."

For decades, doctors assumed that patients who have been diagnosed
as vegetative lack any capacity for conscious thought. Most are
previously healthy people who suffered a traumatic brain injury, or
oxygen deprivation after a heart attack or stroke, and have been
regarded more or less as zombies: patients whose bodies continue to
function--sometimes for decades--but whose minds are incapable of
willed activity. (The term "vegetative" was proposed in 1972, by
Bryan Jennett, a neurosurgeon, and Fred Plum, a neurologist, who
chose it based on a definition in the O.E.D: "an organic body
capable of growth and development but devoid of sensation and
thought.") In the occasional newspaper stories about someone who
suddenly recovered consciousness after spending years in a
vegetative state, the event was invariably described as a medically
inexplicable "miracle." The Mohonk Report, a paper prepared by a
group of experts in brain injury and presented to Congress last
year, cited estimates suggesting that there are approximately
thirty-five thousand Americans in a vegetative state and another
two hundred and eighty thousand in a minimally conscious state--a
less severe condition, in which patients show erratic evidence of
deliberate behavior, such as responding to a simple command or
focussing on a person or an object for a sustained period. Because
insurers typically won't pay for rehabilitation, on the assumption
that such patients are unlikely to improve, most are given little
in the way of therapy. "These people with brain trauma are out of
our view," Joseph Fins, an internist and medical ethicist at Weill
Cornell Medical College, in Manhattan, and a member of the Mohonk
group, told me. "We ignore them, and we sequester them in places
where we can't see them, usually in nursing homes."

According to several American and British studies completed in the
late nineties, patients suffering from what is known as "disorders
of consciousness" are misdiagnosed between fifteen and forty-three
per cent of the time. Physicians, who have traditionally relied on
bedside evaluations to make diagnoses, sometimes misinterpret
patients' behavior, mistaking smiling, grunting, grimacing, crying,
or moaning as evidence of consciousness. A neuroscientist showed me
a video on the Internet of Terri Schiavo, the Florida woman who
spent fifteen years in what most doctors agree was a vegetative
state--tests revealed almost no activity in her cortex--and whose
death, in 2005, provoked fierce debate over the rights of severely
brain-damaged patients. (Schiavo died after the Supreme Court
rejected her parents' appeal of a judge's decision approving her
husband's request that her feeding tube be removed. An autopsy
showed extensive brain damage.) In the video, a man's voice can be
heard praising Schiavo for opening her eyes in response to his
instructions, and the neuroscientist told me that he was impressed
until he muted the sound. "With the sound off, it is clear that her
movements are random," the neuroscientist said. "But, with the
voice-over, it is easy to make a misdiagnosis." (The prognosis for
patients such as Schiavo, who suffered brain damage owing to oxygen
deprivation following cardiac arrest, is much worse than for those
who suffer brain damage as the result of a head injury.)

Doctors can also miss signs of consciousness in vegetative
patients, according to the British and American studies. Ten months
after Owen and his colleagues completed the tennis experiment with
the vegetative woman, she was brought back to the imaging center
and placed in an MRI machine. "We were absolutely dismayed, because
we scanned her and there was nothing," Owen recalled. The team
tested the woman again the next day. This time, in response to a
command to play tennis, her brain showed normal activity in the
regions that mediate arm movements. Owen now repeats scans for each
patient, conducting them twice a day for three days. Patients with
brain injuries have "seriously impaired attention capabilities and
their levels of general arousal are likely to be shot," he said.
Recent research by Owen and other neuroscientists may eventually
help make diagnoses more accurate, but it is not yet clear how the
new brain-scan data will affect the medical understanding of
consciousness. As Owen put it, "The thought of coma, vegetative
state, and other disorders of consciousness troubles us all,
because it awakens the old terror of being buried alive. Can any of
these patients think, feel, or understand those around them? And,
if so, what does this tell us about the nature of consciousness
itself?"

Owen's article in Science was accompanied by an editorial by Lionel
Naccache, a neurologist at the Hôpital Pitié-Salpêtrière, in Paris,
who called the results of the tennis experiment "spectacular."
"Despite the patient's very poor behavioral status, the fMRI
findings indicate the existence of a rich mental life, including
auditory language processing and the ability to perform mental
imagery tasks," Naccache wrote. Yet he cautioned against drawing
general conclusions about vegetative patients from a single case,
and asked, "If this patient is actually conscious, why wouldn't she
be able to engage in intentional motor acts, given that she had not
suffered functional or structural lesion of the motor pathways?"
Prompted by questions like this, Naccache and several of his
colleagues are conducting brain-imaging experiments with the goal
of identifying objective indicators of consciousness, and thus
enabling doctors to better evaluate patients who are unable to
communicate their awareness of themselves or their environment.

We assimilate information unconsciously all the time; at any given
moment, we process thousands of stimuli, of which we pay attention
to only a few. As you read this sentence, you may not be aware of
the birds singing in the back yard, but your brain has analyzed the
sound and concluded that it poses no threat to you. In the past
several decades, scientists have uncovered particularly dramatic
examples of unconscious processing. In the early seventies,
researchers at M.I.T. studied four patients who had experienced
trauma to an area of the brain involved in vision and had been
found to have a condition that was later called "blindsight." These
patients' eyes functioned normally, but they did not perceive much
of what was in their field of vision. When the researchers flashed
a light at the patients and asked them to describe what they saw,
the patients reported that they had seen nothing. Yet the
researchers noticed that their eyes often located the source of the
light. In a second experiment, a blindsight patient was shown
pictures of faces displaying happiness, sadness, anger, and fear.
The patient said that he could not see the faces, yet he was
frequently able to correctly identify the emotions. The researchers
concluded that, despite the patient's injuries, pathways in his
brain had been preserved which allowed him to process at least some
visual data, even though he wasn't consciously aware of doing so.

In the early nineteen-hundreds, the Austrian neurologist Hermann
Zingerle described patients who, because of tumors or other
abnormalities of the parietal lobe on the right side of the brain,
ignored the left side of the body and objects in the left field of
vision. (The right side of the brain controls awareness of the left
side of the body.) For example, some of these patients would shave
only the right side of their faces, since they were unaware of
their left cheeks. In the nineteen-eighties, researchers determined
that patients who had the syndrome--now called "neglect"--could
process some objects in the left field of vision. In one
experiment, a patient was shown two pictures of a house. The images
were identical except that, in one, flames were emerging from a
window on the left side of the façade. The patient said that she
couldn't see any difference between the images, but, when she was
asked which house she would want to occupy, she almost always chose
the one that was not on fire. "This is more complex than
blindsight, because it means that the patient was unconsciously
able to interpret and understand the symbolic meaning of the
pictures," Naccache said. "It is a powerful experiment to
demonstrate that unconscious perception and unconscious cognition
can reach upper levels of the brain."

>From these and other recent experiments, including his own,
Naccache and his research team are developing a working medical
definition of consciousness. "When we are conscious, the key
property is our ability to report to ourselves or to others the
content of the representation--as when I say, for example, `I am
perceiving a flower,' or the fact that I am conscious of speaking
with you now on the telephone," Naccache told me. "You have
patients who are conscious, or who are able to make reports, but
you can prove that some stimuli escaped their conscious reports, as
in the case of blindsight or neglect. You can study the neural fate
of these representations by showing that, even if the stimuli were
not reported by the subject, they were still processed in the
brain." He added that, in the case of Owen's vegetative patient who
imagined playing tennis, it's impossible to know whether she
reported the event to herself--which would suggest that she is
capable of conscious thought--or whether, as in the case of the
blindsight and neglect patients, she had no subjective awareness of
the experience. However, Naccache believes that consciousness also
requires an ability to sustain a representation over time, which
Owen's patient clearly was able to do. "In assessing apparently
vegetative patients who are unable to speak, and thus report, the
direction of research should be to look for sustained
representation," he said. "If we can prove by neuroimaging
techniques that this person is able to actively maintain a given
representation during tens of seconds, it provides strong evidence
of conscious processing."

Naccache has recently incorporated a third neurological feature
into his definition of consciousness: broadcasting. In a person who
is conscious, he explained, information entering the brain is
processed in a few areas and then distributed--or broadcast--to
many others. "It's as though there is a kind of ignition in the
brain, and then information is made available to a very rich number
of regions," Naccache told me. "And that makes sense, that the
information is initially represented locally and then made
available to a vast network, because the person has this ability to
maintain the representation within the network for a long time."

In 2005, Naccache conducted an experiment whose outcome suggested
the importance of broadcasting as a marker of consciousness. First,
he and his research team presented a series of words to three
epileptic patients, who had had electrodes implanted temporarily in
various brain regions, in an effort to locate the source of their
seizures. The electrodes enabled doctors to record the activity in
a given region. Some of the words, such as "blood" and "rape," were
chosen for their negative emotional connotations. The rest of the
words, which included "chair" and "house," were considered neutral.
Each word was shown to the patients for twenty-nine milliseconds
and then replaced with an image of a geometric figure, such as a
rectangle. The patients reported seeing only the geometric figures.
However, Naccache's team discovered that in each patient the
amygdala, a brain structure that is associated with strong negative
emotions, such as fear, displayed much more activity in response to
the negative words than to the neutral words.

"The picture we have now is that, unconsciously, many areas of the
brain can process information, and that unconscious representation
can be very abstract and very rich--much more than neuroscientists
thought some decades ago," Naccache said. "But now we can begin to
identify some limits of unconscious cognition. The activation
picked up by the electrodes is not only evanescent but restricted
to the amygdala and a few other regions, without broadcasting and
amplification through the brain." Owen's tennis-playing patient may
have been broadcasting information during the experiment, Naccache
said, though he added that he is uncertain whether her diagnosis
should be upgraded from vegetative to minimally conscious.
Moreover, he said, brain-scan research cannot yet tell us much
about such a patient's prospects for improvement.

The J.F.K. Johnson Rehabilitation Institute, in Edison, New Jersey,
is among the world's largest centers for the treatment of brain
injuries and one of the few places where patients suffering from
disorders of consciousness participate in research studies and
receive innovative therapy. In 2002, Joseph Giacino, a
neuropsychologist at the institute, was the co-chair of the Aspen
Work Group--which was made up of experts in brain injury--and
helped formulate the criteria for diagnosing a minimally conscious
state. "I think the rehabilitation field was ahead of the curve in
understanding that there were subpopulations of patients who were
not in a coma, were not in a vegetative state, but really were not
conscious, at least in the way we think about normal
consciousness," Giacino told me. "In the medical literature, these
patients were lumped together with everybody else."

The techniques that Giacino uses to diagnose patients require no
sophisticated technology. He recalled making rounds at the
institute with two eminent neurologists and stopping at the bedside
of a woman who had had a brain hemorrhage. The neurologists
examined the woman, who lay with her eyes half closed and did not
respond to the doctors' commands. The neurologists concluded that
she was in a vegetative state. "So I sort of sheepishly said, `Let
me show you what happens when we stimulate her,' " Giacino
recalled. He had been using a technique called "deep-pressure
stimulation," which involves squeezing a patient's muscles with
force and precision. Giacino started with the woman's face and
worked his way down to her toes, pinching her muscles between his
fingers. As he explained, the nerve endings of the muscles send
impulses to the brain stem, which relays them to other brain
structures and rouses the patient to consciousness. "I did a cycle
of deep-pressure stimulation, and within a minute or so she was
talking to us," Giacino said. "The neurologists were
flabbergasted." The woman was able to say her name and her
husband's name, and answer simple questions, such as "Is there a
cup at your bedside?" After a few minutes, however, she became
unresponsive again.

The woman had what Giacino calls a "drive disorder," in which a
patient is unable to speak, move, or, possibly, think unless
physically stimulated--by touch. Doctors believe that such
disorders are caused by damage to the limbic lobes or to other
parts of the brain that trigger and sustain behavioral responses.
Some patients with drive disorders respond to drugs that increase
brain levels of dopamine, a neurotransmitter that is associated
with arousal. "Imagine if the woman were in a nursing home,"
Giacino said. "Somebody would stop by for three minutes, check her
bedpan, and present simple commands like `Squeeze my hand,' `Close
your eyes,' and `Open your mouth.' She is not going to do any of
those things, but she clearly had a significant amount of preserved
function. It had to be harnessed externally." At J.F.K. Johnson,
patients with drive disorders receive behavioral and drug therapy.
(Some patients improve, but prospects for recovery are largely
determined by the extent and nature of the damage to the drive
system.)

Since 2002, the institute has been experimenting with using brain
scans to assist with diagnoses. Giacino cited the case of a male
patient whose condition had been diagnosed as vegetative but who
appeared to have strong emotional responses to people around him.
"If a nurse came in to do his care, it looked like he was screaming
silently," Giacino recalled. "His mouth would be wide open, and he
had an agonized, contorted face, like the one in Edvard Munch's
painting `The Scream.' The expression would occur if there was a
lot of noise around him, or if he was being physically handled, but
then his mother would come into the room, lower the lights, talk
with him in a soothing voice, and it would just go away." When
doctors scanned the man's brain, they discovered that portions of
the right hemisphere involved in emotional processing were intact.
(Other parts of the right hemisphere were damaged.) "This shows you
how treacherous diagnostic assessment can be," Giacino said. "One
can retain one piece of a network but be disconnected from other
structures and other networks, so that there is almost no
subjective awareness associated with this complex behavior. I've
seen other patients with other behaviors that seem to be outside
the scope of a vegetative state. Then you image them and you find
out some circuits are still relatively preserved, while most of the
rest of the brain is not."

However, brain-scan technology has also helped doctors identify one
patient at J.F.K. Johnson as a candidate for an experimental
therapy. The patient, a thirty-eight-year-old man who suffered a
head injury and had been living in a nursing home for six years,
arrived at the institute in 2004. He appeared to be minimally
conscious; he occasionally mouthed single words when prompted, but
he was unable to respond reliably to simple questions, or to chew
and swallow. (He had a feeding tube.) In 2001, PET and fMRI scans
had been taken of the man's brain, and, according to Giacino, one
of many researchers involved in the case, "the findings were
totally unexpected. The PET scan showed little metabolic activity,
but the fMRI scan showed that the region of the cortex involved in
processing language functioned in a fairly normal way." The
researchers speculated that, because of damage to the man's frontal
lobe, thalamus, and brain stem--areas involved in regulating
arousal--the nerve signals in his brain were muted. As Nicholas
Schiff, a neurologist at Weill Cornell Medical College who led the
study of the man's brain, put it, "It's as if a radio were turned
to such a low volume that you couldn't hear the music distinctly."
He added, "The scans confirmed our expectation that this patient
had a greater capacity for language than he demonstrated."

In August, Schiff, Giacino, Joseph Fins, and Ali Rezai, a
neurosurgeon at the Cleveland Clinic, along with twelve other
researchers, published an article about the case in Nature. The
researchers described implanting electrodes in the man's thalamus,
which, by stimulating the brain tissue, had enabled him to regain
considerable physical and mental function. "Deep brain stimulation
can promote significant late functional recovery from severe
traumatic brain injury," they wrote. When the electrodes were
turned on in the man's thalamus, his speech improved, his movements
became more fluid, and he was able to chew and swallow. When the
researchers turned off the electrical stimulation, the man soon
relapsed. He is now being given regular doses of electrical
stimulation and is able to speak in short sentences and to chew and
swallow. The researchers concluded that the case "challenges the
existing practice of early treatment discontinuation" for minimally
conscious patients who show some "interactive behaviors."

Few vegetative or minimally conscious patients ever recover fully,
and many are unlikely to improve. (Some neurologists estimate that
an adult who has been vegetative for six months following a
traumatic brain injury has only a twenty-per-cent chance of
regaining consciousness.) For the past three years, Schiff and Fins
have been studying the brain of Terry Wallis, a
forty-three-year-old man in rural Arkansas who had been the subject
of national news stories in 2003, when it was reported that he had
begun to speak after spending nineteen years in a nursing home, in
a minimally conscious state. Schiff and Fins contacted Wallis's
family and offered to help him obtain medical care during his
recovery, and to use brain scans to document his progress. In 1984,
Wallis, a nineteen-year-old truck mechanic, had been in a car
accident and sustained a severe brain injury; he was also
paralyzed. Wallis's father had asked the nursing home to arrange an
evaluation of his son by a neurologist, but was told that such an
assessment was too expensive and, in any case, would not be useful.
In 2003, when Wallis began to speak, he received twelve weeks of
physical therapy, which was covered by Medicaid, but the Arkansas
Department of Health and Human Services rejected his request for
further treatment, concluding that he had not made sufficient
progress. One day, in 2005, Fins, who had contacted Wallis's
congressman to solicit his help in obtaining additional medical
care for Wallis, asked Mrs. Wallis for her son's Social Security
number. "I was on the phone, and Mrs. Wallis said to Terry, `What's
your Social Security number?' " Fins recalled. "He gives his
number, and I write it down. And I said, `Mrs. Wallis, was that
Terry?' And she said, `Yup. The first time he told us his Social
Security, we thought he was wrong. But we looked it up, and he was
right.' "

Fins was astonished. Not only has Wallis recovered memories from
his life before the accident but, Fins said, "he is picking up
American culture. He now knows the song `Bad boys, bad boys, what
are you gonna do.' Why is that important? It's important because
that song didn't exist in 1984, so Terry is laying down new
memories. It shows sustained improvement." In 2006, Schiff arranged
for Wallis to be taken to Weill Cornell Medical College, where he
examined his brain using a sophisticated technique called diffusion
tensor imaging, which assesses the number and health of axons, long
fibres that transmit nerve impulses from one brain cell to another.
The scans suggested that the axons in Wallis's brain were growing
and forming new connections--a finding that contradicts the
long-standing assumption that a damaged brain is incapable of
healing after such a lengthy period. "We need to do longitudinal
studies, to see if these kinds of changes are accruing over time,
whether they happen frequently or infrequently, and what their
association with the patient's level of function is," Schiff told
me. In some cases, he speculated, the brain may sometimes be able
to bypass an injured area and devise novel ways of connecting
axons. Still, he went on, much about Wallis's recovery--and the
neurological developments that are driving it--remains a mystery.
"After nineteen years, Terry spoke a few words, but within
seventy-two hours he recovered fluent, expressive, and receptive
language," Schiff said.

Kate Bainbridge, the first vegetative patient that Adrian Owen
studied in Cambridge, has also made considerable progress,
recovering the use of her arms, and much of her mental function,
although she is unable to walk. She still has difficulty talking,
and uses a letter board to communicate with people who are not used
to her speech. "Most scans show what is wrong with your brain,
which doctors need to know," Bainbridge wrote to me in an e-mail.
"But Adrian Owen's scans show what is working. I say they found
parts of my brain were working. It really scares me to think what
might have happened to me if I had not had the scans. They show
people it was worth carrying on even though my body was
unresponsive."