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Research Highlights
Restoring consciousness
Researcher explores how to aid recovery from coma
January 6, 2009
Dr. Theresa Pape's work made
headlines last fall when she reported
how a study participant spoke his first
words since suffering a severe brain injury
in a car crash almost a year earlier.
Joshua Villa, age 26 when injured, had
been in a vegetative state for nearly 10
months when his mother agreed to have him
take part in Pape's research on transcranial
magnetic stimulation, or TMS.
The treatment involves holding an
electromagnetic coil over specific areas of
the skull to excite the brain cells beneath the
coil.
It was after the 15th treatment—out of a
total of 30 sessions over six weeks—that
Pape noticed a spike in Villa's responses on
a measure called the Disorders of
Consciousness Scale. The instrument,
developed by Pape, measures an
unconscious person's responses to sensory
stimuli.
"I couldn't believe that the gains were
that dramatic and significant," recalls Pape.
"I must have done the analyses 10 times to
make sure there wasn't a mistake."
Three sessions later, Villa uttered his first
words.
Pape: "There must have been about half
a dozen of us in the room, and our mouths
just hung open. We all looked at each other
thinking,'Did he just say that?'" A couple
of days later, when his mother was with
him, Villa said "Mom" and "Help me."
Pape is a researcher at the Edward Hines
VA Hospital near Chicago. She also
collaborates with staff at several
rehabilitation hospitals in the area. Her
study involving Villa is available online in
the journal Brain Stimulation and will soon
be in print.
TMS, developed in Europe in the 1980s,
has been used successfully to treat
depression, schizophrenia, and other mental
disorders. Pape is among the first to explore
its usefulness in promoting recovery from
coma.
In depression, doctors apply the
magnetic coil to an area of the brain called
the left dorsolateral prefrontal cortex. Pape's
theory is that the same area on the opposite
side might be best for those in coma or
other unconscious states due to traumatic
brain injury.
Stimulating the brain
The term "telehealth" means
TMS is one of several therapies being studied that use
electrical current to stimulate the brain. It is among the least
invasive. Other methods include
- Deep brain stimulation—Electrodes are implanted in the
brain to stimulate specific brain regions. VA researchers who
tested the technique for Parkinson’s disease will be publishing
their results this month.
- Electroconvulsive therapy—The process involves inducing
a seizure in an anesthetized patient by applying electric current
to the brain. It has been found safe and effective for depression
and other conditions when drugs don’t work.
"My challenge is finding the optimal
dose at the optimal site," she says. "I'm
trying to maximize efficacy and minimize
the potential for adverse events while
optimizing the site on the brain. I chose the
dose according to safety data from healthy
controls and efficacy data from patients
with mental illness, but that doesn't mean
it's the optimal dose for traumatic brain
injury. Likewise, I chose the site according
to neurological theory, but that doesn't
mean it's the most optimal site."
Only a handful of other researchers in the
U.S. are exploring the same general topic:
how to promote recovery from coma. So
Pape has reached out to other countries,
such as Denmark, for collaborators. Her
vision is that different groups of researchers
will explore different TMS doses and apply
the magnetic coils to different sites on the
brain. That would speed the research
process.
"I would love it if someone chose a
different site or dose and studied it," she
says.
Familiar voices may stir brain
response
Pape plans additional research on TMS,
but she is also exploring other treatments to
help people in comas or vegetative states
due to brain injury. One example is familiar
vocal stimulation.
The treatment works like this: Family
members tell stories about events they took
part in with their loved one. Transcripts are
written, and the families then recite the
stories into digital recorders, as if talking to
their loved one. Pape offers an example of
how the monologues might sound: "Oh, do
you remember we went to this wedding and
I wore that red dress, and you thought I
looked fantastic?"
The therapy is low-cost and as
noninvasive as they come, although patients
will undergo a brain scan called functional
MRI as they listen to the audio. That will
allow researchers to check for responses in
the form of more blood flow to different parts of the brain. Pape
expects to activate those areas that normally process familiar voices,
such as the temporal lobes and hippocampus.
Her team uses professional audio—editing programs to ensure the
right quality and volume—even amid the clanging of the MRI
machine.
"We're talking about them hearing a tone in a person's voice, an
attitude—all the pragmatic cues mediated in healthy people by the
right side of the brain. These are the verbal cues that let someone
know who's talking to them without them seeing the person."
The study will include 45 patients. One group will listen to their
families' stories for four 10-minute sessions daily, for six weeks. A
second group will listen to familiar voices less frequently. A third
group will receive only "sham" treatment—in this case, the
presence of a CD player but no sound. "Everybody's getting a
similar process," says Pape.
Families find hope through research
TMS and familiar vocal stimulation might work together, says
Pape. TMS would first induce "brain plasticity" by exciting
neurons. Over time, TMS could boost the function of axons—the
fibers nerve cells use to talk with each other. Dormant neurons
could be revived, and new neural networks created. Vocal
stimulation could then "shape and guide that plasticity" and help in
the recovery of auditory skills.
The other focus of her research, the Disorders of Consciousness
Scale, provides a reliable, accurate way to track the effects of
various therapies. It may also yield data to help identify factors
linked to recovery from coma. Why some patients recover from
serious brain injuries while others linger in a coma for many years
is still largely an enigma.
"If I had that answer, I'd win the Nobel," says Pape whimsically.
Her work has taken on special significance for VA, as some 20
percent of troops injured in combat in Iraq or Afghanistan have a
brain injury. Most of the injuries are considered mild, and only a
relatively small percentage result in long-term loss of
consciousness. But for those patients who do remain unconscious,
any new hope is welcome. Pape tells how families of the patients in
her studies are eager for any advances.
"These families believe, and they believe strongly. They believe
in research, and they believe something will be developed. We have
one family member who contacts us regularly: 'Got anything for my
loved one yet?'"
This article originally appeared in the January 2009 issue of VA Research Currents.
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