Scientists working in psychiatric brain imaging are obtaining spectacular
snapshots of the living human brain.
For example, they can see the hippocampus of a posttraumatic stress
disorder patient glow as she experiences a flashback. They can see the basal
ganglia and prefrontal cortex of a Tourette's syndrome patient brighten as he
emits grunts or curses. They can see the visual cortex of a schizophrenia
patient light up while he "experiences" a decapitated head issuing
commands. But what is the point of all this? What has the field achieved so
It all started a quarter century or so ago. Two brain-imaging
techniques—computed tomography (CT) and single photon emission computed
tomography (SPECT)—became available and allowed psychiatrists to peer
into the living human brain as they had never been able to do before. CT and
SPECT were then followed by magnetic resonance imaging (MRI) and positron
emission tomography (PET). And then in the early to mid-1990s, functional
magnetic resonance imaging (fMRI) made its debut.
"Today, with some strong MRI scans, we can see down to the neural
column level, which is really incredible," Anthony Weiss, M.D., a
Massachusetts General Hospital psychiatrist doing brain imaging of
schizophrenia subjects, noted. "So these are beautiful pictures with
exquisite detail of the brain."
And as David Silbersweig, M.D., codirector of the Functional Neuroimaging
Laboratory at Cornell Medical Center, pointed out at a recent meeting of the
American Psychoanalytic Association, "What is so exciting about
functional imaging is that we can make linkages between brain and
These advances have led to a plethora of valuable insights into the
biological underpinnings of psychiatric disorders. For example, the
orbitofrontal cortex and amygdala have been implicated in certain anxiety
disorders. The negative symptoms of schizophrenia have been coupled with
decreased activity in the dorsal lateral prefrontal system of the brain. There
is a raft of neuronal underconnectivity in the brains of children with
Neuroimaging scientists are also starting to see a synthesis of some of
these findings. For instance, the amygdala appears to be a culprit in a number
of psychiatric disorders associated with negative emotional states. The
anterior cingulate gyrus and some regions of the frontal lobe have been
implicated in both anxiety disorders and mood disorders. "These are
probably parts of final common pathways of symptom expression that may not
respect DSM boundaries," Silbersweig told Psychiatric
Yet neuroimaging is not yet a clinical psychiatry tool. "The
translation to clinical practice has actually not worked out as well as we had
hoped," Weiss observed. As Joshua Roffman, M.D., an instructor in
psychiatry at Harvard University who is combining neuroimaging with genetics,
added: "I don't want to knock imaging because it has helped us
understand [mental illnesses] better, but it hasn't translated yet to the
point where it is clinically useful. And many of us who are working with it
are still aiming for that goal."
"Although it looks as if the technique is easy from the colorful
brain pictures that result, actually it is not," Silbersweig pointed
out. "We take thousands of pictures and use statistics to test
hypotheses. It is not just an expensive toy that lights up the brain. Also,
one is dealing with some of the most complex functions in the most complex
organ, and there is a lot of groundwork that needs to be laid to be able to
progress rationally toward evidence-based clinical practice advances.
Furthermore, it is an interdisciplinary field involving lots of high-tech
equipment and therefore expensive work. So there are always issues of funding
so that the field can move ahead."
"To some degree there is a communication gap between researchers
doing high-level imaging work and clinicians who are seeing patients,"
Weiss explained. "Also, it can be difficult to frame imaging research in
a way that can be more immediately relevant. In fact, sometimes if you want to
make your research more clinically relevant, it can reduce the scientific
quality of the study."
Nonetheless, he said, imaging researchers should probably be focusing more
on the clinically pertinent aspects of their work than they are currently
doing. For example, a 2005 neuroimaging study impressed him because the
researchers asked: "What would the sensitivity and specificity of this
neuroimaging test be if it were used to diagnose schizophrenia?"
"One rarely sees such clinically relevant messages in papers about
imaging and mental illness," he said.
There is often a "disconnect between the clinical features of
psychiatric illnesses and their biological underpinnings," Gary Small,
M.D., a professor of psychiatry at UCLA and an Alzheimer's brain-imaging
scientist, observed. "Therefore it is hard to find informative surrogate
markers. And that is what we need" if psychiatrists want to use imaging
for diagnosis or to determine who is going to respond to treatment or to track
whether treatment works.
Nonetheless, what most clinical psychiatrists want to know is, When will
imaging research start benefiting their practices?
"I think that the work done Alzheimer's disease is further along than
in any other area in terms of using imaging," Weiss said. "Some
scientists are now able to detect the plaques occurring in nerve cells while
Alzheimer's patients are still alive. And that is a tremendous advance that
has happened over the past 10 years."
In fact, a brain-imaging test for Alzheimer's could become clinically
available as early as four years from now, Small predicted. Specifically,
Small and his colleagues have developed a radioactively labeled molecule
(probe) called FDDNP that makes plaques visible on PET scans (Psychiatric
News, September 6, 2002). FDDNP has been patented by UCLA and licensed to
Siemens. Siemens has filed an investigational new drug application with the
Food and Drug Administration, and if studies with FDDNP are further
successful, it "could have FDA approval within four years," Small
Some other clinical applications of imaging may also surface during the
next five to 10 years.
Using brain imaging to predict treatment response is one, Weiss contended.
Melissa DelBello, M.D., an associate professor of psychiatry at the University
of Cincinnati and a brain-imaging investigator, believes this as well.
Currently, DelBello and her colleagues are using SPECT and fMRI to identify
predictors of treatment response in subjects with bipolar illness.
Roffman and Silbersweig, in fact, foresee brain imaging being combined with
genotyping to predict treatment response. So does Weiss: "I think it is
the wave of the future. These two streams—genetics and
neuroimaging—have flowed throughout psychiatric research over the past
20 years, and they are starting to be brought together."
Combining brain imaging with genotyping will achieve something else
important, Konasale Prasad, M.D., an assistant professor of psychiatry at the
University of Pittsburgh, said. It will lead to the identification of certain
subgroups of mental disorders, and once such subgroups are identified, then
treatments can be customized for them. "The use of neuroimaging to
provide biomarkers and targets for novel therapeutics is an important
goal," Silbersweig said.
As neuroimaging unmasks the biology of various psychiatric disorders, still
other clinical applications will undoubtedly emerge.
Take the case of autism. Even though autism research is often considered to
be many years behind that for other types of psychiatric disorders,
brain-imaging research in autism may eventually lead to some clinical
applications, Nancy Minshew, M.D., a professor of neurology and psychiatry at
the University of Pittsburgh and an autism expert, anticipates. For instance,
since brain imaging has revealed underconnectivity of nerve cells in the
brains of autism subjects, she and other autism scientists are devising new
interventions for autism based on this finding—"the translation of
this research," she said.
And as new brain-imaging technologies develop, they could give the clinical
application of psychiatric brain imaging a huge push.
A case in point is near infra-red spectroscopy (optical imaging). Like
fMRI, it shows which areas of the brain are activated when someone is
participating in a task or resting. But whereas a magnetic field does the job
in the former, light does it in the latter.
What is especially tantalizing about optical imaging, both Roffman and
Weiss believe, is that it is much less expensive and much more portable than
fMRI. In fact, an optical-imaging unit is small enough to put on a cart and
wheeled around in a psychiatrist's office. Thus, it could be used as an
adjunct to psychiatrists' century-old diagnostic tools—questioning and