From the Archives: Imaging Depression

This month, Helen Mayberg and her colleagues published a study suggesting that patterns of brain connectivity may predict which people with depression would respond best to talk therapy and which would do better with a drug. This video clip from Fox5 Atlanta describes the study, and shows what it could mean to people who need help for their depression.

Our first work with Mayberg, now a member of the Dana Alliance for Brain Initiatives, was more than a decade ago, when she was using first positron emission tomography and then deep brain stimulation for treatment-resistant depression (Dana grants in 2006, 2010). She spoke with us about this work in 2012:

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Unraveling Individual Variability in Hormonal Mood Swings

Guest post by Brenda Patoine

The stereotype of women’s “inexplicable” mood swings has long provided fodder for comics and cartoonists, but for scientists trying to understand the underlying biology, hormonal depression is no joke.

Endocrine-related affective mood disorders show up in different forms in different phases of life, from premenstrual dysphoric disorder (PMDD) during otherwise normal menstrual cycling, to post-partum depression following childbirth, to mood disruptions around and after menopause. Yet these disorders don’t affect all women, and in fact, most women do not experience them.

“How is it that some women experience a change in affective state as a result of hormones whereas a majority of women do not?” Peter Schmidt, M.D. asked in a July 8 webinar sponsored by the National Institute of Mental Health (NIMH). “That really is the million-dollar question.”

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Magnetic brain scans become more attractive

The first image many of us conjure up when someone mentions
brain scanners—whether for medical diagnosis or basic research—is the sterile
white isolation and intimidating din of a magnetic resonance imaging device.
But for many diseases, the key to better diagnosis may not be looking into
brains, as with MRIs, but looking near

A new study appearing
in the Journal of Neural Engineering suggests
that magnetoencephalography (MEG) can identify the vast majority of people
suffering from post-traumatic stress disorder (PTSD).

In MEG, a helmet surrounding the head measures the tiny magnetic
fields generated by the brain’s electrical activity. This offers distinct
advantages and disadvantages over other scanning methods. For instance, MEG is
noninvasive, unlike positron emission tomography (PET), which requires patients
to ingest a mildly radioactive solution. MEG is also very fast—it works in
about 10 milliseconds—because it measures neural activity directly; MRIs
measure blood flow in the brain instead and take 20 times longer. On the other
hand, readings from MEG offer less spatial resolution than many other scanning
methods and provide less precise information about regions deep inside the

In the new research, Apostolos
, a professor of neuroscience at the University of Minnesota
and a member of the Dana Alliance for
Brain Initiatives
, and his colleagues found that MEG correctly identified at
least 67 of 74 veterans suffering from PTSD, from a group that also included
250 people with no reported neurological or mental health issues. The veterans were
a varied group, with participants both from the current Iraq and Afghanistan
campaigns as well as from World War II and Vietnam.

The researchers also reported that the strength of their
readings corresponded with the severity of symptoms in a PTSD sufferer. In other
words, a MEG test might not just identify who has PTSD but also how damaging
the disorder is and even what treatments might work best.

MEG has shown potential to diagnose other brain symptoms. In
2007, for instance, Georgopoulos and his team reported that MEG could
help detect
multiple sclerosis, Alzheimer’s disease, schizophrenia,
Sjögren’s syndrome, chronic alcoholism and facial pain. And earlier this month,
we reported on a small
study that used MEG to identify children with autism

As we mentioned in that post, small tests such as the PTSD
study aren’t useful in the clinic until they have been confirmed in more
expansive tests with more diverse sets of people. Still, many neurological
disorders, including a large percentage of PTSD cases, are difficult and
time-consuming to diagnose. Objective detection methods such as brain scans could
dramatically shorten that process, as well as reduce uncertainty about the
accuracy of a diagnosis or the severity of a particular case.

For soldiers, who are at high risk for PTSD, this is
crucial; their final diagnosis can drastically alter what jobs they are
expected to do, where they are sent during their next deployment and what kind
of benefits they can receive. In the most extreme cases, a doctor’s finding might
mean the difference between re-entering a dangerous war zone and safely recovering
from trauma on U.S. soil. For those kinds of cases, a fast, efficient way to
assess PTSD can’t come fast enough.

—Aalok Mehta

For autism, Parkinson’s, hope for faster diagnosis

For many brain diseases, diagnosis is no exact science.
Because of the complexity of the brain and of the symptoms that it can cause,
there are often no definitive tests, and neurologists lean on years of
experience, long and painstaking observations, and educated guesses to
determine what exactly is afflicting their patients. Not only is this
frustrating for everyone involved, but in some cases a delayed diagnosis can
make a disease much more difficult or even impossible to treat successfully.

Now, scientists have made progress on faster, more objective
methods to detect at least two serious neurological disorders in which early
and correct diagnosis is vital.

A small pilot study conducted by Timothy
and his colleagues at the Children’s Hospital of Philadelphia report
has found that a relatively unobtrusive brain-scanning technique may be useful
in detecting autism-spectrum
(ASD). These conditions, characterized by problems in
communication and social interaction, are often diagnosed after a child has
already begun school, when treatments to prevent reading and other learning
disabilities are less effective. They are also not that uncommon: A recent
study by the Centers for Disease Control and Prevention found that
almost 1 percent of children in the U.S. have an ASD

For the study,
reported online in the journal Autism
this month, the scientists measured brain responses from 25
children with ASDs and 17 without using magnetoencephalography, in which a helmet
surrounding the head is used to measure the brain’s magnetic field. On average,
the ASD group had a tiny delay—about 11 milliseconds—in brain responses to
sounds. According to the researchers, this may be explained by one
of their previous studies
, which found that people with ASDs have reduced
amounts of white matter, or myelination, a type of insulating material that
speeds up transmission of nerve signals.

In the second study, slated
to appear in the February issue of Lancet
researchers from the Feinstein Institute for Medical
Research, led by David
, used positron emission tomography (PET), which measures blood
flow and chemical changes in the brain, to successfully diagnose whether a person
had Parkinson’s disease, multiple system atrophy, or progressive supranuclear
palsy. These movement disorders often show nearly identical symptoms at the
start but require different types of treatments.

In 167 patients, a computer program analyzing PET results
matched the diagnosis made by experienced specialists more than 80 percent of
the time. The doctors, however, had spent an average of 2.6 years assessing the
patients before coming to their judgments.

It remains to be seen whether the results of their studies
will end up reaching the doctor’s office, as many promising brain-scan findings
have ultimately failed to be precise or accurate enough upon additional testing.
The ASD study, for instance, looked at an extremely small number of people and tested
children with an average age of 10; it’s unknown whether such a delay would
still be detectable in young children or infants, for whom early diagnosis
would offer the most advantages.

The computer program used in the PET work will likewise need
additional testing through large, double-blind studies, according to the study
authors. But if confirmed, the findings could extend beyond better diagnosis,
they say; the research may also spur drug development for movement disorders by
allowing doctors to identify candidates for clinical trials much earlier than
previously possible.

—Aalok Mehta

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