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Analyzing Brain Function to Treat Wounded Warriors

March 15, 2011

By Leah Kerkman Fogarty

Frank Krueger

War is tragic, it’s true. But there is a sliver of a silver lining for those injured by war. Over the past century, our understanding of the brain has improved with every modern war. The reason? Wounded soldiers with traumatic brain injuries (TBIs) have provided neuroscientists with prime examples of how different parts of the brain control different functions, such as attention, impulse control, and emotions.

Mason cognitive neuroscientist Frank Krueger has been studying warfighters’ brain injuries and their cognitive effects since 2006, when he was a postdoctoral fellow at the National Institute of Neurological Disorders and Stroke, a part of the National Institutes of Health (NIH), under the mentorship of Jordan Grafman.

Through this study, Grafman and his colleagues have followed a group of Vietnam veterans since 1967. Krueger, an assistant professor at Mason’s Krasnow Institute for Advanced Study, has been involved in the past two phases of the study. Phase 4 began in 2008, when Krueger became lead investigator on the Cognitive Neuroscience Section of the institute’s longitudinal Warfighter Head Injury Study.

In this phase, about 160 Vietnam veterans who suffer from TBI and about 40 control subjects— veterans who did not sustain TBI in the war—are going through a battery of clinical and neuropsychological tests to analyze the cognitive functions of their brains. These tests are complemented with structural and functional neuroimaging. Molecular genetics evaluations are also being performed, says Krueger.

Because of the way the Vietnam War was fought, Krueger says, most of the soldiers sustained focal-penetrating brain lesions from being hit by low-velocity shrapnel.

“So we have this unique population that has specific brain lesions, so you can make better claims about the functions of the brain,” he explains.

Krueger and his colleagues on the study hope to conduct neuropsychological testing on veterans of the Iraq and Afghanistan wars, as well. Warfighters from these wars typically suffer different brain injuries.

“Now, the war is fought differently. These soldiers have what is called mild TBI; these are blast injuries,” Krueger says. “The typical scenario is you’re in your jeep, driving through, you hit a bomb, and you sustain injuries related to the wave from the bomb detonating. At first, you don’t feel anything. But after a couple weeks, you get worse, suffering from concentration and cognitive decline.”

Rather than focal lesions, this type of injury affects large sections of the brain. Blast injuries affect white matter, the part of the brain that connects gray matter. If you imagine the brain as a computer network, the gray matter would be the actual computers and the white matter would be the network cables that connect everything.

“Our main goal in this study is to help the warfighters,” Krueger says. “It’s unfortunate that they have sustained these injuries, but the fact that they have allows us to do more research and figure out new ways to treat them.”

Krueger also is studying warfighters with this type of injury at the Center for Neuroscience and Regenerative Medicine (CNRM), a federal medical research program that has spearheaded collaborative interactions between the U.S. Department of Defense, NIH, Walter Reed Army Medical Center, and the National Naval Medical Center.

He hopes to have access to and include these warfighters in the NIH Warfighter Head Injury Study. Another war-related issue Krueger hopes to help treat is somewhat controversial: posttraumatic stress disorder, or PTSD. PTSD is an anxiety condition that can occur after a person has experienced a traumatic event.

The CNRM study looks at people just back from the wars in Iraq or Afghanistan. These warfighters will be scanned using functional magnetic resonance imaging (fMRI) several times over one year to see how the brain changes over time.

“It’s a rough estimate that 15 to 25 percent of this group will develop PTSD,” Krueger says.

After this yearlong study is complete, Krueger hopes to take the research a step further into the treatment of the disorder. There’s a new method of treating neuropsychiatric conditions, such as PTSD, called real-time fMRI neurofeedback. This cutting-edge treatment that allows patients to retrain the affected areas of their brains is still being researched.

In PTSD, an emotional stimulus triggers a flashback that occurs in response to reminders of the traumatic event. Using neurofeedback training, Krueger hopes to help those suffering from PTSD to control the part of the brain involved in emotional processing—the amygdala—that causes the flashbacks.

“The idea is, if you develop PTSD, it is because you have hyperresponsivity of the amygdala,” Krueger says. “You could do neurofeedback training, so when you see emotional stimuli, your amygdala doesn’t freak out. You try to control it.”

He compares this sort of neurofeedback training to weight training. Over time, the hyperresponsivity of the amygdala decreases, and the patient gains more control over it and its responses.

“It’s like a muscle,” he says. “You can train it to get better.”

At this time, real-time fMRI neurofeedback training is expensive, and the treatment could take several sessions over weeks or even months. Krueger and his colleagues are submitting grant requests for funding of this translational research.

Krueger says, “Because this sort of research is translational, it can directly help someone, which is great.”


  1. Dr. Krueger,
    I believe it’s more than just neurofeedback and your analogy of it to weight training. It’s also appraisal of external stimuli that relate to the internal mechanisms of fear and control-ability that have permanently internalized that memory. Therefore it’s also a negative feedback process by function of the HPA axis.

    Also, are you using any medications? If so have you considered their interactions? or were the participants already taking medications? I’m sure you know of the effects of certain SSRIs and benzodiazepines.

    You can’t forget about the plasticity of the brain with the basal ganglia.

    I’m interested in this study, please contact me.

    Thomas Wooldridge

    Comment by Thomas Wooldridge — November 18, 2011 @ 4:18 pm

  2. This is amazing. I love this subject and I am thirsty for more to hear about it.

    Comment by Neda — April 16, 2013 @ 2:53 am

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