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A picture of stress
24 NOVEMBER 2005

Got a boss hounding you to get more done in less time? Running short of cash? Trying to do math with an academic psycho-nerd badgering you to work faster?

You may not know it, but your levels of stress hormones are probably rising. Ditto for your heart rate. In animals, stress can stunt growth, slow learning, or fluster the immune system. In people, chronic stress can cause high blood pressure, among other problems. The extreme stress of war or personal assault can cause the life-changing condition called post-traumatic stress disorder.

Right front of brain is highlightedThe ventral part of the right prefrontal cortex (red), had extra blood flow during a moderately stressful lab test. This area is just behind the right eye. Brain (plus all images below) courtesy Jiongjiong Wang, University of Pennsylvania School of Medicine.

But how do the minor stresses of daily life affect your brain?

To find out, a team led by Jiongjiong Wang and John Detre of the University of Pennsylvania School of Medicine looked at blood flow in the brain -- an indicator of how hard any particular part of the brain is working. The study, they say, was the first actual picture of how the human brain responds to stress.

Taking pictures
The researchers gathered 25 adults, stuffed them inside a magnetic resonance imager (MRI), and recorded blood flow in the brain four times: before the test, during a low-stress task (count backward from 1,000), during a high-stress task (count backward by 13 from 1,000 -- fast), and about 10 minutes afterwards. Seven members of a control group went through the brain scans, but didn't get the stressful math.

Anxiety and especially stress rose most right after the math test, then subsidedTest subjects were asked about their state of stress and anxiety between MRI scans. While stress and anxiety showed similar trends, stress was even higher after the hard math task.

To complement the brain scans, the researchers asked subjects about their emotional state. Were they stressed, frustrated, or challenged? In most of the subjects who reported increased stress (not all did), blood flow increased in part of the right prefrontal cortex -- a location associated with negative emotions. The frontal cortex -- that huge bulge behind your forehead -- is a brain region responsible for planned action and higher thinking. Humans got 'em, other animals don't.

Tellingly, blood flow in the right frontal cortex corresponded with the subjects' reports of stress level, but not with their reports of frustration or the amount of effort needed to do the math. Reinforcing the finding, some subjects reported feeling a lower level of stress after the math exercise -- and blood flow did not increase in their right prefrontal cortexes.brain illustration with pull quote

Stressing stress
For more than 10 years, neuroscientists have been using MRIs to find out which part of the brain is working as people do quick and simple tasks: recognizing faces or tapping fingers. The present study, however, used a variation on MRI that makes a better picture of slower changes, Detre says. Standard MRIs record blood flow indirectly, by looking at iron in hemoglobin, the compound that carries oxygen in the blood. But for technical reasons, it's not reliable enough to compare readings made more than a few minutes apart, Detre adds, so it cannot easily be used for looking at the effects of stress.

In contrast, "arterial spin labeling perfusion" MRI labeling uses the giant MRI magnet to mark water molecules in blood that is entering the brain, and then the MRI machine detects where that blood goes in the brain. The system, says Detre, who directs Penn's Center for Functional Neuroimaging, allows you to compare blood flow before, during and after the stressful task. It does not insert chemicals or radioactive isotopes into the subject.

Don't be stressin'
Finding that stress affects the prefrontal cortex behind the right eye was a step forward, but even more important was the persistent change in blood flow. According to Wang, the study's primary author, "We also observed a sustained right prefrontal cortex activation, even after the task was complete, that is consistent with the after-effects of stress. If you have a stressful day at work and go back home, you just can't turn off the stress response immediately and play with your kids." Wang is a research assistant professor in Penn's departments of radiology and neurology.

Graph shows that the higher the perceived stress, the higher the blood flow in right prefrontal cortex.
A cutaway view of the brain shows the ventral region of the right prefrontal cortex (red), where blood flow increased during stress. Blood flow also increased in the left insula and putamen, which are also involved in negative emotions.

Finding that stress had a prolonged effect on the brain made us wonder if the research might shed light on how war or rape could cause the long-lasting brain changes of post-traumatic stress disorder (PTSD). But Wang notes that PTSD is caused by a far more severe type of trauma. "The particular stress we study is closer to everyday life. It mimics the experience of people trying to keep up the pace, who are under pressure."

Yet while a five-minute mathematical exercise is not chronic stress, Detre says, "It's interesting to note that there was a persistent effect. That suggests that a mechanism of persistent change in brain activation after stress" could tell us something about the cause of PTSD.

But why bother learning exactly which part of the brain responds to stress? "The hope is that by identifying these biological markers for cognitive or emotional brain function, we can get a better understanding of how the brain works, and how we might be able to modify behavior or treat medical conditions that are associated with brain dysfunction," says Detre. "This type of work could lead to a better understanding of PTSD and its treatment. It could lead to the ability to identify, based on their brain responses, people who are more or less prone to stress. The military might be interested. And it could allow us to assess the efficacy of strategies to mitigate stress, based on meditation or medication."

-- David Tenenbaum

Bibliography
The Stressed Brain - Perfusion FMRI Reveals Cerebral Blood Flow Pattern under Psychological Stress, Jiongjiong Wang et al, PNAS, Nov. 2005.

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