(Philadelphia, PA) -- Using a novel application of an fMRI (functional magnetic resonance imaging) technique, researchers at the University of Pennsylvania School of Medicine have, for the first time, visualized the effects of everyday psychological stress in a healthy human brain. Their work, performed at Penn's Center for Functional Neuroimaging, provides a neuro-imaging marker of psychological stress -- which will pave the way for the development of improved strategies for preventing or correcting the long-term health consequences of chronic stress. The researchers' study appears in the November 21 online edition of Proceedings of the National Academy of Sciences.

In the Penn study, researchers induced stress on healthy subjects by asking them to quickly tackle challenging mental exercises while being monitored for performance. During the fMRI scans, the researchers also recorded subjects' emotional responses -- such as stress, anxiety, and frustration -- and measured the corresponding changes in stress hormone and heart rate. Many subjects described themselves as being "flustered, distracted, rushed and upset" by the stress task.

The results showed increased cerebral blood-flow during the "stress test" in the right anterior portion of the brain (prefrontal cortex) -- an area long associated with anxiety and depression. More interestingly, the increased cerebral blood-flow persisted even when the testing was complete. These results suggest a strong link between psychological stress and negative emotions. On the other hand, the prefrontal cortex is also associated with the ability to perform executive functions -- such as working memory and goal-oriented behavior -- that permit humans to adapt to environmental challenges and threats. "The message from this study is that while stress may be useful in increasing focus, chronic stress could also be detrimental to mental health," concludes Jiongjiong Wang, PhD, Assistant Professor of Radiology and principal investigator of the study.

"How the brain reacts under psychological stress is an untouched subject for cognitive neuroscientists, but it is certainly a critical piece of the puzzle in understanding the health effects of stress," adds Wang. "Our findings should help significantly advance our understanding of this process."

To date, most fMRI studies have indirectly measured changes in cerebral blood-flow and metabolism induced by neural activation, using a technique that is sensitive to the oxygenation levels in blood. “The fMRI technique employed in our study – arterial spin labeling – can measure cerebral flood-flow directly,” states John A. Detre, MD, Associate Professor of Neurology and Radiology, and senior author of the study. “This technique is very similar to PET (positron emission tomography) scanning, except that it’s entirely non-invasive – without the need for injections or radioactivity. In this elegant technique, water molecules in subjects’ own blood are ‘tagged’ by the magnet and used as the natural contrast agent to measure cerebral blood-flow.” Researchers at Penn’s Center for Functional Neuroimaging have been at the forefront of the development of this technique, and its applications to imaging brain-function during cognitive and emotional processes.

The study was sponsored by grants from the National Science Foundation, the National Institutes of Health, and the U.S. Air Force. In addition to Drs. Wang and Detre, the team of investigators included Penn researchers Hengyi Rao, Gabriel S. Wetmore, Patricia M. Furlan, Marc Korczykowski, and David F. Dinges.

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