PITTSBURGH, August 15, 2016 - Neuroscientists at the University of Pittsburgh have identified the neural networks that connect the cerebral cortex to the adrenal medulla, which is responsible for the body's rapid response in stressful situations. These findings, reported in the online Early Edition of the journal Proceedings of the National Academy of Sciences (PNAS), provide evidence for the neural basis of a mind-body connection.
Specifically, the findings shed new light on how stress, depression and other mental states can alter organ function, and show that there is a real anatomical basis for psychosomatic illness. The research also provides a concrete neural substrate that may help explain why meditation and certain exercises such as yoga and Pilates can be so helpful in modulating the body's responses to physical, mental and emotional stress.
"Our results turned out to be much more complex and interesting than we imagined before we began this study," said senior author Peter L. Strick, Ph.D., Thomas Detre Chair of the Department of Neurobiology and scientific director of the University of Pittsburgh Brain Institute.
In their experiments, the scientists traced the neural circuitry that links areas of the cerebral cortex to the adrenal medulla (the inner part of the adrenal gland, which is located above each kidney). The scientific team included lead author Richard P. Dum, Ph.D., research associate professor in the Department of Neurobiology; David J. Levinthal, M.D., Ph.D., assistant professor in the Department of Medicine; and Dr. Strick.
The scientists were surprised by the sheer number of neural networks they uncovered. Other investigators had suspected that one or, perhaps, two cortical areas might be responsible for the control of the adrenal medulla. The actual number and location of the cortical areas were uncertain. In the PNAS study, the Strick laboratory used a unique tracing method that involves rabies virus. This approach is capable of revealing long chains of interconnected neurons. Using this approach, Dr. Strick and his colleagues demonstrated that the control of the adrenal medulla originates from multiple cortical areas. According to the new findings, the biggest influences arise from motor areas of the cerebral cortex and from other cortical areas involved in cognition and affect.
Why does it matter which cortical areas influence the adrenal medulla? Acute responses to stress include a wide variety of changes such as a pounding heart, sweating and dilated pupils. These responses help prepare the body for action and often are characterized as "fight or flight responses." Many situations in modern life call for a more thought-out reaction than simple "fight or flight," and it is clear that we have some cognitive control (or what neuroscientists call "top-down" control) over our responses to stress.
"Because we have a cortex, we have options," said Dr. Strick. "If someone insults you, you don't have to punch them or flee. You might have a more nuanced response and ignore the insult or make a witty comeback. These options are part of what the cerebral cortex provides."
Another surprising result was that motor areas in the cerebral cortex, involved in the planning and performance of movement, provide a substantial input to the adrenal medulla. One of these areas is a portion of the primary motor cortex that is concerned with the control of axial body movement and posture. This input to the adrenal medulla may explain why core body exercises are so helpful in modulating responses to stress. Calming practices such as Pilates, yoga, tai chi and even dancing in a small space all require proper skeletal alignment, coordination and flexibility.
The PNAS study also revealed that the areas of the cortex that are active when we sense conflict, or are aware that we have made an error, are a source of influence over the adrenal medulla. "This observation," said Dr. Strick, "raises the possibility that activity in these cortical areas when you re-imagine an error, or beat yourself up over a mistake, or think about a traumatic event, results in descending signals that influence the adrenal medulla in just the same way as the actual event." These anatomical findings have relevance for therapies that deal with post-traumatic stress.
Additional links with the adrenal medulla were discovered in cortical areas that are active during mindful mediation and areas that show changes in bipolar familial depression. "One way of summarizing our results is that we may have uncovered the stress and depression connectome," says Dr. Strick.
Overall, these results indicate that circuits exist to link movement, cognition and affect to the function of the adrenal medulla and the control of stress. This circuitry may mediate the effects of internal states like chronic stress and depression on organ function and, thus, provide a concrete neural substrate for some psychosomatic illness.
This research was funded by National Institutes of Health grants R01 NS24328, P40 OD010996, P30 NS07605, T32 DK063922 and K08 DK101756-01, and by a grant from the Pennsylvania Department of Health.
About the University of Pittsburgh Brain Institute
The University of Pittsburgh Brain Institute's mission is to unlock the mysteries of normal and abnormal brain function and then translate discoveries into new approaches for overcoming brain disorders. The Brain Institute provides a unifying structure and collaborative framework for more than 150 neuroscientists, who are spread across every school of the University.
About the University of Pittsburgh School of Medicine
As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support.
Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.
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