Brain Imaging Shows Ability, Inability to Cope With Stress

Nancy A. Melville

July 21, 2016

Distinct brain patterns visible on neuroimaging reveal patterns of response that correlate with the ability, or inability, to cope with psychological stress.

"The findings from this paper add to the field by showing how the brain responds to acute stress while it is happening and unfolding," first author Rajita Sinha, PhD, the Foundations Fund Professor of Psychiatry at Yale University and director of the Yale Stress Center, in New Haven, Connecticut, told Medscape Medical News.

"We find that just as there are processes to alert us of danger and threat, there are distinct coping and resilient brain signals that light up somewhat more slowly as the alerting centers process the information."

Although previous studies into the neural processes involved in stress reaction have reported evidence of increased activation in various regions, research has been lacking regarding the acute temporal dynamics in such responses, the authors note.

The findings were published online July 18 in PNAS.

Distinct Brain Patterns

To better understand those relationships, Dr Sinha and colleagues enrolled 30 young adults (mean age, 25.7 years) who had no history of mental or physical health disorders.

During six successive sessions of 60 seconds each, participants were exposed to a series of images while being evaluated with functional MRI (fMRI). The images that were shown, which included those of terror, violence, mutilation, fear, disgust, and desperation, were intended to provoke a stress response. These responses to these images were compared with those recorded during exposure to neutral images that were not stressful.

After each 60-second exposure, participants rated their stress levels and degree of arousal. In addition to fMRI imaging, participants' physiologic parameters, including heart rate and plasma cortisol levels, were assessed.

On analysis, the responses followed three patterns. The first was sustained neural activation in regions known to identify and process potential threats, including the amygdala, striatum, hypothalamus, and other regions.

The second pattern involved an initial increase of activation followed by a decrease in activation in the ventrolateral prefrontal cortex, the dorsal anterior cingulate cortex, the left dorsolateral prefrontal cortex, the hippocampus, and the insula.

The third pattern showed first a decrease in the ventral medial prefrontal cortex (VmPFC), then an unexpected increase in activation, suggesting an adaptive response that, interestingly, corresponded with participants' responses suggesting coping with the sustained stress exposure.

"The VmPFC shows initial decreases in brain activation, but then mobilizes with increased activation, and this dynamic change was correlated with active coping," the authors note.

Patterns "support basic science research and our hypothesis that the VmPFC is a key region of dynamic and flexible neural circuit that may underlie behavioral control and active, resilient coping," they write.

Possible Clinical Implications

Separate interviews with participants further indicated that for those who did not show neural flexibility in the VmPFC, there was a greater likelihood of poor coping behaviors, including binge drinking, emotional eating, and angry outbursts.

"The take-home message from this is that there is a resilient coping brain circuit which can be disrupted, but when it functions well under stress, it supports positive health and adaptation," Dr Sinha said.

In terms of clinical implications, the results provide clues into those areas involved in the assessment of risk. They are also relevant to the promoting of resilience processes for the treatment and prevention of problems realted to stress.

"As we find a distinct brain pattern for resilient and nonresilient/risk coping, we can target those circuits and begin to classify the risk for stress-related illnesses with these brain indicators/markers," Dr Sinha said.

"We can also use these indicators to see if behavioral interventions like mindfulness or cognitive-behavioral strategies or yoga or medications can improve neuroflexibility and bring back resilient coping," she added.

"For example, a doctor looks at our glucose levels, and that functions as an indicator for good metabolism and good insulin sensitivity or risk for diabetes. This and other such indicators can serve as healthy stress or unhealthy stress resilient coping and risk for stress-related illness."

A limitation of the study was its size.

Dr Sinha said future research is planned to better understand and reproduce the results. "We especially want to study sex differences and also want to replicate the findings," she said.

"More importantly, we want to start testing the brain resilience indicator as a valid marker in identifying risk for stress-related illnesses but also in testing interventions to improve resilience behaviorally and then also physiologically in the brain."

Interesting, Exciting

One potential benefit of identifying specific targets of the mechanisms of stress is the potential ability to target therapies, Kenneth Heilman, MD, professor of neurology and health psychology and director of behavioral neurology-neuropsychiatry at the University of Florida, in Gainesville, told Medscape Medical News.

"In the common use of benzodiazepines, for instance, stress is reduced because a lot is being inhibited, whereas this research is interesting because, if it turns out to be correct, there could be a way to modulate that specific system without the need for a medication that is so inhibitory of the brain."

Dr Heilman cautioned that more evidence is needed to build on the fMRI findings.

"One of the problems I have with fMRI imaging is it identifies areas with increased activation, but it's not necessarily clear what that activation is doing in terms of cognitive systems," he said.

"So I think a lot more research needs to be done, but these findings are very interesting and very exciting."

The study received funding from the National Institute of Health Common Fund Roadmap, the National Institutes of Alcohol Abuse and Alcoholism, the National Institute of Drug Abuse, and the National Institutes of Diabetes and Digestive and Kidney Diseases. Dr Heilman has disclosed no relevant financial relationships.

Proc Natl Acad Sci. Published online July 18, 2016. Abstract

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