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Hippocampal Neural Networks Predict Stress Intensity

June 05, 2020

A person’s hippocampal connectivity during a stressful event can predict the intensity of stress experienced, suggests a study published online in the journal Nature Communications. 

“Identified networks were specific to the construct of stress and the hippocampal connectome, and were consistent across dimensions of subjective stress, hippocampal seeds, and participant subgroups,” researchers wrote. “This work uncovers a role for hippocampal networks in the subjective experience of stress.”

Researchers conducted functional magnetic resonance imaging (fMRI) brain scans of healthy participants who were shown stressful and troubling images, such as mutilated faces, snarling dogs, and dirty toilets. Participants also quantified the stress they felt when they viewed each image. 

Neural connections emanating from the hippocampus to the hypothalamus, an area of the brain known to regulate physiological stress, predicted higher levels of subjective stress, researchers found. On the other hand, neural connections from the hippocampus to the dorsal lateral frontal cortex, an area associated with emotional regulation, predicted lower stress levels. 

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When experiencing stress, people with anxiety disorders may have difficulty accessing calming feedback from the frontal cortex, researchers explained.

“These findings may help us tailor therapeutic intervention to multiple targets, such as increasing the strength of the connections from the hippocampus to the frontal cortex or decreasing the signaling to the physiological stress centers,” said senior author Rajita Sinha, PhD, professor at Yale University, New Haven, Connecticut. 

In some cases, participant responses when viewing the disturbing images seemed to be adaptive, the study found, with network connections with the frontal cortex increasing throughout the experiment. Researchers theorized participants may have been accessing memories to help moderate their stress response.

“Similar to recent findings that remembering positive experiences can lower the body’s stress response, our work suggests that memory-related brain networks can be harnessed to create a more resilient emotional response to stress,” said lead author Elizabeth Goldfarb, PhD, associate research scientist at the Yale Stress Center.

—Jolynn Tumolo


Goldfarb EV, Rosenberg MD, Seo D, Constable RT, Sinha R. Hippocampal seed connectome-based modeling predicts the feeling of stress. Nature Communications. 2020;11(1):2650.

Hathaway B. Yale researchers find where stress lives [press release]. New Haven, Connecticut: Yale University; May 27, 2020.

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