A "totally unexplored" brain region explains the physical toll of stress

Sweaty palms, a pounding heart, a heightened sense of alertness — these are some of the physical sensations of stress that make it feel so uncomfortable.

But in the future, we may experience stress very differently. In a new study, researchers say they may have found the brain's master circuit behind stress' physical side effects, which could, one day, help diminish them.

In a "totally unknown" region deep in the mouse brain, scientists believe they have found a circuit that is responsible for the physical feelings that accompany emotional stress. The circuit begins in a cluster of cells that send signals to the hypothalamus, the area of the brain that maintains the body's basic functions, like body temperature, heartbeat, and our desire to eat or reproduce.

"As far as we know, this is the first discovery of the mind-body connection in the brain"

Kazuhiro Nakamura is the lead study author and professor of physiology at Nagoya University Graduate School of Medicine in Japan. The research identifies a "master circuit" for stress in the brain, one that could affect the way other emotions manifest as physical sensations, too, he says.

"As far as we know, this is the first discovery of the mind-body connection in the brain," Nakamura tells Inverse.

"We speculate that this mind-body circuit also mediates body’s responses to other emotions including fear, anxiety, anger, and maybe happiness as well."

Importantly, this study suggests we may one day be able to stop the cascade that turns negative emotions into physical experiences. For people with PTSD or panic disorder, conditions in which emotional experiences may become full-blown physical maladies, Nakamura says the work is "an important step for the development of treatments."

The paper was published Thursday in the journal Science.

A master circuit for stress

Stressful situations activate the sympathetic nervous system, which governs the body's fight-or-flight response. The spike in adrenaline, blood pressure, and elevated heart rate kept humans thousands of years ago, when the ability to quickly recognize and outrun a threat meant the difference between life and death.

Today, we face fewer imminent threats to life and limb, but our sympathetic nervous system still jumps into action when we perceive danger. It is triggered by things like scary movies, or for people with social anxiety, by awkward social situations. But if the sympathetic nervous system is activated frequently, as it may be in people with PTSD or chronic stress, then it can take a long-term toll on our health.

"Excessive stress often causes many problems and disorders, and also likely promotes aging of organs within our body," Nakamura says.

In this study, Nakamura and his team tried to answer a basic question about our fight-or-flight response. Where do these physical symptoms of stress come from in the brain? And can they be controlled?

To do this, the team injected rats with a tracer that would allow them to see which areas of their brains activated in response to social stress. For rats, that means that they were exposed to chronic social defeat (essentially rat-bullying, which stresses them out).

After sustained social rejection, neurons in two specific regions of the rats' brains caught the team's attention: the dorsal peduncular cortex and the dorsal tenia tecta. The latter is largely "unexplored," the researchers say.

When rats are continuously rejected by their peers, they also exhibit physical responses, including increases in blood pressure, or heart rate. But when the team injected the rats with a drug that stopped the neurons from firing, heart rate decreased by 53 percent and blood pressure plummeted by 77 percent.

The dorsal tenia tecta "has not been focused by research so far," so how these neurons function was "totally unknown," Nakamura says. Importantly, these changes don't appear to affect the body's heart beat or temperature overall, which suggests this circuit is solely responsible for the physical toll of stress.

"As a result, we found that the DP/DTT is the sole brain region that provides a master stress signal to the DMH to drive a variety of stress responses," he says.

Should we mess with stress?

The results suggest the cascade of stress symptoms from brain to body can be inhibited. Theoretically, it may be possible to turn down the volume on the physical tolls of stress by targeting this area in the brain, without messing with the body's base functions.

But just because we may be able to mess with the physical tolls of stress, should we?

Nakamura notes that there is a downside to abandoning the physical sides of stress completely. If stress is not persistent or chronic, then it research suggests it may be just a natural part of life that can actually lead to personal growth.

"Even in human societies, an appropriate amount of mental stress would be helpful for better performances in their social activities," Nakamura says.

But when an emotional experience leads to a condition that changes life for the worse, this circuit could offer a target for treatments. This study is in rats and preliminary, so a clinical application for the findings may be a long time coming. But right now, the study does suggest that these brain regions could hold clues to understanding stress in humans — and how to treat it.

"Controlling stress levels into an appropriate range would be very important for our health, and our present discovery is a significant step to understand 'what is stress,'" Nakamura says.

Abstract: The mechanism by which psychological stress elicits various physiological responses is unknown. We discovered a central master neural pathway in rats that drives autonomic and behavioral stress responses by connecting the corticolimbic stress circuits to the hypothalamus. Psychosocial stress signals from emotion-related forebrain regions activated a VGLUT1-positive glutamatergic pathway from the dorsal peduncular cortex and dorsal tenia tecta (DP/DTT), an unexplored prefrontal cortical area, to the dorsomedial hypothalamus (DMH), a hypothalamic autonomic center. Genetic ablation and optogenetics revealed that the DP/DTT→DMH pathway drives thermogenic, hyperthermic, and cardiovascular sympathetic responses to psychosocial stress without contributing to basal homeostasis. This pathway also mediates avoidance behavior from psychosocial stressors. Given the variety of stress responses driven by the DP/DTT→DMH pathway, the DP/DTT can be a potential target for treating psychosomatic disorders.