Uncovering Shared Roots of Fear and Anxiety

The coronavirus pandemic has pushed the most common family of mental illnesses in the United States—anxiety—to epic new heights, with the Centers for Disease Control and Prevention estimating that nearly 1 in 3 U.S. adults and a staggering 41% of people ages 18-29 experienced clinically significant anxiety symptoms in late August.

Despite the scale of the problem, the basic neuroscience of anxiety is still misunderstood, according to a new UMD study published last week in the Journal of Neuroscience.

In the report, an international team of researchers led by psychology Associate Professor Alex Shackman and Juyoen Hur, an assistant professor of psychology at Yonsei University in Seoul, provide new evidence that fear and anxiety reflect overlapping brain circuits. The findings run counter to popular scientific accounts, highlighting the need for a major theoretical reckoning.

“The conceptual distinction between ‘fear’ and ‘anxiety’ dates back to the time of Freud, if not the Greek philosophers of antiquity,” said Shackman, a core faculty member of the Neuroscience and Cognitive Science Program and a 2018 recipient of a seed grant award from UMD’s Brain and Behavior Initiative. “In recent years, brain imagers and clinicians have extended this distinction, arguing that fear and anxiety are orchestrated by distinct neural networks. Our study adds to a rapidly growing body of new evidence suggesting that it just ain’t so. If anything, fear and anxiety seem to be constructed in the brain using a massively overlapping set of neural building blocks.”

In prevailing scientific theory, fear—a fleeting reaction to certain danger—is thought to be controlled by the amygdala, an almond-shaped region of the brain beneath the cerebral cortex. Anxiety—a persistent state of heightened apprehension and arousal elicited when threat is uncertain—is believed to be orchestrated by the neighboring bed nucleus of the stria terminalis (BNST).

But new evidence from Shackman and his colleagues suggests that these two brain regions are equally sensitive to the two kinds of threat. Leveraging cutting-edge neuroimaging techniques available at the Maryland Neuroimaging Center, the research team used fMRI to quantify neural activity while participants anticipated receiving a painful shock paired with an unpleasant image and sound—a new task that the researchers dubbed the “Maryland Threat Countdown.”

The timing of this “threat” was signaled either by a conventional countdown timer—i.e. “3, 2, 1…”—or by a random string of numbers—e.g. “16, 21, 8.” In both conditions, threat anticipation recruited a remarkably similar network of brain regions, including the amygdala and the BNST. Across a range of head-to-head comparisons, the two showed statistically indistinguishable responses.

These observations raise important questions for the Research Domain Criteria (RDoC) framework that currently guides the U.S. National Institute of Mental Health’s quest to discover the brain circuitry underlying anxiety disorders, depression and other common mental illnesses.

“As it is currently written, RDoC embodies the idea that certain and uncertain threats are processed by circuits centered on the amygdala and BNST, respectively. It’s very black-and-white thinking” based on data collected at the turn of the century, Shackman said: “It’s time to update the RDoC so that it reflects the actual state of the science. It’s not just our study; in fact, a whole slew of mechanistic studies in rodents and monkeys, and new meta-analyses of the published human imaging literature are all coalescing around the same fundamental scientific lesson: Certain and uncertain threats are processed by a shared network of brain regions, a common core.”

Other team members include Jason F. Smith and Rachael M. Tillman of the UMD Department of Psychology, Hyung Cho Kim of UMD’s Neuroscience and Cognitive Science Program, Kathryn DeYoung of the Department of Family Sciences, Allegra S. Anderson of Vanderbilt University, Jinyi Kuang of the University of Pennsylvania, Manuel Kuhn of Harvard Medical School and Andrew S. Fox of the University of California, Davis.