In what is the first brain imaging study of dread, new research has shown that people who experience substantial dread about an adverse experience can be biologically distinguished from those who can better tolerate the experience.

"Most people don’t like waiting for an unpleasant outcome and want to get it over with as soon as possible," said Gregory Berns, MD, PhD, of Emory University School of Medicine, Atlanta. "The only explanation for this is that the dread of having something hanging over your head is worse than the thing that you are dreading. It is a commonplace experience, but standard economic models of decision making don’t deal with this issue. So we decided to take a biologic approach and see what happens in the brain that might cause people to make such rash decisions."

DREADFUL INQUISITION

The study, which was supported by the National Institute on Drug Abuse (NIDA), was published in the May 5 Science. Dr. Berns and colleagues examined brain activity in 32 non–drug abusing participants awaiting brief electrical shocks to their feet. The investigators determined each participant’s maximal pain threshold and then presented him or her with a series of choices from 36 possibilities. For example, each person could elect to receive a shock at 30% of their pain threshold after a delay of 27 seconds—or at 60% after a delay of nine seconds.

Of the 32 participants, 27 chose the shorter delay more than 50% of the time, "indicating that the majority of individuals dreaded waiting for a shock," said Dr. Berns, Associate Professor of Psychiatry and Behavioral Sciences. The participants were then assigned to one of two groups: "extreme dreaders, who could not tolerate a delay and preferred an immediate—and stronger—painful stimulus; and mild dreaders, who could tolerate a delay for a milder shock," he added.

There were nine extreme dreaders and 23 mild dreaders. "Comparing the brain responses between these two groups during the shock-waiting period allowed us to test the predictions made by a utility-based theory of waiting about the biological flow of dread," Dr. Berns noted.

IN THE PAIN MATRIX

Using fMRI, the investigators localized the brain’s response to dread to the pain matrix, which includes the primary and secondary somatosensory cortices, the posterior and anterior insula, the amygdala, the supplementary motor area, and various regions of the anterior cingulate cortex.

"We saw that the extreme dreaders could be distinguished from the mild dreaders by virtue of the information captured on the brain scans," Dr. Berns noted. "All of the contralateral regions of interest and the caudal anterior cingulate cortex displayed time courses with dread factors significantly different from zero, but this was an effect observed primarily in the extreme dreaders and not the mild dreaders." Additionally, both somatosensory cortices "showed marked elevations in activity after the presentation of the cue—an elevation which continued to rise in advance of the shock," though the initial elevation was significantly greater in extreme dreaders. The amygdala also had a significant dread factor, but there was no between-group distinction.

"We conclude that the component of anticipation that can be specifically attributed to dread is manifest in the posterior elements of the cortical pain matrix and not the anterior ones," the researchers reported.

"Taken together, the anatomic locations of dread responses suggest that the subjective experience of dread comes from the attention devoted to the expected physical response and not simply a fear or anxiety response," Dr. Berns elaborated. "The key factor seems to be that extreme dreaders devoted more attention toward the part of their body that was about to be shocked. This means that dread is not quite the same as fear or anxiety. These findings underscore the very real nature of dread."

ADDICTION APPLICATION

"The neurobiologic mechanisms governing dreading behavior may hold clues for both better pain management and improvements in public health," Dr. Berns remarked. A specific application may be in the area of addiction. Understanding how the brains of nonaddicted people guide them in selecting which actions to take when the outcome of a decision is unpleasant may be useful in illuminating how drug abusers’ brains make such choices.

"There is substantial evidence that drug abusers place more value on short-term rather than long-term outcomes," elaborated NIDA Director Nora D. Volkow, MD. "Past investigations that have looked at how drug abusers make choices have used positive rewards. But this study looked at how people made choices when faced with unpleasant stimuli, [and] continuing to use drugs despite the expectation of the practice’s negative effects is a hallmark of addiction. The results of this study form the foundation for future research to determine whether drug abusers exhibit disruption in the brain systems that process the anticipation of unpleasant consequences."

—C. Justin Romano

Suggested Reading
Berns GS, Chappelow J, Cekic M, et al. Neurobiological substrates of dread. Science. 2006;312:754-758.
Koyama T, McHaffie JG, Laurienti PI, Coghill RC. The subjective experience of pain: where expectations become reality. Proc Natl Acad Sci U S A. 2005;102:12950-12955.
Raij TT, Numminen I, Narvanen S, et al. Brain correlates of subjective reality of physically and psychologically induced pain. Proc Natl Acad Sci U S A. 2005;102:2147-2151.

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