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Brain Activity Patterns in Anxiety-Prone People Suggest Deficits in Handling Fear

Science Update

stressed man in crowd, lost

Anxiety as a personality trait appears to be linked to the functioning of two key brain regions involved in fear and its suppression, according to an NIMH-funded study. Differences in how these two regions function and interact may help explain the wide range of symptoms seen in people who have anxiety disorders. The study was published February 10, 2011 in the journal, Neuron.


Anxiety disorders are characterized by an excessive, irrational dread of everyday situations. Some people may experience general, chronic anxiety, while others become anxious in response to one or more specific triggers. Many studies have implicated two brain regions in anxiety—the amygdala in fear responses and the ventral prefrontal cortex (vPFC) in suppressing or regulating fear. Questions remain, however, about how trait anxiety—a person's typical anxiety level on any given day—affects amygdala and vPFC functioning.

To explore these questions, Sonia Bishop, Ph.D., of the University of California Berkeley (at the University of Cambridge (UK) at the time of data collection), and colleagues designed a series of experiments to determine how the amygdala and vPFC responded in three types of situations:

  • Cued fear—a neutral signal or cue is followed by an aversive event. In this study, the cue was an actor in a video placing his hands over his ears and the aversive event was a loud scream. The cue provided a reliable prediction of the aversive event. Cued fear can be compared to the situation-specific type of anxiety experienced by those with a specific phobia, such as a fear of heights.
  • Contextual fear—a neutral cue and an aversive event occur independently of each other. The cue did not provide a reliable prediction of the aversive event. Contextual fear may be similar to the non-specific anxiety that affects people with generalized anxiety disorder.
  • Safety—a neutral signal or cue occurs alone without an aversive event. The safety situation served as a comparison for the other two situations.

The researchers assessed the level of trait anxiety of 23 healthy study participants, ages 18 to 41. Each participant underwent a training session that exposed them to the above conditions. Two days after the training session, participants had their brain activity recorded through functional magenetic resonance imaging (fMRI), a noninvasive imaging method, while re-exposed to the cued fear, contextual fear, and safety conditions in the scanner.

Results from the Study

Participants with high trait anxiety showed greater amygdala response to cued fear situations compared to those with low trait anxiety. According to the researchers, this finding suggests that individual differences in amygdala response may contribute to differences in vulnerability to cue-specific anxiety disorders, such as specific phobia.

Participants with low trait anxiety showed increased vPFC activity in response to cued fear and more strongly sustained vPFC activity during contextual fear situations, compared to those with high trait anxiety. Notably, vPFC activity in participants with low trait anxiety occurred before the aversive event had ceased. The researchers suggest that this process—engaging brain areas that help to suppress fear even when the source of fear is still present—may help to protect against chronic anxiety disorders even when stressful life events are ongoing.


The study's findings support a potential role of the amygdala in vulnerability to anxiety disorders and a potential role of the vPFC in protection against them.

"Individual differences in the functioning of one or both of these brain regions may help account for the variability in symptoms across different anxiety disorders," said Bishop. "A better understanding of these processes may help inform treatment choice and predict treatment response."

This study was supported in part by a Biobehavioral Research Award for Innovative New Scientists (BRAINS) from NIMH. Dr. Bishop was one of 12 researchers to receive this award in 2010.


Indovina I, Robbins TW, Núñez-Elizalde AO, Dunn BD, Bishop SJ. Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans . Neuron. 2011 Feb 10;69(3):563-71.