Anxiety Linked to Specific Areas in the Brain

The researchers of this study were trying to determine the sections of the brain that responded to different types of fear. Sustained anxiety caused by fear can lead to phobias and other anxiety disorders in certain human beings. Using brain imaging and brain activity detection techniques in volunteers, they identified a brain region called the amygdala which was activated in response to fear cues. When using non-cue fear conditioning in their experiments, a different part of the brain called the ventromedial prefrontal cortex was found to prevent the development of general anxiety.

“Both fear and anxiety are biologically adaptive responses to environmental threat. However, when experienced over a long period of time, they can have a devastating effect, as sufferers of anxiety disorders know only too well.” Human and rodent studies have implicated brain regions such as the amygdala, ventromedial prefrontal cortex and the hippocampus in reacting to conditioned and unconditioned fear inputs. But the role played by them, sustaining anxiety in specific individuals, is not clear. It is not known why certain individuals are more prone to higher levels of anxiety than others. The purpose of this study was to, therefore, determine how the amygdala or ventromedial prefrontal cortex responded differently in individuals with increased vulnerability for anxiety disorders.


  • In this study, 23 male and female participants without a neurological or psychiatric history volunteered to undergo fear conditioning experiments.
  • Anxiety scores were measured using the Spielberger State-Trait Anxiety Inventory. Activated brain regions were detected as oxygenation-images using functional magnetic resonance imaging (fMRI) or by using galvanic skin conductance readings.
  • Fear conditioning involved volunteers viewing an image of an actor covering their ears (conditioned stimulus), and/or listening to a loud scream (unconditioned stimulus). The order of the presentation varied according to the experiment.


  • Volunteers with higher anxiety scores demonstrated a higher reaction in the amygdala in response to cued fear (or a conditioned stimulus followed by the unconditioned stimulus).
  • Those with high anxiety traits also showed decreased usage of the ventromedial prefrontal cortex for both cued and contextual fear inputs (conditioned and unconditioned stimuli in random order).
  • The hippocampus-ventromedial prefrontal cortex co-recruitment levels were found to be reduced in individuals with elevated anxiety scores.

Shortcomings/next steps
Only 23 individuals were recruited for this study. A larger group would have represented the general population better. As ventromedial prefrontal cortex recruitment was shown to reduce responses to cued and contextual fear, the authors suggest that individuals with trait-anxiety defects should be trained using emotion regulation techniques to reduce fear responses. These techniques are known to activate the ventromedial prefrontal cortex, thereby increasing its usage and hence enabling fear reduction in these individuals. Additionally, as different regions of the brain seem to be involved in response to cued and general fear inputs, the medicines used in this study needed to be suitably tailored for different anxiety disorders.

The study demonstrated that there are two dimensions to the dissimilar brain activities of those individuals with anxiety disorders, compared to people without anxiety disorders. While the amygdala was activated in response only to fear cues, the ventromedial prefrontal cortex was needed to curb responses to both cued and non-cued fear inputs. These results thus demonstrate that both brain regions were involved in modifying fear responses only for phobias or cued fears. The difference in recruitment of specific brain regions for cued and contextual fears, therefore, suggests the reason for the different symptoms for different anxiety disorders. Additionally, those individuals with higher levels of anxiety typically had reduced ventromedial prefrontal cortex recruitment and/or higher amygdala activity when exposed to frightening situations.

For More Information:
Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans
Neuron, February 2011
By Iole Indovina; Trevor W. Robbins
From the University of Cambridge, Cambridge, United Kingdom, and the Santa Lucia Foundation, Rome, Italy

*FYI Living Lab Reports Are Summaries of the Original Research.

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