Threat visibility modulates the defensive brain circuit underlying fear and anxiety

Recent theories distinguish anxiety from fear in the brain. Anxiety is associated with activation in ventromedial prefrontal cortex and hippocampus, while fear is associated with activation in periaqueductal gray, with amygdala involved in processing aspects of both emotional responses. These theories propose that the amount of information available about threat determines which of the two defensive responses is elicited, with fear and anxiety associated with well-defined and uncertain threats respectively. However, a direct test of this hypothesis is lacking. Here we provide such a test using fMRI to record participants’ brain activity while they performed a computer-based task which required to press a button to move an artificial agent to a target position while an artificial predator chased the agent. In one condition (associated with fear) the predator was visible, while in another condition (associated with anxiety) the predator was invisible. Ventromedial prefrontal cortex, hippocampus, and amygdala showed increased activity when the predator was invisible compared to visible, while the opposite effect was observed in periaqueductal gray. We also observed that participants with high but not low trait-anxiety showed an hippocampal activation with invisible threat at an earlier time stage during the trial. These findings help clarify the neural mechanisms that underlie different defensive emotions and shed light on how these mechanisms may contribute to exaggerated anxiety.