Fear-Conditioning Mechanisms Associated with Trait Vulnerability to Anxiety in Humans

Summary

Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms underlying cued and contextual fear. A critical question is how personality dimensions such as trait anxiety act through these mechanisms to confer vulnerability to anxiety disorders, and whether humans' ability to overcome acquired fears depends on regulatory skills not characterized in animal models. In a neuroimaging study of fear conditioning in humans, we found evidence for two independent dimensions of neurocognitive function associated with trait vulnerability to anxiety. The first entailed increased amygdala responsivity to phasic fear cues. The second involved impoverished ventral prefrontal cortical (vPFC) recruitment to downregulate both cued and contextual fear prior to omission (extinction) of the aversive unconditioned stimulus. These two dimensions may contribute to symptomatology differences across anxiety disorders; the amygdala mechanism affecting the development of phobic fear and the frontal mechanism influencing the maintenance of both specific fears and generalized anxiety.

Highlights

► Amygdala and frontal dysfunction independently linked to vulnerability to anxiety ► Amygdala dysregulation contributes to elevated cued fear in trait anxious subjects ► Anxiety resilience linked to greater vPFC activity during cued and contextual fear ► vPFC role not limited to extinction, but also pre-extinction fear downregulation