Fear extinction requires a functional ventral-medial prefrontal cortex, rostral anterior cingulate cortex, and hippocampus. Activation of these regions leads to decreased amygdala activity. Clinical studies have demonstrated that the addition of D-cycloserine, a partial N-methyl-D-aspartate (NMDA) glutamate agonist, may improve outcomes in exposure-based therapies for acrophobia and social phobias.

 Conversely, NMDA antagonists, by decreasing NMDA activity, can inhibit the formation of long-term fear extinction.

While decreasing the activity in the amygdala leads to an acute reduction in perceived fear, the long-term persistence of fear extinction requires the activity of the ventral-medial prefrontal cortex and rostral anterior cingulate cortex. These appear to be vital in connecting the cognitive and emotional experiences and solidifying the learning.

The hippocampus aids in fear extinction by placing events into a context. This context helps determine how generally the brain applies the new learning. Because the previous fear is not erased, when the individual encounters the once feared stimuli there is activation of both the fearful and fear extinguished pathways. The context, provided by interactions between the hippocampus and ventromedial prefrontal cortex, determines which set of behaviors is predominately activated. The work of the psychotherapist is to help solidify the most healthy and adaptive responses.

1. Britton JC, Gold AL, Feczko EJ, et al. D-cycloserine inhibits amygdala responses during repeated presentations of faces. 

Quizzes

Neuropsychiatry

When treating social phobias, the addition of D-cycloserine has been noted to enhance the response to behavior therapy. How does D-cycloserine promote fear extinction?

Mini Quiz: Social Phobias