Characterizing the nature of emotional-associative learning deficits in panic disorder: An fMRI study on fear conditioning, extinction training and recall

Emotional-associative learning represents a translational model for the development, maintenance and treatment of anxiety disorders such as panic disorder (PD). The exact nature of the underlying fear learning and extinction deficits however, remains under debate. Using a three-day paradigm to separate the distinct learning and consolidation processes, we aimed to gain insights into the neurofunctional substrates of altered fear conditioning, extinction training and recall in PD. In contrast to studies employing one-session fear conditioning paradigms, a differential fear conditioning and delayed extinction task was conducted for the purpose of disentangling neural networks involved in fear acquisition, extinction training and recall of extinction memories. Using functional magnetic resonance imaging (fMRI), quality-controlled datasets from 10 patients with PD and 10 healthy controls were available from three consecutive days (day 1: acquisition; day 2: extinction training; day 3: extinction recall) with neutral faces serving as CSs and an aversive auditory stimulus (panic scream) as US. PD patients showed heightened fear circuitry (e.g. right amygdala and left insula) activation during early acquisition and prolonged activation in the right insula, left inferior frontal operculum and left inferior frontal gyrus during extinction recall compared to healthy controls. Stronger neural activation in structures conferring defensive reactivity during early acquisition and extinction recall may indicate the accelerated acquisition of conditioned responses, while extinction recall may be attenuated as a function of PD pathophysiology. Future studies should investigate the predictive value of experimental measures of extinction recall for clinical relapse.