Neural correlates of aversive conditioning: development of a functional imaging paradigm for the investigation of anxiety disorders

The purpose of the present study was to establish a short paradigm for the examination of classical aversive conditioning processes for application in patients with anxiety disorders. We measured behavioral, autonomic and neural correlates of the paradigm in healthy subjects, applying functional magnetic resonance imaging (fMRI) and measurement of skin conductance. Therefore, neutral visual stimuli were paired with an unpleasant white noise as unconditioned stimulus. Twenty healthy subjects performed three experimental phases of learning: familiarization, acquisition and extinction. Subjective ratings of valence and arousal after each phase of conditioning as well as skin conductance measurement indicated successful conditioning. During acquisition, fMRI results showed increased activation for the conditioned stimulus (CS+(unpaired)) when compared with the non-conditioned stimulus (CS-) in the right amygdala, the insulae, the anterior cingulate cortex and the parahippocampal gyrus, all regions known to be involved in emotional processing. In addition, a linearly decreasing activation in the right amygdala/hippocampus for the CS- across the acquisition phase was found. There were no significant differences between CS+ and CS- during extinction. In conclusion, the applicability of this paradigm for the evaluation of neural correlates in conditioning and extinction processes has been proven. Thus, we present a promising paradigm for the examination of the fear-circuit in patients with anxiety disorders and additionally effects of cognitive-behavioral interventions.