Open Access

Extinction learning is suggested to be a central mechanism during exposure-based cognitive behavioralpsychotherapy. A positive association between the patients’pretreatment extinction learning performance andtreatment outcome would corroborate the hypothesis. Indeed, there isfirst correlational evidence between reducedextinction learning and therapy efficacy. However, the results of these association studies may be hampered byextinction-training protocols that do not match treatment procedures. Therefore, we developed an extinction-trainingprotocol highly tailored to the procedure of exposure therapy and tested it in two samples of 46 subjects in total. Byusing instructed fear acquisition training, including a consolidation period overnight, we wanted to ensure that theconditioned fear response was well established prior to extinction training, which is the case in patients with anxietydisorders prior to treatment. Moreover, the extinction learning process was analyzed on multiple response levels,comprising unconditioned stimulus (US) expectancy ratings, autonomic responses, defensive brain stem reflexes, andneural activation using functional magnetic resonance imaging. Using this protocol, we found robust fearconditioning and slow-speed extinction learning. We also observed within-group heterogeneity in extinction learning,albeit a stable fear response at the beginning of the extinction training. Finally, we found discordance betweendifferent response systems, suggesting that multiple processes are involved in extinction learning. The paradigmpresented here might help to ameliorate the association between extinction learning performance assessed in thelaboratory and therapy outcomes and thus facilitate translational science in anxiety disorders