Neural evidence for the effects of behavioral memory updating following fear conditioning.

Exposure therapy for the treatment of pain-related disability relies on extinction learning, forming new safety memories inhibiting fear expression. However, fear often returns. The behavioral memory updating hypothesis posits that a fear memory can be 'updated' to a safe memory while in a malleable state, preventing return-of-fear. To test this hypothesis, 78 adolescents with and without chronic pain (age: Mean=15 y, range=10-24 y) were recruited for a two-day neuroimaging study. Due to incomplete data/excess motion, 55 participants (pain=38; pain-free=17) were included in MRI data analysis. Participants underwent a fear conditioning protocol with a within-subjects 'updating' manipulation: one CS+ (CS+Reminded [CS+R]) was reactivated to achieve a malleable state before extinction, while a second (CS+Not Reminded [CS+NR]) was not. We observed significantly less functional connectivity between the ventromedial prefrontal cortex and the amygdala for the CS+R and CS- compared to the CS+NR, consistent with the purported change in neural circuitry underlying the 'updating' effect, however observed no credible difference in fear ratings between the CS+R and CS+NR. This discrepancy may be crucial to understanding the mixed findings in the field and indicates that while some form of 'updating' may occur, it may be insufficient to reduce reported fear.