Updating fearful memories with extinction training during reconsolidation: a human study using auditory aversive stimuli

Abstract

Learning to fear danger in the environment is essential to survival, but dysregulation of the fear system is at the core of many anxiety disorders. As a consequence, a great interest has emerged in developing strategies for suppressing fear memories in maladaptive cases. Recent research has focused in the process of reconsolidation where memories become labile after being retrieved. In a behavioral manipulation, Schiller et al., (2010) reported that extinction training, administrated during memory reconsolidation, could erase fear responses. The implications of this study are crucial for the possible treatment of anxiety disorders without the administration of drugs. However, attempts to replicate this effect by other groups have been so far unsuccessful. We sought out to reproduce Schiller et al., (2010) findings in a different fear conditioning paradigm based on auditory aversive stimuli instead of electric shock. Following a within-subject design, participants were conditioned to two different sounds and skin conductance response (SCR) was recorded as a measure of fear. Our results demonstrated that only the conditioned stimulus that was reminded 10 minutes before extinction training did not reinstate a fear response after a reminder trial consisting of the presentation of the unconditioned stimuli. For the first time, we replicated Schiller et al., (2010) behavioral manipulation and extended it to an auditory fear conditioning paradigm.

Figure 1. Comparative Experimental Designs of Schiller et al., (2010), current experiment and Kindt et al., (2011).

Note that our current design (B) uses a different aversive stimulus modality (sounds instead of electric shocks). It uses a within-subject design and includes a habituation phase for all stimuli. Note that design C (Kind et al., 2011) uses additional measures of fear such as: fear potentiated startle responses and online ratings of US expectancy (in every experimental phase). Design C also uses higher percentage of CS-US pairing, fear relevant pictures instead of colour squares and includes three tests of fear recovery on Day 3 (reinstatement, spontaneous recovery and re-acquisition, last one not shown in the figure). Note also that design C inserts startle probes during CS and NS presentations and during intertrial interval in every experimental phase.

Figure 2. Mean Skin Conductance Response for Acquisition Extinction and Re-Extinction phases.

Mean SCRs (reactivated CSa, not reactivated CSb and NS) during Acquisition (mean of the three final trials), Extinction (last trial) and Re-Extinction (first trial). CSs were equally fear conditioned and extinguished. After reinstatement, only CSb showed a significant increment of SCR in Re-Extinction. In contrast, CSa and NS maintained same levels of SCR between Extinction and Re-Extinction. CSa presented a significant reduction of SCR from Acquisition to Re-Extinction. *p<.05. Error bars represent standard errors.

Figure 3. Mean Skin Conductance Response per trials across days.

Mean SCRs (reactivated CSa, not reactivated CSb and NS) in non-reinforced trials. CSa and CSb acquired fear conditioning on Acquisition on Day 1. Ten minutes after memory reactivation (of CSa and NS), SCR decreased during Extinction training. On Day 3, ten minutes after reinstatement, CSb recovered fear response in the first trials, whereas CSa maintained equivalent levels of SCR from Extinction to Re-extinction. Error bars represent standard errors.