3 - (SYM 106) Rewarded Extinction as an Efficacious Alternative to Standard Extinction Techniques for PTSD: Neurobiological Framework and Initial Functional MRI Evidence

Background: Exposure therapy for PTSD is based on prolific threat extinction work. In extinction paradigms, a danger cue (CS+) is no longer paired with an aversive outcome (US), forming a new inhibitory safety memory that outcompetes the established fear memory. Similarly, exposure therapies for PTSD provide patients with trauma-relevant situations that cannot actually result in the expected negative outcome. Unfortunately, some patients fail to respond or experience symptom relapse. One issue is that although fear might habituate during exposure, a robust safety memory does not reliably emerge and fear returns. Thus, effective and noninvasive techniques to augment extinction and enhance safety learning are vital for PTSD treatment research. Human neuroimaging work indicates that rewarded extinction strengthens safety learning relative to standard extinction, but this has not yet been tested in PTSD. We address this gap by testing if rewarded extinction outperforms standard extinction in PTSD, and approximates successful extinction as seen in non-PTSD comparisons.

Method: Participants (24 comparison, 22 PTSD, 73% women, 27% Hispanic [representative of recruitment population]) completed a 2-day fMRI experiment. Two CS+’s were paired with an aversive US on Day 1, followed by one CS+ being paired with a pleasant US (CS+Rew) and the other undergoing standard extinction (CS+Ext). Neural responding to both CS+’s was measured 24-hours later.

Results: Univariate fMRI Day 2 analyses found relatively lower CS+Rew neural activity in threat regions (insula, dorsal anterior cingulate [dACC]) compared with CS+Ext for all participants, indicating rewarded extinction facilitated increased safety learning over standard extinction. Importantly, activity in dACC, a key threat salience region, was exaggerated only for PTSD participants on CS+Ext, but not CS+Rew trials, indicating that standard extinction was not effective in the PTSD group but that rewarded extinction resulted in neural activity similar to those without PTSD.

Discussion: Our results offer promising evidence for rewarded extinction’s efficacy in PTSD and accord with increasing focus on enhancing inhibitory learning during exposure therapy. Limitations include: sample size precluded analyses of individual PTSD symptom dimensions in relation to rewarded extinction, and durability of learning over longer time periods (e.g., months) was not tested. We discuss next steps and neuroscience-informed considerations in implementing rewarded extinction within exposure therapy.