Maximizing exposure therapy: An inhibitory learning approach

Different mnemonic outcomes have been observed when associative memories are reactivated by CS exposure and followed by amnestics. These outcomes include mere retrieval, destabilization-reconsolidation, a transitional period (which is insensitive to amnestics), and extinction learning. However, little is known about the interaction between initial learning conditions and these outcomes during a reinforced or nonreinforced reactivation. Here we systematically combined temporally specific memories with different reactivation parameters to observe whether these four outcomes are determined by the conditions established during training. First, we validated two training regimens with different temporal expectations about US arrival. Then, using Midazolam (MDZ) as an amnestic agent, fear memories in both learning conditions were submitted to retraining either under identical or different parameters to the original training. Destabilization (i.e., susceptibly to MDZ) occurred when reactivation was reinforced, provided the occurrence of a temporal prediction error about US arrival. In subsequent experiments, both treatments were systematically reactivated by nonreinforced context exposure of different lengths, which allowed to explore the interaction between training and reactivation lengths. These results suggest that temporal prediction error and trace dominance determine the extent to which reactivation produces the different outcomes.

Background: Suboptimal response and high dropout rates leave room for improvement of trauma-focused treatment (TFT) effectiveness in ameliorating posttraumatic stress disorder (PTSD) symptoms. Objective: To explore the effectiveness and safety of intensive prolonged exposure (iPE) targeting chronic PTSD patients with a likely diagnosis of ICD-11 Complex PTSD following multiple interpersonal trauma and a history of multiple treatment attempts. Method: Participants (N = 73) received iPE in 12 × 90-minute sessions over four days (intensive phase) followed by four weekly 90-minute booster prolonged exposure (PE) sessions (booster phase). The primary outcomes, clinician-rated severity of PTSD symptoms, and diagnostic status (Clinician-Administered PTSD Scale; CAPS-IV) were assessed at baseline, post-treatment, and at three and six months. Treatment response trajectories were identified and predictors of these trajectories explored. Results: Mixed model repeated measures analysis of CAPS-IV scores showed a baseline-to-posttreatment decrease in PTSD symptom severity (p < .001) that persisted during the three- and six-month follow-ups with large effect sizes (Cohen’s d > 1.2); 71% of the participants responded. None of the participants dropped out during the intensive phase and only 5% during the booster phase. Adverse events were extremely low and only a minority showed symptom exacerbation. Cluster analysis demonstrated four treatment response trajectories: Fast responders (13%), Slow responders (26%), Partial responders (32%), and Non-responders (29%). Living condition and between-session fear habituation were found to predict outcome. Participants living alone were more likely to belong to the Partial responders than to the Non-responders cluster, and participants showing more between-session fear habituation were more likely to belong to the Fast responders than to the Non-responders cluster. Conclusions: The results of this open study suggest that iPE can be effective in PTSD patients with multiple interpersonal trauma and after multiple previous treatment attempts. In addition, in this chronic PTSD population iPE was safe.

Extinction is a very relevant learning phenomenon from a theoretical and applied point of view. One of its most relevant features is that relapse phenomena often take place once the extinction training has been completed. Accordingly, as extinction-based therapies constitute the most widespread empirically validated treatment of anxiety disorders, one of their most important limitation is this potential relapse. We provide the first demonstration of relapse reduction in human contingency learning using mild aversive stimuli. This effect was found after partial extinction (i.e., reinforced trials were occasionally experienced during extinction, Experiment 1) and progressive extinction treatments (Experiment 3), and it was not only due to differences in uncertainty levels between the partial and a standard extinction group (Experiment 2). The theoretical explanation of these results, the potential uses of this strategy in applied situations, and its current limitations are discussed.Keywords: Extinction, contingency learning, relapse, aversive learning Slower reacquisition after partial extinction 2 Learning relationships between different events relevant to organisms is ubiquitous, and takes place almost constantly (Clark, 2013;Friston, 2003). Most of the time, this acquired knowledge is helpful, as it is the basis of useful predictions about future events or inferences about their relationships. However, it can also be maladaptive. For example, in many anxiety disorders, seemingly harmless cues may become associated to strong and disruptive emotional responses, leading to distress and daily problems for those suffering them (Beckers, Krypotos, Boddez, Effting, & Kindt, 2013;Mineka & Zinbarg, 2006).Fortunately, this type of learning is flexible in the sense that, once it has been acquired, it may be modified or altered. One of the ways in which this modification can take place is through extinction, the repeated presentation of a given cue in the absence of the consequences with which it had been previously associated (Pavlov, 1927). A progressive reduction in the acquired response to this cue is observed after experiencing a series of presentations of the cue alone. This flexibility allows the organism not only to adapt to changes in the cue-outcome relationships as they occur in the environment but also to ease those maladaptive forms of learning that lead to disruptive emotional responses. For example, in cognitive and behavioral therapies of anxiety disorders, exposure therapy -a repeated, systematic, and controlled exposure to the feared cue, in the absence of any traumatic event-seems to be a key component to success (Bouton, 2002, Longmore & Worrell, 2007Norton & Price, 2007). Unfortunately, extinction is not such a robust effect as acquisition itself, and several factors can lead to a recovery of the original fear response, or relapse. Thus, the current challenge is not so much to achieve the fear reduction but to prevent its relapse (Vervliet, Craske, & Hermans, 2013). The return of fear was firs...