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Pain is evolutionarily hardwired to signal potential danger and threat. It has been proposed that altered pain-related associative learning processes, i.e., emotional or fear conditioning, might contribute to the development and maintenance of chronic pain. Pain in or near the face plays a special role in pain perception and processing, especially with regard to increased pain-related fear and unpleasantness. However, differences in pain-related learning mechanisms between the face and other body parts have not yet been investigated. Here, we examined body-site specific differences in associative emotional conditioning using electrical stimuli applied to the face and the hand. Acquisition, extinction, and reinstatement of cue-pain associations were assessed in a 2-day emotional conditioning paradigm using a within-subject design. Data of 34 healthy subjects revealed higher fear of face pain as compared to hand pain. During acquisition, face pain (as compared to hand pain) led to a steeper increase in pain-related negative emotions in response to conditioned stimuli (CS) as assessed using valence ratings. While no significant differences between both conditions were observed during the extinction phase, a reinstatement effect for face but not for hand pain was revealed on the descriptive level and contingency awareness was higher for face pain compared to hand pain. Our results indicate a stronger propensity to acquire cue-pain-associations for face compared to hand pain, which might also be reinstated more easily. These differences in learning and resultant pain-related emotions might play an important role in the chronification and high prevalence of chronic facial pain and stress the evolutionary significance of pain in the head and face. CA - Schmidt

Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with non-clinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm.

BackgroundExtinction-based procedures are often used to inhibit maladaptive fear responses. However, because extinction procedures show efficacy limitations, transcranial direct current stimulation (tDCS) has been suggested as a promising add-on enhancer.ObjectiveIn this study, we tested how cathodal tDCS over the right dorsolateral prefrontal cortex affects extinction and tried to unveil the processes at play that boost the effectiveness of extinction procedures and its translational potential to the treatment of anxiety disorders.MethodsWe implemented a fear conditioning paradigm whereby 41 healthy women (mean age = 20.51 +/- 5.0) were assigned to either cathodal tDCS (n = 27) or sham tDCS (n = 16). Fear responses were measured with self-reports, autonomic responses, and implicit avoidance tendencies.ResultsCathodal tDCS shows no statistically significant effect in extinction, according to selfreports, and seems to even negatively affect fear conditioned skin conductance responses. However, one to three months after the tDCS session and extinction, we found a group difference in the action tendencies towards the neutral stimuli (F (1, 41) = 12.04, p =.001,.p2 =.227), with the cathodal tDCS group (as opposed to the sham group) showing a safety learning (a positive bias towards the CS-), with a moderate effect size. This suggests that cathodal tDCS may foster stimuli discrimination, leading to a decreased generalization effect.DiscussionCathodal tDCS may have enhanced long-term distinctiveness between threatening cues and perceptively similar neutral cues through a disambiguation process of the value of the neutral stimuli-a therapeutic target in anxiety disorders. Future studies should confirm these results and extend the study of cathodal tDCS effect on short term avoidance tendencies., AGA is supported by the Foundation for Science and Technology, Portugal and Programa COMPETE [grants numbers SFRH/BD/80945/2011, PTDC/MHC-PAP/5618/2014 (POCI-01-0145FEDER-016836); http://www.poci-compete2020.pt/].JA is supported by the Foundation for Science and Technology, Portugal and Programa COMPETE [grants numbers PTDC/MHC-PAP/5618/2014 (POCI-01-0145-FEDER-016836), PTDC/MHC-PCN/3575/2012, PTDC/MHC-PCN/0522/2014, PTDC/MHC-PCN/6805/2014; https://www.fct.pt/index.phtml.en].The Cognitive and Behavioral Center for Research and Intervention of the Faculty of Psychology and Educational Sciences of the University of Coimbra is supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement [UID/PSI/01662/2013; https://www.portugal2020.pt].The Psychology Research Centre of the University of Minho is supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Education and Science through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER007653). The Proaction Laboratory and the PTDC/MHC-PAP/5618/2014 (POCI-01-0145-FEDER016836) directly supported this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Introduction It has long been posited that threat learning operates and forms under an affective and a cognitive learning system that is supported by different brain circuits. A primary drawback in exposure‐based therapies is the high rate of relapse that occurs when higher order areas fail to inhibit responses driven by the defensive circuit. It has been shown that implicit exposure of fearful stimuli leads to a long‐lasting reduction in avoidance behavior in patients with phobia. Despite the potential benefits of this approach in the treatment of phobias and posttraumatic stress disorder, implicit extinction is still underinvestigated. Methods Two groups of healthy participants were threat conditioned. The following day, extinction training was conducted using a stereoscope. One group of participants was explicitly exposed with the threat‐conditioned image, while the other group was implicitly exposed using a continuous flash suppression (CFS) technique. On the third day, we tested the spontaneous recovery of defensive responses using explicit presentations of the images. Results On the third day, we found that only the implicit extinction group showed reduced spontaneous recovery of defensive responses to the threat‐conditioned stimulus, measured by threat‐potentiated startle responses but not by the electrodermal activity. Conclusion Our results suggest that implicit extinction using CFS might facilitate the modulation of the affective component of fearful memories, attenuating its expression after 24 hr. The limitations of the CFS technique using threatful stimuli urge the development of new strategies to improve implicit presentations and circumvent such limitations. Our study encourages further investigations of implicit extinction as a potential therapeutic target to further advance exposure‐based psychotherapies.