Enhancing extinction learning: Occasional presentations of the unconditioned stimulus during extinction eliminate spontaneous recovery, but not necessarily reacquisition of fear.

Fears underlying anxiety disorders are commonly treated with exposure-based therapies, which are based on the principles of extinction learning. While these treatments are efficacious, fears may return after successful treatment. Past research suggested that post-extinction recovery of fear could be reduced through extinction training that involves occasional presentations of the aversive unconditioned stimulus (US), paired with the conditioned stimulus (CS). Here, we examined whether extinction training with occasionally paired or unpaired US presentations is superior in the reduction of fear recovery to non-reinforced extinction. Following differential fear conditioning to neutral cues, participants (N = 72; M age = 21.61 years, SD = 3.95) underwent either non-reinforced, partially reinforced, or unpaired extinction training. Extinction involving paired or unpaired US presentations, but not non-reinforced extinction, eliminated spontaneous recovery of differential skin conductance responses (SCRs). Results further suggested that unpaired, but not paired, US presentations may guard against rapid reacquisition of differential SCRs. No benefits of US presentations during extinction were found on the reinstatement of SCRs or recovery of differential negative CS+ valence. Presenting USs during extinction training was more effective than non-reinforced extinction in the reduction of fear recovery, as indexed by SCRs, with unpaired extinction being more effective than partially reinforced extinction.

Thompson A ，McEvoy PM ，Lipp OV 《-》

Building physiological toughness: Some aversive events during extinction may attenuate return of fear.

Although exposure therapy is an effective treatment for anxiety disorders, fear sometimes returns following successful therapy. Recent literature in animal models indicates that incorporating some aversive events into extinction training may offset these return of fear effects. The effect of occasional reinforced extinction trials was investigated in a sample of thirty-nine participants using a fear conditioning and extinction paradigm. Participants either underwent traditional extinction procedures during which the conditional stimulus which had been paired with the unconditional stimulus (US) during acquisition training (CS+) was presented alone with no presentations of the US or partially reinforced extinction during which there were several unpredicted CS+/US pairings. As measured by skin conductance responses, physiological fear responding remained elevated during extinction for participants who experienced partially reinforced extinction; however, these participants demonstrated protection from rapid reacquisition effects. Results from the subjective US-expectancy ratings did not provide evidence of protection against rapid reacquisition in the partially reinforced extinction group; however, there was evidence of protection from spontaneous recovery effects. Lastly, as measured by valence ratings, it was unclear whether partially reinforced extinction provided protection from fear recovery effects. Although participants who experienced partially reinforced extinction demonstrated protection from rapid reacquisition as measured by skin conductance responses, they also demonstrated significantly higher levels of physiological fear responding during extinction which made the results of the spontaneous recovery test more difficult to interpret. Occasional CS-US pairings during extinction may protect against return of fear effects. Clinical implications are discussed.

Culver NC ，Stevens S ，Fanselow MS ，Craske MG ... -  《-》

Presentation of unpaired unconditional stimuli during extinction reduces renewal of conditional fear and slows re-acquisition.

Past research has shown that presenting unconditional stimuli (US) during extinction training, either paired with the conditional stimulus (CS) or explicitly unpaired, can reduce spontaneous recovery and slow the re-acquisition of conditional fear. Whether contextual renewal of conditioned fear as indexed by electrodermal responses and self-report measures of anxiety and CS evaluations is also reduced after presentation of paired or unpaired USs during extinction training is currently unclear. Three groups of participants (Paired, Unpaired, Standard Extinction) completed a sequence of habituation, acquisition, extinction, renewal, and re-acquisition phases. During extinction, five CS-US pairings were presented in group Paired, whereas five US were presented alone in group Unpaired. No US were presented during standard extinction. For all groups, extinction was conducted in a context that was different from that of the other phases. Extinction of differential electrodermal responding was evident in groups Unpaired and Standard, but not in group Paired. Contextual renewal and fast re-acquisition, as indexed by differential electrodermal responding, were evident in group Standard, but not in group Unpaired and differential electrodermal responding persisted in group Paired. After extinction, self-reported anxiety was higher in groups Paired and Unpaired, but differential CS evaluations were evident in group Paired only. The current results suggest that presenting additional unpaired USs during extinction training strengthens extinction and protects against the renewal of differential electrodermal responding.

Lipp OV ，Ryan KM ，Luck CC ，Craske MG ，Waters AM ... -  《-》

Learning pain-related fear: neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain.

There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes. In N=24 healthy men and women, "rapid" fear acquisition was accomplished by pairing visual conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US (differential delay conditioning with five CS(+) and five CS(-) presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS-US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS(+)>CS(-); CS(+)<CS(-)) was analyzed without and subsequently also with a linear parametric modulation including trial number as a regressor. A significant valence change (i.e. increased CS(+) unpleasantness) was observed following acquisition, indicating successful differential aversive learning. On the other hand, CS-US contingency awareness was not fully established. These behavioral results were paralleled by differential activation of the putamen (pFWE<.05), insula (pFWE<.05) and secondary somatosensory cortex (S2, p<.001 uncorrected) in response to the CS(+) during acquisition. The same analysis with a linear parametric modulation confirmed but also strengthened the resulting activations, which were all highly significant in ROI analyses at pFWE<.05. Extinction and reinstatement involved differential activation in response to the CS(-), involving the cingulate cortex and primary motor cortex (M1) during extinction and the posterior cingulate cortex (PCC) during reinstatement (all p<.001 uncorrected), without obvious effects upon linear parametric modulation analysis. Abdominal pain stimuli are effective US that elicit conditioned pain-related fear even after very few learning experiences without full contingency awareness. These findings extend similar evidence of "rapid learning" in response to interoceptive US (e.g., conditioned taste aversion, conditioned nausea), and have implications for the pathophysiology and treatment of chronic abdominal pain such as in IBS.

Gramsch C ，Kattoor J ，Icenhour A ，Forsting M ，Schedlowski M ，Gizewski ER ，Elsenbruch S ... -  《-》

Reinstatement of fear in humans: autonomic and experiential responses in a differential conditioning paradigm.

The present study investigated reinstatement of fear in humans using an aversive differential conditioning paradigm. Two neutral human face pictures were presented during habituation, acquisition, extinction, and postreinstatement phases. One picture served as a conditioned stimulus (CS) reinforced by an unconditioned stimulus (US) in the form of electrical stimulation (CS+) and the second picture as a control stimulus that was never reinforced (CS-). The prediction that in a reinstatement manipulation a previously extinguished fear response in humans can be reinstated in a reinstatement group by the mere presentation of three unpredicted electrical stimulations (USs) was tested. Participants in the control group were not exposed to unpredicted USs and no reinstatement effect was expected. Outcome measures included subjective US expectancy ratings and skin conductance responses. Results showed non-selective return of the fear response due to fear recovery associated with both CSs (CS+/CS-) in the reinstatement group. Unexpected fear recovery was observed for both CSs (CS+/CS-) in control participants. Results are discussed with respect to context conditioning, fear generalisation, and anxiety-related cognitive mechanisms underlying fear recovery after extinction.

Kull S ，Müller BH ，Blechert J ，Wilhelm FH ，Michael T ... -  《-》