Stronger renewal in human fear conditioning when tested with an acquisition retrieval cue than with an extinction retrieval cue

It was previously demonstrated in our laboratory that conditioned fear in humans can renew after extinction, when this procedure took place in a different context (ABA-renewal [Vansteenwegen et al. (2005). Return of fear in a human differential conditioning paradigm caused by a return to the original acquisition context. Behaviour Research and Therapy, 43(3), 323–336]). Using the same experimental design, we now tested the power of retrieval cues to interact with this contextual renewal phenomenon. Two groups went through acquisition and extinction (in a different context). They were then tested in the original acquisition context and in the presence of a retrieval cue. In the acquisition-cue group, this cue previously featured during the acquisition procedure; in the extinction-cue group, the cue previously featured during the extinction procedure. As expected, renewal of conditioned electro-dermal responding and retrospective expectancy ratings was strongest in the acquisition-cue group. Theoretical and clinical implications of this finding are discussed.     

Effects of multiple contexts and context similarity on the renewal of extinguished conditioned behaviour in an ABA design with humans

The ABA renewal procedure involves pairing a conditional stimulus (CS) and an unconditional stimulus (US) in one context (A), presenting extinction trials of the CS alone in a second context (B), and nonreinforced test trials of the CS in the acquisition context (A). The renewal of extinguished conditioned behaviour is observed during test. The current study tested the effects of multiple extinction contexts and context similarity in attenuating renewal. Participants (N = 99) took part in a fear conditioning ABA renewal procedure. Using a measure of self-reported expectancy of the US, ABA renewal was observed when a single extinction context that was dissimilar to the test context was used. Renewal was attenuated, though still present, when extinction occurred in multiple dissimilar extinction contexts or in a single extinction context that was similar to the test context. Renewal was completely abolished when multiple extinction contexts that were similar to the test context were combined. Multiple extinction contexts and context similarity act additively in their effect on attenuating renewal. The results are discussed in relation to the design of exposure therapy programs that seek to reduce relapse that can occur via renewal.     

Renewal of Extinguished Lever-Press Responses upon Return to the Training Context

Two experiments with rats explored renewal effects in operant conditioning preparations. When pressing a lever was trained in one context and then extinguished in a second context, the responding was renewed by returning to the original context (ABA renewal) in Experiment 1. This finding was replicated in Experiment 2 with discriminative operant performance signaled by a localized light cue. In spite of the successful demonstration of ABA renewal effect in these experiments, AAB renewal was detected in neither experiment: When the responses had been extinguished in the context of acquisition, testing the rats in a second context did not renew the responses. The demonstration of ABA renewal but no AAB renewal suggests that extinction in another context and/or a return to the original context are critical for renewal of extinguished operant performance.     

Contextual control of human fear associations in a renewal paradigm

The original model of behavior change suggests that extinction is context dependent whereas fear acquisition is context independent [Bouton, M. E. & Ricker, S. T. (1994). Renewal of extinguished responding in a second context. Animal Learning and Behavior, 22, 317-324]. Supportive evidence stems mainly from animal studies, showing that after acquisition (conditioned stimulus-unconditioned stimulus (CS-US)) in Context A and extinction in Context B, fear is renewed by presenting the CS in acquisition Context A (ABA renewal) or in a novel Context C (ABC renewal). By implication, the model predicts equal ABA and ABC renewal. However, there is also evidence to suggest that the context dependency of extinction and the context independency of acquisition may be less stringent than originally proposed. The present study investigated renewal in humans using a differential fear conditioning paradigm with a shock US and online shock expectancy ratings and electrodermal responses as dependent variables. Experiment 1 compared an ABA condition with an AAA condition. Experiment 2 compared three conditions: ABA, ABC, and AAA. Both experiments demonstrated ABA renewal. Most importantly, Experiment 2 showed larger ABA than ABC renewal. Overall, results for expectancy ratings were more convincing than for electrodermal responses. In line with the extinction model, the present findings support the context dependency of extinction in humans. In contrast to the model, the findings suggest that in humans not only extinction learning, but also fear acquisition is controlled by its current context.     

The effects of physical context changes and multiple extinction contexts on two forms of renewal in a conditioned suppression task with humans

Three experiments examined the effects of physical context changes and multiple extinction contexts on the renewal of conditioned suppression in humans. A conditioned suppression task used an undesirable event as the unconditional stimulus (US). One conditional stimulus (CS+) predicted the occurrence of the US and another (CS−) predicted US absence. In Experiment 1 (N = 32), conditioned suppression was acquired to the CS+ in one context and extinguished in a different context. An increase in suppression was found for the CS+ and not for the CS− when subsequent test trials were conducted in the acquisition context (ABA renewal). Experiment 2 (N = 32) tested for ABC Renewal and showed increased suppression to both the CS+ and CS− when test was conducted in a novel context. Experiment 3 (N = 80) showed that these two effects were abolished when extinction was conducted in multiple contexts. The experiments extend the ABA renewal of conditioned suppression found with non-human animal subjects and the reduction of renewal by extinction in multiple contexts. Context changes may also facilitate cue competition effects after training with elementary stimuli, as shown by the effects of US omission in the ABA and ABC renewal groups.     

Extinction in multiple contexts does not necessarily make extinction less vulnerable to relapse

Three fear-conditioning experiments with rat subjects examined the effects of extinction in multiple contexts on a final relapse (renewal) effect that occurred when the extinguished fear cue was tested in a new context (Experiments 1 and 3) or in the context in which fear conditioning had first occurred (Experiment 2). Rats that received extinction in three contexts demonstrated more fear during extinction than rats that received the same number and temporal distribution of extinction trials in one context; extinction was partially lost with each context switch. Although extinction in multiple contexts thus had an impact on extinction behavior, it did not reduce the size of the final renewal effect. Fear during extinction was occasionally positively correlated with fear during final testing, but the two were never negatively correlated. The results suggest that extinction in multiple contexts does not necessarily weaken fear renewal, and that extinction procedures that generate high levels of responding in extinction do not necessarily make extinction learning less context-specific.     

Dissociations between ABA-, ABC-, and AAB-renewal of Pavlovian modulation in human sequential feature positive discrimination learning

Using a conditioned suppression preparation, we investigated extinction and aba-, abc-, and aab-renewal of Pavlovian modulation in human sequential Feature Positive (FP) discrimination learning, X → A+/A-. Extinction treatment was administered in the acquisition context a (aaa- and aab-groups) or in a new context b (aba- and abc-groups) and comprised X → A- extinction trials. Discriminative X → A/A responding was lost in all groups when tested in the extinction context. In the aba-group, the discriminative X → A/A responding totally recovered when retested in the acquisition context a. For the aaa-, the aab-, and the abc-group, discriminative X → A/A responding did not reappear when tested for renewal in, respectively, contexts a, b, and c. The demonstration of aba-renewal of extinguished modulation, but not abc- and aab-renewal, suggests that extinction in a context different from the acquisition context and a return to the original acquisition context might both be critical for renewal of Pavlovian modulation in human FP-discrimination learning.     

Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala

Extinction is the reduction in drug seeking when the contingency between drug seeking behavior and the delivery of drug reward is broken. Here, we investigated a role for the nucleus accumbens shell (AcbSh). Rats were trained to respond for 4% (v/v) alcoholic beer in one context (Context A) followed by extinction in a second context (Context B). Rats were subsequently tested in the training context, A (ABA), or the extinction context, B (ABB). Pre-test injections of the glutamate AMPA receptor antagonist, NBQX (1 μg) into AcbSh had no effect on renewal of alcoholic beer seeking when rats were returned to the training context (ABA). However, NBQX increased responding when rats were tested in the extinction context (ABB). In a second experiment, rats received training, extinction, and test in the same context. Pre-test injections of NBQX (0, 0.3, and 1 μg) into the AcbSh dose-dependently attenuated expression of extinction. We also found that NBQX in the AcbSh had no effect on initial acquisition of extinction or the motivation to respond for reward as measured by break point on a progressive ratio schedule. Finally, we show that pharmacological disconnection of a basolateral amygdala (BLA) → AcbSh pathway via NBQX in AcbSh combined with reversible inactivation of the contralateral BLA attenuates expression of extinction. Together, these results suggest that AcbSh AMPA receptors mediate expression of extinguished reward seeking through glutamatergic inputs from the BLA.     

Extinction and renewal of Pavlovian modulation in human sequential Feature Positive discrimination learning

Using a conditioned suppression task, we investigated extinction and renewal of Pavlovian modulation in human sequential Feature Positive (FP) discrimination learning. In Experiment 1, in context a participants were first trained on two FP discriminations, X-->A+/A- and Y-->B+/B-. Extinction treatment was administered in the acquisition context a (aaa group) or in a new context b (aba group), and comprised X-->A- extinction and Y- control trials. Discriminative X-->A/A responding was lost in both groups when tested in the extinction context, but partially recovered in the aba and not in the aaa group when tested in the acquisition context, suggesting extinction and renewal of extinguished modulation. The same was observed for the Y-->B/B control pair, however, questioning whether the loss of discriminative X-->A/A responding represented genuine extinction of modulation. In Experiment 2, including only aba groups, participants were trained in context a on two FP discriminations, X-->A+/A- and Y-->B+/B-, after which the group "Extinction" was exposed to X-->A- extinction trials in context b, whereas the group "Control" was exposed to X- control trials; concurrently, both groups received further Y-->B+/B- training. In the group Control, differential Y-->B/B and X-->A/A responding were acquired and maintained throughout the experiment. In the group Extinction, while Y-->B/B responding was also maintained throughout, differential X-->A/A responding disappeared because of X-->A- extinction treatment when tested in the extinction context b, but partially reappeared when tested in the acquisition context a. This evidences aba-renewal of extinguished modulation.     

Use of the ABA fear renewal paradigm to assess the effects of extinction with co-present fear inhibitors or excitors: Implications for theories of extinction and for treating human fears and phobias

In four experiments using albino rats in an ABA fear renewal paradigm, we studied conditioned fear in the A test context following extinction in Context B. Conditioned suppression of operant responding was the index of fear. In Experiments 1-3, we found that extinguishing a feared cue in compound with a putative conditioned inhibitor of fear led to more fear in the test context than did a conventional extinction procedure. In Experiments 4a and 4b, we found that extinguishing three feared cues in compound required one third the time and generally led to less fear to the cues in the test context than did the extinction of each cue separately. Thus, fear in the test context seems to vary inversely with the values of co-present cues during extinction in Context B. Results imply that cue value is actually reduced by extinction procedures rather than merely being opposed by a growing inhibitory process. Implications for theories of renewal and for clinical practice are discussed.     

Context switch effects on acquisition and extinction in human predictive learning

Four experiments tested context switch effects on acquisition and extinction in human predictive learning. A context switch impaired probability judgments about a cue-outcome relationship when the cue was trained in a context in which a different cue underwent extinction. The context switch also impaired judgments about a cue trained in a context different from the extinction context, whenever this training was concurrent with extinction of another cue. After extinction, new cue-outcome relationships learned, even in a different task, became context specific. Moreover, renewal was consistently observed. It is suggested that context switch effects result from a process by which ambiguity leads participants to attend to the contexts.     

Conducting extinction in multiple contexts does not necessarily attenuate the renewal of shock expectancy in a fear-conditioning procedure with humans

The renewal of Pavlovian-conditioned responses may provide a model for the relapse of fear following extinction-based treatments for anxiety disorders. Renewal can be observed if conditional stimulus (CS) and unconditional stimulus (US) pairings are given in one context, extinction trials of CS presentations in a second context, prior to test trials of CS presentations in the original acquisition context (ABA renewal). We examined ABA renewal in humans by using a fear-conditioning procedure with an unpleasant shock US. A renewal of rated shock expectancy was demonstrated with this procedure. Conducting extinction treatment in multiple contexts was expected to attenuate the renewal effect. However, the renewal of shock expectancy persisted when extinction treatment was given across three or five different contexts. With the current renewal design, learning task, and measure of conditioned behaviour, extinction treatment does not appear to readily generalise to the test context. The use of multiple extinction treatments in a clinical setting may not necessarily reduce the likelihood of relapse via a renewal effect.     

Contextual specificity of extinction of delay but not trace eyeblink conditioning in humans

Renewal of an extinguished conditioned response has been demonstrated in humans and in animals using various types of procedures, except renewal of motor learning such as eyeblink conditioning. We tested renewal of delay and trace eyeblink conditioning in a virtual environment in an ABA design. Following acquisition in one context (A, e.g., an airport) and extinction in a different context (B, e.g., a city), tests for renewal took place in the acquisition (A) and extinction context (B), in a counterbalanced order. Results showed renewal of the extinguished conditioned response in the delay but not trace condition.     

All we need is a cue to remember: the effect of an extinction cue on renewal

In the present study, it was investigated by employing a human fear conditioning paradigm whether an extinction retrieval cue can attenuate renewal of conditioned responding after an extinction treatment procedure, and if so, what the precise role of such an extinction cue comprises. It was hypothesized that such a cue can attenuate renewal and would function as a safety signal capable of directly inhibiting the expectancy of an aversive outcome and conditioned skin conductance responding to a conditioned stimulus. The results demonstrated that the extinguished expectancy of an aversive outcome was renewed when the CS was presented outside the extinction context and that an extinction cue attenuated this effect. This extinction cue, however, only transferred its inhibitory properties to other, non-extinguished stimuli when there was no contextual switch. This safety signal function was not observed after a switch in context. Possible functions of the extinction cue and its application in extinction-based exposure treatments are discussed.     

Contextual-specificity of short-delay extinction in humans: renewal of fear-potentiated startle in a virtual environment

A recent fear-potentiated startle study in rodents suggested that extinction was not context dependent when extinction was conducted after a short delay following acquisition, suggesting that extinction can lead to erasure of fear learning in some circumstances. The main objective of this study was to attempt to replicate these findings in humans by examining the context specificity of short-delay extinction in an ABA renewal procedure using virtual reality environments. A second objective was to examine whether renewal, if any, would be influenced by context conditioning. Subjects underwent differential aversive conditioning in virtual context A, which was immediately followed by extinction in virtual context B. Extinction was followed by tests of renewal in context A and B, with the order counterbalanced across subjects. Results showed that extinction was context dependent. Evidence for renewal was established using fear-potentiated startle as well as skin conductance and fear ratings. In addition, although contextual anxiety was greater in the acquisition context than in the extinction context during renewal, as assessed with startle, context conditioning did not influence the renewal effect. These data do not support the view that extinction conducted shortly after acquisition is context independent. Hence, they do not provide evidence that extinction can lead to erasure of a fear memory established via Pavlovian conditioning.     

Kappa opioid receptors mediate where fear is expressed following extinction training

Six experiments used a within-subjects renewal design to examine the involvement of kappa opioid receptors (KORs) in regulating the expression and recovery of extinguished fear. Rats were trained to fear a tone conditioned stimulus (CS) via pairings with foot shock in a distinctive context (A). This was followed by extinction training of the CS in a second context (B). Finally, all rats were tested for fear to the tone in the extinction context (ABB) and the training (ABA) or a novel (ABC) context. Intracerebroventricular (ICV) infusion of the KOR antagonist nor-binaltorphimine dihydrochloride (nor-BNI) dose-dependently prevented ABA renewal of fear, but had no effect on the expression of ABC renewal, the expression of extinction, or the expression of nonextinguished fear. Conversely, pretest infusion of the KOR agonist U50,488 hydrochloride (U50,488) selectively facilitated the expression of ABA renewal and had no effect on the expression of extinction. Pretest infusion of nor-BNI had no effect on the expression of context-specific latent inhibition. Collectively, these results suggest that KORs gate the expression of fear following extinction training and may comprise a critical neuropeptide component of the circuitry underlying context-dependent expression of fear.     

Relapse of operant behavior after response elimination with an extinction or an omission contingency

The present study compared relapse after responding was eliminated by extinction or omission training in rats. In Experiment 1, lever pressing was reinforced with food pellets in Context A and then eliminated with either extinction or omission training in Context B. The response was then tested in Contexts A and B in either the presence or absence of free food pellets delivered on a random time schedule. All rats showed higher responding when tested in Context A than Context B, and there was little evidence that omission training attenuated this ABA renewal effect. Noncontingent pellets increased responding after extinction but not after omission. However, when responding on the last day of response elimination was compared to responding during the test in the response-elimination context, there was some evidence that omission-trained rats showed a small increase in responding even when tested with free pellets. Results of Experiment 2 suggest this increase was not due to differences in the temporal distribution of pellets during elimination and the test, and that the result might be due to mere removal of the omission contingency, but any such effect is small and difficult to detect statistically. The results provide new information about factors generating relapse after omission training.     

Transdermal nicotine during cue reactivity in adult smokers with and without anxiety disorders

Transdermal nicotine almost doubles tobacco cessation rates; however, little is known about what happens to smokers during the quit process when they are wearing the nicotine patch and are confronted with high-risk smoking triggers. This is particularly important for smokers with psychological disorders who disproportionately represent today's smokers and have more trouble quitting. Using a mixed between- and within-subjects design, smokers with anxiety disorders (n = 61) and smokers without any current Axis I disorders (n = 38) received transdermal nicotine (21 mg) or a placebo patch over two assessment days separated by 48 hr. Urge to smoke was evaluated during a 5-hr patch absorption period (reflecting general smoking deprivation) and during imaginal exposure to theoretically high-risk triggers containing smoking cues, anxiety cues, both, or neutral cues. No differences were observed between smokers with and without anxiety disorders. Significant Patch × Time and Patch × Cue Content interactions were found. Both patch conditions experienced an increase in urge during the deprivation period, but postabsorption urge was significantly higher in the placebo condition, suggesting that transdermal nicotine attenuated the degree to which urge to smoke increased over time. During the cue reactivity trials, when participants received the nicotine patch, they experienced significantly lower urge in response to both smoking-only and neutral cues, but not when anxiety cues were present (alone or in combination with smoking cues). These data suggest that transdermal nicotine alleviates urge only under certain circumstances and that adjunctive interventions are likely necessary to address smoking urges in response to spikes in distress among smokers trying to quit. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Return of experimentally induced chocolate craving after extinction in a different context: divergence between craving for and expecting to eat chocolate

Unlike in fear conditioning, little attention has been devoted to extinction and renewal in appetitive conditioning, despite its relevance for extinction-based addiction treatments. We developed a paradigm, using a specific tray as a conditioned stimulus (CS) for eating chocolate (unconditioned stimulus, US), to investigate the effects of context change on acquisition and extinction of conditioned chocolate craving using an ABA renewal design. In Study 1 (n=32), participants successfully acquired chocolate craving, but unlike what is commonly observed in fear conditioning, craving did not extinguish. In Study 2, we separately assessed craving and US expectancy in a between-subjects design (n=64). US-expectancy data showed acquisition, extinction and renewal in the ABA group. The craving data did not follow this pattern, suggesting different mechanisms for craving and US expectancy. Similarities and differences between craving and US expectancy, as well as practical implications, are discussed.     

Investigations of operant ABA renewal during differential reinforcement

Operant renewal is a form of relapse in which a previously extinguished response recurs due to a change in context. We designed two experiments to examine the impact of differential reinforcement of alternative behavior on ABA renewal in a translational model of relapse with 12 children. We compared levels of renewal in two 3-phase arrangements. In one arrangement, we reinforced target responding in Context A, extinguished responding in Context B, and returned to Context A while continuing to implement extinction. In a second arrangement, an alternative response produced reinforcement in Context B and during the return to Context A. Results across the 2 experiments indicated 3 general findings. First, extinction plus differential reinforcement disrupted target behavior more consistently in Context B relative to extinction alone. Second, renewal tended to be greater and more persistent during extinction alone relative to extinction plus differential reinforcement. Third, the renewal effect appeared to depend on whether the alternative response had a history of extinction in Context A. We discuss methodological implications for the treatment of severe destructive behavior.