Non-differential return of fear in humans after a reinstatement procedure

The present experiment investigated reinstatement of fear in humans using a differential fear conditioning preparation. In this experiment, one neutral stimulus (conditioned stimulus; CS+) was paired with an aversive stimulus (unconditioned stimulus; US) during the acquisition phase, while another neutral stimulus was not (CS−). This procedure led to a difference in responding between the CS+ and the CS− (i.e., differential conditioning). After this acquisition phase, an extinction phase followed, during which both CSs were presented without the US, resulting in a decrease in differential conditioned responding. Reinstatement refers to the return of extinguished conditioned responses due to the experience of US-only trials after the extinction phase. This phenomenon was investigated by presenting half of the participants (reinstatement group) with unpredictable USs after the extinction phase. The control group did not receive these USs after the extinction procedure. The results show that return of fear was clearly apparent after the reinstating USs. This return of fear was, however, not limited to the CS+. An increase in ‘conditioned’ responding was also observed for the control stimulus. This interesting observation will be discussed against the background of a number of recent theoretical conceptualizations of reinstatement.     

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.     

Reinstatement of extinguished conditioned responses and negative stimulus valence as a pathway to return of fear in humans

The present study investigated reinstatement of conditioned responses in humans by using a differential Pavlovian conditioning procedure. Evidence for reinstatement was established in a direct (fear rating) and in an indirect measure (secondary reaction time task) of conditioning. Moreover, the amount of reinstatement in the secondary reaction time task was significantly correlated with the difference in valence between the conditioned stimulus (CS)+ and the CS-after extinction. These data provide clear evidence for reinstatement and for the role of negative stimulus valence in the return of conditioned responding after extinction.     

The effects of context changes on the reinstatement of extinguished conditioned behavior in a conditioned suppression task with humans

Reinstatement refers to the return of previously extinguished conditioned responses to test trials of a conditional stimulus (CS) when presentations of the unconditional stimulus (US) alone are given following extinction. Four experiments were conducted to determine whether reinstatement could be found in a conditioned suppression task with humans and whether contextual changes can abolish it. Experiment 1 demonstrated the reinstatement of conditioned suppression when acquisition, extinction, US alone, and test trials were all given in the same context. Experiments 2 and 3 suggested that the reinstatement effect was still present when the US alone presentations were given in a different context to the subsequent test trials. Experiment 4 replicated this effect using additional controls over the amount of exposure to the various contexts. The results suggest that reinstatement can be robust across changing contexts. Aspects of the conditioned suppression task that promote the transfer of learning across contexts or the establishment of configural context-CS stimuli may underlie the apparent lack of contextual control over reinstatement.     

Differential acquisition,extinction, and reinstatement of conditioned suppression in mice

In animals, the reappearance of conditioned fear responses after extinction has been primarily investigated using single-cue conditioning paradigms. However, a differential paradigm can overcome several of the disadvantages associated with a single-cue procedure. In the present study, the reinstatement phenomenon was assessed in mice using a differential conditioned suppression paradigm. In a first phase, one conditioned stimulus (CS + ) was consistently paired with an unconditioned stimulus (US; footshock) while another CS (CS–) was not, resulting in selective suppression of previously trained instrumental behaviour during the CS + . After the extinction phase, half of the animals (reinstatement group) were presented with unsignalled USs, while the other half were not (control group). A differential return of conditioned responding was observed in the reinstatement group, but not in the control group. The implications of these findings for future conditioning research are discussed.     

Differential acquisition, extinction, and reinstatement of conditioned suppression in mice

In animals, the reappearance of conditioned fear responses after extinction has been primarily investigated using single-cue conditioning paradigms. However, a differential paradigm can overcome several of the disadvantages associated with a single-cue procedure. In the present study, the reinstatement phenomenon was assessed in mice using a differential conditioned suppression paradigm. In a first phase, one conditioned stimulus (CS + ) was consistently paired with an unconditioned stimulus (US; footshock) while another CS (CS-) was not, resulting in selective suppression of previously trained instrumental behaviour during the CS + . After the extinction phase, half of the animals (reinstatement group) were presented with unsignalled USs, while the other half were not (control group). A differential return of conditioned responding was observed in the reinstatement group, but not in the control group. The implications of these findings for future conditioning research are discussed.     

Fear expression and return of fear following threat instruction with or without direct contingency experience

Prior research showed that mere instructions about the contingency between a conditioned stimulus (CS) and an unconditioned stimulus (US) can generate fear reactions to the CS. Little is known, however, about the extent to which actual CS–US contingency experience adds anything beyond the effect of contingency instructions. Our results extend previous studies on this topic in that it included fear potentiated startle as an additional dependent variable and examined return of fear (ROF) following reinstatement. We observed that CS–US pairings can enhance fear reactions beyond the effect of contingency instructions. Moreover, for all measures of fear, instructions elicited immediate fear reactions that could not be completely overridden by subsequent situational safety information. Finally, ROF following reinstatement for instructed CS+s was unaffected by actual experience. In summary, our results demonstrate the power of contingency instructions and reveal the additional impact of actual experience of CS–US pairings.     

Different mechanisms of fear extinction dependent on length of time since fear acquisition

Fear extinction is defined as a decline in conditioned fear responses (CRs) following nonreinforced exposure to a feared conditioned stimulus (CS). Behavioral evidence indicates that extinction is a form of inhibitory learning: Extinguished fear responses reappear with the passage of time (spontaneous recovery), a shift of context (renewal), and unsignaled presentations of the unconditioned stimulus (reinstatement). However, there also is evidence to suggest that extinction is an "unlearning" process corresponding to depotentiation of potentiated synapses within the amygdala. Because depotentiation is induced more readily at short intervals following LTP induction and is not inducible at all at a sufficient delay, it may be that extinction initiated shortly following fear acquisition preferentially engages depotentiation/"unlearning," whereas extinction initiated at longer delays recruits a different mechanism. We investigated this possibility through a series of behavioral experiments examining the recoverability of conditioned fear following extinction. Consistent with an inhibitory learning mechanism of extinction, rats extinguished 24-72 h following acquisition exhibited moderate to strong reinstatement, renewal, and spontaneous recovery. In contrast, and consistent with an erasure mechanism, rats extinguished 10 min to 1 h after acquisition exhibited little or no reinstatement, renewal, or spontaneous recovery. These data support a model in which different neural mechanisms are recruited depending on the temporal delay of fear extinction.     

Conditioned fear extinction and reinstatement in a human fear-potentiated startle paradigm

The purpose of this study was to analyze fear extinction and reinstatement in humans using fear-potentiated startle. Participants were fear conditioned using a simple discrimination procedure with colored lights as the conditioned stimuli (CSs) and an airblast to the throat as the unconditioned stimulus (US). Participants were extinguished 24 h after fear conditioning. Upon presentation of unsignaled USs after extinction, participants displayed significant fear reinstatement. In summary, these procedures produced robust fear-potentiated startle, significant CS+/CS- discrimination, within-session extinction, and significant reinstatement. This is the first demonstration of fear extinction and reinstatement in humans using startle measures.     

Concurrent excitors limit the extinction of conditioned fear in humans

In a human fear conditioning experiment, with on-line expectancy ratings and electrodermal responding as indices of fear, two neutral stimuli (pictures of geometric shapes) were first established as reliable predictors of an electric shock. In the subsequent extinction phase, the two stimuli were repeatedly presented in compound, without the shock. The final test phase consisted of individual stimulus presentations again, which resulted in a strong return of the conditioned responses. This effect was not observed in non-conditioned control stimuli. Hence, behavioral effects of extinction seem highly specific to the stimulus constellation that has gone through the extinction procedure. We argue that pharmacological, behavioral and/or cognitive manipulations that could prevent configural processing of stimulus constellations have direct clinical potential.     

The effect of an aversive event on the return of fear

An experiment on the return-of-fear (ROF) was carried out on 40 snake- or spider-phobic subjects in order to determine whether an arousing event that occurs shortly before retest influences the magnitude of the ROF. Additionally, we attempted to produce a reinstatement of fear by introducing an unrelated aversive event (shock) after the fear had been reduced. The arousal manipulation successfully increased subjective arousal but not heartrate responsiveness. The increases in subjective arousal were not followed by increases in ROF, and the attempt to produce a reinstatement of fear did not succeed. A significant correlation between speed of fear-reduction and ROF was obtained.     

Post-extinction conditional stimulus valence predicts reinstatement fear: Relevance for long-term outcomes of exposure therapy

Exposure therapy for anxiety disorders is translated from fear conditioning and extinction. While exposure therapy is effective in treating anxiety, fear sometimes returns after exposure. One pathway for return of fear is reinstatement: unsignaled unconditional stimuli following completion of extinction. The present study investigated the extent to which valence of the conditional stimulus (CS+) after extinction predicts return of CS+ fear after reinstatement. Participants (N = 84) engaged in a differential fear conditioning paradigm and were randomised to reinstatement or non-reinstatement. We hypothesised that more negative post-extinction CS+ valence would predict higher CS+ fear after reinstatement relative to non-reinstatement and relative to extinction retest. Results supported the hypotheses and suggest that strategies designed to decrease negative valence of the CS+ may reduce the return of fear via reinstatement following exposure therapy.     

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.     

Extinction treatment in multiple contexts attenuates ABC renewal in humans

Renewal has been implicated as one of the underlying mechanisms in return of fear following exposure therapy. ABC renewal is clinically more relevant than ABA renewal and yet it is a weaker form of renewal, suggesting that conducting extinction treatment in multiple contexts may be sufficient to attenuate ABC renewal. Using self-reported expectancy of shock and startle blink responses the current study examined the effects of conducting extinction treatment in multiple contexts on ABC fear renewal. Participants (N = 68) received conditional stimulus (CS) and unconditional stimulus (US) pairings in one context (A) followed by extinction treatment (CS presentations alone) in either one other context (B) or three other contexts (BCD). Non-reinforced test trials in a novel context (E) resulted in renewal of extinguished conditioned behaviour for those who received extinction in only one context. However, renewal was attenuated for those who received extinction treatment in three contexts. No renewal was found for the control group that received the test trial in the same context as during extinction. Suggestions are provided for clinicians seeking to prevent or attenuate return of fear following exposure therapy.     

Re-emergence of extinguished auditory-cued conditioned fear following a sub-conditioning procedure: effects of hippocampal and prefrontal tetanic stimulations

Post-extinction exposure of rats to a sub-conditioning procedure can evoke conditioned fear, which may correspond to fear return and/or fear learning potentiation. The aim of the present study was to clarify this issue and examine the effects of tetanic stimulation of the hippocampus (HPC) and medial prefrontal cortex (mPFC), two brain regions implicated in post-extinction modulation of conditioned fear. Rats were initially submitted to five tone-shock pairings with either a 0.7-mA or 0.1-mA shock. Tone-evoked freezing was observed only with the higher shock intensity, indicating that the 0.1-mA shock corresponded to a sub-conditioning procedure. All conditioned rats underwent fear extinction with 20 tone-alone trials. When retrained with the sub-conditioning procedure, they displayed again tone-evoked freezing, except when the initial tone was unpaired or a new tone was paired with the 0.1-mA shock, demonstrating fear return rather than fear learning potentiation. We also found that HPC and mPFC tetanic stimulations, applied 24h after the sub-conditioning procedure, similarly reduced this fear return. However, mPFC inactivation abolished temporary HPC tetanus effect, whereas HPC inactivation did not interfere with mPFC tetanus effect. These data confirm our previous findings and reveal the nature of HPC-mPFC interactions in post-extinction modulation of conditioned fear.     

Predicting return of fear following exposure therapy with an implicit measure of attitudes

We sought to advance understanding of the processes underlying the efficacy of exposure therapy and particularly the phenomenon of return of fear (ROF) following treatment by drawing on a social psychological view of phobias as attitudes. Specifically, a dual process theory of attitude-related behavior predicts that a positive response to exposure therapy may reflect change in either the automatic (the attitude representation itself) or controlled (skills and confidence at coping with the fear) responses to the phobic stimulus, or both. However, if the attitude representation remains negative following treatment, ROF should be more likely. We tested this hypothesis in a clinical sample of individuals with public speaking phobia using a single-session exposure therapy protocol previously shown to be efficacious but also associated with some ROF. Consistent with predictions, a post-treatment implicit measure of attitudes toward public speaking (the Personalized Implicit Association Test [PIAT]) predicted ROF at 1-month follow-up. These results suggest that change in the automatically activated attitude toward the phobic stimulus is an important goal of exposure therapy and that an implicit measure like the PIAT can provide a useful measure of such change by which to gauge the adequacy of exposure treatment and predict its long-term efficacy.     

A randomized controlled trial of the effect of D-cycloserine on extinction and fear conditioning in humans

Previous research has shown that D-cycloserine (DCS) facilitates extinction of Pavlovian fear conditioning in rats and enhances exposure therapy in humans. The aim of this study was to test the effect of DCS on extinction of fear conditioning in humans. In three experiments, 238 participants were given either DCS (50 or 500 mg) or placebo 2-3 h before extinction training following a differential shock conditioning paradigm. Clear extinction and recovery (return of fear) effects were observed on both skin conductance and self-reported shock expectancy measures in three studies. DCS had no influence on these effects. The same pattern was observed when the analysis was restricted to aware participants or to good conditioners, when fear-relevant cues (pictures of snakes) were used as the conditioned stimuli, or when analysis was restricted to heightened snake-fearful participants. These results suggest that DCS may not enhance the extinction, or prevent the recovery, of learned fear in a differential Pavlovian conditioning paradigm in humans. Further experimental research is needed to better understand the mechanisms underlying the therapeutic effects of DCS.     

Safety behaviours preserve threat beliefs: Protection from extinction of human fear conditioning by an avoidance response

A laboratory autonomic conditioning procedure was used to establish fear conditioning in human participants by pairing neutral stimuli with electric shock. Participants were also trained to make a button-press response to avoid shock. A target fear stimulus was then extinguished by presenting it without shock. The experimental group was given the opportunity to make the avoidance response during extinction whereas the control group was not. When the fear stimulus was tested without the response available, the control group showed normal extinction of both shock expectancy ratings and skin conductance responses, but the experimental group showed “protection from extinction”: they continued to give high expectancy ratings and strong skin conductance responses. We interpret this effect as analogous to the role of within-situation safety behaviours in preserving threat beliefs during exposure therapy for anxiety disorders. The results support a cognitive account of learning and anxiety. The procedure provides a potential laboratory model for further examination of the cognitive and neural mechanisms underlying anxiety and its reduction.     

Extinction of an emotional response in the presence of facial expressions of emotion

Previous studies (Lanzetta & Orr, 1980, 1981; Orr & Lanzetta, 1980) have demonstrated that fear facial expressions have the functional properties of conditioned excitatory stimuli, while happy expressions behave as conditioned inhibitors of emotional responses. The present study uses a summation conditioning procedure to distinguish between associative and nonassociative (selective sensitizations, attentional) interpretations of these findings. A neutral tone was first established as a conditioned excitatory CS by reinforcing tone presentations with shock. In subsequent nonreinforced test trials the excitatory tone was paired with either fear, happy, or neutral facial expressions. A tone alone and a tone/nonface slide compound were used as controls. The results indicate that phasic and tonic skin conductance responses to the tone/fear expression compound were significantly larger during extinction than for all other experimental and control groups. No significant differences were found among these latter conditions. The findings support the assumption that the excitatory characteristics of fear expressions do not depend on associative mechanisms. In the presence of fear cues, fear facial expressions intensify the emotional reaction and disrupt extinction of a previously acquired fear response. Happy facial expressions however, do not function as conditioned inhibitors in the absence of reinforcement, suggesting that the previously found inhibition was associative in nature.This research was supported by NSF grant No. 77-08926 and by funds from the Lincoln Filene Endowment to Dartmouth College.     

Mental reinstatement of context and return of fear in spider-fearful participants

Extant findings in the animal and human conditioning literature demonstrate that renewal, termed return of fear in studies with humans, occurs when reexposure to a previously feared phobic stimulus occurs in a context different than the one present during extinction. The present study investigated whether mental reinstatement of the treatment context at follow-up could attenuate context-based return of fear. Forty-eight spider-fearful individuals received exposure therapy in one of two contexts, and were followed-up 1 week later in the treatment or a new context. Half of the participants received instructions to mentally reinstate the treatment context before the follow-up test. Self-report data replicated previous research on contextually driven return of fear. Furthermore, participants who mentally reinstated the treatment context, before encountering the phobic stimulus in a new context at follow-up, had less return of fear than those who did not. Limitations of the current study, as well as implications for phobia treatment, are discussed.