Reinstatement of fear to an extinguished conditioned stimulus: Two roles for context.

The authors studied the role of context in reinstatement. Freezing was reinstated when the conditioned stimulus (CS) was extinguished in 1 context and rats moved to another context for reexposure to the shock unconditioned stimulus (US) and test. It was also reinstated (rather than renewed) when rats were shocked in the extinction context and moved to another context for test. This reinstatement was CS specific and reduced by nonreinforced exposures to the extinction context. Rats shocked in the context in which a stimulus had been preexposed froze when tested in another context. These findings suggest 2 roles for context in reinstatement: conditioning of the test context (M. E. Bouton, 1993) and mediated conditioning by the extinction context (P. C. Holland, 1990). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response.

The effect of D-cycloserine (DCS), an NMDA partial agonist, on extinction of fear was investigated in rats using the conditioned emotional response preparation. Fear extinction was facilitated when the first 4 trials occurred with a 30-mg/kg dose of DCS. However, extinguished fear was "renewed" regardless of the drug treatment when the rats were returned to the context in which fear had been conditioned. Additional results suggest that DCS's facilitation of extinction is a small but meaningful effect in the current method. The results suggest caution regarding the use of DCS as an adjunct to extinction: Although the drug may modestly facilitate extinction learning, it does not necessarily destroy the potential for relapse. Behavioral mechanisms are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of yohimbine on the extinction of conditioned fear: A role for context.

Six experiments with rat subjects examined the effect of yohimbine, an alpha-2 adrenergic autoreceptor antagonist, on the extinction of conditioned fear to a tone. Experiments 1 and 2 demonstrated that systemic administration of yohimbine (1.0 mg/kg) facilitated a long-term decrease in freezing after extinction, and this depended on pairing drug administration with extinction training. However, Experiments 3 and 4 demonstrated that yohimbine did not eradicate the original fear learning: Freezing was renewed when the tone was tested outside of the extinction context. Experiments 5 and 6 found that the contextually specific attenuation of fear produced by yohimbine transferred to another extinguished conditional stimulus (CS) and not to a nonextinguished CS. The results suggest that yohimbine, when administered in the presence of a neutral context, creates a form of inhibition in that context that allows that specific context to reduce fear of an extinguished CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporally massed CS presentations generate more fear extinction than spaced presentations.

Rodent fear conditioning models both excitatory learning and the pathogenesis of human anxiety, whereas extinction of conditional fear is a paradigm of inhibitory learning and the explicit model for behavior therapy. Many studies support a general learning rule for acquisition: Temporally spaced training is more effective than massed training. The authors asked whether this rule applies to extinction of conditional fear in mice. The authors find that both short- and long-term fear extinction are greater with temporally massed presentations of the conditional stimulus (CS). The data also indicate that once CS presentations are sufficiently massed to initiate, or "induce," extinction learning, further CS presentations are more effective when spaced. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed extinction attenuates conditioned fear renewal and spontaneous recovery in humans.

This study investigated whether the retention interval after an aversive learning experience influences the return of fear after extinction training. After fear conditioning, participants underwent extinction training either 5 min or 1 day later and in either the same room (same context) or a different room (context shift). The next day, conditioned fear was tested in the original room. When extinction took place immediately, fear renewal was robust and prolonged for context-shift participants, and spontaneous recovery was observed in the same-context participants. Delayed extinction, by contrast, yielded a brief form of fear renewal that reextinguished within the testing session for context-shift participants, and there was no spontaneous recovery in the same-context participants. The authors conclude that the passage of time allows for memory consolidation processes to promote the formation of distinct yet flexible emotional memory traces that confer an ability to recall extinction, even in an alternate context, and minimize the return of fear. Furthermore, immediate extinction can yield spontaneous recovery and prolong fear renewal. These findings have potential implications for ameliorating fear relapse in anxiety disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rapid reacquisition of fear to a completely extinguished context is replaced by transient impairment with additional extinction training.

A series of experiments studied reacquisition of fear reactions to a completely extinguished context. Reacquisition was rapid when reconditioning occurred as soon as the fear reactions were completely extinguished, showing that the original conditioning was intact. However, when reconditioning occurred after massive extinction training, fear reactions were depressed but then recovered across a long retention interval. This recovery was due to reconditioning and was similar to that produced by conditioning a massively preexposed context. These results show that massive extinction converts a potentially dangerous context into one that is merely familiar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction.

Several recent studies have shown that chromatin, the DNA-protein complex that packages genomic DNA, has an important function in learning and memory. Dynamic chromatin modification via histone deacetylase (HDAC) inhibitors and histone acetyltransferases may enhance hippocampal synaptic plasticity and hippocampus-dependent memory. Little is known about the effects of HDAC inhibitors on extinction, a learning process through which the ability of a previously conditioned stimulus, such as a conditioning context, to evoke a conditioned response is diminished. The authors demonstrate that administration of the HDAC inhibitors sodium butyrate (NaB) systemically or trichostatin A (TSA) intrahippocampally prior to a brief (3-min) contextual extinction session causes context-evoked fear to decrease to levels observed with a long (24-min) extinction session. These results suggest that HDAC inhibitors may enhance learning during extinction and are consistent with other studies demonstrating a role for the hippocampus in contextual extinction. Molecular and behavioral mechanisms through which this enhanced extinction effect may occur are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased spontaneous recovery with increases in conditioned stimulus alone exposures.

A series of experiments used the compound test procedure (Rescorla, 2002) to measure the size of spontaneous recovery of freezing responses by rats to a latently inhibited and/or extinguished conditioned stimulus (CS). The size of recovery was greater: to a pre-exposed and conditioned CS than to a CS just conditioned or just pre-exposed; to an extensively pre-exposed or extinguished CS than to a moderately pre-exposed or extinguished CS; and to a pre-exposed and extinguished CS than to a CS just pre-exposed or just extinguished. These results show that the size of recovery is proportional to the size of the depression produced by CS-alone exposures regardless of whether they occurred before, after, or both before and after conditioning. The results are discussed in terms of some contemporary models of recovery and of the inferences permitted by the use of the compound assessment technique. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-Cycloserine and the Facilitation of Extinction of Conditioned Fear: Consequences for Reinstatement.

Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Duration sensitivity depends on stimulus familiarity.

When people are asked to assess or compare the value of experienced or hypothetical events, one of the most intriguing observations is their apparent insensitivity to event duration. The authors propose that duration insensitivity occurs when stimuli are evaluated in isolation because they typically lack comparison information. People should be able to evaluate the duration of stimuli in isolation, however, when stimuli are familiar and evoke comparison information. The results of 3 experiments support the hypothesis. Participants were insensitive to the duration of hypothetical (Experiment 1) and real (Experiment 2) unfamiliar experiences but sensitive to the duration of familiar experiences. In Experiment 3, participants were insensitive to the duration of an unfamiliar noise when it was unlabeled but sensitive to its duration when it was given a familiar label (i.e., a telephone ring). Rather than being a unique phenomenon, duration neglect (and perhaps other forms of scope insensitivity) appears to be a particular case of insensitivity to unfamiliar attributes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Massed extinction trials produce better short-term but worse long-term loss of context conditioned fear responses than spaced trials.

A series of experiments studied the effects of the interval between extinction trials on the loss of context conditioned freezing responses. Rats were shocked in one context (A) but not in another (B) and subjected to extinction trials in context A. In Experiment 1, massed trials produced more rapid loss than spaced trials. A shift from spaced to massed trials maintained this loss, but the shift from massed to spaced trials restored lost responses. Experiments 2-5 examined this effect of massed trials on responding across spaced trials. They provided evidence that (a) a single trial was as effective as multiple daily massed trials, (b) learning occurred on the first of the massed trials but not on later ones, and (c) the first trial reduced the amount learned across subsequent massed trials. Finally, alternating extinction trials in A and B produced more response loss across spaced trials than blocks of trials in A and B. The results were discussed in terms of the role accorded to self-generated priming in the models developed by A. R. Wagner (1978, 1981). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time and stimulus specificity in extinction of the conditioned nictitating membrane response in the rabbit (Oryctolagus cuniculus).

The present experiments demonstrated that, in the rabbit nictitating membrane preparation, a conditioned response (CR) can be selectively eliminated in one portion of a conditioned stimulus (CS) while it is still paired with the unconditioned stimulus (US). Rabbits were initially trained with two stimuli (tone, light). Each was paired with the US by using a mixture of two CS-US interstimulus intervals (ISIs): 200 ms and 1,200 ms in Experiment 1; 150 ms and 500 ms in Experiment 2. The CRs showed double peaks, one for each ISI. Subsequently, one CS (A) was trained with only the longer ISI, whereas the other CS (B) continued to be trained with both ISIs. Consequently, the CR peak based on the shorter ISI disappeared for CSA but not for CSB. The later CR peaks during both CSA and CSB were maintained. These results support time-based models of conditioning. Implications for proposed mechanisms of extinction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deepened extinction from compound stimulus presentation.

Three experiments with rats and 2 with pigeons explored the effect of presenting 2 extinguished excitatory stimuli in compound. Four learning situations were used: Pavlovian magazine approach, Pavlovian fear conditioning, and instrumental discriminative instrumental learning in rats, as well as Pavlovian sign tracking in pigeons. All 5 experiments confirmed D. Reberg's (1972) observation that even after extinction of the individual stimuli, presenting them in compound evoked substantial responding. Moreover, nonreinforcement of that compound deepened extinction of an element more substantially than did additional presentation of that element alone. Such compound exposure reduced spontaneous recovery, reduced reinstatement, and slowed subsequent reconditioning. The primary determinant seemed to be the enhanced associative strength rather than the enhanced conditioned responding that occurred during the nonreinforced compound. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans.

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of the stimulus object upon the complimentary and supplementary projection of fear.

2 studies were conducted bearing on the hypothesis that frightened boys attribute malice to male adults but attribute fear to other boys. In the 1st experiment, a Halloween setting was used to elicit fear. The experimental group, in comparison to a matched control group, manifested a reliable increment in attribution of maliciousness to pictures of men and boys but no significant change in attribution of fear. Because of possible complications due to hostility arousal, a 2nd experiment was carried out in which judgments were elicited from boys who thought they were going to participate in a study involving frightening equipment. Under these conditions, the experimental Ss attributed reliably more maliciousness to men and reliably more fear to boys. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reinstatement of extinguished fear by β-adrenergic arousal elicited by a conditioned context.

Five experiments examined the reinstatement of fear (freezing) produced by recent reexposure to a dangerous context. Rats were trained to fear a conditioned stimulus (CS) and a distinctive context with shock. The CS was then extinguished. A 2-min interval between reexposure to the dangerous context and presentation of the extinguished CS in a different context reinstated freezing when the CS was tested the next day. Propranolol (a β-adrenergic antagonist) blocked reinstatement of extinguished fear without decreasing freezing to a nonextinguished CS. Administration of epinephrine (an adrenergic agonist) reinstated extinguished fear without reexposure to the dangerous context. The results suggest a role for β-adrenergic activity elicited by exposure to a conditioned context in the reinstatement of extinguished fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous recovery of extinguished fear responses deepens their extinction: A role for error-correction mechanisms.

A series of experiments used a within-subject design to study spontaneous recovery of fear responses (freezing) to an extinguished conditioned stimulus (CS) in rats. Experiments 1, 2, 3, and 4 demonstrated that: a remotely extinguished CS elicited more freezing than a recently extinguished one on a common test; that the CS showing recovery underwent greater response loss across additional extinction than the one lacking recovery; and that spontaneous recovery and deepening of response loss survived reconditioning. Experiment 5 demonstrated that an excitor extinguished in compound with a CS showing recovery suffered greater loss than an excitor extinguished in compound with a CS not showing recovery, implying that the differential change is regulated by a common error term. Experiments 6 and 7 demonstrated that extinction of a compound composed of two CSs, one showing recovery and a second lacking recovery, produced greater loss to the CS that showed recovery, implying that the change is also regulated by individual error term. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning.

During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Anterograde amnesia for Pavlovian fear conditioning and the role of one trial overshadowing: Effects of preconditioning exposures to morphine in rat.

Four experiments studied anterograde deficits in Pavlovian fear conditioning following prolonged exposure to the μ-opioid receptor agonist morphine. Injections of morphine produced temporally graded anterograde amnesia characterized by deficits in contextual and conditioned-stimulus (CS) conditioning 1 or 7 days and selective impairment in CS conditioning 21 days after last injection. This anterograde deficit in conditioning did not recover across a retention interval, was absent when rats were tested immediately after conditioning, and required the presence of an auditory CS. These results suggest that anterograde deficits in Pavlovian fear conditioning emerged from differences in susceptibility to 1-trial overshadowing of context by CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The moderating effects of stimulus valence and arousal on memory suppression.

This study examined the separate and combined effects of stimulus valence and arousal on retrieval inhibition. Participants performed Anderson and Green's (2001) memory suppression task with stimuli varying across dimensions of valence and arousal. Memory was tested through free and cued recall as well as speeded recognition. Results showed that both stimulus valence and arousal influenced the extent to which participants successfully inhibited retrieval, but not in the ways anticipated. Specifically, the strongest inhibition effects were for highly arousing, pleasant words. In addition, unpleasant stimuli that were suppressed were better recalled during both cued and free-recall tasks than pleasant stimuli that were suppressed. Across all tests of memory performance, there were no significant differences between the experimental conditions for highly arousing, unpleasant words. The implications of these findings are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)