Long-term maintenance of immediate or delayed extinction is determined by the extinction-test interval

Short acquisition-extinction intervals (immediate extinction) can lead to either more or less spontaneous recovery than long acquisition-extinction intervals (delayed extinction). Using rat subjects, we observed less spontaneous recovery following immediate than delayed extinction (Experiment 1). However, this was the case only if a relatively long extinction-test interval was used; a relatively short extinction-test interval yielded the opposite result (Experiment 2). Previous data appear consistent with this observation suggesting that, although delayed extinction appears more beneficial in the short term, immediate extinction may have more favorable long-term effects. These observations may have important implications for attenuation of relapse in clinical situations.     

Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear

Extinction of conditioned fear is an important model both of inhibitory learning and of behavior therapy for human anxiety disorders. Like other forms of learning, extinction learning is long-lasting and depends on regulated gene expression. Epigenetic mechanisms make an important contribution to persistent changes in gene expression; therefore, in these studies, we have investigated whether epigenetic regulation of gene expression contributes to fear extinction. Since brain-derived neurotrophic factor (BDNF) is crucial for synaptic plasticity and for the maintenance of long-term memory, we examined histone modifications around two BDNF gene promoters after extinction of cued fear, as potential targets of learning-induced epigenetic regulation of gene expression. Valproic acid (VPA), used for some time as an anticonvulsant and a mood stabilizer, modulates the expression of BDNF, and is a histone deacetylase (HDAC) inhibitor. Here, we report that extinction of conditioned fear is accompanied by a significant increase in histone H4 acetylation around the BDNF P4 gene promoter and increases in BDNF exon I and IV mRNA expression in prefrontal cortex, that VPA enhances long-term memory for extinction because of its HDAC inhibitor effects, and that VPA potentiates the effect of weak extinction training on histone H4 acetylation around both the BDNF P1 and P4 gene promoters and on BDNF exon IV mRNA expression. These results suggest a relationship between histone H4 modification, epigenetic regulation of BDNF gene expression, and long-term memory for extinction of conditioned fear. In addition, they suggest that HDAC inhibitors may become a useful pharmacological adjunct to psychotherapy for human anxiety disorders.     

The basolateral amygdala is necessary for learning but not relearning extinction of context conditioned fear

Extinction of conditioned fear involves new learning that inhibits but does not eliminate the original fear memory. This inhibitory learning is thought to require activation of NMDA receptors (NMDAr) within the basolateral amygdala (BLA). However, once extinction has been learned, the role played by the BLA during subsequent extinction procedures remains unknown. The present study examined the role of neuronal activity and NMDAr activation in rats receiving their first or second extinction of context fear. We found that BLA infusion of DL-APV, a competitive antagonist of NMDAr, depressed fear responses at both the first and second extinction. It impaired learning extinction but spared and even facilitated relearning extinction. BLA infusion of muscimol, a GABA(A) agonist, produced a similar outcome, suggesting that DL-APV not only blocked NMDAr-dependent plasticity but also disrupted neuronal activity. In contrast, infusion of ifenprodil, a more selective antagonist of NMDAr containing the NR2B subunit, did not depress fear responses but impaired short- and long-term inhibition of fear at both the first and second extinction. Therefore, we suggest that relearning extinction normally requires NMDAr containing the NR2B subunit in the BLA. However, simultaneous blockade of these receptors and neuronal activity in the BLA results in compensatory learning that is able to promote long-term re-extinction. These data are consistent with a current model that attributes fear extinction to interactions between several neural substrates, including the amygdala and the medial prefrontal cortex.     

The extinction of within-compound flavor associations

Three experiments studied extinction of the associations which are formed between two flavors presented in a simultaneous compound. In Experiment 1 those associations were identified by a sensory preconditioning procedure in which the poisoning of one element of the compound led to the rejection of the other element. Separate presentation of either element between their joint occurence and the poisoning of one element sharply attenuated the rejection of the other element. That attenuation was interpreted in terms of the extinction of within-compound associations. Experiment 2 obtained similar results with an alternative extinction procedure in which the elements of the original compound were presented in other compounds. Experiment 3 obtained similar results when the existence of the within-compound associations was determined by an alternative assessment procedure in which one element of the compound was made more attractive by the induction of a specific hunger. These experiments suggest that within-compound associations can be extinguished when the elements are separately presented outside of the compound. Experiments 2 and 3 make less plausible an alternative interpretation of the effects of separate element presentation in terms of reduction of the novelty of the element. The findings may be taken as implying that the elements of a simultaneously presented compound are joined by a single symmetrical association which acts at various points during a sensory preconditioning experiment.     

Outcome-specific transfer between predictive and instrumental learning is unaffected by extinction but reversed by counterconditioning in human participants

Three experiments were conducted to explore the effects of different interference treatments upon outcome-specific transfer from predictive learning to instrumental responding. A computer game was designed in which participants had to defend Andalusia from navy and air-force attacks. Participants learned the relationship between two instrumental responses (two keys in a standard keyboard) and two different outcomes (destruction of the ships or destruction of the planes). Then, they learned to predict which of two different cues predicted either outcome. Finally, participants were allowed to give either of the two instrumental responses in the presence of each cue. Outcome-specific transfer was shown as a preference for the response that shared the outcome with the current cue. Extinction of the cue before the transfer test had no effect upon transfer, regardless of the level of extinction (Experiments 1-3). However, pairing the cue with the alternative outcome (counterconditioning) reversed the outcome-based transfer effect (Experiment 3). The implications of these results for the contents of extinction in human predictive learning are discussed.     

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.     

Increment of the extinction illusion by long stimulation

We quantitatively examined the effect of stimulus duration on the extinction illusion. A white disc was presented or not presented at an intersection of a grey grid (intersection configuration) or on a homogeneous background (background configuration). The extinction illusion was quantified as the subtraction of no-disc responses in the background configuration (ie baseline) from no-disc responses in the intersection configuration, when the disc was presented. Experiment 1 showed a temporal effect: the extinction illusion increased as stimulus duration increased; this temporal effect was observed when the disc was presented at 9 deg from the fixation point and when the stimulus duration was 1000-6000 ms. Experiment 2 showed a visual field anisotropy: the extinction illusion occurred more frequently in the upper visual field than in the lower visual field, when the stimulus duration was 200 ms; the anisotropy was not observed when the stimulus duration was 6000 ms. Experiment 3 showed an alley-length effect: when the grid alley was long, the extinction illusion occurred more frequently in the 6000 ms condition than in the 200 ms condition; the temporal effect was not observed when the grid alley was short. These results suggest that the temporal effect of the extinction illusion might be due to perceptual filling-in of luminance information of the grid alley.     

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.     

Response decrements produced by extinction and by response-independent reinforcement

The effects of extinction and of response-independent (free) reinforcement in decreasing rates of key pecking by pigeons were compared in single schedule (Phase 1) and multiple (Phase 2) conditions. In both phases, response rates decreased more rapidly with extinction than with free reinforcement conditions. Behavioral contrast was obtained from subjects trained in a multiple schedule involving extinction in Phase 2, whereas subjects trained in a multiple schedule involving free reinforcement showed a slight negative induction effect. Whether subjects experienced extinction or free reinforcement under single stimulus conditions did not affect subsequent performance in the discrimination situation of the second phase. Disinhibition testing was carried out at the end of both phases, but there was no evidence for disinhibitory effects under any condition.     

The formation of a semantic network by induction

Summary A semantic network describing the relations between ten words has been elaborated. The raw-data for the formation of the network were 660 natural-language sentences gained in the following experiment: The ten words were presented to 12 Ss, single, in pairs, and in triplets. Ss had to form, for each given combination, a sentence containing the presented words. The sentences gained by this method were parsed and got uniform codings. Each stimulus word then has been assigned to a node, containing all words or parts of sentences to which it was related in the sentences. Nodes with similar contents have been subsumed under a higher-level node containing the relations which are common to it's constituents. The reaction times in sentence formation strongly depend on the relations between the words in the semantic network. The correlation between association strengths and the proximities between the words in the semantic network augments to 0.70. The limitations due to the purely inductive approach in the formation of the network are discussed.

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Zusammenfassung Es wurde ein semantisehes Netzwerk aufgebaut, welches die bedeutungsmäßigen Beziehungen zwischen 10 Wörtern darstellt. Die Ausgangsdaten für die Bildung des Netzwerkes bildeten experimentell gewonnene Sätze der natürlichen Sprache: 12 Versuchspersonen erhielten die 10 Wörter einzeln, in Paaroder Dreierkombinationen dargeboten und mußten Sätze bilden, in denen diese Wörter oder Wortkombinationen vorkommen. Die so gewonnenen 660 Sätze wurden in einem einheitlichen grammatischen System kodiert. Für jedes der 10 Stimuluswörter wurde darauf ein sog. Knoten aufgebaut; dieser enthält alle Wörter und Satzteile, die bei der Satzbildung zum Stimuluswort in Beziehung gesetzt wurden. Knoten mit ähnlichem Inhalt wurden unter Oberbegriffe subsumiert. Solche Knoten höherer Ordnung enthalten alle diejenigen Wörter und Wortgruppen, die bei den Knoten niedriger Ordnung gemeinsam vorkommen. Es kann gezeigt werden, daß die Reaktionszeiten bei der Satzbildung von den Relationen zwischen den Wörtern im semantischen Netzwerk abhängen. Die Korrelation zwischen den Assoziationsstärken zwischen den Stimuluswörtern einerseits und deren Nähe im semantischen Netzwerk andererseits beträgt 0.70. Die Beschränktheit eines ausschließlich induktiven Vorgehens beim Aufbau von semantischen Netzwerken wird diskutiert.

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This research was supported by a grant of the Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung.     

Elimination of behavior of mental patients by response-produced extinction

Mental hospital patients were conditioned to respond at a high rate. Then an attempt was made to eliminate the response by means of a mild punishment consisting of a period of timeout from reinforcement (response-produced extinction). When only one response was available for obtaining the reinforcement, the mild punishment was not effective in eliminating that response. When an alternative response was also made available for obtaining the reinforcement, the mild punishment was completely effective. It appears that even very mild punishment may be effective if the over-all frequency of reinforcement can be maintained by means of an alternative unpunished response.     

Resistance to extinction of conditioned odor perceptions: evaluative conditioning is not unique

A tasteless odor will smell sweeter after being sampled by mouth with sucrose and will smell sourer after being sampled with citric acid. This tasty-smell effect was found in experiments that compared odor-taste and color-taste pairings. Using odors and colors with minimal taste (Experiment 1), the authors found that repeated experience of odor-taste mixtures produced conditioned changes in odor qualities that were unaffected by intermixed color-taste trials (Experiment 2). An extinction procedure, consisting of postconditioning presentations of the odor in water, had no detectable effect on the changed perception of an odor (Experiments 3 and 4). In contrast, this procedure altered judgments about the expected taste of colored solutions. Evaluative conditioning (conditioned changes in liking) is claimed to be resistant to extinction. However, these results suggest that resistance to extinction in odors is related to the way they are encoded rather than to their hedonic properties.