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PubMed1999

Effectiveness of sensory stimulation on tactile extinction.

Eleven brain-damaged patients with extinction were asked to report double tactile stimuli before, during, and after optokinetic stimulation and transcutaneous electrical stimulation of the posterior neck region. The goal of the study was to test whether tactile extinction is sensitive to these experimental manipulations in order to better understand the nature of the disorder. Both of these sensory stimulations are known to be effective in modulating only higher-order (cognitive) disorders of spatial coding, such as visual hemineglect, deficit of position sense, hemianesthesia, etc. When applied to the side contralateral to the cerebral lesion, both optokinetic and transcutaneous electrical stimulation significantly affected patients' performances, increasing the amount of detections of contralesional double stimuli. A tendency towards worse performance was observed when sensory stimulation was applied to the ipsilesional side. The reported effectiveness in reducing tactile extinction suggests that the deficit can not be fully ascribed to a peripheral sensory disorder and that it reflects damage to a higher-order cognitive function involved in contralesional space representation or in the deployment of attention to that side of space. The nature of the close relationship between extinction and hemineglect is also discussed from the point of view of extinction as a deficit of space coding.

Aged↗
PubMed2005

Retrieval and the extinction of memory.

1. Memory is assessed by measuring retrieval which is often elicited by the solely presentation of the conditioned stimulus (CS). However, as known since Pavlov, presentation of the CS alone generates extinction. 2. One-trial avoidance (IA) is a much used conditioned fear paradigm in which the CS is the safe part of a training apparatus, the unconditioned stimulus (US) is a footshock and the conditioned response (CR) is to stay in the safe area. Retrieval of the memory for the step-down version of this task is measured in the absence of the US, as latency to step-down from the safe area (i.e., a platform). 3. Extinction of the IA response is installed at the moment of the first non-reinforced test session, as clearly shown by the fact that many drugs, including PKA, ERK and protein synthesis inhibitors as well as NMDA receptor antagonists, hinder extinction when infused into the hippocampus or the basolateral amygdala at the moment of the first test session but not later. 4. Some, but not all the molecular systems required for extinction are also activated by retrieval, further endorsing the hypothesis that although retrieval is necessary for the generation of extinction this last process constitutes a new learning secondary to the non-reinforced expression of the original trace.

Animals↗
PubMed1990

Extinction of a conditioned emotional response: massed and distributed exposures.

Using the lick-suppression methodology of Jacobs, Buttrick & Kennedy (Pavlovian Journal of Biological Science, 23, 29-34, 1988), a conditioned emotional response (CER) was established in 24 rats using off-the-baseline pairings of a light (the conditional stimulus) and brief footshock (the unconditioned stimulus). Following conditioning, the rats were assigned to one of three extinction groups differing in whether they received massed or distributed off-the-baseline exposure to the conditional stimulus. The effects of differential treatment were assessed on-the-baseline on test days, when the extinction of the CER was monitored. Rats receiving a single, long exposure to the conditional stimulus showed greater resistance to extinction than the rats in the distributed groups. They also showed a difference pattern of CER extinction. The results were discussed and compared to similar studies that have explored the massed vs distributed dimension, both in CER and avoidance-extinction (using response prevention or flooding). The relation of animal studies to parallel human studies using exposure therapy was also discussed.

Animals↗
PubMed1982

Locus coeruleus lesions and resistance to extinction of a classically conditioned response: involvement of the neocortex and hippocampus.

Bilateral electrolytic lesions of the locus coeruleus were made in rabbits prior to classical conditioning of the nictitating membrane (NM) response. After recovery, the animals received one session of unpaired training followed by 3 days of paired acquisition training and 4 days of unpaired training (extinction). At the end of extinction norepinephrine (NE) and dopamine (DA) levels were measured in several brain regions. Each lesioned animal was placed into one of two groups according to whether or not the animal exhibited a significant depletion of cortical/hippocampal NE. A third group was formed by non-lesioned controls. There were no significant differences between the 3 groups during acquisition; however, during days 3 and 4 of unpaired extinction the group with cortical/hippocampal NE depletion showed significantly larger NM responses on the conditioned stimulus-alone trials than either of the two control groups. This extinction deficit appeared mainly in the unconditioned stimulus-period component of the tone-alone conditioned responses. The magnitude of the extinction deficit was highly correlated with the depletion of NE in both cortical and hippocampal samples but not with the depletion of NE in the hypothalamus/mid-thalamus, or cerebellum.

Animals↗
PubMed1987

Beta-endorphin impairs forced extinction of an inhibitory avoidance response in rats.

The effect of subcutaneous administration of beta-endorphin on forced extinction (FE) of an inhibitory avoidance behavior has been studied in rats. Animals subjected to FE displayed significantly shorter retention latencies than those of the corresponding control group, not subjected to FE. Subcutaneous administration of 0.1, 1 and 10 micrograms/kg of beta-endorphin 10 min before or immediately after FE session, delayed extinction of the inhibitory avoidance behavior in an inverted U-shaped dependent manner. The opiate antagonist naloxone (NX) administered subcutaneously (0.4 mg/kg) did not influence extinction behavior. However, the same dose of NX, when injected previously to the administration of beta-endorphin (1 microgram/kg), prevented the effect on extinction induced by the opioid. Our results suggest that beta-endorphin may be involved in modulating forced extinction of a recently acquired information, likely influencing relearning phenomena associated with this particular way of forgetting.

Animals↗
PubMed1984

Auditory extinction following hemisphere damage.

Extinction to the simultaneous presentation of sounds to both ears was investigated in patients with acute cerebrovascular disease and found to be present in nearly half of the patients in the early stage of stroke. The occurrence of the symptom was not significantly different following damage to either hemisphere, but a higher percentage of right brain-damaged patients tended to show extinction for a longer time. However, this finding must be evaluated with caution since a greater number of left- than right-hemisphere patients had to be excluded from the investigation because aphasia precluded their understanding test instructions. The presence of auditory extinction was not related to that of visual extinction and there were patients with severe visual neglect who did not extinguish in the auditory modality. These findings and CT scan evidence, indicating that patients with long-lasting extinction had lesions encroaching upon the auditory pathways, suggest that in number of cases the phenomenon may have a sensory and not an attentional basis.

Attention↗
PubMed1982

Decreased resistance to extinction in ob/ob mice following operant training.

Inconsistent results have emerged from past studies in which operant conditioning paradigms were used to assess the hunger motivation of genetically obese mice relative to that of normal mice. Methodological considerations indicated the need to examine operant performance to a criterion, rather than performance during time-based sessions, and then to focus upon response differences in resistance to extinction. Therefore, genetically obese (ob/ob) mice and normal littermates were trained successfully to bar-press for 100 food rewards on either a CRF or a FR-10 schedule of reinforcement. Extinction behavior was then examined over 9 daily 1-hr sessions. While obese and normal mice evidenced similar patterns of learning, or response discrimination for food rewards, they evidenced different levels of hunger motivation during extinction conditions. Obese mice displayed a greater reduction in responding across extinction sessions, or less resistance to extinction, than normal mice following training on both schedules of reinforcement. These findings suggest that ob/ob mice exhibit lower levels of hunger motivation than normal littermates.

Animals↗
PubMed1989

The effects of amphetamine on a multitrial partial reinforcement extinction effect (PREE) in a runway.

Three experiments examined the effects of d-amphetamine (1 mg/kg) administration on the partial reinforcement extinction effect (PREE) using a multitrial procedure. Two groups of rats were trained to run in a straight alley. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Experiments 1 and 2 used 6 trials/day with an intertrial interval (ITI) of 5 min. In Experiment 1 the drug was administered only during acquisition, whereas in Experiment 2 it was administered throughout acquisition and extinction. Experiment 3 used 3 trials/day with a 20 min ITI. The drug was administered throughout acquisition and extinction. In all three experiments, amphetamine-treated animals showed a normal PREE, i.e., increased resistance to extinction in PRF as compared to CRF animals. These results stand in marked contrast to the amphetamine-induced abolition of the PREE with 1 trial/day procedure.

Amphetamine↗
PubMed1992

Amphetamine and the multitrial partial reinforcement extinction effect (PREE) in an operant chamber: procedural modifications that lead to an attenuation of the PREE.

The partial reinforcement extinction effect (PREE) consists of the fact that animals receiving partial reinforcement (PRF) exhibit higher resistance to extinction than animals receiving continuous reinforcement (CRF). In previous studies, we found that amphetamine (AMPH) did not affect resistance to extinction of PRF animals trained with a multitrial procedure, but abolished resistance to extinction of PRF animals trained with a 1 trial/day procedure. Based on theoretical distinctions regarding the processes underlying the development of increased resistance to extinction at short and long intertrial intervals, we suggested that AMPH disrupts the formation of a context-mediated association between stimuli associated with nonreinforcement and subsequent reinforcement. To examine further this possibility, we designed conditions in a multitrial PRF procedure that do not allow a direct association between stimuli associated with nonreinforcement and reinforcement, and thus promote a context-mediated association between them. Two experiments were conducted in an operant chamber. In experiment 1, instead of the conventional 50% schedule of reinforcement throughout PRF training, days of 33% schedule of reinforcement were interspersed with days of continuous reinforcement; in experiment 2, a block (5 days) of 50% PRF schedule was alternated with a block (5 days) of CRF training, given either prior to or following PRF. In experiment 1, interspersing days of CRF training with days of 33% reinforcement schedule led to an attenuation of the PREE in AMPH-treated animals. In experiment 2, control animals that received CRF training either prior to or following PRF training exhibited a PREE similar to animals trained on PRF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMed1993

Early postnatal estrogen organizes sex differences in the extinction of a CRF running response.

In the present study the organizational effects of sex steroids on the sexually dimorphic extinction of a continuously food-rewarded running response were investigated. Gonadally intact female rats neonatally treated from day 1 to day 8 of the postnatal life with estradiol benzoate (EB), dihydrotestosterone (DHT) or vehicle, and males treated in the same period with the antiandrogen ciproterone acetate (AC), the estrogen antagonist tamoxifen (TX) or vehicle were studied in adulthood during the acquisition and extinction phases of the response in a short and narrow runway. No difference in performance between groups was obtained in the response acquisition. However, during extinction control males extinguished faster than control females. DHT treatment to females and neonatal CA administration to males had no effect on the expression of sexual dimorphism. Conversely, TX administration to the males increased male's resistance to extinction at the levels shown by control or DHT females, whereas the females treated with EB exhibited similar extinction rates to those observed in nonhormonal treated or CA males. This finding suggests that the organizational effect of testosterone on the sexually dimorphic behavior studied in the present report are mediated by testosterone conversion to estradiol throughout the aromatization pathway in the brain.

Animals↗
PubMed2005

Differences in extinction of conditioned fear in C57BL/6 substrains are unrelated to expression of alpha-synuclein.

C57BL/6 mice are commonly used as background strains for genetically modified mice, and little attention is usually paid to the notification of the specific substrain. However, it is known that C57BL/6NCrl (B6N) and C57BL/6JOlaHsd (B6JOla) mice differ in the course of extinction of conditioned fear (Stiedl O, Radulovic J, Lohmann R, Birkenfeld K, Palve M, Kammermeier J, et al. Strain and substrain differences in context- and tone-dependent fear conditioning of inbred mice. Behav Brain Res 1999;104:1-12), as well as in the expression of alpha-synuclein (Specht CG, Schoepfer R. Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice. BMC Neurosci 2001;2:11). We tested for a causal relationship between the two findings by employing B6N (expressing alpha-synuclein), B6JOla (not expressing alpha-syn) and the third strain C57BL/6JCrl (B6Jax, expressing alpha-syn). We show that alpha-syn does not account for differences in extinction in a fear conditioning task, as its expression did not covary with the decrease of freezing on repeated non-reinforced tone and context exposure in the three strains: B6Jax exhibited fastest extinction followed by B6JOla. In contrast, B6N showed persistent fear over the course of extinction training. The differences in extinction between B6JOla and B6N were unrelated to sensorimotor processing (pain threshold and basal tone reaction) and innate fear (light-dark test). However, B6Jax displayed less innate fear than B6JOla and B6N. Our results of marked differences in innate and conditioned fear in three B6 substrains illustrate the necessity of a strict adherence to an exact mouse strain nomenclature.

Analysis of Variance↗
PubMed2005

Slower extinction of responses maintained by intra-cranial self-stimulation (ICSS) in an animal model of attention-deficit/hyperactivity disorder (ADHD).

Children with attention-deficit/hyperactivity disorder (ADHD) show performance deficits and excessive motor activity during extinction and in situations where no reinforcer can be identified, suggesting an extinction deficit in ADHD possibly linked to dopamine dysfunction. The present study examined extinction of responding previously maintained by intra-cranial self-stimulation (ICSS) in spontaneously hypertensive rats (SHR), an animal model of ADHD using three different extinction procedures. Delivery of electrical pulses were terminated altogether or presented independently of responding using two different current intensities. The results showed that more responses were retained in the SHR, especially during the initial transition from ICSS-maintained responding to response-independent delivery of electrical pulses with current reduced relative to that given during reinforcement. Slower extinction of previously reinforced behavior is suggested as an alternative explanation for the frequently observed increased behavioral output that has previously been interpreted as "disinhibition" of behavior in ADHD.

Analysis of Variance↗
PubMed2004

Effect of amount of context extinction on revaluation of a target CS.

In two experiments using rats in a conditioned lick suppression paradigm the effects of posttraining extinction of the conditioning context on responding to the target conditioned stimulus (CS) which had previously been paired with a footshock was examined in a neutral context. Experiment 1 replicated Marlin's [Learn. Motiv. 13 (1981) 526] observation that this treatment can reduce responding to the target CS. This finding is contrary to other reports that context extinction enhances responding to the target CS. Experiment 2 examined the amount of posttraining context extinction as a variable potentially controlling this effect. It found the mediated extinction effect following one, but not 10 h of context extinction.

Animals↗
PubMed2004

Dynamic processing of taste aversion extinction in the brain.

While substantial advances have been made in discovering how the brain learns and remembers, less is known about how the brain discards information, reorganizes information, or both. These topics are not only relevant to normal brain functioning but also speak to pathologies in which painful memories do not wane but are evoked time and again (e.g., post-traumatic stress disorder; PTSD). Here, we measured brain activity (as indicated by the regional expression of c-Fos protein) in rats during acquisition and throughout extinction of a conditioned taste aversion (CTA). We compared that brain activity with animals that had intact CTA memories or those that experienced an explicitly unpaired (EU) conditioned stimulus (CS; saccharin, SAC) and unconditioned stimulus (US; lithium chloride, LiCl). The data show a dynamic and nonuniform pattern of c-Fos protein expression in brain nuclei known to mediate gustation and CTAs. In particular, brainstem nuclei (e.g., nucleus of the solitary tract; NTS) and the basolateral nucleus of the amygdala (BLA) are active early as CTAs are formed and as extinction of the learned response begins. Later in the extinction process, the BLA reduces c-Fos expression relative to nonextinguished controls. Finally, as almost full reacceptance of the taste is achieved, the gustatory neocortex (GNC) expresses enhanced levels of c-Fos protein. Thus, extinction of a CTA is not represented by a simple reversal of the c-Fos activity evoked by CTA conditioning. Rather, the data demonstrate that extinction of conditioned responses is a dynamic process in which the activity levels of particular nuclei along the brain's taste pathway change depending on the extent to which the conditioned response has been extinguished.

Analysis of Variance↗
PubMed2006

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.

Adult↗
PubMed2004

Excitotoxic lesions of the medial striatum delay extinction of a reinforcement color discrimination operant task in domestic chicks; a functional role of reward anticipation.

To reveal the functional roles of the striatum, we examined the effects of excitotoxic lesions to the bilateral medial striatum (mSt) and nucleus accumbens (Ac) in a food reinforcement color discrimination operant task. With a food reward as reinforcement, 1-week-old domestic chicks were trained to peck selectively at red and yellow beads (S+) and not to peck at a blue bead (S-). Those chicks then received either lesions or sham operations and were tested in extinction training sessions, during which yellow turned out to be nonrewarding (S-), whereas red and blue remained unchanged. To further examine the effects on postoperant noninstrumental aspects of behavior, we also measured the "waiting time", during which chicks stayed at the empty feeder after pecking at yellow. Although the lesioned chicks showed significantly higher error rates in the nonrewarding yellow trials, their postoperant waiting time gradually decreased similarly to the sham controls. Furthermore, the lesioned chicks waited significantly longer than the controls, even from the first extinction block. In the blue trials, both lesioned and sham chicks consistently refrained from pecking, indicating that the delayed extinction was not due to a general disinhibition of pecking. Similarly, no effects were found in the novel training sessions, suggesting that the lesions had selective effects on the extinction of a learned operant. These results suggest that a neural representation of memory-based reward anticipation in the mSt/Ac could contribute to the anticipation error required for extinction.

Analysis of Variance↗
PubMed2004

Dental use wear in extinct lemurs: evidence of diet and niche differentiation.

A new technique for molar use-wear analysis is applied to samples of all 16 species of extinct lemurs with known dentitions, as well as to a large comparative sample of extant primates. This technique, which relies on the light refractive properties of wear pits and scratches as seen under a standard stereoscopic microscope, has shown itself to be effective in distinguishing the diets of ungulates and extant primates. We draw dietary inferences for each of the 16 extinct lemur species in our database. There is a strong phylogenetic signal, with the Palaeopropithecidae showing use-wear signatures similar to those of the Indriidae; extinct lemurids (Pachylemur spp.) showing striking similarities to extant lemurids (except Hapalemur spp.); and Megaladapis showing similarities to Lepilemur spp. Only the Archaeolemuridae have dietary signatures unlike those of any extant lemurs, with the partial exception of Daubentonia. We conclude that the Archaeolemuridae were hard-object feeders; the Palaeopropithecidae were seed predators, consuming a mixed diet of foliage and fruit to varying degrees; Pachylemur was a fruit-dominated mixed feeder, but not a seed predator; and all Megaladapis were leaf browsers. There is no molar use wear evidence that any of the extinct lemurs relied on terrestrial foods (C4 grasses, tubers, rhizomes). This has possible implications for the role of the disappearance of wooded habitats in the extinction of lemurs.

Analysis of Variance↗
PubMed2003

Effects of acetylcholine antagonist injection into the prefrontal cortex on the progress of lever-press extinction in rats.

To determine the relationship between cholinergic modulation within the rat medial prefrontal cortex (mPFC) and the progress of lever-press extinction, we conducted an experiment in which muscarinic and nicotinic acetylcholine (ACh) receptor antagonists were microinjected into the mPFC. The muscarinic antagonist injected immediately before the initial extinction training did not affect the progress of extinction during the training (no within-session effect), but disrupted a second re-training session the next day (across-session effect). By contrast, the nicotinic antagonist disrupted the progress of extinction both within and across training sessions. These results confirm that ACh in the mPFC modulates lever-press extinction and suggest that nicotinic and muscarinic receptors are involved in short- and long-term memory processes.

Acetylcholine↗