Fear conditioning in panic disorder: Enhanced resistance to extinction

Enhanced conditionability has been proposed as a crucial factor in the etiology and maintenance of panic disorder (PD). To test this assumption, the authors of the current study examined the acquisition and extinction of conditioned responses to aversive stimuli in PD. Thirty-nine PD patients and 33 healthy control participants took part in a differential aversive conditioning experiment. A highly annoying but not painful electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures were used as either the paired conditioned stimulus (CS+) or the unpaired conditioned stimulus (CS-). Results indicate that PD patients do not show larger conditioned responses during acquisition than control participants. However, in contrast to control participants, PD patients exhibited larger skin conductance responses to CS+ stimuli during extinction and maintained a more negative evaluation of them, as indicated by valence ratings obtained several times throughout the experiment. This suggests that PD patients show enhanced conditionability with respect to extinction.     

Sex,stress, and fear: Individual differences in conditioned learning

It has long been recognized that humans vary in their conditionability, yet the factors that contribute to individual variation in emotional learning remain to be delineated. The goal of the present study was to investigate the relationship among sex, stress hormones, and fear conditioning in humans. Forty-five healthy adults (22 females) underwent differential delay conditioning, using fear-relevant conditioned stimuli and a shock unconditioned stimulus. Salivary cortisol samples were taken at baseline and after acquisition training and a 24-h-delayed retention test. The results showed that acquisition of conditioning significantly correlated with postacquisition cortisol levels in males, but not in females. This sex-specific relationship was found despite similar overall levels of conditioning, unconditioned responding, and cortisol. There was no effect of postacquisition cortisol on consolidation of fear learning in either sex. These findings have implications for the understanding of individual differences in fear acquisition and risk factors for the development of affective disorders.     

The incubation theory of fear/anxiety: experimental investigation in a human laboratory model of Pavlovian conditioning

The aim of this work was to test Eysenck's incubation theory of fear/anxiety in human Pavlovian B conditioning of heart rate (HR) responses. The conditioned stimuli (CSs) were phobia-relevant slides (snakes and spiders) and the unconditioned stimuli (UCSs) were aversive noises. The subjects were presented with two levels of noise intensity during acquisition and three levels of nonreinforced CS presentation (CS-only) in a delay differential (CS+/CS-) conditioning paradigm (2 x 3 x 2). Consistent with the incubation theory, conditioned HR acceleratory responses were sustained (resistance to extinction) for high-noise intensity and short-presentations of CS-only subjects. During the extinction phase, HR acceleratory responses quickly extinguished in low-noise intensity groups after the first presentations of CS-only. These findings were interpreted as support for the incubation theory of phobic fear.     

‘Preparedness’ and ‘arousability’ as determinants of electrodermal conditioning

‘Arousability’, as defined through spontaneous electrodermal responses, has been empirically linked to anxiety, phobic symptoms and outcome of systematic desensitization. Previous data from our laboratory indicate that ‘preparedness’, as defined through potentially phobic vs. fear-irrelevant or ‘neutral’ conditioned stimuh, is an important determinant of electrodermal conditioning. The present experiment compared groups selected to be high or low in spontaneous responding during differential conditioning to potentially phobic or neutral stimuh. It was found that the effects of these two factors were essentially additive, i.e. conditioning and resistance to extinction were better for phobic stimuli and for high-arousal groups. The high-aroused group with phobic stimuh showed diffuse responding during acquisition, not differentiating between reinforced and unreinforced cues. However, it was the only group that failed to extinguish during 20 trials, which indicates that high arousal gives superior resistance to extinction particularly for phobic stimuli.     

Biological vs experiential factors in phobic conditioning

The present study was performed as a test of phobic conditioning being a case of prepared learning (Seligman, 1971). Skin conductance responses were conditioned in three groups of subjects to either slides of snakes and spiders; electric outlets; or geometric shapes, as conditioned stimuli (CSs) with shock to the forearm as the unconditioned stimulus (UCS). The purpose of the experiment was to compare electrodermal conditioning to potentially phobic CSs, i.e. snakes and spiders, with conditioning to fear-relevant, but non-phobic, CSs, i.e. electric outlets.Each subject saw two pictures, either a snake or a spider; or two different slides of electric outlets; or two different geometric shapes. Only one of the two cues (the CS + ) was immediately followed by the shock-UCS during the acquisition phase. Thus, a differential paradigm was used. There were 4 habituation, 12 acquisition, and 16 extinction trials. The duration of the pictures was 8 sec with an intertrial interval of between 35–45 sec.The results showed reliable effects of conditioning in all three groups during the acquisition phase. Furthermore, a significant interaction during extinction is reported, indicating responses to potentially phobic CSs to be more resistant to extinction than responses to the other two classes of stimuli. It is concluded that the present results favor an interpretation of phobic conditioning in terms of biologically prepared learning.     

Excitatory conditioning of individual Drosophila melanogaster

Testing individual animals from a heterogenic population of Drosophila melanogaster, we demonstrate conditioning of the proboscis extension reflex. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses over trials, (b) measured differences in performance levels among individual subjects, and (c) a sex difference, with more males conditioned than females, and those that did did so more quickly. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned or unconditioned stimuli directly affected the conditioned response, whereas unconditioned stimulus preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the unconditioned stimulus. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large number of individuals that can be tested simultaneously on the automated stimulation apparatus, it is now possible to make precise behavioral measurements on samples large enough for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype.     

Classical conditioning and information processing: Different mechanism for prepared and unprepared stimuli?

Although learning without awareness conflicts with recent theories of classical human Pavlovian conditioning, there is at least one type of conditioning in which CS-US contingency is processed without awareness—the so-called prepared conditioning. Therefore, presenting a secondary reaction time probe to measure the amount of information processing capacity required should produce interference with the secondary task in unprepared, but not in prepared conditioning, since in the latter information should be processed in parallel. In a previous study, the authors could not find differences between both types of conditioning, neither in reaction time nor in electrodermal indicators of information processing. The present study was conducted to replicate and extend these findings, using a differential autonomic conditioning paradigm. One half of 42 subjects received spider and snake slides as prepared stimuli, while the other half received flower slides as unprepared stimuli. Both kinds of stimuli were used as CS+ and as CS-. An electric shock served as unconditioned stimulus. During 24 acquisition and 24 extinction trials, electrodermal and heart rate responses, as well as reaction times to a probe stimulus, were recorded. The results revealed significant conditioning effects in terms of CS-/CS+ differences. However, no differences were found between prepared and unprepared stimuli, neither in autonomic measures nor in reaction time. Again, our results are in favor of serial information processing in both prepared and unprepared stimuli, suggesting that the so-called prepared conditioning may be treated as a subclass of classical autonomic conditioning instead of forming a specific class of learning.     

Electrodermal conditioning to potentially phobic stimuli: Effects of instructed extinction

It was hypothesized that electrodermal responses to potentially phobic stimuli “conditioned” through verbal threats about an aversive UCS should be equally resistant to instructed extinction as the responses obtained by actual CS-UCS pairings. Two groups of human subjects were exposed to pictures of either snakes and spiders (phobic CSs), or circles and triangles (neutral CSs) in a differential Pavlovian conditioning paradigm. Changes in skin conductance were recorded. Half of the subjects in each group were threatened with a shock-UCS while the other half were given shock-reinforced CS presentations. At the onset of extinction, all subjects in each of the four groups were informed that no more UCSs were to be delivered, and the shock electrodes were removed. All groups showed evidence of conditioning during acquisition. During extinction there was an immediate drop in responding in the two neutral groups, whereas the two phobic groups showed reliable evidence of resistance to extinction, with no differences between the threatened- and the CS-UCS-group. The observed resistance to extinction found in the phobic groups implies a similarity to the irrationality of real-life phobias. Furthermore, the data are in accordance with analysis of electrodermal fear-conditioning as a case of prepared learning.     

Anticipatory nausea in cancer patients receiving chemotherapy: Classical conditioning etiology and therapeutical implications

The delivery of cytotoxic drugs in cancer treatment is often accompanied by posttreatment side effects (e.g., nausea). Moreover, there is evidence that cancer patients are at risk to develop these side effects in anticipation of chemotherapy (i.e., anticipatory nausea [AN]). AN can be explained as the result of a classical conditioning process with the cytotoxic drug as the unconditioned stimulus (US). Stimuli paired with the US (e.g., smells, tastes) can become conditioned stimuli (CSs) eliciting AN as the conditioned response (CR). The present study was conducted to test whether AN shows characteristics of a CR. Fifty-five ambulatory cancer patients were asked to record nine kinds of physical symptoms (e.g., nausea, vomiting, sweating) on time-scheduled symptom lists: after an infusion (indicating posttreatment symptoms) and prior to their next infusion (indicating anticipatory symptoms). Each measurement period covered a maximum of 48 hours. AN was reported by ten patients (18.08%). Data revealed (a) a statistically significant association between posttreatment nausea and vomiting, respectively, and AN; (b) the occurrence of AN increased with drug emetogenity (i.e., US-intensity); and (c) the duration of AN increased with temporal proximity to the infusion. The results support the conditioning model. Thus, it is proposed to prevent AN by classical conditioning techniques (e.g., overshadowing).     

Verbal instruction abolishes fear conditioned to racial out-group faces

Previous research has shown resistance to extinction of fear conditioned to racial out-group faces, suggesting that these stimuli may be subject to prepared fear learning. The current study replicated and extended previous research by using a different racial out-group, and testing the prediction that prepared fear learning is unaffected by verbal instructions. Four groups of Caucasian participants were trained with male in-group (Caucasian) or out-group (Chinese) faces as conditional stimuli; one paired with an electro-tactile shock (CS+) and one presented alone (CS−). Before extinction, half the participants were instructed that no more shocks would be presented. Fear conditioning, indexed by larger electrodermal responses to, and blink startle modulation during the CS+, occurred during acquisition in all groups. Resistance to extinction of fear learning was found only in the racial out-group, no instruction condition. Fear conditioned to a racial out-group face was reduced following verbal instructions, contrary to predictions for the nature of prepared fear learning.     

Reaction time task as unconditional stimulus

Nonaversive unconditional stimuli (USs) are seldom used in human classic conditioning of autonomic responses. One major objection to their use is that they produce deficits in electrodermal (ED) second- and third-interval response conditioning. However, a nonaversive reaction time (RT) task that includes feedback of success has been shown to be an effective US while avoiding this disadvantage (Lipp and Vaitl 1988). The present study compared this new RT task (RT-new) with a traditional RT task (RT-old) and with a standard aversive US (shock) in differential classic conditioning of ED, heart rate (HR), and digital pulse volume (DPV) responses. Eight-second-delay differential conditioning was applied in three groups of 12 subjects each. Simple geometric features (square, cross) displayed on a television screen served as conditional stimuli (CS⁺ and CS^?). In acquisition, there were no statistically significant differences among the groups; differential conditioning did occur in HR, first- and second-interval ED responses, and first-interval DPV responses. Separate analyses within each group, however, revealed that there was no second-interval ED conditioning in the RT-old group. During extinction, neither DPV nor second-interval ED conditioning could be obtained, whereas HR and first-interval ED conditioning occurred in each group. In third-interval omission ED responses, RT-old and shock groups exhibited extinction, while response differentiation was maintained in the RT-new group throughout extinction. The RT task including feedback proved to be as reliable a US as a standard aversive US, whereas application of a traditional RT task again yielded some weaknesses in second-interval ED conditioning.     

Effects of contextual conditioning and unconditional stimulus presentation on performance in appetitive conditioning

Four experiments with rat subjects examined the effects of contextual conditioning on conditioned appetitive performance. Experiment 1 compared the effects of contextual conditioning on performance to conditioned stimuli (CSs) with different conditioning histories. Contextual conditioning enhanced performance to the CS if the CS had first been conditioned and then extinguished, but had no effect on performance when the CS had been merely paired or unpaired with food. Experiments 2 and 3 then asked whether the effect on the extinguished CS was due to contextual conditioning acting as a cue for conditioning. In Experiment 2, extinction procedures in which extra unconditioned stimuli (USs) were presented during the intertrial intervals were found to reduce the CS's sensitivity to enhancement by contextual conditioning, but had no effect on spontaneous recovery. In Experiment 3, USs added to conditioning or extinction acquired the ability to cue the corresponding performance. Under some conditions, USs added to conditioning could suppress performance (Experiment 4). The results suggest that contextual conditioning has complex effects that can be better understood by recognizing that contextual conditioning, as well as the USs that create it,Mayacquire discriminative control over conditioned responding.     

"Pseudoconditioned" jaw movements of the rabbit reflect associations conditioned to contextual background cues.

Two experiments employing 180 rabbits and involving tone conditioned stimuli (CSs) and intraoral water unconditioned stimuli (UCSs) investigated pseudoconditioning of jaw movement. CS-alone, UCS-alone, paired CS-UCS, and four explicitly unpaired CS-UCS treatments were compared to no stimulus presentation. UCS-alone presentations were sufficient to produce pseudo-CR (conditioned response) acquisition. Pseudo-CRs were retained and gradually extinguished over 30 days of CS-alone presentations. Random sequences of unpaired CSc and UCSs produced higher pseudo-CR frequencies than fixed sequences. A pseudo-CR partial reinforcement extinction effect was observed. Background extinction, that is, simply confining the subject in the experimental environment without stimulation, was effective in extinguishing both pseudo-CRs and CRs. Pseudo-CR results could not be attributed to CS-UCS trace conditioning, sensory preconditioning, second-order conditioning, or intra-analyzer conditioning. Results indicate that the associative mechanisms underlying pseudoconditioning phenomena involve conditioning of associations to contextual background (apparatus, trace, temporal, and sequential aftereffect) cues by UCS-alone and unpaired UCS presentations.     

Hemispheric asymmetry and electrodermal activity in orienting and pavlovian conditioning paradigms

Three experiments on lateralization of electrodermal orienting and conditioned behavior are reported. The basic findings show effects of hemispheric asymmetry on initial magnitude and rate of habituation of phasic stimulus-elicited electrodermal responses. In summary, responses to verbal stimuli repeatedly flashed to the right visual half-field are larger than corresponding responses in the left half-field. Similarily, spatially relevant stimuli initially presented to the left half-field result in larger responses than when the same stimuli are repeatedly presented in the right half-field. In the auditory modality, data show asymmetrical control of responding to verbal material in a dichotic conditioning paradigm with greater resistance to extinction when the conditioned stimulus is initially fed only to the left hemisphere as compared to when it is fed only to the right hemisphere. It is argued that the present approach taps on basic mechanisms for the lateralization of attentional and associative functions.     

Differential effects of progesterone and medroxyprogesterone on delay eyeblink conditioning in ovariectomized rats

Ovarian hormones modulate acquisition processes involved in classical conditioning. Although progesterone has been indirectly implicated, its role in classical conditioning of the eyeblink response has not been directly investigated. We assessed the effects of daily dosing of progesterone or medroxyprogesterone (MPA), a non-metabolized synthetic progestin, upon the acquisition of a classically conditioned eyeblink response in ovariectomized (OVX) female rats. Rats were dosed 4h prior to each training session with 0.1 or 1.5 mg/kg of either of these hormones or sesame oil. A delay conditioning paradigm was employed using a 500 ms conditioned stimulus coterminating with a 10 ms 10 V unconditioned stimulus. At the low dose, progesterone and MPA rats did differ from each other, with MPA-treated rats learning slower, but neither group differed from OVX-oil or Sham-oil controls. No group differences in acquisition were observed at the higher dose. During extinction trials, high-dose MPA-treatment and OVX-oil groups extinguished quicker than the high-dose progesterone-treated group. In addition, unconditional response (UR) amplitudes were lower in all OVX groups, regardless of hormone or oil treatment, compared to the sham-oil group. Since MPA did not affect extinction, it is likely the slower extinction in the progesterone-treated rats is due to a metabolite of progesterone. Corticosterone is discussed as a likely candidate for such a role. In addition, we found chronic absence of ovarian hormones decreased UR amplitudes, although differences in UR amplitudes were not associated with changes in the acquisition process. These results are discussed with respect to differences in the hormonal effects upon acquisition versus extinction processes and how these data may explain reports of learning differences in women based on oral contraceptive usage.     

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.     

Brain asymmetry and human electrodermal conditioning

Two experiments are reviewed that demonstrate effects of brain laterality on human classical conditioning. Pictures of facial emotional expressions were used as conditioned stimuli (CSs) together with shock as unconditioned stimlus (UCS). Bilateral electrodermal responses were recorded as dependent measures. In the first experiment, one group was conditioned to an angry face, and one group to a happy face. During extinction, the face-CSs were presented to the right hemisphere on half of the trials and to the left hemisphere on the other half of the trials. Results showed that the right hemisphere was superior in showing persisting effects of learning, and especially to the angry CS+. In the second experiment, lateralized presentations of the angry and happy faces were made during acquisition, with foveal presentations during extinction. Once again, the angry face elicited greater skin conductance responses (SCRs) during extinction in the group that had this stimulus presented to the right hemisphere during acquisition. It is concluded that emotional conditioning is differentially regulated by the two hemispheres of the brain.     

Conditioned Inhibition Produced by Extinction of a Conditioned Stimulus

Four experiments used a conditioned taste aversion procedure to examine the potential for CS-alone extinction treatment to produce a conditioned stimulus that possesses inhibitory properties. In Experiment 1, saccharin was paired with LiCl, and then saccharin was presented alone for several trials to produce extensive behavioral extinction. Animals receiving this treatment were retarded in reacquiring conditioned responding to saccharin relative to control subjects receiving conditioning to the flavor for the first time. In Experiment 2, the extinguished saccharin stimulus was shown to decrease conditioned responding to a known excitor when the two stimuli were presented in compound as a summation test. Experiments 3A and 3B replicated the findings of Experiments 1 and 2 while providing evidence that the effects were not due to the differential effects of neophobia during testing. These three experiments revealed that an extinguished conditioned excitor passes retardation and summation tests for conditioned inhibition. Experiment 4 found that extinction of a known excitor was slowed when the excitor was extinguished in compound with a previously extinguished conditioned stimulus. That is, an extinguished CS provided protection from extinction to another CS, a finding also consistent with the view that extinction produces conditioned inhibition.     

Selection for conditionability in Drosophila melanogaster.

Successful bidirectional selective breeding of Drosophila melanogaster for excitatory conditionability is reported, using the reliable measures of individual differences (first described by Holliday & Hirsch, 1984, 1986a, 1986b) to test 1,324 animals. Bidirectional selective breeding for good and poor conditioning has produced, respectively, one population in which the percentage of animals showing good conditioning has increased over 25 generations from 19% to 77% and another in which it has decreased over 23 generations to 0%-4%. No increase in a measure of sensitization induced by an unconditioned stimulus (the central excitatory state) accompanied the increase in the percentage of good conditioners in the population selected for good conditioning, whose level of conditioned responding exceeds that of the sensitization measure.     

Extinguishing conditioned inhibition in flavour-aversion learning: Effects of repeated testing and extinction of the excitatory element

Three conditioned inhibition experiments using an A+/AX- design are reported in which lithium-mediated excitatory conditioning occurred to distinctive environmental stimuli and inhibitory conditioning to a vinegar flavour. Increased vinegar preferences were observed (i.e., conditioned inhibition) in each experiment, and these preferences extinguished with repeated testing as well as following extinction of the excitatory element. Vinegar preferences could be reinstated through reconditioning of the extinguished excitatory stimulus. These experiments speak to the status of inhibitory responding as a “slave” process to conditioned excitation.