Multimodal classical conditioning of fear: contributions of direct, observational, and verbal experiences to current fears

The authors propose that a multimodal classical conditioning model be considered when clinicians or clinical researchers study the etiology of fears and anxieties learned by human beings. They argue that fears can be built through the combined effects of direct, observed, and verbally presented classical conditioning trials. Multimodal classical conditioning is offered as an alternative to the three pathways to fear argument prominent in the human fear literature. In contrast to the three pathways position, the authors present theoretical arguments for why "learning by observation" and "learning through the receipt of verbal information" should be considered classical conditioning through observational and verbal modes. The paper includes a demonstration of how data, commonly collected in research on the three pathways to fear, would be studied differently using a multimodal classical conditioning perspective. Finally, the authors discuss implications for assessment, treatment, and prevention of learned fears in humans.     

Stimulus properties of facial expressions and their influence on the classical conditioning of fear

The influence of particular stimulus properties of facial expressions of emotion upon associative learning to a neutral cue was examined in the present investigation. A compound stimulus, composed of either a fearful, happy, or neutral facial expression paired with a neutral cue (tone), signaled an aversive event (mild electric shock). Phasic change in skin conductance (SC) was used as the measure of associative learning. Analyses of variance revealed that subjects who saw a fearful expression paired with the tone gave larger SC responses to the fearful expression than to the tone. The opposite pattern was obtained for subjects who had a happy expression paired with the tone. Subjects who had the neutral expression paired with the tone showed no significant difference in their responses to the two stimuli. Results of the present investigation were consistent with those of an earlier study by Lanzetta and Orr (1980), and extend the earlier theoretical interpretations by suggesting that fear expressions function as excitatory stimuli and happy expressions act as inhibitory stimuli. Methodological changes in the present study, which include a shorter CS interval and asynchronous stimulus onsets, also extend the previous findings.This research was supported by National Science Foundation Grant No. 7912422-AO1 and by funds from the Lincoln Filene endowment to Dartmouth College.     

Pathways to fear in spider phobic children

Twenty-two children with spider phobia were interviewed about the origins of their fear. More specifically, children were asked about conditioning events, modeling experiences, and negative information transmission. To evaluate the reliability of the information provided by the children, parents were independently interviewed about the origins of their children's phobias. While 46% of the children claimed to have always been afraid, 41% ascribed the onset of their fear to aversive conditioning events. The large majority of these events were confirmed by parents. These findings cast doubts on a strong version of the non-associative account of spider phobia, i.e. the idea that spider phobia is acquired in the complete absence of learning experiences.     

Memory enhancement of classical fear conditioning by post-training injections of corticosterone in rats

There is extensive evidence that post-training administration of the adrenocortical hormone corticosterone facilitates memory consolidation processes in a variety of contextual and spatial-dependent learning situations. The present experiments examine whether corticosterone can modulate memory of auditory-cue classical fear conditioning, a learning task that is not contingent on contextual or spatial representations. Male Sprague-Dawley rats received three pairings of a single-frequency auditory stimulus and footshock, followed immediately by a post-training subcutaneous injection of either corticosterone (1.0 or 3.0mg/kg) or vehicle. Retention was tested 24h later in a novel test chamber and suppression of ongoing motor behavior served as the measure of conditioned fear. Corticosterone dose-dependently facilitated suppression of motor activity during the 10-s presentation of the auditory cue. As corticosterone administration did not alter responding after unpaired presentations of tone and shock, tone alone, shock alone or absence of tone/shock, the findings indicated that corticosterone selectively facilitated memory of the tone-shock association. Furthermore, injections of corticosterone given 3h after training did not alter motor activity during retention testing, demonstrating that corticosterone enhanced time-dependent memory consolidation processes. These findings provide evidence that corticosterone modulates the consolidation of memory for auditory-cue classical fear conditioning and are consistent with a wealth of data indicating that glucocorticoids can modulate a wide variety of emotionally influenced memories.     

The development of an attentional bias for angry faces following Pavlovian fear conditioning

Although it is well documented that fear responses develop following aversive Pavlovian conditioning, it is unclear whether fear learning also manifests in the form of attentional biases for fear-related stimuli. Boschen, Parker, and Neumann (Boschen, M. J., Parker, I., & Neumann, D. L. (2007). Changes in implicit associations do not occur simultaneously to Pavlovian conditioning of physiological anxiety responses. Journal of Anxiety Disorders, 21, 788-803.) showed that despite the acquisition of differential skin conductance conditioned responses to angry faces paired (CS+) and unpaired (CS−) with an aversive shock, development of implicit associations was not subsequently observed on the Implicit Association Test. In the present study, participants (N = 76) were assigned either to a Shock or NoShock group and completed a similar aversive Pavlovian conditioning procedure with angry face CS+ and CS− stimuli. Participants next completed a visual probe task in which the angry face CS+ and CS− stimuli were paired with angry face control stimuli and neutral faces. Results confirmed that differential fear conditioning was observed in the Shock group but not in the NoShock group, and that the Shock group subsequently showed a selective attentional bias for the angry face CS+ compared with the CS− and control stimuli during the visual probe task. The findings confirm the interplay between learning-based mechanisms and cognitive processes, such as attentional biases, in models of fear acquisition and have implications for treatment of the anxiety disorders.     

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.     

Naloxone and Pavlovian fear conditioning

Previous research has shown that pretreating rats with the opiate antagonist naloxone increases the freezing that follows painful electric shock. Three experiments, using freezing behavior as a dependent variable, were carried out to determine whether the drug might cause this effect by enhancing fear conditioning. Two of the studies employed a differential context fear-conditioning paradigm. Naloxone did not affect freezing behavior during the preshock adaptation period. In Experiment 1, naloxone was found to increase resistance to extinction in the S+ context. In Experiment 2, naloxone was found to increase freezing in the S+ context. This effect was dependent upon administering naloxone during training but not dependent on administering it during testing. The third study employed a generalization paradigm. It was found that naloxone's effect on postshock freezing was dependent on the place of testing; as the contextual cues of the test chamber were changed from those of the conditioning chamber, the effect of naloxone on freezing was reduced. The results of these experiments lend strong support to the hypothesis that naloxone increases freezing by enhancing the conditioning of fear to contextual stimuli associated with shock.     

Human classical conditioning

Recent reports of failure to obtain blocking in human galvanic skin response (GSR) conditioning, together with our own equivocal results with eyelid conditioning, have motivated us to re-examine the status of the conditioned stimulus (CS) in human conditioning studies. The issues raised by compound stimuli, by contextual cues and occasion setting stimuli, and by cross-modal transfer are considered in the light of data from our laboratories. These data include observations on the interchangeability of stimulus modalities during acquisition, the use of varying information loads embedded in occasion setting displays, the comparison of alternative blocking designs and the analysis of response topography in relation to stimulus variability. They suggested that an adequate account of the CS in human conditioning studies must recognize that it is dynamically processed and reprocessed both during and after acquisition.     

Conjunctive representations,the hippocampus,and contextual fear conditioning

The context in which events occur can be represented as both (1) a set of independent features, the feature representation view, and (2) a set of features bound into a unitary representation, the conjunction representation view. It is assumed that extrahippocampal (e.g., neocortical) areas provide a basis for feature representations, but the hippocampal formation makes an essential contribution to the automatic storage of conjunctive representations. We develop this dual-representation view and explore its implications for hippocampal contributions to contextual fear conditioning processes. To this end, we discuss how our framework can resolve some of the conflicts in the recent literature relating the hippocampus to contextual fear conditioning. We also present new data supporting the role of a key mechanism afforded by conjunctive representations—pattern completion (the ability of a subset of a memory pattern to activate the complete memory)—in contextual fear conditioning. As is implied by this mechanism, we report that fear can be conditioned to the memory representation of a context that is not actually present at the time of shock. Moreover, this result is predicted by our computational model of cortical and hippocampal function. We suggest that pattern completion demonstrated in animals and by our model provides a mechanistic bridge to human declarative memory.     

Macromolecular synthesis, distributed synaptic plasticity, and fear conditioning

Recent work from a number of laboratories has provided new and important insights about how gene expression is altered by experience and how these molecular changes may provide a substrate for the long-term storage of new memories. Here, we review a series of recent studies using aversive Pavlovian conditioning in rats as a well characterized model system in which experience-dependent alterations in gene expression can be manipulated and quantified within a specific neural circuit. We highlight some of the issues involved in using broad-spectrum inhibitors of mRNA and protein synthesis to study cellular changes underlying the formation and long-term stability of memory and discuss the idea that these changes occur over widespread, behaviorally-defined, networks of cells. We also discuss the idea that the maintenance of memory and its susceptibly to disruption after retrieval may relate to local protein synthesis in dendrites. Finally, a series of recent experiments from our laboratory studying the role of a specific signaling pathway (mTOR) which regulates translational processes and memory formation in the amygdala and hippocampus during fear conditioning are reviewed.     

Observational fear conditioning in the acquisition and extinction of attentional bias for threat: an experimental evaluation

Anxious persons show automatic and strategic attentional biases for threatening information. Yet, the mechanisms and processes that underlie such biases remain unclear. The central aim of the present study was to elucidate the relation between observational threat learning and the acquisition and extinction of biased threat processing by integrating emotional Stroop color naming tasks within an observational differential fear conditioning procedure. Forty-three healthy female participants underwent several consecutive observational fear conditioning phases. During acquisition, participants watched a confederate displaying mock panic attacks (UCS) paired with a verbal stimulus (CS+), but not with a second nonreinforced verbal stimulus (CS-). As expected, participants showed greater magnitude electrodermal and verbal-evaluative (e.g., distress, fear) conditioned responses to the CS+ over the CS- word. Participants also demonstrated slower color-naming latencies to CS+ compared to the CS- word following acquisition and showed attenuation of this preferential processing bias for threat following extinction. Findings are discussed broadly in the context of the interplay between fear learning and processing biases for threat as observed in persons suffering from anxiety disorders.     

The fear potentiated startle effect. Blink reflex modulation as a result of classical aversive conditioning

A differential conditioning study examined whether an acoustic startle probe, presented during extinction of an aversively conditioned visual stimulus, potentiated the reflex eyeblink response in humans and whether this potentiation varied with the change in affective valence of the conditioned stimulus. Sixty college students were randomly assigned to view a series of two slides, depicting either unpleasant/highly arousing, unpleasant/moderate arousing, neutral/calm, pleasant/moderate arousing or pleasant/highly arousing scenes and objects (duration: 8 sec). During preconditioning (8 trials) and extinction (24 trials) acoustic startle probes (white noise bursts [50 ms; 95 dBA] were administered during and between slide presentation). During acquisition (16 trials) CS+ was reinforced by an electric shock. Startle response magnitudes significantly increased from preconditioning to extinction and were substantially larger to CS+. Conditioned startle reflex augmentation linearly increased with the pleasantness of the slides. Furthermore, subjects showed a greater post-conditioning increase of judged aversiveness to slides that they had previously reported to be more pleasant, exactly paralleling the startle reflex results.     

Learning strategies during fear conditioning

This paper describes a model of fear learning, in which subjects have an option of behavioral responses to impending social defeat. The model generates two types of learning: social avoidance and classical conditioning, dependent upon (1) escape from or (2) social subordination to an aggressor. We hypothesized that social stress provides the impetus as well as the necessary information to stimulate dichotomous goal-oriented learning. Specialized tanks were constructed to subject rainbow trout to a conditioning paradigm where the conditioned stimulus (CS) is cessation of tank water flow (water off) and the unconditioned stimulus (US) is social aggression from a larger conspecific. Following seven daily CS/US pairings, approximately half of the test fish learned to consistently escape the aggression to a neutral chamber through a small escape hole available only during the interaction. The learning curve for escaping fish was dramatic, with an 1100% improvement in escape time over 7 days. Fish that did not escape exhibited a 400% increase in plasma cortisol and altered brain monoamine response to presentation of the CS alone. Elevated plasma cortisol levels represent classical fear conditioning in non-escaping fish, while a lack of fear conditioning and a decreased latency to escape over the training period in escapers indicates learned escape.     

Unblocking in Pavlovian fear conditioning

Six experiments used rats to study blocking and unblocking of fear learning. An excitatory stimulus (A) blocked fear learning to a neutral stimulus (B). Unblocking of B occurred if the AB compound signaled an increase in unconditioned stimulus (US) intensity or number. Assessments of associative change during blocking showed that more was learned about B than A. Such assessments during unblocking revealed that more was learned about B than A following an increase in US intensity but not US number. These US manipulations had no differential effects on single-cue learning. The results show that variations in US intensity or number produce unblocking of fear learning, but for each there is a different profile of associative change and a potentially different mechanism.     

Coantagonism of glutamate receptors and nicotinic acetylcholinergic receptors disrupts fear conditioning and latent inhibition of fear conditioning

The present study investigated the hypothesis that both nicotinic acetylcholinergic receptors (nAChRs) and glutamate receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPARs) and N-methyl-d-aspartate glutamate receptors (NMDARs)) are involved in fear conditioning, and may modulate similar processes. The effects of the nAChR antagonist mecamylamine administered alone, the AMPAR antagonist NBQX administered alone, and the NMDAR antagonist MK-801 administered alone on cued fear conditioning, contextual fear conditioning, and latent inhibition of cued fear conditioning were examined. In addition, the effects of coadministration of either mecamylamine and NBQX or mecamylamine and MK-801 on these behaviors were examined. Consistent with previous studies, neither mecamylamine nor NBQX administered alone disrupted any of the tasks. However, coadministration of mecamylamine and NBQX disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. In addition, coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting either task disrupted both contextual fear conditioning and latent inhibition of cued fear conditioning. Coadministration of mecamylamine and NBQX, and coadministration of mecamylamine with a dose of MK-801 subthreshold for disrupting fear conditioning had little effect on cued fear conditioning. These results suggest that nAChRs and glutamate receptors may support similar processes mediating acquisition of contextual fear conditioning and latent inhibition of fear conditioning.