A longitudinal study of the etiology of separation anxiety

A longitudinal examination of the relation between separation experiences and the development of separation anxiety at age 3, 11 and 18 years was conducted. Three associative pathways (Rachman, S.J. (1978). Fear and courage. San Francisco: W.H. Freeman) were assessed. Conditioning events were not related to separation anxiety at age 3. Vicarious learning (modelling) in middle childhood (age 9 years) was the conditioning variable most strongly related to separation anxiety at age 11, accounting for 1.8% of the variance in symptoms. Separation experiences (hospitalisations) before the age of 9 were inversely correlated with separation anxiety at age 18. That is, more overnight hospital stays in childhood were related to less separation anxiety in late adolescence. However, none of these conditioning correlates remained significant predictors of separation anxiety in adjusted regression models. In contrast, certain “planned” separations in early–mid childhood were associated with lower levels of separation anxiety at later ages. Generally, the findings were consistent with predictions from the non-associative theory of fear acquisition. That vicarious learning processes appeared to modulate, albeit to a minor degree, the expression of separation anxiety during mid–late childhood suggests that there may be critical periods during which some individuals are susceptible to the interactive effects of both associative and non-associative processes. These findings serve to illustrate the complexity of fear acquisition, the relevance of developmental factors and the likely interplay between associative and non-associative processes in the etiology of fear and anxiety.     

The origins of height fear: an evaluation of neoconditioning explanations

The present research sought to establish a reliable and valid instrument for assessing the relevance of neoconditioning factors (e.g. latent inhibition, UCS inflation/revaluation, prior fear levels, prior expectancies of harm, fear and pain levels experienced during supposed learning events), in the development of human fear. Fifty-four undergraduate height-fearful students completed the new origins instrument (OQ-II), while 54 matched controls completed a modified version (OQM-II) that examined their prior experiences with heights. In general, few differences between groups were found. Height-fearful and control subjects did not differ on trait anxiety, the frequency of negative encounters with heights, the age at which these events had occurred, prior fear levels, prior expectancies of harm, or reports of UCS inflation/revaluation procedures. However, in a finding directly opposite to that expected from a conditioning account, the mean fear and pain scores reported by subjects who had experienced direct conditioning events were significantly higher in the non-fearful group than in the height-fearful group. These findings are discussed in terms of associative and non-associative models of fear.     

The effect of amygdala lesions on conditional and unconditional vocalizations in rats

Electrolytic lesions centered on the amygdaloid central nucleus (ACe) resulted in the inability of rats to acquire a Pavlovian conditional vocalization response. Conditioning consisted of pairing a light conditional stimulus with a tailshock unconditional stimulus (US). The thresholds of three unconditional responses (URs) to tailshock were assessed prior to conditioning. These URs are organized at spinal (spinal motor reflexes), medullary (vocalizations during shock), and forebrain (vocalization afterdischarges, VADs) levels of the neuraxis. Compared to sham-lesioned controls, rats with amygdala lesions exhibited a selective elevation in the threshold of VADs. During conditioning the amplitude and duration of VADs were selectively reduced in amygdala-lesioned rats. These findings support earlier observations of that elicitation of VADs by tailshock correlates with the capacity of this US to support fear conditioning. The ACe may be involved in both associative and non-associative aspects of fear conditioning, but for progress in our understanding it is essential to evaluate its role in the generation of conditioning relevant URs.     

Non-associative fear acquisition: a review of the evidence from retrospective and longitudinal research

It is axiomatic that the capacity to experience fear is adaptive, enabling rapid and energetic response to imminent threat or danger. Despite the generally accepted utility of functional fear, the nature of maladaptive fear remains controversial. There is still no consensus about how specific fears and phobias are acquired and modulated. Two major schools of thought are apparent: those suggesting dysfunctional fear arises largely as the result of associative-conditioning processes versus those who favour more biologically based etiological explanations. In this regard, the non-associative model of fear acquisition postulates the existence of a limited number of innate, evolutionary-relevant fears, while emphasising conditioning modes of onset for evolutionary-neutral fears. Recent retrospective and longitudinal studies have tested predictions from the non-associative model. In general, findings support non-associative hypotheses and are difficult to reconcile with neo-conditioning explanations of fear acquisition. These data suggest that four pathways to fear may provide the most parsimonious theory of fear etiology. The theoretical and practical implications of adding a fourth, non-associative path to Rachman's (Behav. Res. Ther. (1977) 15, 375-387) three 'associative' pathways are discussed. Unresolved issues requiring further investigation are considered.     

On nonassociative fear emergence

Poulton and Menzies have articulated a nonassociative alternative to traditional conditioning theories of phobia emergence. Prompted by their essay, I address several issues including controversies about what counts as a conditioning event, difficulties establishing whether a fear functioned as an adaptation throughout evolutionary history, hazards of attempting to recover conditioning events in the histories of patients, and problems with the contingency view of associative learning.     

Nonassociative learning processes determine expression and extinction of conditioned fear in mice

Freezing to a tone following auditory fear conditioning is commonly considered as a measure of the strength of the tone-shock association. The decrease in freezing on repeated nonreinforced tone presentation following conditioning, in turn, is attributed to the formation of an inhibitory association between tone and shock that leads to a suppression of the expression of fear. This study challenges these concepts for auditory fear conditioning in mice. We show that acquisition of conditioned fear by a few tone-shock pairings is accompanied by a nonassociative sensitization process. As a consequence, the freezing response of conditioned mice seems to be determined by both associative and nonassociative memory components. Our data suggest that the intensity of freezing as a function of footshock intensity is primarily determined by the nonassociative component, whereas the associative component is more or less categorical. We next demonstrate that the decrease in freezing on repeated nonreinforced tone presentation following conditioning shows fundamental properties of habituation. Thus, it might be regarded as a habituation-like process, which abolishes the influence of sensitization on the freezing response to the tone without affecting the expression of the associative memory component. Taken together, this study merges the dual-process theory of habituation with the concept of classical fear conditioning and demonstrates that sensitization and habituation as two nonassociative learning processes may critically determine the expression of conditioned fear in mice.     

Neuroscience of Pavlovian conditioning: a brief review

Current knowledge on the neuronal substrates of Pavlovian conditioning in animals and man is briefly reviewed. First, work on conditioning in aplysia, that has showed amplified pre-synaptic facilitation as the basic mechanism of associative learning, is summarized. Then, two exemplars of associative learning in vertebrates, fear conditioning in rodents and eyelid conditioning in rabbits, are described and research into its neuronal substrates discussed. Research showing the role of the amygdala in fear conditioning and of the cerebellum in eyelid conditioning is reviewed, both at the circuit and cellular plasticity levels. Special attention is given to the parallelism suggested by this research between the neuronal mechanisms of conditioning and the principles of formal learning theory. Finally, recent evidence showing a similar role of the amygdala and of the cerebellum in human Pavlovian conditioning is discussed.     

Trait Anxiety and Fear Responses to Safety Cues: Stimulus Generalization or Sensitization?

Abnormal fear responding to threat cues may contribute to the aetiology and maintenance of persistent fears and pathological anxiety. Chronic anxiety may also involve abnormal fear responding to ??safety?? cues, which do not signal danger. Yet investigations of fear responding to acquired safety cues are scarce and the basis of such responding remains unclear. Moreover, previous studies do not distinguish between stimulus generalization (an associative mechanism based on perceptual similarity between threat and safety cues) and sensitization (a non-associative mechanism whereby fear responses to any novel, intense, or fear-related stimulus are temporarily elevated). This study investigated responses to acquired safety cues in volunteers with varying trait anxiety, using a novel fear conditioning paradigm designed to distinguish between effects of trait anxiety on generalization and sensitization. The paradigm used three conditioned stimuli: a threat cue (CS+) and two safety cues (CS?), one perceptually similar to the CS+ and one perceptually dissimilar. Conditioned fear to these cues was indexed by fear potentiation of the startle blink reflex, skin conductance responses, and self-report. To examine how trait anxiety moderated responses to safety cues, participants were divided into high and low trait anxiety subgroups. Startle, skin conductance, and self-reported fear measures indicated that generalization of fear occurred for the safety cue which resembled the threat cue, but not for the perceptually dissimilar safety cue, consistent with the stimulus generalization hypothesis. There was some evidence that stimulus generalization was exaggerated in anxious individuals. The current study sheds light on the mechanism by which fear responses to safety cues arise in healthy individuals, and offers some insight into the influence of this mechanism in chronic anxiety.     

Born to fear: non-associative vs associative factors in the etiology of phobias

Poulton and Menzies (Behaviour Research & Therapy 40 (2001) 127-149) review two lines of evidence as supporting a non-associative pathway to the origins of "evolutionary relevant phobias". First, in retrospective studies of mode of onset some recall they have always had this fear. We review here solid evidence that retrospective recall is notoriously unreliable. Second, they note as many nonphobics recall relevant associative learning experiences as do phobics. We argue such studies are very inconclusive because they fail to consider many experiential and personality vulnerability (and invulnerability) factors that strongly impact the outcome of any putative learning experience. Their argument also does not explain the transition from developmental fears to phobias that is central to their thesis. Overall, we call for major methodological improvements in this area, in the context of theoretical developments pointing to interacting vulnerability and invulnerability factors.     

Contingency theory and the distinction between associative and non-associative effects in classical conditioning

There is evidence to suggest that CS-US contingency is the variable that determines the associative effects of a CS. It has been claimed that experiments where contingency is manipulated allow us to distinguish between excitatory and inhibitory associative effects, and suggest a solution to the problem of finding a control procedure for non-associative effects. It is argued, however, that unless we can find a priori grounds for defining a level of contingency at which there are no associative effects, these claims are not justified. The reasons for this are that we have no way of distinguishing experimentally between associative and non-associative contributions to the effect of a CS, and that without such a technique there is no possibility of locating the point of associative neutrality empirically.     

Within-compound associations between the context and the conditioned stimulus

Three experiments were conducted to test for the presence of associations between contextual cues and the nominal conditioned stimulus (CS) in fear conditioning. Rats were given tone-footshock pairings and were tested for their fear of the nominal CS, the tone, in a different context. Experiments 1 and 2 demonstrated that rats given nonreinforced exposure to the training context following conditioning were less fearful of the CS. Experiment 3 indicated that additional footshock presentations in the training context following conditioning produced greater fear of the CS. In both procedures postconditioning treatments designed to directly alter only the associative strength of the training context yielded parallel changes in the conditioned response to the CS. These data suggest that within-compound associations are formed between the context and the CS during classical conditioning.     

Sensitization,conditioning, and learning: Can they help us understand somatization and disability?

This paper reviews those features of non-associative and associative forms of learning, as elaborated in the experimental literature, that might contribute to experienced and reported discomfort in the workplace. Emphasis is given to sensitization, while noting that some models of habituation (e.g. the opponent process model) also produce sensitization-like effects as a by-product that could contribute to persistent complaints. Also noted are ways in which these non-associative processes may enhance associative learning of workplace-avoidance behaviors that are exceptionally persistent - even in the absence of further somatic discomfort.     

The etiology of specific fears and phobias in children: a critique of the non-associative account

The non-associative account of phobic etiology assumes that a number of specific fears (e.g., fear of heights, water, spiders, strangers, and separation) have an evolutionary background and may occur in the absence of learning experiences (e.g., conditioning). By this view, these specific fears pertain to stimuli that once posed a challenge to the survival of our prehistoric ancestors. Accordingly, they would emerge spontaneously during the course of normal development and only in a minority of individuals, these specific fears would persist into adulthood. While the non-associative approach has generated interesting findings, several critical points can be raised. First, it capitalizes on negative findings, i.e., the failure to document learning experiences (e.g., conditioning, modeling) in the history of phobic children. Second, it largely ignores factors that have been found to be crucial for the acquisition of early childhood fears (e.g., the developmental level of the child, stimulus characteristics such as novelty, aversiveness, and unpredictability, and early experience with uncontrollable events). As an alternative to the non-associative account, we briefly describe a multifactorial model of childhood fears and phobias.     

Failure to overcome 'innate' fear: a developmental test of the non-associative model of fear acquisition

The non-associative, Darwinian theory of fear acquisition proposes that some individuals fail to overcome biologically-relevant fears (e.g. height) because they (1) do not have sufficient safe exposure to the relevant stimuli early in life or (2) are poor habituators who have difficulty 'learning not to fear'. These two hypotheses were tested in a longitudinal birth cohort study. Study 1 found evidence for reduced exposure to height stimuli in childhood for individuals with a fear of heights compared to study members without fear. Study 2 found evidence for higher levels of stress reactivity (a proxy for habituation) in childhood and adolescence among 18-year-old height phobics compared to study members with dental phobia and those with no fear. The results were discussed in relation to recent findings suggesting that some evolutionary-relevant fears may appear in the absence of traumatic 'learning' experiences. The merits of adding a fourth, non-associative pathway to Rachman's [Rachman, S. (1977)]. The conditioning theory of fear acquisition: a critical examination. Behaviour Research and Therapy, 15, 375-387) three pathways model of fear acquisition were briefly considered.     

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.     

Dishabituation processes in height fear and dental fear: an indirect test of the non-associative model of fear acquisition

The fear dishabituation hypothesis described in the non-associative model of fear acquisition was tested in a longitudinal birth cohort study. Results were consistent with height fear and phobia dishabituation. That is, 're-emergence' of a fear of heights occurred between age 11 and 18 years among individuals who reported higher levels of non-specific stress at age 15. Interestingly, there was no evidence for dental fear dishabituation--a finding consistent with the non-associative model of fear acquisition. Strengths and weaknesses of the study were considered and the results discussed in relation to laboratory-based findings on (dis)habituation.     

Trace eyeblink conditioning requires the hippocampus but not autophosphorylation of alphaCaMKII in mice

Little is known about signaling mechanisms underlying temporal associative learning. Here, we show that mice with a targeted point mutation that prevents autophosphorylation of alphaCaMKII (alphaCaMKII(T286A)) learn trace eyeblink conditioning normally. This forms a sharp contrast to the severely impaired spatial learning in the water maze and contextual fear conditioning observed in alphaCaMKII(T286A) mutants. Importantly, hippocampal lesions impaired trace eyeblink conditioning in alphaCaMKII(T286A) mice, suggesting a potential role of hippocampal alphaCaMKII-independent mechanisms. These results indicate that hippocampal signaling mechanisms that underlie temporal associative learning as assessed by trace eyeblink conditioning may differ from those of spatial and contextual learning.     

Generalization of contextual fear as a function of familiarity: the role of within- and between-context associations

Three experiments in rats investigated the generalization of conditioned fear from one context (B) to both a preexposed context (A) and a novel context (C). In each experiment, when the conditioning context (B) had been preexposed, there was greater generalization to context A than to context C; but when B was novel at the outset of conditioning this difference between A and C was not observed. The implications of these results for associative treatments of the development of contextual memories are evaluated.     

Translocation and activation of Rac in the hippocampus during associative contextual fear learning

Small G proteins including Rac are mediators of changes in neuronal morphology associated with synaptic plasticity. Previous studies in our laboratory showed that Rac is highly expressed in the adult mouse hippocampus, a brain area that exhibits robust synaptic plasticity and is crucial for the acquisition of memories. In this study, we investigated whether Rac was involved in NMDA receptor-dependent associative fear learning in the area CA1 of adult mouse hippocampus. We found that Rac translocation and activation was increased in the hippocampus following associative fear conditioning in mice, and that these increases are blocked by intraperitoneal injection of the NMDA receptor channel blocker MK801 at the acquisition stage. Our data indicate that NMDA receptor-dependent associative fear learning alters Rac localization and function in the mouse hippocampus.