Understanding clinical fear and anxiety through the lens of human fear conditioning

Abstract

Fear is an adaptive emotion that mobilizes defensive resources upon confrontation with danger. However, fear becomes maladaptive and can give rise to the development of clinical anxiety when it exceeds the degree of threat, generalizes broadly across stimuli and contexts, persists after the danger is gone or promotes excessive avoidance behaviour. Pavlovian fear conditioning has been the prime research instrument that has led to substantial progress in understanding the multi-faceted psychological and neurobiological mechanisms of fear in past decades. In this Perspective, we suggest that fruitful use of Pavlovian fear conditioning as a laboratory model of clinical anxiety requires moving beyond the study of fear acquisition to associated fear conditioning phenomena: fear extinction, generalization of conditioned fear and fearful avoidance. Understanding individual differences in each of these phenomena, not only in isolation but also in how they interact, will further strengthen the external validity of the fear conditioning model as a tool with which to study maladaptive fear as it manifests in clinical anxiety.

Keywords: Anxiety; Fear conditioning; Human behaviour; Psychology.

Fig. 1. Pavlovian fear conditioning.

In a Pavlovian fear conditioning procedure, an initially neutral conditioned stimulus (for example, a tone or a coloured circle presented on a computer screen) is paired with an inherently aversive stimulus (for example, electrical stimulation). After repeated pairings, the conditioned stimulus will come to elicit defensive responses even in the absence of the unconditioned stimulus. In rodents, this response is typically measured through freezing, suppression of lever-pressing or startle potentiation. In human fear conditioning, trials on which a conditioned stimulus (threat cue) is paired with the aversive unconditioned stimulus are typically interleaved with trials where a different conditioned stimulus (safety cue) is never followed by the unconditioned stimulus. Typical measurements in humans include skin conductance, startle potentiation, verbal reports and behavioural responses.

Fig. 2. Additional fear conditioning processes.

After fear acquisition via Pavlovian fear conditioning, various procedures can be used to study three key features of pathological anxiety in the laboratory. a, Extinction can be examined by repeatedly presenting the conditioned stimulus without the unconditioned stimulus. Evidence suggests that extinction is slower and less likely to be retained on a delayed test in individuals with clinical anxiety relative to non-anxious controls. b, Generalization can be investigated by presenting stimuli that vary in their perceptual or conceptual similarity to the conditioned stimulus. Evidence suggests that fear generalizes more broadly along a continuum of similarity in individuals with clinical anxiety relative to non-anxious controls. c, Avoidance can be studied by introducing a behavioural response that allows participants to avoid or escape the unconditioned stimulus, for example, giving participants access to a button that can prevent or stop the unconditioned stimulus. Emerging evidence suggests that imposing a cost for avoidance discourages avoidance less in individuals with clinical anxiety than in non-anxious controls.

Fig. 3. An integrated model of maladaptive fear learning.

a, After a threatening event, extinction, generalization and avoidance processes collectively and interactively determine an individual’s trajectory towards more or less adaptive fear responding, influenced by individual traits. As such, specific individual combinations (profiles) of extinction impairment, overgeneralization and excessive avoidance will confer differential risk for the development of clinical anxiety. b, Causal relations between extinction, avoidance and generalization that have been documented in the literature^,–. c, Further potential relationships between extinction, generalization and avoidance suggested in this article.