Bram Vervliet

Beyond extinction: erasing human fear responses and preventing the return of fear

Animal studies have shown that fear memories can change when recalled, a process referred to as reconsolidation. We found that oral administration of the β-adrenergic receptor antagonist propranolol before memory reactivation in humans erased the behavioral expression of the fear memory 24 h later and prevented the return of fear. Disrupting the reconsolidation of fear memory opens up new avenues for providing a long-term cure for patients with emotional disorders.

Dissociable Roles for the Hippocampus and the Amygdala in Human Cued versus Context Fear Conditioning

Lesion studies in animals have identified a critical role of the hippocampus in context fear conditioning. To extend these findings to human volunteers, we used functional magnetic resonance imaging to investigate neural responses associated with context fear conditioning in humans. Our novel conditioning paradigm consisted of aversive electrical shocks (unconditioned stimulus) that were delivered either cue or context related. Differential evoked responses, related to the conditioned stimulus (CS), were found in the anterior cingulate cortex and the bilateral insular cortices, regions that have been implicated in anticipatory anxiety. In case of context conditioning, a similar pattern was observed during the presentation of the entire context. In line with previous conditioning studies, differential responses in the amygdala showed a time by stimulus interaction, suggesting rapid adaptation of CS-specific responses. More importantly, a similar differential decay of activation was observed during context conditioning in the hippocampus, in agreement with a role of the hippocampus in the acquisition phase of human context fear conditioning.

Timing of extinction relative to acquisition: A parametric analysis of fear extinction in humans

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans.

Fear Generalization in Humans: Systematic Review and Implications for Anxiety Disorder Research

Fear generalization, in which conditioned fear responses generalize or spread to related stimuli, is a defining feature of anxiety disorders. The behavioral consequences of maladaptive fear generalization are that aversive experiences with one stimulus or event may lead one to regard other cues or situations as potential threats that should be avoided, despite variations in physical form. Theoretical and empirical interest in the generalization of conditioned learning dates to the earliest research on classical conditioning in nonhumans. Recently, there has been renewed focus on fear generalization in humans due in part to its explanatory power in characterizing disorders of fear and anxiety. Here, we review existing behavioral and neuroimaging empirical research on the perceptual and non-perceptual (conceptual and symbolic) generalization of fear and avoidance in healthy humans and patients with anxiety disorders. The clinical implications of this research for understanding the etiology and treatment of anxiety is considered and directions for future research described.

Role of Inhibition in Exposure Therapy

While many researchers have largely focused on principles of systematic desensitization and habituation in explaining fear extinction, these processes have mixed evidence at best. In particular, these models do not account for spontaneous recovery or reinstatement of fear, nor do they explain the context dependency of extinction or rapid reacquisition. This may in part account for the significant number of patients who fail to respond to our available treatments which rely on these principles in designing exposure sessions. However, recent research is converging to suggest that an inhibitory model of fear reduction, in which the original feared association (CS-US) remains but is inhibited by a newly formed association (CS-noUS) representing safety, holds promise in explaining the long-term attenuation of fear and anxiety. This paper reviews research in a number of areas, including neuroimaging, psychophysiology, and psychopharmacology that all provide support for the inhibition model of anxiety. Limitations to this body of research are discussed, along with recommendations for future research and suggestions for improving exposure therapy for fear and anxiety disorders. Clinical implications discussed in this paper include incorporating random and variable practice in exposure sessions, multiple contexts, and pharmacological aides, among others.

Advancing psychotherapy and evidence-based psychological interventions

Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom‐based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state‐of‐the‐art in psychotherapy treatment research, “component analyses” aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large‐scale public health strategies and treatments that can be applied to more patients in a simpler and cost‐effective way. Increased research on efficacy and moderators of Internet‐based treatments and e‐mental health tools (e.g. to support “real time” clinical decision‐making to prevent treatment failure or relapse) might be one promising way forward. Copyright

Extinction, generalization, and return of fear: A critical review of renewal research in humans

The main behavioral signature of fear extinction is its fragility. This is exemplified by the renewal effect, where a change in the background context produces recovery of fear to a conditioned-and-extinguished stimulus. Renewal is the backbone of a widely accepted theory of extinction in animal research, as well as an important experimental model to screen novel treatment techniques. This has led to an explosion of fear renewal research in humans. However, the mere observation of return of fear in a renewal procedure is not sufficient to validate this particular theory of extinction in the tested sample/procedure. Here, we systematically outline a set of experimental tests that aid in evaluating alternative extinction/renewal mechanisms. We examine published renewal studies in human fear conditioning and conclude that the prevailing theory of extinction is often taken for granted, but critical tests are lacking. Including these tests in future research will not only reveal the fear extinction mechanism in humans, but also inspire further developments in extinction treatment research.

Generalization versus contextualization in automatic evaluation.

Research has shown that automatic evaluations can be highly robust and difficult to change, highly malleable and easy to change, and highly context dependent. We tested a representational account of these disparate findings, which specifies the conditions under which automatic evaluations reflect (a) initially acquired information, (b) subsequently acquired, counterattitudinal information, or (c) a mixture of both. The account postulates that attention to contextual cues during the encoding of evaluative information determines whether this information is stored in a context-free representation or a contextualized representation. To the extent that attention to context cues is low during the encoding of initial information but is enhanced by exposure to expectancy-violating counterattitudinal information, initial experiences are stored in context-free representations, whereas counterattitudinal experiences are stored in contextualized representations. Hence, automatic evaluations tend to reflect the valence of counterattitudinal information only in the context in which this information was learned (occasion setting) and the valence of initial experiences in any other context (renewal effect). Four experiments confirmed these predictions, additionally showing that (a) the impact of initial experiences was reduced for automatic evaluations in novel contexts when context salience during the encoding of initial information was enhanced, (b) context effects were eliminated altogether when context salience during the encoding of counterattitudinal information was reduced, and (c) enhanced context salience during the encoding of counterattitudinal information produced context-dependent automatic evaluations even when there was no contingency between valence and contextual cues. Implications for automatic evaluation, learning theory, and interventions in applied settings are discussed.

Resistance to extinction in evaluative conditioning

A well-demonstrated phenomenon in traditional Pavlovian conditioning research with humans is that of experimental extinction. In contrast, human evaluative conditioning research suggests that evaluative learning shows marked resistance to extinction. Here, the authors replicate both findings concurrently. Two differential fear conditioning experiments with an electrocutaneous stimulus as the unconditioned stimulus evidenced (a) sensitivity to extinction using an autonomic skin-conductance measure and (b) complete resistance to extinction using an affective-priming measure. The results corroborate the idea that evaluative conditioning is more resistant to extinction than is expectancy learning (F. Baeyens, P. Eelen, & G. Crombez, 1995).

Contextual fear induced by unpredictability in a human fear conditioning preparation is related to the chronic expectation of a threatening US

The present study was set up to investigate cued and contextual fear in situations of (un)predictability in a human fear conditioning paradigm. Forty-nine participants were presented with two different contexts (switching on and off the central lighting of the experimental room). In the predictable context, a visual cue (CS1) was systematically followed by an electrocutaneous stimulus (US). In the unpredictable context, CS2 was presented explicitly unpaired with the US. Dependent variables were online US-expectancy ratings and fear-potentiated startle. First, in both measures, the results showed significantly more fear elicited by CS1 than by CS2. Second, larger startle amplitudes during the intertrial intervals demonstrated more contextual fear in the unpredictable than in the predictable context. Hence, these findings illustrate that unpredictability increases contextual fear. Moreover, the US-expectancy ratings during the intertrial intervals were also higher in the unpredictable than in the predictable context. This last finding suggests that a chronic expectation of the threatening US is responsible for sustained levels of anxiety in unpredictable situations.