From Extinction Learning to Anxiety Treatment: Mind the Gap (original) (raw)
Related papers
Modulation of the extinction of fear learning
Brain Research Bulletin, 2014
We review recent work on extinction learning with emphasis on its modulation. Extinction is the learned inhibition of responding to previously acquired tasks. Like other forms of learning, it can be modulated by a variety of neurotransmitter systems and behavioral procedures. This bears on its use in the treatment of fear memories, particularly in posttraumatic stress disorder (PTSD), for which it is the treatment of choice, often under the name of exposure therapy. There have not been many laboratories interested in the modulation of extinction, but the available data, although not very abundant, are quite conclusive. Most studies on the nature of extinction and on its modulation have been carried out on fear motivated behaviors, possibly because of their applicability to the therapy of PTSD. A role for d-serine and the glycine site of NMDA receptors has been ascertained in two forms of extinction in the ventromedial prefrontal cortex, basolateral amygdala and dorsal hippocampus. The serine analog, d-cycloserine, has received clinical trials as an enhancer of extinction. The brain histaminergic system acting via H2 receptors, and the endocannabinoid system using CB1 receptors in the ventromedial prefrontal cortex, hippocampus and basolateral amygdala enhance extinction. Dopaminergic D1 and -noradrenergic receptors also modulate extinction by actions on these three structures. Isolated findings suggest roles for on serotonin-1A, dopaminergic-D2 and ␣and -noradrenergic receptors in extinction modulation. Importantly, behavioral tagging and capture mechanisms in the hippocampus have been shown to play a major modulatory role in extinction. In addition, extinction of at least one aversive task (inhibitory avoidance) can be made state dependent on peripheral epinephrine.
The inhibition of acquired fear
2004
A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of disorders, among which are phobias, generalized anxiety, and the posttraumatic stress disorder (PTSD). The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "ïnternal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolida-tion, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most commonly studied in rodents. Therefore, it seems safe to continue using extinction-based forms of therapy for anxiety disorders secondary to acquired fear. Further, it is useful and desirable to devise procedures by which the "no US" component of the extinction is strengthened in order to alleviate the symptoms of victims of acquired fear.
Different forms of fear extinction are supported by distinct cortical substrates
Understanding how learned fear can be reduced is at the heart of treatments for anxiety disorders. Tremendous progress has been made in this regard through extinction training in which an expected aversive outcome is omitted. However, current progress almost entirely rests on this single paradigm, resulting in a very specialized knowledgebase at the behavioural and neural level of analysis. Here, we used a paradigm-independent approach to show that different methods that lead to reduction in learned fear are dissociated in the cortex. We report that the infralimbic cortex has a very specific role in fear reduction that depends on the omission of aversive events but not on overexpectation. The orbitofrontal cortex, a structure generally overlooked in fear, is critical for downregulating fear when fear is inflated or overexpected, but not when an aversive event is omitted.
A translational perspective on neural circuits of fear extinction: Current promises and challenges
Neurobiology of Learning and Memory
Fear extinction is the well-known process of fear reduction through repeated re-exposure to a feared stimulus without the aversive outcome. The last two decades have witnessed a surge of interest in extinction learning. First, extinction learning is observed across species, and especially research on rodents has made great strides in characterising the physical substrate underlying extinction learning. Second, extinction learning is considered of great clinical significance since it constitutes a crucial component of exposure treatment. While effective in reducing fear responding in the short term, extinction learning can lose its grip, resulting in a return of fear (i.e., laboratory model for relapse of anxiety symptoms in patients). Optimization of extinction learning is, therefore, the subject of intense investigation. It is thought that the success of extinction learning is, at least partly, determined by the mismatch between what is expected and what actually happens (prediction error). However, while much of our knowledge about the neural circuitry of extinction learning and factors that contribute to successful extinction learning comes from animal models, translating these findings to humans has been challenging for a number of reasons. Here, we present an overview of what is known about the animal circuitry underlying extinction of fear, and the role of prediction error. In addition, we conducted a systematic literature search to evaluate the degree to which state-of-the-art neuroimaging methods have contributed to translating these findings to humans. Results show substantial overlap between networks in animals and humans at a macroscale, but current imaging techniques preclude comparisons at a smaller scale, especially in sub-cortical areas that are functionally heterogeneous. Moreover, human neuroimaging shows the involvement of numerous areas that are not typically studied in animals. Results obtained in research aimed to map the extinction circuit are largely dependent on the methods employed, not only across species, but also across human neuroimaging studies. Directions for future research are discussed.
Evidence for recovery of fear following immediate extinction in rats and humans
Learning & Memory, 2008
Fear responses can be eliminated through extinction, a procedure involving the presentation of fear-eliciting stimuli without aversive outcomes. Extinction is believed to be mediated by new inhibitory learning that acts to suppress fear expression without erasing the original memory trace. This hypothesis is supported mainly by behavioral data demonstrating that fear can recover following extinction. However, a recent report by Myers and coworkers suggests that extinction conducted immediately after fear learning may erase or prevent the consolidation of the fear memory trace. Since extinction is a major component of nearly all behavioral therapies for human fear disorders, this finding supports the notion that therapeutic intervention beginning very soon after a traumatic event will be more efficacious. Given the importance of this issue, and the controversy regarding immediate versus delayed therapeutic interventions, we examined two fear recovery phenomena in both rats and humans: spontaneous recovery (SR) and reinstatement. We found evidence for SR and reinstatement in both rats and humans even when extinction was conducted immediately after fear learning. Thus, our data do not support the hypothesis that immediate extinction erases the original memory trace, nor do they suggest that a close temporal proximity of therapeutic intervention to the traumatic event might be advantageous. ; fax (212) 995-4349. Article is online at
Overlapping neural systems mediating extinction, reversal and regulation of fear
Trends in Cognitive Sciences, 2010
Learned fear is a process allowing quick detection of associations between cues in the environment and prediction of imminent threat. Adaptive function in a changing environment, however, requires organisms to quickly update this learning and have the ability to hinder fear responses when predictions are no longer correct. Here we focus on three strategies that can modify conditioned fear, namely extinction, reversal and regulation of fear, and review their underlying neural mechanisms. By directly comparing neuroimaging data from three separate studies that employ each strategy, we highlight overlapping brain structures that comprise a general circuitry in the human brain. This circuitry potentially enables the flexible control of fear, regardless of the particular task demands.
Neuronal circuits of fear memory and fear extinction
e-Neuroforum
The paradigm“eat or be eaten” has proven to be a critical guiding element during the evolution of both humans and animals. This helps to explain the fact that the ability to detect danger or a threat has been highly conserved throughout evolution and thus exhibits a high degree of homology between species. Studies in laboratory animals thereby enable the identification of key neurochemical, cellular and molecular mechanisms underlying fear and anxiety, and importantly, permit conclusions to be drawn regarding the situation in humans. This, in turn, provides a highly valuable basis for further improvements in prognosis, diagnosis, prevention and therapy of anxiety disorders. The present article focuses on one aspect central to translational anxiety research: the neuronal substrates and circuits of fear memory and fear extinction. Following a brief introduction into the principles of fear conditioning, the synaptic circuits that underlie the acquisition and extinction...
Behaviour Research and Therapy, 2018
Background: Fears underlying anxiety disorders are commonly treated with exposure-based therapies, which are based on the principles of extinction learning. While these treatments are efficacious, fears may return after successful treatment. Past research suggested that post-extinction recovery of fear could be reduced through extinction training that involves occasional presentations of the aversive unconditioned stimulus (US), paired with the conditioned stimulus (CS). Here, we examined whether extinction training with occasionally paired or unpaired US presentations is superior in the reduction of fear recovery to non-reinforced extinction. Method: Following differential fear conditioning to neutral cues, participants (N=72; M age=21.61 years, SD=3.95) underwent either non-reinforced, partially reinforced, or unpaired extinction training. Results: Extinction involving paired or unpaired US presentations, but not non-reinforced extinction, eliminated spontaneous recovery of differential skin conductance responses (SCRs). Results further suggested that unpaired, but not paired, US presentations may guard against rapid reacquisition of differential SCRs. No benefits of US presentations during extinction were found on the reinstatement of SCRs or recovery of differential negative CS+ valence. Conclusion: Presenting USs during extinction training was more effective than non-reinforced extinction in the reduction of fear recovery, as indexed by SCRs, with unpaired extinction being more effective than partially reinforced extinction.
Australian Journal of Psychology, 2016
Instructed extinction is an experimental manipulation which involves informing participants after the acquisition of fear learning that the unconditional stimulus will no longer be presented. It has been used as a laboratory analogue to assess the capacity of cognitive interventions to reduce experimentally induced fear. In this review we examine and integrate research on instructed extinction and discuss its implications for clinical practice. Overall, the results suggest that instructed extinction reduces conditional fear responding and facilitates extinction learning, except when conditional stimulus valence is assessed as an index of fear or when fear is conditioned to images of animal fear relevant stimuli (snakes and spiders) or with a very intense unconditional stimulus. These exceptions highlight potential boundary conditions for the reliance on cognitive interventions when treating fear in clinical settings.