ReviewNature and causes of the immediate extinction deficit: A brief review
Introduction
Behavioral interventions for pathological fear often involve exposure therapy in which cues or reminders of trauma-related events are used to evoke fear memories in a safe and controlled setting. It is widely believed that exposure therapy relies, at least in part, on extinction learning (Bouton et al., 2001, Craske et al., 2008, Rothbaum and Davis, 2003). In this form of learning, subjects learn that once fearful cues no longer predict an aversive consequence. Extinction procedures do not erase fear memories, but result in new inhibitory associations between the now safe cue and its formerly aversive outcome (Bouton, 1993). The inhibitory associations acquired during exposure therapy lead to a reduction of fear and have considerable therapeutic benefits. Not surprisingly, extinction learning has become an important translational model for developing behavioral interventions for fear and anxiety disorders (Milad & Quirk, 2012).
Curiously, recent data in both rodents and humans suggests that the timing of extinction relative to fear conditioning influences the magnitude of fear reduction after extinction (Golkar and Öhman, 2012, Huff et al., 2009, Maren and Chang, 2006, Myers et al., 2006, Norrholm et al., 2008). In many cases, administering extinction trials soon after fear conditioning results in no long-term fear suppression at all – the so-called immediate extinction deficit (Chang et al., 2010, Chang and Maren, 2009, Chang and Maren, 2011, Kim et al., 2010, MacPherson et al., 2013, Maren and Chang, 2006). Interestingly, the administration of extinction trials soon after fear conditioning often produces within-session decrements in fear, but this is not maintained over long retention intervals resulting in the spontaneous recovery of fear. The clinical implications of this finding are clear: widely practiced early interventions after psychological trauma may be ineffective in producing long-term fear reduction. Indeed, a review of several studies of early intervention after trauma finds that they are largely ineffective at reducing post-traumatic stress and other anxiety disorders (Bryant, 2002, McNally et al., 2003). Because of the difficult clinical problem of fear relapse after behavioral therapies, the last several years have witnessed a swell of interest in understanding the factors, including the acquisition–extinction interval, that regulate the recovery of fear after extinction (Maren, 2011).
Here I review recent work in rodents and humans examining the influence of the timing of extinction relative to conditioning on the subsequent suppression of fear. In many cases, delivering extinction trials soon after conditioning produces weak long-term extinction, which, in the case of fear conditioning, is associated with a rapid return of fear responses. I suggest that extinction is most effective at some delay after conditioning, because the severe stress that accompanies trauma engages brain systems involved in acquiring fear memories, and these systems in turn inhibit those involved in fear extinction.
Section snippets
Nature of the immediate extinction deficit
In an extinction procedure, subjects receive non-reinforced presentations of a conditioned stimulus (CS), which ultimately yield suppression of the conditional response (CR). The loss of conditional responding that occurs after extinction is both temporary and context-dependent (Bouton, 1993, Delamater, 2004). That is, extinguished CRs return with the passage of time (i.e., spontaneous recovery) and with changes in context (i.e., renewal). Clearly, spontaneous recovery indicates that the
Causes of the immediate extinction deficit
Two general classes of explanations have been offered to account for the spontaneous recovery of conditional responding after immediate extinction (Maren & Chang, 2006). Importantly, these explanations are not mutually exclusive. One class of explanation appeals to the interference of acquisition and extinction memories during memory retrieval at the time of retention testing. The notion that the resolution of interference between competing memories has had considerable success in accounting
Neural mechanisms underlying the immediate extinction deficit
Neurobiological investigation of the immediate extinction deficit has focused on the medial prefrontal cortex (mPFC) given its prominent role in the encoding and retrieval of extinction memories (Herry et al., 2010, Milad and Quirk, 2012, Orsini and Maren, 2012, Quirk and Mueller, 2008). The initial studies to investigate the phenomenon used Fos immunohistochemistry (Kim et al., 2010) and single-unit recording methods (Chang et al., 2010) to examine neuronal activity in the mPFC after immediate
Conclusions
A considerable body of evidence now suggests that the timing of extinction after conditioning influences the durability of extinction memory. Short intervals between fear conditioning and extinction result in the spontaneous recovery of fear within 24 h after extinction. Although the precise mechanisms underlying this effect are under active investigation, mounting evidence suggests that the arousal of fear before extinction may interfere with the brain systems involved in encoding and
Acknowledgment
Supported by the National Institutes of Health (R01MH065961).
References (57)
- et al.
Consolidation of fear extinction requires NMDA receptor-dependent bursting in the ventromedial prefrontal cortex
Neuron
(2007) - et al.
Optimizing inhibitory learning during exposure therapy
Behaviour Research and Therapy
(2008) - et al.
Fear extinction in humans: Effects of acquisition–extinction delay and masked stimulus presentations
Biological Psychology
(2012) - et al.
Auditory-evoked spike firing in the lateral amygdala and Pavlovian fear conditioning: Mnemonic code or fear bias?
Neuron
(2003) Seeking a spotless mind: Extinction, deconsolidation, and erasure of fear memory
Neuron
(2011)- et al.
The brain on stress: Vulnerability and plasticity of the prefrontal cortex over the life course
Neuron
(2013) - et al.
Chronic stress impairs recall of extinction of conditioned fear
Neurobiology of Learning and Memory
(2006) - et al.
Neural and cellular mechanisms of fear and extinction memory formation
Neuroscience and Biobehavioral Reviews
(2012) - et al.
Fear conditioning enhances short-latency auditory responses of lateral amygdala neurons: Parallel recordings in the freely behaving rat
Neuron
(1995) - et al.
Chronic stress alters neural activity in medial prefrontal cortex during retrieval of extinction
Neuroscience
(2011)