Elsevier

Biological Psychiatry

Volume 60, Issue 4, 15 August 2006, Pages 329-336
Biological Psychiatry

Review
Brain Mechanisms of Fear Extinction: Historical Perspectives on the Contribution of Prefrontal Cortex

https://doi.org/10.1016/j.biopsych.2005.10.012Get rights and content

What brain regions are involved in regulating behavior when the emotional consequence of a stimulus changes from harmful to harmless? One way to address this question is to study the neural mechanisms underlying extinction of Pavlovian fear conditioning, an important form of emotional regulation that has direct relevance to the treatment of human fear and anxiety disorders. In fear extinction, the capacity of a conditioned stimulus to elicit fear is gradually reduced by repeatedly presenting it in the absence of any aversive consequence. In recent years there has been a dramatic increase in research on the brain mechanisms of fear extinction. One region that has received considerable attention as a component of the brain’s extinction circuitry is the medial prefrontal cortex (mPFC). In the present article, we review the historical foundations of the modern notion that the mPFC plays a critical role in emotional regulation, a literature that was largely responsible for studies that explored the role of the mPFC in fear extinction. We also consider the role of the mPFC in a broader neural circuit for extinction that includes the amygdala and hippocampus.

Section snippets

What Is Extinction?

The term extinction is usually used to refer to the weakening of a response to a stimulus that acquired aversive properties through learning. In addition to studying the conditioning and extinction of salivation in response to a CS that predicts food, Pavlov also studied defensive CRs, which were responses elicited by a CS paired with aversive stimulation (Pavlov 1927). In contemporary parlance, defensive conditioning is called fear conditioning. After pairing of the CS and US, usually a tone

How Does the Brain Mediate Extinction?

Given the central role the amygdala plays in fear learning (Davis 1992, Fendt and Fanselow 1999, LeDoux 2000, Paré et al 2004, Sah et al 2003), it is not surprising that contemporary research considers the amygdala to be a key brain region related to extinction, either as a site of critical plasticity or as a site of expression. Indeed, several recent electrophysiological (Hobin et al 2003, Quirk et al 1995, Quirk et al 1997, Repa et al 2001, Rogan et al 1997), molecular (Davis 2002, Lin et al

Clinical Implications

Understanding the neural mechanisms of Pavlovian fear extinction is likely to have important implications for the treatment of humans with fear and anxiety disorders. Cognitive–behavior therapy (CBT) in humans is based on extinction and typically involves exposure to fear-eliciting cues in a safe setting (Barlow 2002, Foa and Jaycox 1999, Wolpe 1968). Cognitive–behavior therapy is widely used today and remains one of the most effective therapies for pathological anxiety, such as phobias, panic,

Future Considerations

The brain mechanisms of emotional regulation have been a topic of interest for centuries, and for good reason. Emotional regulation is critical for adapting to change and for the maintenance of stable social groups. Pavlovian fear extinction is a particularly important, and relatively simple, form of emotional regulation.

Future research will undoubtedly seek to understand how the PFC, amygdala, and hippocampus interact to fully encode the extinction memory and coordinate its expression. These

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