Brain Mechanisms of Fear Extinction: Historical Perspectives on the Contribution of Prefrontal Cortex Francisco Sotres-Bayon, Christopher K. Cain, and Joseph E. LeDoux 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. Key Words: Emotion, conditioning, history, amygdala, hippocampus, exposure therapy over, a major approach to the treatment of emotional disorders involves the promotion of extinction (Barlow 2002; Craske 1999; Foa and Jaycox 1999; Wolpe 1968). Elucidation of the extinction process and how the brain mediates this process could thus lead to better understanding of, and therapies for, emotional disorders. In this introductory article, we will briefly discuss the nature of extinction and then consider the historical origins of contemporary work on the brain mechanisms of extinction. We concentrate on extinction of learned fear, because much of the recent work on extinction has involved fear conditioning. In discussing the brain mechanisms of extinction, we focus on research that led to the idea that the prefrontal cortex (PFC) plays a key role; however, in considering the contribution of the PFC to extinction we do not mean to minimize the importance of other areas. Thus, we discuss the PFC as a component of a broad fear extinction circuit involving the amygdala and hippocampus, among other areas.
he question of how the brain controls and regulates emotional expression is of great interest. Emotional regulation is likely to have evolutionary advantages, especially in highly social animals, such as humans (Darwin 1872). Indeed, society depends on the collective regulation of emotional expression. For example, certain forms of extreme emotional expression are viewed as immoral and/or illegal. The conference represented in this issue of Biological Psychiatry focused on a specific and important form of emotion regulation, extinction. Extinction was first formally studied by the Russian physiologist Ivan Pavlov (Pavlov 1927). In his famous experiments with dogs, a sound was presented just before the delivery of food. At first, the dog only salivated when food was in its mouth. After several repetitions of the sound and food, salivation began to occur at the sound in anticipation of the food. The food was called an unconditioned stimulus (US) and the sound a conditioned stimulus (CS). Accordingly, salivation to the food was designated an unconditioned response (UR) and salivation to the sound a conditioned response (CR). Pavlov then showed that when the CS was repeatedly presented without the US, the ability of the CS to elicit the CR weakened. He called this weakening of the CR experimental extinction. Although extinction has been studied experimentally for almost a century, it has recently become one of the hottest topics in neuroscience. Part of the reason for this new interest is that several key discoveries...
Please join StudyMode to read the full document