Prefrontal involvement in the regulation of emotion: convergence of rat and human studies

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Emotion regulation is a process by which we control when and where emotions are expressed. Paradigms used to study the regulation of emotion in humans examine controlled responses to emotional stimuli and/or the inhibition of emotional influences on subsequent behavior. These processes of regulation of emotion trigger activation of the ventromedial prefrontal cortex and inhibition of the amygdala. A similar pattern of activation is seen in rodents during recall of fear extinction, an example of emotional regulation. The overlap in circuitry is consistent with a common mechanism, and points toward future experiments designed to bridge human and rodent models of emotion regulation.

Section snippets

Introduction: definition of emotion regulation

Regulation of emotion is a diverse set of control processes aimed at manipulating when, where, how and which emotion we experience and express [1]. These control processes can occur at both automatic and conscious levels of processing. Emotion can be regulated to accomplish various goals. For example, from an intrapersonal perspective, we regulate our emotions in at least two ways: to maximize opportunities for positive emotions and to minimize opportunities for negative emotions. First, we

Paradigms in humans: suppression, reappraisal and integration with cognition

Within the past two years, most of the human research in regulation of emotion has consisted of suppression or reappraisal paradigms. In suppression paradigms, participants are instructed to inhibit any reaction to emotional stimuli (e.g. sad films [3]; unpleasant pictures [4••]). In reappraisal paradigms, participants are instructed to reinterpret the picture in a new way to reduce or increase their emotional reaction (unpleasant pictures [5, 6, 7]). These paradigms focus on the regulation of

Regulation circuits in humans

What common neural substrates have emerged from human studies using these paradigms to examine regulation of emotion? Research in the past two years has reinforced the role of the prefrontal cortex in the regulation of emotion. In particular, a host of brain imaging studies have found activation in the orbitofrontal and/or inferior frontal cortex in association with suppressing or reappraising negative emotional stimuli (e.g. Brodmann's area [BA] 11 [3, 4••, 7]; BA 47 [3, 5, 6]) and with

Paradigms and circuits in rats: extinction of conditioned fear

Although it is a challenge to study regulation of emotion in rats, recent progress has been made on extinction of conditioned fear. In extinction, a tone previously paired with footshock is repeatedly presented without the shock, so that conditioned fear responses diminish. Because extinction does not erase the fear association, it can be thought of as regulating fear expression [13]. Similar to other forms of learning, extinction occurs in two phases: an initial learning phase and a subsequent

Extinction circuits in humans

Recently, functional and structural imaging techniques have been used to map extinction in humans. In agreement with rodent studies, extinction training activated the vmPFC in addition to the lateral amygdala [30]. Spurred by across-day extinction studies in rats, researchers are starting to test for recall of extinction in human subjects [31, 32]. Paralleling the results of rat studies, in humans recall of extinction (fear inhibition) learned the previous day is correlated with vmPFC blood

The prefrontal cortex is not purely inhibitory

Recent findings in rats suggest that the mPFC can also stimulate fear expression, under certain circumstances. Pharmacological inactivation of the mPFC in rats that have previously been fear conditioned reduces the expression of conditioned fear [18•, 34, 35], and interfering with molecular events necessary for plasticity in mPFC prevents acquisition of olfactory conditioning [36••] and trace fear conditioning [37]. The apparent discrepancy between these findings and the role of the mPFC

Conclusions and future directions

From the preceding discussion, there are several apparent areas of convergence between rat and human studies on regulation of emotion. Re-evaluation of negative stimuli, either through cognitive re-appraisal or suppression (humans) or through extinction (humans and rats), activates vmPFC and inhibits the amygdala. This suggests the existence of a medial inhibitory system capable of controlling amygdala responsiveness and expression of negative emotion. The circuitry of cognitive and Pavlovian

Update

Since writing this paper, a new fMRI study by Kalisch et al. [48] has appeared showing that recall of extinction learned the previous day activates the vmPFC and hippocampus in a context-dependent manner, suggesting that regulation of fear after extinction in humans involves a hippocampal-prefrontal circuit.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

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