Review
Emotional processing in anterior cingulate and medial prefrontal cortex

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Negative emotional stimuli activate a broad network of brain regions, including the medial prefrontal (mPFC) and anterior cingulate (ACC) cortices. An early influential view dichotomized these regions into dorsal–caudal cognitive and ventral–rostral affective subdivisions. In this review, we examine a wealth of recent research on negative emotions in animals and humans, using the example of fear or anxiety, and conclude that, contrary to the traditional dichotomy, both subdivisions make key contributions to emotional processing. Specifically, dorsal–caudal regions of the ACC and mPFC are involved in appraisal and expression of negative emotion, whereas ventral–rostral portions of the ACC and mPFC have a regulatory role with respect to limbic regions involved in generating emotional responses. Moreover, this new framework is broadly consistent with emerging data on other negative and positive emotions.

Section snippets

Controversies about anterior cingulate and medial prefrontal functions

Although the medial walls of the frontal lobes, comprising the anterior cingulate cortex (ACC) and the medial prefrontal cortex (mPFC), have long been thought to play a critical role in emotional processing [1], it remains uncertain what exactly their functional contributions might be. Some investigators have described evaluative (appraisal) functions of the ACC and mPFC, such as representation of the value of stimuli or actions 2, 3, 4 and the monitoring of somatic states [5]. Others hold that

Fear conditioning and extinction in humans

The paradigms used in the acquisition and extinction of learned fear are particularly valuable for isolating the neural substrates of fear processing because the anticipatory fear or anxiety triggered by the previously neutral conditioned stimulus (CS) can be dissociated from the reaction to the aversive unconditioned stimulus (US) per se. This is not possible in studies that, for example, use aversive images to evoke emotional responses. Furthermore, comparison between fear conditioning and

Emotional conflict regulation

Convergent evidence of the functional differentiation between dorsal and ventral ACC and mPFC comes from work on emotional conflict. Two recent studies used a task that required subjects to categorize face stimuli according to their emotional expression (fearful vs happy) while attempting to ignore emotionally congruent or incongruent word labels (Happy, Fear) superimposed over the faces. Emotional conflict, created by a word label incongruent with the facial expression, substantially slowed

Top-down control of emotion

During emotional conflict regulation, emotional processing is spontaneously modulated in the absence of an explicit instruction to regulate emotion. Emotional processing can also be modulated through deliberate and conscious application of top-down executive control over processing of an emotional stimulus. The best-studied strategy for the latter type of regulation is reappraisal, a cognitive technique whereby appraisal of a stimulus is modified to change its ability to elicit an emotional

Amygdala–ACC and –mPFC functional connectivity

Our analysis of the neuroimaging data has emphasized task-based activation studies. Complementary evidence can be found in analyses of functional connectivity, because ACC and mPFC subregions can be distinguished through their differential anatomical connectivity (Box 1). In some ways, psychological context-specific temporal covariation (i.e. task-dependent connectivity) between regions might provide an even stronger test of the nature of inter-regional relationships than consistency with

Integration with other perspectives on ACC and mPFC function and other emotions

Although less developed than the literature on fear and anxiety, studies on other emotions are broadly consistent with our formulation of ACC and mPFC function. On the negative emotion appraisal and expression side, direct experience of pain, or empathy for others experiencing pain, activates the dorsal ACC and mPFC [49], and lesions of the dACC also serve as treatment for chronic pain [50]. Similarly, increased sensitivity to a range of negative emotions is associated with greater engagement

Concluding remarks

This review has highlighted several important themes. First, the empirical data do not support the long-held popular view that dorsal ACC and mPFC regions are involved in cognitive but not emotional functions, whereas ventral regions do the reverse [12]. Rather, the key functional distinction between these regions relates to evaluative function on the one hand, and regulatory function on the other hand for the dorsal and ventral ACC and mPFC, respectively (Figure 3). This new framework can also

Disclosure statement

Amit Etkin receives consulting fees from NeoStim. The other authors report no financial conflicts.

Acknowledgements

We would like to thank Gregory Quirk, Kevin LaBar, James Gross and Carsten Wotjak for their helpful comments and criticisms of this manuscript. This work was supported by NIH grants P30MH089888 and R01MH091860, and the Sierra-Pacific Mental Illness Research Education and Clinical Center at the Palo Alto VA Health Care System.

Glossary

Appraisal
evaluation of the meaning of an internal or external stimulus to the organism. Only stimuli that are appraised as motivationally significant will induce an emotional reaction, and the magnitude, duration and quality of the emotional reaction are a direct result of the appraisal process. Moreover, appraisal can be automatic and focus on basic affective stimulus dimensions such as novelty, valence or value, or expectation discrepancy, or may be slower and sometimes even require

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