PrefaceIt has been argued that emotion, pain, and cognitive control are functionally segregated in distinct subdivisions of the cingulate cortex. But recent observations encourage a fundamentally different view. Imaging studies indicate that negative affect, pain, and cognitive control activate an overlapping region of dorsal cingulate, the anterior midcingulate cortex (aMCC). Anatomical studies reveal that aMCC constitutes a hub where information about reinforcers can be linked to motor centers responsible for expressing affect and executing goal-directed behavior. Computational modeling and other kinds of evidence suggest that this intimacy reflects control processes that are common to all three domains. These observations compel a reconsideration of dorsal cingulate's contribution to negative affect and pain. † Manuscript Correspondence: Alexander J. Shackman (shackman@wisc.edu) or Tim V. Salomons (tvsalomons@gmail.com) Competing Interests StatementThe authors declare no competing financial interests. NIH Public Access Author ManuscriptNat Rev Neurosci. Author manuscript; available in PMC 2011 September 1. IntroductionIn humans and other primates, the cingulate, a thick belt of cortex encircling the corpus callosum, is one of the most prominent features on the mesial surface of the brain ( Figure 1a). Early research suggested that the rostral cingulate gyrus (Brodmann's 'precingulate' 1 ; architectonic areas 24, 25, 32, and 33) plays a key role in affect and motivation (Figure 1b) 2 .More recent research has enlarged the breadth of functions ascribed to this region; in addition to emotion 3 , the rostral cingulate plays a central role in contemporary models of pain 4, 5 and cognitive control 6,7 . Work in these three basic domains has, in turn, strongly influenced prominent models of social behavior 8 , psychopathology [9][10][11] , and neurological disorders 12 .Despite this progress, key questions about the functional organization and significance of activity in the rostral cingulate remain unresolved. Perhaps the most basic question is whether emotion, pain, and cognitive control are segregated into distinct subdivisions of the rostral cingulate or are instead integrated in a common region. In a pair of landmark reviews, Devinsky et al. 13 and Bush et al. 14 marshaled a broad range of functional imaging, electrophysiological, and anatomical data in support of functional segregation, arguing that the anterior cingulate cortex (ACC or 'rostral' ACC) is specialized for affective processes, whereas the midcingulate cortex (MCC or 'dorsal' ACC) is specialized for cognitive processes (Figure 1c, 1d). Subsequent meta-analyses of imaging studies have provided some support for this claim 15 .Although the segregationist model remains highly influential, new data suggests that it is no longer tenable. For instance, recent imaging data implicate MCC in the regulation of autonomic activity 16,17 and the perception and production of emotion 3,18 . Likewise, neuronal recordings demonstrate that MCC is responsive to ...

Evidence from imaging and anatomical studies suggests that the midcingulate cortex (MCC) is a dynamic hub lying at the interface of affect and cognition. In particular, this neural system appears to integrate information about conflict and punishment in order to optimize behavior in the face of action-outcome uncertainty. In a series of meta-analyses, we show how recent human electrophysiological research provides compelling evidence that frontal-midline theta signals reflecting MCC activity are moderated by anxiety and predict adaptive behavioral adjustments. These findings underscore the importance of frontal theta activity to a broad spectrum of control operations. We argue that frontal-midline theta provides a neurophysiologically plausible mechanism for optimally adjusting behavior to uncertainty, a hallmark of situations that elicit anxiety and demand cognitive control. These observations compel a new perspective on the mechanisms guiding motivated learning and behavior and provide a framework for understanding the role of the MCC in temperament and psychopathology.

Compassion is a key motivator of altruistic behavior, but little is known about individuals’ capacity to cultivate compassion through training. We examined whether compassion may be systematically trained by testing whether (i) short-term compassion training increases altruistic behavior, and (ii) individual differences in altruism are associated with training-induced changes in neural responses to suffering. In healthy young adults, we found that compassion training increased altruistic redistribution of funds to a victim encountered outside of the training context. Furthermore, greater altruistic behavior after compassion training was associated with altered activation in regions implicated in social cognition and emotion regulation, including the inferior parietal cortex, dorsolateral prefrontal cortex (DLPFC), and DLPFC connectivity with the nucleus accumbens. These results suggest that compassion can be cultivated with training, where greater altruistic behavior may emerge from increased engagement in neural systems implicated in understanding the suffering of others, executive and emotional control, and reward processing.

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad "spectrum level" dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the "problem of comorbidity" by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach.

On the basis of a review of the extant literature describing emotion-cognition interactions, the authors propose 4 methodological desiderata for studying how task-irrelevant affect modulates cognition and present data from an experiment satisfying them. Consistent with accounts of the hemispheric asymmetries characterizing withdrawal-related negative affect and visuospatial working memory (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively disrupted accuracy of spatial but not verbal WM performance. Furthermore, individual differences in physiological measures of anxiety statistically mediated the degree of disruption. A second experiment revealed that individuals characterized by high levels of behavioral inhibition exhibited more intense anxiety and relatively worse spatial WM performance in the absence of threat, solidifying the authors' inference that anxiety causally mediates disruption. These observations suggest a revision of extant models of how anxiety sculpts cognition and underscore the utility of the desiderata.

Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While upregulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in selfreported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.anhedonia ͉ emotion regulation ͉ nucleus accumbens

Two experiments using event-related potentials (ERPs) examined the extent to which early traumatic experiences affect children's ability to regulate voluntary and involuntary attention to threat. The authors presented physically abused and nonabused comparison children with conflicting auditory and visual emotion cues, posed by children's mothers or a stranger, to examine the effect of emotion, modality, and poser familiarity on attention regulation. Relative to controls, abused children overattended to task-relevant visual and auditory anger cues. They also attended more to task-irrelevant auditory anger cues. Furthermore, the degree of attention allocated to threat statistically mediated the relationship between physical abuse and child-reported anxiety. These findings indicate that extreme emotional experiences may promote vulnerability for anxiety by influencing the development of attention regulation abilities.

Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders.