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 ...

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.

The impact of using motion estimates as covariates of no interest was examined in general linear modeling (GLM) of both block design and rapid event-related functional magnetic resonance imaging (fMRI) data. The purpose of motion correction is to identify and eliminate artifacts caused by task-correlated motion while maximizing sensitivity to true activations. To optimize this process, a combination of motion correction approaches was applied to data from 33 subjects performing both a block-design and an event-related fMRI experiment, including analysis: (1) without motion correction; (2) with motion correction alone; (3) with motion-corrected data and motion covariates included in the GLM; and (4) with non-motion-corrected data and motion covariates included in the GLM. Inclusion of covariates was found to be generally useful for increasing the sensitivity of GLM results in the analysis of event-related data. When motion parameters were included in the GLM for event-related data, it made little difference if motion correction was actually applied to the data. For the block design, inclusion of motion covariates had a deleterious impact on GLM sensitivity when even moderate correlation existed between motion and the experimental design. Based on these results, we present a general strategy for block designs, event-related designs, and hybrid designs to identify and eliminate probable motion artifacts while maximizing sensitivity to true activations.

Anxious temperament (AT) in human and non-human primates is a trait-like phenotype evident early in life that is characterized by increased behavioural and physiological reactivity to mildly threatening stimuli 1–4. Studies in children demonstrate that AT is an important risk factor for the later development of anxiety disorders, depression, and comorbid substance abuse 5. Despite its importance as an early predictor of psychopathology, little is known about the factors that predispose vulnerable children to develop AT and the brain systems that underlie its expression. To characterize the neural circuitry associated with AT and the extent to which the function of this circuit is heritable, we performed a study in a large sample of rhesus monkeys phenotyped for AT. Using 238 young monkeys from a multigenerational single-family pedigree, we simultaneously assessed brain metabolic activity and AT while monkeys were exposed to the relevant ethological condition that elicits the phenotype. High-resolution 18F-deoxyglucose positron emission tomography (FDG-PET) was selected as the imaging modality since it provides semi-quantitative indices of absolute glucose metabolic rate, allows for simultaneous measurement of behaviour and brain activity, and has a time course suited to assess temperament-associated sustained brain responses. Results demonstrated that the central nucleus region of amygdala and the anterior hippocampus are key components of the neural circuit predictive of AT. Quantitative genetic analysis demonstrated significant heritability of the AT phenotype. Additionally, a voxelwise analysis revealed significant heritability of metabolic activity in AT-associated hippocampal regions. However, activity in the amygdala region predictive of AT was not significantly heritable. Furthermore, the heritabilities of the hippocampal and amygdala regions significantly differed from each other. Even though these structures are closely linked, the results suggest differential influences of genes and environment on how these brain regions mediate AT and the ongoing risk to develop anxiety and depression.

Dispositional negativity—the propensity to experience and express more frequent, intense, or enduring negative affect—is a fundamental dimension of childhood temperament and adult personality. Elevated levels of dispositional negativity can have profound consequences for health, wealth, and happiness, drawing the attention of clinicians, researchers, and policy makers. Here, we highlight recent advances in our understanding of the psychological and neurobiological processes linking stable individual differences in dispositional negativity to momentary emotional states. Self-report data suggest that three key pathways—increased stressor reactivity, tonic increases in negative affect, and increased stressor exposure—explain most of the heightened negative affect that characterizes individuals with a more negative disposition. Of these three pathways, tonically elevated, indiscriminate negative affect appears to be most central to daily life and most relevant to the development of psychopathology. New behavioral and biological data provide insights into the neural systems underlying these three pathways and motivate the hypothesis that seemingly ‘tonic’ increases in negative affect may actually reflect increased reactivity to stressors that are remote, uncertain, or diffuse. Research focused on humans, monkeys, and rodents suggests that this indiscriminate negative affect reflects trait-like variation in the activity and connectivity of several key brain regions, including the central extended amygdala and parts of the prefrontal cortex. Collectively, these observations provide an integrative psychobiological framework for understanding the dynamic cascade of processes that bind emotional traits to emotional states and, ultimately, to emotional disorders and other kinds of adverse outcomes.