Background Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia—namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood. Methods Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards. Results Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward. Conclusions The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.

Although research has demonstrated a relationship between proinflammatory cytokine activity and depressive symptoms, the neurocognitive processes underlying this relationship have remained largely unexplored. Here, we examined the effect of proinflammatory cytokine activation on the neural correlates of socially painful experience and associated depressed mood. Participants received either low-dose endotoxin or placebo through intravenous injection. Levels of the proinflammatory cytokine, IL-6, were repeatedly assessed through hourly blood draws; self-reported depressed mood was assessed hourly as well. Two hours post-injection, participants completed a neuroimaging session in which they were socially excluded during an online ball-tossing game. Replicating previous research, individuals exposed to endotoxin, compared to placebo, showed increases in IL-6 levels and depressed mood. Although there were no meaningful differences between the endotoxin and control groups in neural responses to social exclusion, there were sex differences in the relationships between IL-6 increases and neural responses to exclusion among subjects exposed to endotoxin. Among females, but not males, exposed to endotoxin, increases in IL-6 were associated with increases in social pain-related neural activity (dorsal anterior cingulate cortex, anterior insula) that mediated the relationship between IL-6 increases and depressed mood increases. Implications of these sex differences in the neural correlates of cytokine-associated depressed mood and social pain are discussed.

Previous neuroimaging studies on empathy have not clearly identified neural systems that support the three components of empathy: affective congruence, perspective-taking, and prosocial motivation. These limitations stem from a focus on a single emotion per study, minimal variation in amount of social context provided, and lack of prosocial motivation assessment. In the current investigation, 32 participants completed a functional magnetic resonance imaging session assessing empathic responses to individuals experiencing painful, anxious, and happy events that varied in valence and amount of social context provided. They also completed a 14-day experience sampling survey that assessed real-world helping behaviors. The results demonstrate that empathy for positive and negative emotions selectively activates regions associated with positive and negative affect, respectively. In addition, the mirror system was more active during empathy for context-independent events (pain), whereas the mentalizing system was more active during empathy for context-dependent events (anxiety, happiness). Finally, the septal area, previously linked to prosocial motivation, was the only region that was commonly activated across empathy for pain, anxiety, and happiness. Septal activity during each of these empathic experiences was predictive of daily helping. These findings suggest that empathy has multiple input pathways, produces affect-congruent activations, and results in septally mediated prosocial motivation.

Empathy is a critical aspect of human emotion that influences the behavior of individuals as well as the functioning of society. Although empathy is fundamentally a subjective experience, no studies have yet examined the neural correlates of the self-reported experience of empathy. Furthermore, although behavioral research has linked empathy to prosocial behavior, no work has yet connected empathy-related neural activity to everyday, real-world helping behavior. Lastly, the widespread assumption that empathy is an automatic experience remains largely untested. It is also unknown whether differences in trait empathy reflect either variability in the automaticity of empathic responses or the capacity to feel empathy. In this study, 32 participants completed a diary study of helping behavior followed by an fMRI session, assessing empathic responses to sad images under three conditions: watching naturally, under cognitive load, and while empathizing. Across conditions, higher levels of self-reported experienced empathy were associated with greater activity in medial PFC (MPFC). Activity in MPFC was also correlated with daily helping behavior. Self-report of empathic experience and activity in empathy-related areas, notably MPFC, were higher in the empathize condition than in the load condition, suggesting that empathy is not a fully automatic experience. Additionally, high trait empathy participants displayed greater experienced empathy and stronger MPFC responses than low trait empathy individuals under cognitive load, suggesting that empathy is more automatic for individuals high in trait empathy. These results underline the critical role that MPFC plays in the instantiation of empathic experience and consequent behavior.

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There has been recent widespread interest in the neural underpinnings of the experience of empathy. In this review, we take a social cognitive neuroscience approach to understanding the existing literature on the neuroscience of empathy. A growing body of work suggests that we come to understand and share in the experiences of others by commonly recruiting the same neural structures both during our own experience and while observing others undergoing the same experience. This literature supports a simulation theory of empathy, which proposes that we understand the thoughts and feelings of others by using our own mind as a model. In contrast, theory of mind research suggests that medial prefrontal regions are critical for understanding the minds of others. In this review, we offer ideas about how to integrate these two perspectives, point out unresolved issues in the literature, and suggest avenues for future research.

Persuasion is at the root of countless social exchanges in which one person or group is motivated to have another share its beliefs, desires, or behavioral intentions. Here, we report the first three functional magnetic resonance imaging studies to investigate the neurocognitive networks associated with feeling persuaded by an argument. In the first two studies, American and Korean participants, respectively, were exposed to a number of text-based persuasive messages. In both Study 1 and Study 2, feeling persuaded was associated with increased activity in posterior superior temporal sulcus bilaterally, temporal pole bilaterally, and dorsomedial prefrontal cortex. The findings suggest a discrete set of underlying mechanisms in the moment that the persuasion process occurs, and are strengthened by the fact that the results replicated across two diverse linguistic and cultural groups. Additionally, a third study using region-of-interest analyses demonstrated that neural activity in this network was also associated with persuasion when a sample of American participants viewed video-based messages. In sum, across three studies, including two different cultural groups and two types of media, persuasion was associated with a consistent network of regions in the brain. Activity in this network has been associated with social cognition and mentalizing and is consistent with models of persuasion that emphasize the importance of social cognitive processing in determining the efficacy of persuasive communication. Here, we report the first three functional magnetic resonance imaging studies to investigate the neurocognitive networks associated with feeling persuaded by an argument. In the first two studies, American and Korean participants, respectively, were exposed to a number of text-based persuasive messages. In both Study 1 and Study 2, feeling persuaded was associated with increased activity in posterior superior temporal sulcus bilaterally, temporal pole bilaterally, and dorsomedial prefrontal cortex. The findings suggest a discrete set of underlying mechanisms in the moment that the persuasion process occurs, and are strengthened by the fact that the results replicated across two diverse linguistic and cultural groups. Additionally, a third study using region-of-interest analyses demonstrated that neural activity in this network was also associated with persuasion when a sample of American participants viewed video-based messages. In sum, across three studies, including two different cultural groups and two types of media, persuasion was associated with a consistent network of regions in the brain. Activity in this network has been associated with social cognition and mentalizing and is consistent with models of persuasion that emphasize the importance of social cognitive processing in determining the efficacy of persuasive communication. ■

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