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Accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention which refers to attention towards physiological signals arising from the body. However, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. Results showed that interoceptive attention was associated with increased AIC activation, as well as enhanced coupling between the AIC and somatosensory areas along with reduced coupling between the AIC and visual sensory areas. In addition, AIC activation was predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. These results provide compelling evidence that the AIC plays a critical role in interoceptive attention.

Recent brain imaging studies have shown that the neural substrates underlying the ability to infer and share the feeling of pain of other individuals overlap with the pain matrix that mediates the process of one's own pain. While there has been evidence that the neural activity mediating pain experience is influenced by top–down attention, it remains unclear whether the neural substrates of empathy for pain are modulated by top–down controlled mechanisms. The current work investigated whether the neural correlates of empathic processes of pain are altered by task demand and prior knowledge of stimulus reality. Subjects were scanned using functional magnetic resonance imaging (fMRI) while watching pictures or cartoons of hands that were in painful or neutral situations. Subjects were asked either to evaluate pain intensity supposedly felt by the model or to count the number of hands in the stimulus displays. Relative to counting neutral stimuli, rating pain intensity of painful pictures and cartoons induced increased activation in ACC/paracingulate and the right middle frontal gyrus. Rating pain intensity also activated the inferior frontal cortex bilaterally and the right insula/putamen for pictures but activated the left parietal cortex, the postcentral gyrus, and the occipito-temporal cortex for cartoons. However, the neural activities related to pain rating were eliminated when subjects counted the number of hands in the painful stimuli. In addition, the ACC activity associated with empathy for pain was stronger for the pictures than for the cartoons. Our findings indicate that the involvement of the neural substrates underlying pain-related empathy is constrained by top–down attention and contextual reality of stimuli.

Understanding how humans represent others’ pain is critical for understanding pro-social behavior. ‘Shared experience’ theories propose common brain representations for somatic and vicarious pain, but other evidence suggests that specialized circuits are required to experience others’ suffering. Combining functional neuroimaging with multivariate pattern analyses, we identified dissociable patterns that predicted somatic (high versus low: 100%) and vicarious (high versus low: 100%) pain intensity in out-of-sample individuals. Critically, each pattern was at chance in predicting the other experience, demonstrating separate modifiability of both patterns. Somatotopy (upper versus lower limb: 93% accuracy for both conditions) was also distinct, located in somatosensory versus mentalizing-related circuits for somatic and vicarious pain, respectively. Two additional studies demonstrated the generalizability of the somatic pain pattern (which was originally developed on thermal pain) to mechanical and electrical pain, and also demonstrated the replicability of the somatic/vicarious dissociation. These findings suggest possible mechanisms underlying limitations in feeling others’ pain, and present new, more specific, brain targets for studying pain empathy. The ability to experience others’ pain is a cornerstone of empathy, and binds us together in times of hardship. However, we have not yet fully understood the complex interactions in the brain that make people empathetic to others’ suffering. One possibility is that we experience others’ pain through the activation of the same brain regions as those that enable us to experience physical pain ourselves. To test this idea, Krishnan et al. compared patterns of brain activity in human volunteers as they experienced pain (from heat being applied to their forearm or foot) or watched images of others’ hands or feet being injured. While watching these images, the volunteers were asked to try to imagine that the injuries were happening to their own bodies. The patterns of brain activity that arose when the volunteers observed someone else in pain did not overlap with the patterns produced when the volunteers experienced pain themselves. Instead, seeing someone else in pain activated regions involved in taking another person’s perspective. This process, which is known as mentalizing, involves thinking about the other person’s thoughts, intentions and preferences. Thus within the brain, the experience of observing someone else in pain is distinct from that of experiencing physical pain in oneself. The results presented by Krishnan et al. raise new questions about how the brain regions involved in empathy help us to relate to other people when they experience different types of pain. Future studies should explore the factors that influence our ability to adopt another’s perspective, and whether it might be possible to improve this ability.

•We investigated belief updating in two tasks, with and without explicit feedback.•Model-based fMRI revealed similar confidence-encoding networks across tasks.•The anterior hippocampus led the confidence-encoding network, w/o feedbacks.•The medial PFC and amygdala led a confidence-encoding network, with feedbacks. Classic decision theories typically assume the presence of explicit value-based outcomes after action selections to update beliefs about action-outcome contingencies. However, ecological environments are often opaque, and it remains unclear whether the neural dynamics underlying belief updating vary under conditions characterized by the presence or absence of such explicit value-based information, after each choice selection. We investigated this question in healthy humans (n = 28) using Bayesian inference and two multi-option fMRI tasks: a multi-armed bandit task, and a probabilistic perceptual task, respectively with and without explicit value-based feedback after choice selections. Model-based fMRI analysis revealed a network encoding belief updating which did not change depending on the task. More precisely, we found a confidence-building network that included anterior hippocampus, amygdala, and medial prefrontal cortex (mPFC), which became more active as beliefs about action-outcome probabilities were confirmed by newly acquired information. Despite these consistent responses across tasks, dynamic causal modeling estimated that the network dynamics changed depending on the presence or absence of trial-by-trial value-based outcomes. In the task deprived of immediate feedback, the hippocampus increased its influence towards both amygdala and mPFC, in association with increased strength in the confidence signal. However, the opposite causal relations were found (i.e., from both mPFC and amygdala towards the hippocampus), in presence of immediate outcomes. This finding revealed an asymmetric relationship between decision confidence computations, which were based on similar computational models across tasks, and neural implementation, which varied depending on the availability of outcomes after choice selections. [Display omitted]

The controllability of our social environment has a profound impact on our behavior and mental health. Nevertheless, neurocomputational mechanisms underlying social controllability remain elusive. Here, 48 participants performed a task where their current choices either did (Controllable), or did not (Uncontrollable), influence partners’ future proposals. Computational modeling revealed that people engaged a mental model of forward thinking (FT; i.e., calculating the downstream effects of current actions) to estimate social controllability in both Controllable and Uncontrollable conditions. A large-scale online replication study (n=1342) supported this finding. Using functional magnetic resonance imaging (n=48), we further demonstrated that the ventromedial prefrontal cortex (vmPFC) computed the projected total values of current actions during forward planning, supporting the neural realization of the forward-thinking model. These findings demonstrate that humans use vmPFC-dependent FT to estimate and exploit social controllability, expanding the role of this neurocomputational mechanism beyond spatial and cognitive contexts.

Crises such as the COVID-19 pandemic are known to exacerbate depression and anxiety, though their temporal trajectories remain under-investigated. The present study aims to investigate fluctuations in depression and anxiety using the COVID-19 pandemic as a model crisis. A total of 1512 adults living in the United States enrolled in this online study beginning April 2, 2020 and were assessed weekly for 10 weeks (until June 4, 2020). We measured depression and anxiety using the Zung Self-Rating Depression scale and State-Trait Anxiety Inventory (state subscale), respectively, along with demographic and COVID-related surveys. Linear mixed-effects models were used to examine factors contributing to longitudinal changes in depression and anxiety. We found that depression and anxiety levels were high in early April, but declined over time. Being female, younger age, lower-income, and previous psychiatric diagnosis correlated with higher overall levels of anxiety and depression; being married additionally correlated with lower overall levels of depression, but not anxiety. Importantly, worsening of COVID-related economic impact and increase in projected pandemic duration exacerbated both depression and anxiety over time. Finally, increasing levels of informedness correlated with decreasing levels of depression, while increased COVID-19 severity (i.e., 7-day change in cases) and social media use were positively associated with anxiety over time. These findings not only provide evidence for overall emotional adaptation during the initial weeks of the pandemic, but also provide insight into overlapping, yet distinct, factors contributing to depression and anxiety throughout the first wave of the pandemic.

Under the threat of public health challenges such as the recent COVID-19 pandemic, individual citizens’ active and cooperative participation in precautionary measures is crucial. Although non-compliance is recognized as a recurring problem, it remains unknown why some individuals tend to comply less than others and whether violations of preventive behaviors are observed consistently across different public health issues. To test our hypothesis that individuals would show consistent public health behavior transcending domains, we collected self-reports from two independent samples of participants (total N = 2983) on health risk beliefs and behavioral choices. Participants’ responses were collected in regard to two separate yet closely related public health issues: smoking and the COVID-19 pandemic. Our data reveal that on average, individuals’ beliefs and behaviors are consistent across different public health domains. In particular, smokers showed diminished compliance behaviors during the pandemic, which was mediated by their lower motives to protect public health. These results provide a psychological mechanism of how individuals’ health risk behaviors are generalized across different public health domains that may explain why some individuals (here, current-smokers) are more prone to violate public health behaviors.

When making risky choices in social contexts, humans typically combine social information with individual preferences about the options at stake. It remains unknown how such decisions are made when these preferences are inaccessible or disrupted, as might be the case for individuals confronting novel options or experiencing cognitive impairment. Thus, we examined participants with lesions in insular or dorsal anterior cingulate cortex, key regions implicated in risky decision-making, as they played a gambling task where choices were made both alone and after observing others’ choices. Participants in both lesion groups showed disrupted use of standard utility-based computations about risky options. For socially situated decisions, these participants showed increased conformity with the choices of others, independent from social utility-based computations. These findings suggest that in social contexts, following others’ choices may be a heuristic for decision-making when utility-based risk processing is disrupted.

The sense of agency, or the belief in action causality, is an elusive construct that impacts day-to-day experience and decision-making. Despite its relevance in a range of neuropsychiatric disorders, it is widely under-studied and remains difficult to measure objectively in patient populations. We developed and tested a novel cognitive measure of reward-dependent agency perception in an in-person and online cohort. The in-person cohort consisted of 52 healthy control subjects and 20 subjects with depression and anxiety disorders (DA), including major depressive disorder and generalized anxiety disorder. The online sample consisted of 254 participants. The task consisted of an effort implementation for monetary rewards with computerized visual feedback interference and trial-by-trial ratings of self versus other agency. All subjects across both cohorts demonstrated higher self-agency after receiving positive-win feedback, compared to negative-loss feedback when the level of computer inference was kept constant. Patients with DA showed reduced positive feedback-dependent agency compared to healthy controls. Finally, in our online sample, we found that higher self-agency following negative-loss feedback was associated with worse anhedonia symptoms. Together this work suggests how positive and negative environmental information impacts the sense of self-agency in healthy subjects, and how it is perturbed in patients with depression and anxiety.

The nascent field computational psychiatry has undergone exponential growth since its inception. To date, much of the published work has focused on choice behaviors, which are primarily modeled within a reinforcement learning framework. While this initial normative effort represents a milestone in psychiatry research, the reality is that many psychiatric disorders are defined by disturbances in subjective states (e.g., depression, anxiety) and associated beliefs (e.g., dysmorphophobia, paranoid ideation), which are not considered in normative models. In this paper, we present interoceptive inference as a candidate framework for modeling subjective—and associated belief—states in computational psychiatry. We first introduce the notion and significance of modeling subjective states in computational psychiatry. Next, we present the interoceptive inference framework, and in particular focus on the relationship between interoceptive inference (i.e., belief updating) and emotions. Lastly, we will use drug craving as an example of subjective states to demonstrate the feasibility of using interoceptive inference to model the psychopathology of subjective states.