Activity In Anterior Insula Research Articles

Anterior insula activity reflects the effects of intentionality on the anticipation of aversive stimulation.

If someone causes you harm, your affective reaction to that person might be profoundly influenced by your inferences about the intentionality of their actions. In the present study, we aimed to understand how affective responses to a biologically salient aversive outcome administered by others are modulated by the extent to which a given individual is judged to have deliberately or inadvertently delivered the outcome. Using fMRI, we examined how neural responses to anticipation and receipt of an aversive stimulus are modulated by this fundamental social judgment. We found that affective evaluations about an individual whose actions led to either noxious or neutral consequences for the subject did indeed depend on the perceived intentions of that individual. At the neural level, activity in the anterior insula correlated with the interaction between perceived intentionality and anticipated outcome valence, suggesting that this region reflects the influence of mental state attribution on aversive expectations.

The neural correlates of the decoy effect in decisions.

Human choices are remarkably susceptible to the context in which options are presented. The introduction of an inferior option (a decoy) into the choice set can make one of the original options (the target) more attractive than and the other original option (the competitor). This so called “decoy effect” represents a striking violation of the “context-invariant” axiom, yet its underlying neural mechanisms are not well understood. Here, we used a novel gambling task in conjunction with functional magnetic resonance imaging (fMRI) to elucidate its neural basis. At both the stimulus and decision phases, choice sets with decoys activated the occipital gyrus and deactivated the inferior parietal gyrus. At the decision phase, choosing the targets vs. the competitors elicited stronger anterior insula activation, suggesting that perceptual salience drives heuristic decision making in the decoy effect. Moreover, across participants, activity in anterior cingulate cortex (ACC) predicted a reduced susceptibility to the decoy effect, indicating that resisting the tendency to make heuristic decisions is taxing. Our findings highlight the power of the decoy effect in laboratory settings and document the neural mechanisms underlying the decoy effect.

Capgras' and Cotard's Delusions Associated With a Particular Pattern of Cerebral Activity in a Severely Depressed Patient.

To the Editor: Major depressive disorder is a heterogenous disease considered as a cluster of symptoms associated with disordered processing within specific neurobiological circuits. We report the case of a patient suffering from a melancholic depression with Capgras’ and Cotard’s delusions in which the clinical picture was associated with a particular pattern of cerebral activity. Case report. Mr A is a 72-year-old man, who was brought to the emergency service with complaints of insomnia, nonsense talk, and aggressive behavior. For 2 weeks, Mr A had lived in complete withdrawal and showed great suspicion toward close relatives and friends. He also presented a depressed mood, pessimism, major sleep disturbances, and marked weight loss. Mr A’s psychiatric history was notable for at least 2 depressive episodes that were not treated. Although he lived in a retirement home, he had full cognitive ability and maintained a reasonable level of autonomy. At the initial assessment, Mr A claimed that his relatives had been replaced by actors. He also told us that his body vanished and that the devil replaced it with a younger one. Initial physical examination, laboratory tests, and magnetic resonance imaging were unremarkable. Single photon emission computerized tomography (SPECT) showed a moderate prefrontal hypoperfusion. Pharmacologic management combining an antidepressant treatment of citalopram 20 mg per day and risperidone 2 mg per day was initiated at the first visit. Throughout the following month, Mr A dramatically improved. A second brain SPECT performed at 5-week follow-up showed a persistent prefrontal hypoperfusion. To further explore brain perfusion, the second SPECT was subtracted from the first one using a computer-aided method. A statistically significant increased perfusion (> 2 SD) was shown in the anterior cingulate (ACC) and the left anterior insula (LAI) (Figure 1). Figure 1. Increased Perfusion in the Left Anterior Insula (upper) and in the Anterior Cingulate (lower) During Capgras’ and Cotard’s Delusions We report the case of a 72-year-old patient who developed a severe depressive episode with melancholic features as well as Capras’ and Cotard’s delusions. This clinical picture was associated with a particular pattern of cerebral activation. Co-occurrence of Capgras’ syndrome and Cotard’s syndrome has been reported in the literature.1 The 2 disorders seem to share similar mechanisms and to arise from a marked external or internal perceptual-affective dissonance, which produces a major feeling of strangeness of the external world and of one’s own body commonly called derealization/depersonalization.2 Cerebral blood flow normalization at 5 weeks of successful antidepressant and antipsychotic treatment suggests that LAI and ACC hyperactivity is probably involved in the pathophysiologic mechanisms of the disease. Anterior insula is suggested to be a supermodal structure, involved with ACC, in association with affective and perceptual recognition processes.3 Disturbances in anterior insula activity might result in an atmosphere of strangeness in which Cotard’s and Capgras’ delusions seem to emerge. If we assume that symptom dimensions in depressive disorder reflect dysfunction in specific neuronal circuits, we could speculate that depression with major depersonalization/derealization in Mr A is related to a complex neuronal network in which LAI and ACC seem to play a major role.

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain.

Self-regulation of brain activation using real-time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level-dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain-related brain activation is site-specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain-evoked activation and its behavioral effects.

You are the danger: Attenuated insula response in methamphetamine users during aversive interoceptive decision-making

BackgroundDrug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing. MethodsWe investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI. ResultsMETH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to AI/IFG attenuation across trials. ConclusionsAI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH.

Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food

Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.

The neural correlates of emotion alignment in social interaction.

Talking about emotion and sharing emotional experiences is a key component of human interaction. Specifically, individuals often consider the reactions of other people when evaluating the meaning and impact of an emotional stimulus. It has not yet been investigated, however, how emotional arousal ratings and physiological responses elicited by affective stimuli are influenced by the rating of an interaction partner. In the present study, pairs of participants were asked to rate and communicate the degree of their emotional arousal while viewing affective pictures. Strikingly, participants adjusted their arousal ratings to match up with their interaction partner. In anticipation of the affective picture, the interaction partner's arousal ratings correlated positively with activity in anterior insula and prefrontal cortex. During picture presentation, social influence was reflected in the ventral striatum, that is, activity in the ventral striatum correlated negatively with the interaction partner's ratings. Results of the study show that emotional alignment through the influence of another person's communicated experience has to be considered as a complex phenomenon integrating different components including emotion anticipation and conformity.

The consumption of beef vs. soy lunch meals on food cravings and cortico‐limbic brain regions controlling food motivation/reward in healthy adults (120.5)

Objective: To determine whether protein source, specifically comparing beef vs. soy‐rich foods, alters food cravings and neural responses controlling food motivation and reward in healthy adults. Methods: Using a randomized, crossover design, 23 healthy adults (age 23 ± 1 y; BMI: 23.4 ± 0.6 kg/m2) consumed, on separate days, 400 kcal beef vs. soy‐based lunch meals that were 1) matched for macronutrient and fiber content or 2) matched for serving size (which allowed macronutrient and fiber content to vary). Pre and post‐lunch food craving questionnaires and food cue‐stimulated functional MRI (fMRI) brain scans were completed. Results: When comparing macronutrient and fiber‐matched meals, the consumption of beef tended to reduce post‐lunch cravings for sweet foods vs. soy (P=0.09) and tended to reduce hippocampal brain activation vs. soy (P=0.08). When comparing serving size‐matched meals, the consumption of beef tended to reduce post‐lunch cravings for sweet foods vs. soy (P=0.08) and reduced anterior cingulate and insular brain activation vs. soy (both, P<0.05). Conclusions: Taken together, these data suggest that protein source significantly alters the signals that control food cravings and reward with the consumption of beef‐rich foods leading to greater reductions in sweet cravings and cortico‐limbic activation in regions controlling food motivation/reward compared to soy‐rich foods.Grant Funding Source: Supported by The Beef Checkoff

Working Memory in Schizophrenia: Behavioral and Neural Evidence for Reduced Susceptibility to Item-Specific Proactive Interference

Susceptibility to item-specific proactive interference (PI) contributes to interindividual differences in working memory (WM) capacity and complex cognition relying on WM. Although WM deficits are a well-recognized impairment in schizophrenia, the underlying pathophysiological effects on specific WM control functions, such as the ability to resist item-specific PI, remain unknown. Moreover, opposing hypotheses on increased versus reduced PI susceptibility in schizophrenia are both justifiable by the extant literature. To provide first insights into the behavioral and neural correlates of PI-related WM control in schizophrenia, a functional magnetic resonance imaging experiment was conducted in a sample of 20 patients and 20 well-matched control subjects. Demands on item-specific PI were experimentally manipulated in a recent-probes task (three runs, 64 trials each) requiring subjects to encode and maintain a set of four target items per trial. Compared with healthy control subjects, schizophrenia patients showed a significantly reduced PI susceptibility in both accuracy and latency measures. Notably, reduced PI susceptibility in schizophrenia was not associated with overall WM impairments and thus constituted an independent phenomenon. In addition, PI-related activations in inferior frontal gyrus and anterior insula, typically assumed to support PI resistance, were reduced in schizophrenia, thus ruling out increased neural efforts as a potential cause of the patients' reduced PI susceptibility. The present study provides first evidence for a diminished vulnerability of schizophrenia patients to item-specific PI, which is presumably a consequence of the patients' more efficient clearing of previously relevant WM traces and the accordingly reduced likelihood for item-specific PI to occur.

Reward sensitivity modulation of brain activity during response inhibition

This work investigated the relationship between individual differences in reward sensitivity and the activity of brain regions involved in response inhibition. Participants (n = 51, 20 females) performed a stop-signal task while undergoing fMRI scanning. Inhibition of dominant responses during the task was associated to activation of bilateral anterior insula. Parameter estimates from these activation clusters were extracted to run an ROI analysis. Reward sensitivity, as measured by the Sensitivity to Reward (SR) scale from the SPSRQ (Torrubia et al., 2001), was negatively correlated with activity in right anterior insula. A whole-brain correlation analysis was also conducted, in which SR scores were negatively correlated with activity in the anterior cingulate cortex and the left supramarginal gyrus. These results suggest that individual differences in reward sensitivity may involve differences in cognitive processing that are manifested as distinct patterns of brain activation, even in the absence of explicit reward contingencies.

Significance of Right Anterior Insula Activity for Mental Health Intervention

Significance of Right Anterior Insula Activity for Mental Health Intervention

Sequential inhibitory control processes assessed through simultaneous EEG–fMRI

Inhibitory response control has been extensively investigated in both electrophysiological (ERP) and hemodynamic (fMRI) studies. However, very few multimodal results address the coupling of these inhibition markers. In fMRI, response inhibition has been most consistently linked to activation of the anterior insula and inferior frontal cortex (IFC), often also the anterior cingulate cortex (ACC). ERP work has established increased N2 and P3 amplitudes during NoGo compared to Go conditions in most studies. Previous simultaneous EEG–fMRI imaging reported association of the N2/P3 complex with activation of areas like the anterior midcingulate cortex (aMCC) and anterior insula. In this study we investigated inhibitory control in 23 healthy young adults (mean age=24.7, n=17 for EEG during fMRI) using a combined Flanker/NoGo task during simultaneous EEG and fMRI recording. Separate fMRI and ERP analysis yielded higher activation in the anterior insula, IFG and ACC as well as increased N2 and P3 amplitudes during NoGo trials in accordance with the literature. Combined analysis modelling sequential N2 and P3 effects through joint parametric modulation revealed correlation of higher N2 amplitude with deactivation in parts of the default mode network (DMN) and the cingulate motor area (CMA) as well as correlation of higher central P3 amplitude with activation of the left anterior insula, IFG and posterior cingulate. The EEG–fMRI results resolve the localizations of these sequential activations. They suggest a general role for allocation of attentional resources and motor inhibition for N2 and link memory recollection and internal reflection to P3 amplitude, in addition to previously described response inhibition as reflected by the anterior insula.

Dissociation of Neural Mechanisms for Intersensory Timing Deficits in Parkinson's Disease.

This study investigated the ability of individuals with Parkinson's disease (PD) to synthesize temporal information across the senses, namely audition and vision. Auditory signals (A) are perceived as lasting longer than visual signals (V) when they are compared together, since attentsion is captured and sustained more easily than for visual information. We used the audiovisual illusion to probe for disturbances in brain networks that govern the resolution of time in two intersensory conditions that putatively differ in their attention demands. PD patients and controls judged the relative duration of successively presented pairs of unimodal (AA, VV) and crossmodal (VA, AV) signals whilst undergoing fMRI. There were four main findings. First, underestimation of time was exaggerated in PD when timing depended on controlled attention (AV), whereas subtle deficits were found when audition dominated and attention was more easily sustained (VA). Second, group differences in regional activation were observed only for the AV-unimodal comparison, where the PD group failed to modulate basal ganglia, anterior insula, and inferior cerebellum activity in accord with the timing condition. Third, the intersensory timing conditions were dissociated by patterns of abnormal functional connectivity. When intersensory timing emphasized controlled attention, patients showed weakened connectivity of the cortico-thalamus-basal ganglia (CTBG) circuit and the anterior insula with widespread cortical regions, yet enhanced cerebellar connectivity. When audition dominated intersensory timing, patients showed enhanced connectivity of CTBG elements, the anterior insula, and the cerebellum with the caudate tail and frontal cortex. Fourth, abnormal connectivity measures showed excellent sensitivity and specificity in accurately classifying subjects. The results demonstrate that intersensory timing deficits in PD were well characterized by context-dependent patterns of functional connectivity within a presumed core timing system (CTBG) and a ventral attention hub (anterior insula), and enhanced cerebellar connectivity irrespective of the hypothesized attention demands of timing.

Dissociable Influences of Skewness and Valence on Economic Choice and Neural Activity

Asymmetry in distributions of potential outcomes (i.e. skewness), and whether those potential outcomes reflect gains or losses (i.e. their valence), both exert a powerful influence on value-based choice. How valence affects the impact of skewness on choice is unknown. Here by orthogonally manipulating the skewness and valence of economic stimuli we show that both have an influence on choice. We show that the influence of skewness on choice is independent of valence, both across and within subjects. fMRI data revealed skew-related activity in bilateral anterior insula and dorsomedial prefrontal cortex, which shows no interaction with valence. Further, the expression of skew-related activity depends on an individual’s preference for skewness, and this was again independent of valence-related preference. Our findings highlight the importance of skewness in choice and show that its influence, both behaviourally and neurally, is distinct from an influence of valence.

Behavioral and genetic correlates of the neural response to infant crying among human fathers

Although evolution has shaped human infant crying and the corresponding response from caregivers, there is marked variation in paternal involvement and caretaking behavior, highlighting the importance of understanding the neurobiology supporting optimal paternal responses to cries. We explored the neural response to infant cries in fathers of children aged 1-2, and its relationship with hormone levels, variation in the androgen receptor (AR) gene, parental attitudes and parental behavior. Although number of AR CAG trinucleotide repeats was positively correlated with neural activity in brain regions important for empathy (anterior insula and inferior frontal gyrus), restrictive attitudes were inversely correlated with neural activity in these regions and with regions involved with emotion regulation (orbitofrontal cortex). Anterior insula activity had a non-linear relationship with paternal caregiving, such that fathers with intermediate activation were most involved. These results suggest that restrictive attitudes may be associated with decreased empathy and emotion regulation in response to a child in distress, and that moderate anterior insula activity reflects an optimal level of arousal that supports engaged fathering.

Attentional modulation of reward processing in the human brain

Although neural signals of reward anticipation have been studied extensively, the functional relationship between reward and attention has remained unclear: Neural signals implicated in reward processing could either reflect attentional biases towards motivationally salient stimuli, or proceed independently of attentional processes. Here, we sought to disentangle reward and attention-related neural processes by independently modulating reward value and attentional task demands in a functional magnetic resonance imaging study in healthy human participants. During presentation of a visual reward cue that indicated whether monetary reward could be obtained in a subsequent reaction time task, participants either attended to the reward cue or performed an unrelated attention-demanding task at two different levels of difficulty. In ventral striatum and ventral tegmental area, neural responses were modulated by reward anticipation irrespective of attentional demands, thus indicating attention-independent processing of reward cues. By contrast, additive effects of reward and attention were observed in visual cortex. Critically, reward-related activations in right anterior insula strongly depended on attention to the reward cue. Dynamic causal modelling revealed that the attentional modulation of reward processing in insular cortex was mediated by enhanced effective connectivity from ventral striatum to anterior insula. Our results provide evidence for distinct functional roles of the brain regions involved in the processing of reward-indicating information: While subcortical structures signal the motivational salience of reward cues even when attention is fully engaged elsewhere, reward-related responses in anterior insula depend on available attentional resources, likely reflecting the conscious evaluation of sensory information with respect to motivational value.

It’s all about money

Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.

Preserved Working Memory and Altered Brain Activation in Persons at Risk for Psychosis

Patients with schizophrenia exhibit impairments in working memory that often appear in attenuated form in persons at high risk for the illness. The authors hypothesized that deviations in task-related brain activation and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed the maintenance and manipulation of letters. Participants at ultra high risk for developing psychosis (N=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI while performing a verbal working memory task. Group differences in brain activation were identified using analysis of covariance. The two groups did not show significant differences in speed or accuracy of performance, even after accounting for differences in education. Irrespective of task condition, at-risk participants exhibited significantly less activation than healthy comparison subjects in the left anterior insula. During letter manipulation, at-risk persons exhibited greater task-related deactivation within the default-mode network than comparison subjects. Region-of-interest analysis in the at-risk group revealed significantly greater right dorsolateral prefrontal cortex activation during manipulation of letters. Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.

Medial frontal cortex and anterior insula are less sensitive to outcome predictability when monetary stakes are higher

Prior research links greater activation of posterior medial frontal cortex (pMFC) and anterior insula (AI) with decreasing outcome predictability during decision making, as measured by decreasing probability for the more likely outcome out of two or increasing outcome variance. In addition to predictability, much work indicates that the magnitude or 'stakes' of the outcome is also important. Despite the interest in the neural correlates of these decision variables, it is unknown whether pMFC and AI are differentially sensitive to predictability when magnitude is varied. This study examined brain activity during decision making in relation to decreasing outcome predictability for low as compared with high magnitude decisions. For low magnitude decisions, reduced predictability of the outcome was associated with greater activity in pMFC and bilateral AI, replicating prior studies. In contrast, there was no relationship between predictability and brain activity for high magnitude decisions, which tended to elicit greater pMFC and AI activity than low magnitude decisions for more predictable outcomes. These data indicate that the relationship between outcome predictability and pMFC and AI activity during decision making depends on magnitude, and suggest that these regions may be responding to the motivational salience of the decision rather than predictability information per se.

Task modulations of racial bias in neural responses to others' suffering

Recent event related brain potential research observed a greater frontal activity to pain expressions of racial in-group than out-group members and such racial bias in neural responses to others' suffering was modulated by task demands that emphasize race identity or painful feeling. However, as pain expressions activate multiple brain regions in the pain matrix, it remains unclear which part of the neural circuit in response to others' suffering undergoes modulations by task demands. We scanned Chinese adults, using functional MRI, while they categorized Asian and Caucasian faces with pain or neutral expressions in terms of race or identified painful feelings of each individual face. We found that pain vs. neutral expressions of Asian but not Caucasian faces activated the anterior cingulate (ACC) and anterior insular (AI) activity during race judgments. However, pain compared to race judgments increased ACC and AI activity to pain expressions of Caucasian but not Asian faces. Moreover, race judgments induced increased activity in the dorsal medial prefrontal cortex whereas pain judgments increased activity in the bilateral temporoparietal junction. The results suggest that task demands emphasizing an individual's painful feeling increase ACC/AI activities to pain expressions of racial out-group members and reduce the racial bias in empathic neural responses.