Overlapping and specific neural correlates for empathizing,affective mentalizing,and cognitive mentalizing: A coordinate‐based meta‐analytic study

While the discussion on the foundations of social understanding mainly revolves around the notions of empathy, affective mentalizing, and cognitive mentalizing, their degree of overlap versus specificity is still unclear. We took a meta‐analytic approach to unveil the neural bases of cognitive mentalizing, affective mentalizing, and empathy, both in healthy individuals and pathological conditions characterized by social deficits such as schizophrenia and autism. We observed partially overlapping networks for cognitive and affective mentalizing in the medial prefrontal, posterior cingulate, and lateral temporal cortex, while empathy mainly engaged fronto‐insular, somatosensory, and anterior cingulate cortex. Adjacent process‐specific regions in the posterior lateral temporal, ventrolateral, and dorsomedial prefrontal cortex might underpin a transition from abstract representations of cognitive mental states detached from sensory facets to emotionally‐charged representations of affective mental states. Altered mentalizing‐related activity involved distinct sectors of the posterior lateral temporal cortex in schizophrenia and autism, while only the latter group displayed abnormal empathy related activity in the amygdala. These data might inform the design of rehabilitative treatments for social cognitive deficits.     

Emotional reactivity to threat modulates activity in mentalizing network during aggression

Aggression is a common response to provocation, albeit with considerable interindividual differences. In this fMRI study, we investigated emotional reactivity to threat as possible link between provocation and aggression, as well as the neural correlates of this relationship. We hypothesized that emotional reactivity, measured as fear potentiation (FP) of the startle response, would be negatively associated with aggressive behavior and would modulate neural activity during an aggressive interaction. In 30 healthy female participants, FP was measured as the difference between blink amplitudes while watching threatening vs neutral pictures. Participants subsequently engaged in a variant of the Taylor Aggression Paradigm (TAP), while being scanned. During the TAP, participants selected a punishment level for either a highly provoking or a nonprovoking opponent. There was no difference in aggressive behavior between participants high and low in FP. However, we found a negative correlation between FP and the neural provocation effect in several regions of a network previously associated with mentalizing including the medial prefrontal cortex, precuneus and the temporo-parietal junction. Independently of the FP variability, aggressive behavior correlated with the provocation effect on activity in the caudate nucleus. Our results indicate that during a provocative confrontation, high emotional reactivity to threat suppresses recruitment of the mentalizing network.     

Early and late neural correlates of mentalizing: ALE meta-analyses in adults,children and adolescents

The ability to understand mental states of others is referred to as mentalizing and enabled by our Theory of Mind. This social skill relies on brain regions comprising the mentalizing network as robustly observed in adults but also in a growing number of developmental studies. We summarized and compared neuroimaging evidence in children/adolescents and adults during mentalizing using coordinate-based activation likelihood estimation meta-analyses to inform about brain regions consistently or differentially engaged across age categories. Adults (N = 5286) recruited medial prefrontal and middle/inferior frontal cortices, precuneus, temporoparietal junction and middle temporal gyri during mentalizing, which were functionally connected to bilateral inferior/superior parietal lobule and thalamus/striatum. Conjunction and contrast analyses revealed that children and adolescents (N = 479) recruit similar but fewer regions within core mentalizing regions. Subgroup analyses revealed an early continuous engagement of middle medial prefrontal cortex, precuneus and right temporoparietal junction in younger children (8–11 years) and adolescents (12–18 years). Adolescents additionally recruited the left temporoparietal junction and middle/inferior temporal cortex. Overall, the observed engagement of the medial prefrontal cortex, precuneus and right temporoparietal junction during mentalizing across all ages reflects an early specialization of some key regions of the social brain.     

Resting-state functional brain connectivity for human mentalizing: biobehavioral mechanisms of theory of mind in multiple sclerosis

Although neural hubs of mentalizing are acknowledged, the brain mechanisms underlying mentalizing deficit, characterizing different neurological conditions, are still a matter of debate. To investigate the neural underpinning of theory of mind (ToM) deficit in multiple sclerosis (MS), a region of interest (ROI)-based resting-state fMRI study was proposed. In total, 37 MS patients (23 females, mean age = 54.08 ± 11.37 years, median Expanded Disability Status Scale = 6.00) underwent an MRI and a neuro-psychosocial examination and were compared with 20 sex-age-education matched healthy subjects. A neuroanatomical ToM model was constructed deriving 11 bilateral ROIs and then between and within-functional connectivity (FCs) were assessed to test for group differences. Correlation with psychosocial scores was also investigated. Lower ToM performance was registered for MS both in cognitive and affective ToM, significantly associated with processing speed. A disconnection between limbic–paralimbic network and prefrontal execution loops was observed. A trend of aberrant intrinsic connectivity in MS within the anterior cingulate cortex (ACC) was also reported. Finally, a correlation between cognitive ToM and intrinsic FC was detected in ACC and dorsal striatum, belonging to the limbic–paralimbic network, likely explaining the behavioral deficit in MS. The results suggest that aberrant intrinsic and extrinsic connectivity constitutes a crucial neural mechanism underlying ToM deficit in MS.     

Damage to the left ventromedial prefrontal cortex impacts affective theory of mind

Studies investigating theory of mind (ToM) abilities (i.e. ability to understand and predict others’ mental states) have revealed that affective and cognitive functions play a significant role and that each of those functions are associated with distinct neural networks. Cognitive facets of ToM have implicated the medial prefrontal cortex, temporo-parietal junction and the anterior paracingulate cortex, whereas affective facets have implicated the ventromedial prefrontal cortex (vmPFC). Although the vmPFC has repeatedly shown to be critical for affective functions, knowledge regarding the exact role of the left and right vmPFC in affective ToM is still obscure. Here, we compared performances of 30 patients with left, right and bilateral vmPFC lesions to two comparison groups (one without and one with brain injuries) on the Faux Pas Recognition task measuring the facets of ToM. We also investigated whether any deficits may be associated with other emotional measures, namely emotional empathy and emotional intelligence. Our results extend earlier findings by showing that the vmPFC is associated with abilities in affective ToM. More importantly, our results revealed that the left, and not the right vmPFC as indicated previously, is involved in affective ToM and that this deficit is associated with emotional intelligence.     

Intentional social distance regulation alters affective responses towards victims of violence: an FMRI study

We used functional magnetic resonance imaging (fMRI) to investigate brain processes underlying control of emotional responses towards a person in distress by cognitive social distance modulation. fMRI and peripheral physiological responses (startle response and electrodermal activity) were recorded from 24 women while they watched victim-offender scenes and modulated their social distance to the victim by cognitive reappraisal. We found that emotional responses, including startle eyeblink and amygdala responses, can effectively be modulated by social distance modulation. Furthermore, our data provide evidence that activity in the dorsomedial prefrontal cortex (dmPFC) and the anterior paracingulate cortex (aPCC), two brain regions that have previously been associated with brain processes related to distant and close others, is differentially modulated by intentional social distance modulation: activity in the dmPFC increased with increasing disengagement from the victim and activity in the aPCC increased with increasing engagement with the victim. We suggest that these two regions play opposing roles in cognitive modulation of social distance and affective responses towards persons in distress that enable the adaptive and flexible social behavior observed in humans.     

Substrates of metacognition on perception and metacognition on higher‐order cognition relate to different subsystems of the mentalizing network

Humans have the ability to reflect upon their perception, thoughts, and actions, known as metacognition (MC). The brain basis of MC is incompletely understood, and it is debated whether MC on different processes is subserved by common or divergent networks. We combined behavioral phenotyping with multi‐modal neuroimaging to investigate whether structural substrates of individual differences in MC on higher‐order cognition (MC‐C) are dissociable from those underlying MC on perceptual accuracy (MC‐P). Motivated by conceptual work suggesting a link between MC and cognitive perspective taking, we furthermore tested for overlaps between MC substrates and mentalizing networks. In a large sample of healthy adults, individual differences in MC‐C and MC‐P did not correlate. MRI‐based cortical thickness mapping revealed a structural basis of this independence, by showing that individual differences in MC‐P related to right prefrontal cortical thickness, while MC‐C scores correlated with measures in lateral prefrontal, temporo‐parietal, and posterior midline regions. Surface‐based superficial white matter diffusivity analysis revealed substrates resembling those seen for cortical thickness, confirming the divergence of both MC faculties using an independent imaging marker. Despite their specificity, substrates of MC‐C and MC‐P fell clearly within networks known to participate in mentalizing, confirmed by task‐based fMRI in the same subjects, previous meta‐analytical findings, and ad‐hoc Neurosynth‐based meta‐analyses. Our integrative multi‐method approach indicates domain‐specific substrates of MC; despite their divergence, these nevertheless likely rely on component processes mediated by circuits also involved in mentalizing. Hum Brain Mapp 37:3388–3399, 2016. © 2016 Wiley Periodicals, Inc.     

Involvement of the mentalizing network in social and non-social high construal

The dorsomedial prefrontal cortex (dmPFC) is consistently involved in tasks requiring the processing of mental states, and much rarer so by tasks that do not involve mental state inferences. We hypothesized that the dmPFC might be more generally involved in high construal of stimuli, defined as the formation of concepts or ideas by omitting non-essential features of stimuli, irrespective of their social or non-social nature. In an fMRI study, we presented pictures of a person engaged in everyday activities (social stimuli) or of objects (non-social stimuli) and induced a higher level of construal by instructing participants to generate personality traits of the person or categories to which the objects belonged. This was contrasted against a lower level task where participants had to describe these same pictures visually. As predicted, we found strong involvement of the dmPFC in high construal, with substantial overlap across social and non-social stimuli, including shared activation in the vmPFC/OFC, parahippocampal, fusiform and angular gyrus, precuneus, posterior cingulate and right cerebellum.     

The neuroanatomical basis of affective mentalizing in schizophrenia: comparison of patients with schizophrenia and patients with localized prefrontal lesions

Patients with schizophrenia show impaired emotional and social behavior, such as misinterpretation of social situations and lack of Theory of Mind (ToM). However, the neuroanatomical basis of impaired ToM and its nature in schizophrenia is still largely unknown. Based on previous findings, the present study suggests that impaired social cognition observed in schizophrenic patients may be similar to that observed in patients with prefrontal (PFC) damage due to impaired ‘affective ToM’ abilities, rather than to a general impairment in ToM. We examined the behavioral and neural mechanisms that underlie the social and communicative impairments observed in patients with schizophrenia and with PFC damage, by looking at differential patterns of ToM impairment in these individuals. The performance of 24 patients with schizophrenia was compared to the responses of patients with localized lesions in the ventromedial (VM) or dorsolateral PFC, patients with non-frontal lesions, and healthy control subjects. Patients with schizophrenia and those with VM lesions were impaired on ‘affective ToM’ tasks but not in cognitive ToM conditions. It was concluded that the pattern of mentalizing impairments in schizophrenia resembled those seen in patients with lesions of the frontal lobe, particularly with VM damage, providing support for the notion of a disturbance of the fronto-limbic circuits in schizophrenia.     

Unimpaired social cognition in adult patients with ADHD: brain volumetric and behavioral results

The present study aimed to investigate whether adult patients with attention deficit hyperactivity disorder (ADHD) show deficits in social cognition and to identify the structural neural correlates of social cognitive skills in ADHD. Twenty-six adult patients with ADHD and 26 matched healthy control participants performed the Movie for the Assessment of Social Cognition and underwent a structural magnetic resonance imaging scan. We compared theory of mind (ToM) performance between ADHD patients and healthy controls. Using voxel-based morphometry, we further compared gray matter volumes in regions that are critical for social cognition between the two groups and examined whether ToM performance was correlated with brain morphometry measures. We did not observe any between-group differences in ToM abilities or regional gray matter volumes. Across both groups, performance on affective aspects of ToM correlated positively with gray matter volumes in the medial part of the superior frontal gyri, which is typically involved in social cognition. This study is the first to relate brain structure to social cognitive abilities in adult patients with ADHD. Although our sample was small and heterogeneous, with half of the patients showing mild-to-moderate psychiatric comorbidities, our results may encourage longitudinal studies that relate social cognitive development in childhood and adolescence to brain maturation of ADHD patients.     

Distinct neural substrates of affective and cognitive theory of mind impairment in semantic dementia

Using structural MRI, we investigated the brain substrates of both affective and cognitive theory of mind (ToM) in 19 patients with semantic dementia. We also ran intrinsic connectivity analyses to identify the networks to which the substrates belong and whether they are functionally disturbed in semantic dementia. In line with previous studies, we observed a ToM impairment in patients with semantic dementia even when semantic memory was regressed out. Our results also highlighted different neural bases according to the nature (affective or cognitive) of the representations being inferred. The affective ToM deficit was associated with atrophy in the amygdala, suggesting the involvement of emotion-processing deficits in this impairment. By contrast, cognitive ToM performances were correlated with the volume of medial prefrontal and parietal regions, as well as the right frontal operculum. Intrinsic connectivity analyses revealed decreased functional connectivity, mainly between midline cortical regions and temporal regions. They also showed that left medial temporal regions were functionally isolated, a further possible hindrance to normal social cognitive functioning in semantic dementia. Overall, this study addressed for the first time the neuroanatomical substrates of both cognitive and affective ToM disruption in semantic dementia, highlighting disturbed connectivity within the networks that sustain these abilities.     

Understanding embarrassment among those with autism: breaking down the complex emotion of embarrassment among those with autism

Scenarios manipulating various factors within the emotion of embarrassment, such as whether or not an audience was present when an embarrassing act was committed, the type of audience present, empathic embarrassment, etc., were presented to high-functioning participants with autism and comparison groups of those with learning difficulties and typically developing participants matched for verbal and nonverbal mental age. Participants were required to rate the level of embarrassment of the protagonist and justify their responses. It was predicted that those with autism would differ significantly from the comparison groups in their ratings and also their ability to provide justifications. The results showed those with autism to have difficulty with such concepts as empathic embarrassment but showed a surprisingly good understanding of other variables manipulated such as the presence of an audience.     

Specific default mode subnetworks support mentalizing as revealed through opposing network recruitment by social and semantic FMRI tasks

The ability to attribute mental states to others, or “mentalizing,” is posited to involve specific subnetworks within the overall default mode network (DMN), but this question needs clarification. To determine which default mode (DM) subnetworks are engaged by mentalizing processes, we assessed task‐related recruitment of DM subnetworks. Spatial independent component analysis (sICA) applied to fMRI data using relatively high‐order model (75 components). Healthy participants (n = 53, ages 17–60) performed two fMRI tasks: an interactive game involving mentalizing (Domino), a semantic memory task (SORT), and a resting state fMRI scan. sICA of the two tasks split the DMN into 10 subnetworks located in three core regions: medial prefrontal cortex (mPFC; five subnetworks), posterior cingulate/precuneus (PCC/PrC; three subnetworks), and bilateral temporoparietal junction (TPJ). Mentalizing events increased recruitment in five of 10 DM subnetworks, located in all three core DMN regions. In addition, three of these five DM subnetworks, one dmPFC subnetwork, one PCC/PrC subnetwork, and the right TPJ subnetwork, showed reduced recruitment by semantic memory task events. The opposing modulation by the two tasks suggests that these three DM subnetworks are specifically engaged in mentalizing. Our findings, therefore, suggest the unique involvement of mentalizing processes in only three of 10 DM subnetworks, and support the importance of the dmPFC, PCC/PrC, and right TPJ in mentalizing as described in prior studies. Hum Brain Mapp 36:3047–3063, 2015. © 2015 Wiley Periodicals, Inc.     

Social interaction recruits mentalizing and reward systems in middle childhood

Social cognition develops in the context of reciprocal social interaction. However, most neuroimaging studies of mentalizing have used noninteractive tasks that may fail to capture important aspects of real‐world mentalizing. In adults, social‐interactive context modulates activity in regions linked to social cognition and reward, but few interactive studies have been done with children. The current fMRI study examines children aged 8–12 using a novel paradigm in which children believed they were interacting online with a peer. We compared mental and non‐mental state reasoning about a live partner (Peer) versus a story character (Character), testing the effects of mentalizing and social interaction in a 2 × 2 design. Mental versus Non‐Mental reasoning engaged regions identified in prior mentalizing studies, including the temporoparietal junction, superior temporal sulcus, and dorsomedial prefrontal cortex. Moreover, peer interaction, even in conditions without explicit mentalizing demands, activated many of the same mentalizing regions. Peer interaction also activated areas outside the traditional mentalizing network, including the reward system. Our results demonstrate that social interaction engages multiple neural systems during middle childhood and contribute further evidence that social‐interactive paradigms are needed to fully capture how the brain supports social processing in the real world.     

Social cognition in schizophrenia: an overview

The purpose of this column is to provide an overview of social cognition in schizophrenia. The column begins with a short introduction to social cognition. Then, we describe the application of social cognition to the study of schizophrenia, with an emphasis on key domains (i.e., emotion perception, Theory of Mind, and attributional style). We conclude the column by discussing the relationship of social cognition to neurocognition, negative symptoms, and functioning, with an eye toward strategies for improving social cognition in schizophrenia.     

Cry for her or cry with her: context-dependent dissociation of two modes of cinematic empathy reflected in network cohesion dynamics

Two empathy-related processes were recently distinguished neuroscientifically: automatic embodied-simulation (ES) based on visceromotor representation of another’s affective state via cingulo-insulary circuit, and emotional sharing relying on cognitive ‘theory of mind’ (ToM) via prefrontal-temporo-parietal circuit. Evidence that these regions are not only activated but also function as networks during empathic experience has yet to been shown. Employing a novel approach by analyzing fMRI fluctuations of network cohesion while viewing films portraying personal loss, this study demonstrates increased connectivity during empathic engagement (probed by behavioral and parasympathetic indices) both within these circuits, and between them and a set of limbic regions. Notably, this effect was context-dependent: when witnessing as a determined-loss presented as a future event, the ToM and ToM-limbic cohesion positively correlated with state- and empathy indices. During the dramatic peak of this condition, the ToM cohesion was positively correlated with the trait-empathy index of personal distress. However, when the loss was presented as a probabilistic real-time occurrence, ToM cohesion negatively correlated with state-empathy index, which positively correlated with ES-limbic cohesion. In this case, it was the ES-limbic cohesion during the emotional peak which was correlated with personal distress scores. The findings indicate a dichotomy between regulated empathy toward determined-loss and vicarious empathy toward a real-time occurrence.     

Shared and nonshared neural networks of cognitive and affective theory‐of‐mind: A neuroimaging study using cartoon picture stories

Theory of mind (ToM) refers to the ability to represent one's own and others' cognitive and affective mental states. Recent imaging studies have aimed to disentangle the neural networks involved in cognitive as opposed to affective ToM, based on clinical observations that the two can functionally dissociate. Due to large differences in stimulus material and task complexity findings are, however, inconclusive. Here, we investigated the neural correlates of cognitive and affective ToM in psychologically healthy male participants (n = 39) using functional brain imaging, whereby the same set of stimuli was presented for all conditions (affective, cognitive and control), but associated with different questions prompting either a cognitive or affective ToM inference. Direct contrasts of cognitive versus affective ToM showed that cognitive ToM recruited the precuneus and cuneus, as well as regions in the temporal lobes bilaterally. Affective ToM, in contrast, involved a neural network comprising prefrontal cortical structures, as well as smaller regions in the posterior cingulate cortex and the basal ganglia. Notably, these results were complemented by a multivariate pattern analysis (leave one study subject out), yielding a classifier with an accuracy rate of more than 85% in distinguishing between the two ToM‐conditions. The regions contributing most to successful classification corresponded to those found in the univariate analyses. The study contributes to the differentiation of neural patterns involved in the representation of cognitive and affective mental states of others. Hum Brain Mapp, 36:29–39, 2015. © 2014 Wiley Periodicals, Inc.     

Mentalizing about emotion and its relationship to empathy

Mentalizing involves the ability to predict someone else''s behavior based on their belief state. More advanced mentalizing skills involve integrating knowledge about beliefs with knowledge about the emotional impact of those beliefs. Recent research indicates that advanced mentalizing skills may be related to the capacity to empathize with others. However, it is not clear what aspect of mentalizing is most related to empathy. In this study, we used a novel, advanced mentalizing task to identify neural mechanisms involved in predicting a future emotional response based on a belief state. Subjects viewed social scenes in which one character had a False Belief and one character had a True Belief. In the primary condition, subjects were asked to predict what emotion the False Belief Character would feel if they had a full understanding about the situation. We found that neural regions related to both mentalizing and emotion were involved when predicting a future emotional response, including the superior temporal sulcus, medial prefrontal cortex, temporal poles, somatosensory related cortices (SRC), inferior frontal gyrus and thalamus. In addition, greater neural activity in primarily emotion-related regions, including right SRC and bilateral thalamus, when predicting emotional response was significantly correlated with more self-reported empathy. The findings suggest that predicting emotional response involves generating and using internal affective representations and that greater use of these affective representations when trying to understand the emotional experience of others is related to more empathy.