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.     

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.     

Motherhood and theory of mind: increased activation in the posterior cingulate cortex and insulae

Despite growing evidence on effects of parenthood on social understanding, little is known about the influence of parenthood on theory of mind (ToM), the capacity to infer mental and affective states of others. It is also unclear whether any possible effects of parenthood on ToM would generalise to inferring states of adults or are specific to children. We investigated neural activation in mothers and women without children while they predicted action intentions from child and adult faces. Region-of-interest analyses showed stronger activation in mothers in the bilateral posterior cingulate cortex, precuneus (ToM-related areas) and insulae (emotion-related areas). Whole-brain analyses revealed that mothers compared to non-mothers more strongly activated areas including the left angular gyrus and the ventral prefrontal cortex but less strongly activated the right supramarginal gyrus and the dorsal prefrontal cortex. These differences were not specific to child stimuli but occurred in response to both adult and child stimuli and might indicate that mothers and non-mothers employ different strategies to infer action intentions from affective faces. Whether these general differences in affective ToM between mothers and non-mothers are due to biological or experience-related changes should be subject of further investigation.     

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.     

Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study

The underlying mechanisms and neuroanatomical correlates of theory of mind (ToM), the ability to make inferences on others' mental states, remain largely unknown. While numerous studies have implicated the ventromedial (VM) frontal lobes in ToM, recent findings have questioned the role of the prefrontal cortex. We designed two novel tasks that examined the hypothesis that affective ToM processing is distinct from that related to cognitive ToM and depends in part on separate anatomical substrates. The performance of patients with localized lesions in the VM was compared to responses of patients with dorsolateral lesions, mixed prefrontal lesions, and posterior lesions and with healthy control subjects. While controls made fewer errors on affective as compared to cognitive ToM conditions in both tasks, patients with VM damage showed a different trend. Furthermore, while affective ToM was mostly impaired by VM damage, cognitive ToM was mostly impaired by extensive prefrontal damage, suggesting that cognitive and affective mentalizing abilities are partly dissociable. By introducing the concept of 'affective ToM' to the study of social cognition, these results offer new insights into the mediating role of the VM in the affective facets of social behavior that may underlie the behavioral disturbances observed in these patients.     

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.     

Somatic engagement alters subsequent neurobehavioral correlates of affective mentalizing

Socio‐emotional encounters involve a resonance of others'' affective states, known as affect sharing (AS); and attribution of mental states to others, known as theory‐of‐mind (ToM). Empathy necessitates the integration of both processes, yet their interaction during emotional episodes and subsequent generation of inferences on others'' affective states has rarely been tested. To address this, we developed a novel experimental design, wherein we manipulated AS by presenting nonverbal emotionally negative movies twice—each time accompanied by one of two soundtracks that accentuated either somatic cues or externally generated sounds. Movies were followed by questions addressing affective‐ToM (emotional inferences), cognitive‐ToM (inferences on beliefs and knowledge), and non‐ToM aspects. Results revealed a neural differentiation between AS, affective‐ToM, and cognitive‐ToM. AS movies activated regions that have been implicated in emotional (e.g., amygdala) and somatosensory processing, and synchronized brain activity between participants in the latter. Affective‐ToM activated the middle insula, limbic regions, and both ventral and dorsal portions of the medial prefrontal cortex (ventral medial prefrontal cortex [VMPFC] and dorsal medial prefrontal cortex [DMPFC], respectively), whereas cognitive‐ToM activated posteromedial and lateral–prefrontal and temporal cortices. Critically, AS movies specifically altered neural activation in AS and ToM‐related regions during subsequent affective‐ToM inferences, most notably in the DMPFC. Moreover, DMPFC–VMPFC connectivity correlated with affective‐ToM accuracy, when such questions followed AS movies. Our results associate empathic processes with designated neural activations and shed light on how neuro‐behavioral indices of affective ToM are shaped by preceding somatic engagement.     

Changes of brain activity in the neural substrates for theory of mind during childhood and adolescence

Theory of mind (ToM) refers to the ability to attribute independent mental states, such as beliefs, preferences and desires, to the self and others. Neuroimaging studies of normal adults have consistently demonstrated the importance of particular brain regions for ToM, the superior temporal sulcus (STS), temporal pole (TP) and the medial prefrontal cortex (MPFC). However, there are little data showing how ToM develops during childhood and adolescence. Such data are important for understanding the development of social functioning and its disorders. The authors used functional magnetic resonance imaging to study age-related changes in brain activity associated with ToM during childhood and early adolescence (9-16 years). Normally developed children and adolescents demonstrated significant activation in the bilateral STS, the TP adjacent to the amygdala (TP/Amy) and the MPFC. Furthermore, the authors found a positive correlation between age and the degree of activation in the dorsal part of the MPFC; in contrast, a negative correlation was found for the ventral part of the MPFC. The authors also found a positive correlation between the Z coordinate of the peak activation in the MPFC and age. The data indicated that activity in the MPFC associated with ToM shifted from the ventral to the dorsal part of the MPFC during late childhood and adolescence. No age-related changes were found in the STS and the TP/Amy regions. The authors consider that the age-related brain activity observed in the present study may be associated with the maturation of the prefrontal cortex and the associated development of cognitive functions.     

Neurobiological correlates of theory of mind in psychosis proneness

Theory of mind (ToM) refers to the capacity to infer one's own and other persons’ mental states. ToM abilities are compromised in schizophrenia, in association with dysfunctional activity in predominantly prefrontal brain regions. Prior behavioral studies have also suggested ToM deficits in healthy individuals with psychosis proneness (PP), although no study to date had investigated the associated neural mechanisms in such a sample. Here we used functional magnetic resonance imaging (fMRI) to compare brain activation of subjects with high versus low scores on positive-dimension PP and a ToM task. The ToM task involved first and second order attribution of cognitive and affective mental states to a cartoon character based on verbal and eye-gaze cues. No between-group differences were found on behavioral performance. fMRI analyses revealed a group interaction in anterior prefrontal cortex (BA 10), with the high PP group showing significantly more activity thereof, relative to the low PP, during second order mentalizing than during first order mentalizing. Further between-group differences were observed in dorsomedial and lateral prefrontal regions (BA 46/9), with the high PP group also showing greater activation during second order mentalizing. These results suggest that subjects with positive-dimension PP require more activation of prefrontal areas to adequately mentalize. Differences in the neural mechanisms underlying ToM might be associated with vulnerability to psychosis.     

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.     

Theory of mind and empathy in preclinical and clinical Huntington’s disease

We investigated cognitive and affective Theory of Mind (ToM) and empathy in patients with premanifest and manifest Huntington’s disease (HD). The relationship between ToM performance and executive skills was also examined. Sixteen preclinical and 23 clinical HD patients, and 39 healthy subjects divided into 2 control groups were given a French adaptation of the Yoni test (Shamay-Tsoory, S.G., Aharon-Peretz, J. (2007). Dissociable prefrontal networks for cognitive and affective theory of mind: a lesion study. Neuropsychologia, 45(3), 3054–67) that examines first- and second-order cognitive and affective ToM processing in separate conditions with a physical control condition. Participants were also given questionnaires of empathy and cognitive tests which mainly assessed executive functions (inhibition and mental flexibility). Clinical HD patients made significantly more errors than their controls in the first- and second-order cognitive and affective ToM conditions of the Yoni task, but exhibited no empathy deficits. However, there was no evidence that ToM impairment was related to cognitive deficits in these patients. Preclinical HD patients were unimpaired in ToM tasks and empathy measures compared with their controls. Our results are consistent with the idea that impaired affective and cognitive mentalizing emerges with the clinical manifestation of HD, but is not necessarily part of the preclinical stage. Furthermore, these impairments appear independent of executive dysfunction and empathy.     

Theory of mind in Parkinson's disease and related basal ganglia disorders: A systematic review

Theory of mind (ToM), defined as the ability to infer other people's mental states, is a crucial prerequisite of human social interaction and a major topic of interest in the recent neuroscientific research. It has been proposed that ToM is mediated by a complex neuroanatomical network that includes the medial prefrontal cortex, the anterior gyrus cinguli, the sulcus temporalis superior, the temporal poles, and the amygdala. Various neurological and psychiatric diseases are accompanied by aspects of dysfunctional ToM processing. In this review, the association between basal ganglia, involved in the organization of complex cognitive and emotional behavior, and ToM processing is discussed. The purpose of this review is to provide an overview of research on ToM abilities in basal ganglia disorders, especially Parkinson's Disease and related disorders. © 2009 Movement Disorder Society     

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.     

Self-development: integrating cognitive, socioemotional, and neuroimaging perspectives

This review integrates cognitive, socioemotional, and neuroimaging perspectives on self-development. Neural correlates of key processes implicated in personal and social identity are reported from studies of children, adolescents, and adults, including autobiographical memory, direct and reflected self-appraisals, and social exclusion. While cortical midline structures of medial prefrontal cortex and medial posterior parietal cortex are consistently identified in neuroimaging studies considering personal identity from a primarily cognitive perspective (“who am I?”), additional regions are implicated by studies considering personal and social identity from a more socioemotional perspective (“what do others think about me, where do I fit in?”), especially in child or adolescent samples. The involvement of these additional regions (including tempo–parietal junction and posterior superior temporal sulcus, temporal poles, anterior insula, ventral striatum, anterior cingulate cortex, middle cingulate cortex, and ventrolateral prefrontal cortex) suggests mentalizing, emotion, and emotion regulation are central to self-development. In addition, these regions appear to function atypically during personal and social identity tasks in autism and depression, exhibiting a broad pattern of hypoactivation and hyperactivation, respectively.     

Do we mind other minds when we mind other minds' actions? A functional magnetic resonance imaging study

Action observation engages higher motor areas, possibly reflecting an internal simulation. However, actions considered odd or unusual were found to trigger additional activity in the so-called theory of mind (ToM) network, pointing to deliberations on the actor's mental states. In this functional magnetic resonance imaging study, the hypothesis was tested that an allocentric perspective on a normal action, and even more so the sight of the actor's face, suffices to evoke ToM activity. Subjects observed short videos of object manipulation filmed from either the egocentric or the allocentric perspective, the latter including the actor's face in half of the trials. On the basis of a regions of interest analysis using ToM coordinates, we found increased neural activity in several regions of the ToM network. First, perceiving actions from an allocentric compared with the egocentric perspective enhanced activity in the left temporoparietal junction (TPJ). Second, the presence of the actor's face enhanced activation in the TPJ bilaterally, the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC). Finally, the mPFC and PCC showed increased responses when the actor changed with respect to the preceding trial. These findings were further corroborated by zmap findings for the latter two contrasts. Together, findings indicate that observation of normal everyday actions can engage ToM areas and that an allocentric perspective, seeing the actor's face and seeing a face switch, are effective triggers.     

Neurobiology of emotion perception II: Implications for major psychiatric disorders.

To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and functional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability, and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.     

Neurobiology of emotion perception I: The neural basis of normal emotion perception.

There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.     

Influence of emotional complexity on the neural substrates of affective theory of mind

Affective theory of mind (ToM) depends on both the decoding of emotional expressions and the reasoning on emotional mental states from social situations. While previous studies characterized the neural substrates underlying these processes, it remains unclear whether the nature of the emotional state inferred from others can influence the brain activation associated with affective ToM. In the present study, we focused on two types of emotions: basic emotions (BEs) (e.g., anger and surprise), which are innate and universal and self‐conscious emotions (e.g., pride and embarrassment), which correspond to a special class of emotions involving the self and including a representation of one's relative reactions to internal and external standards. Specifically, we used an ecological functional MRI paradigm, on 21 healthy young subjects, to compare brain activations during the decoding of and the reasoning on others' self‐conscious, basic and neutral mental states. Our results showed that compared to neutral states, the inference of self‐conscious and basic emotional states from others elicited more activation in several core regions of affective ToM. Direct comparisons between emotional conditions revealed more activation for self‐conscious than BEs in the right temporoparietal junction during the reasoning process and in left middle occipital regions during the decoding process. Further analyses using a localizer task showed that the extrastriate body area was more recruited for decoding others' self‐conscious versus BEs, which emphasize the importance of body clues to properly infer these emotions. Using an original task allowing for an ecological assessment of the affective ToM, these results demonstrate that the complexity of the emotion inferred to others can influence the recruitment of ToM network. This study also validates the use of our task as an ecological tool to assess the affective ToM, constituting an avenue for the characterization of ToM impairments in neurological conditions.