Brain Activation for Social Cognition and Emotion Processing Tasks in Borderline Personality Disorder: A Meta-Analysis of Neuroimaging Studies.

The present meta-analysis summarizes brain activation for social cognition and emotion-processing tasks in borderline personality disorder (BPD). We carried out two meta-analyses to elaborate on commonalities and potential differences between the two types of tasks. In the first meta-analysis, we implemented a more liberal strategy for task selection (including social and emotional content). The results confirmed previously reported hyperactivations in patients with BPD in the bilateral amygdala and prefrontal cortex and hypoactivations in bilateral inferior frontal gyri. When applying a stricter approach to task selection, focusing narrowly on social cognition tasks, we only found activation in prefrontal areas, particularly in the anterior cingulate and ventromedial prefrontal cortex. We review the role of these areas in social cognition in healthy adults, suggesting that the observed BPD hyperactivations may reflect an overreliance on self-related thought in social cognition.

How do bipolar disease states affect positive and negative emotion processing? Insights from a meta-analysis on the neural fingerprints of emotional processing.

BACKGROUND: Functional magnetic resonance imaging studies on emotion processing in patients with bipolar disorder (BD) show hyperactivity of limbic-striatal brain areas and hypoactivity in inferior frontal areas compared to healthy participants. However, heterogeneous results in patients with different disease states and different valences of emotional stimuli have been identified. METHODS: To integrate previous results and elucidate the impact of disease state and stimulus valence, we conducted a systematic literature search for journal articles in the Web of Science Core Collection including MEDLINE databases and employed a coordinate-based-meta-analysis of functional-MRI studies comparing emotion processing in BD-patients with healthy participants using seed-based d mapping (SDM) to test for between-subjects-effects. We included 31 studies published before 11/2022 with a total of N = 766 BD-patients and N = 836 controls. RESULTS: Patients with BD showed hyperactivated regions involved in salience processing of emotional stimuli (e.g., the bilateral insula) and hypoactivation of regions associated with emotion regulation (e.g., inferior frontal gyrus) during emotion processing, compared to healthy participants. A more detailed descriptive analysis revealed a hypoactive (anterior) insula in manic BD-patients specifically for negative in comparison to positive emotion processing. DISCUSSION: This meta-analysis corroborates the overall tenor of existing literature that patients with BD show an increased emotional reactivity (hyperactivity of salience-processing regions) together with a lower (cognitive) control (hypoactivity of brain areas associated with emotion regulation) over emotional states. Our analysis suggests reduced interoceptive processing of negative stimuli in mania, pointing out the need for longitudinal within-subject analyses of emotion processing.

Interactions within the social brain: Co-activation and connectivity among networks enabling empathy and Theory of Mind.

Empathy and Theory of Mind (ToM) have classically been studied as separate social functions, however, recent advances demonstrate the need to investigate the two in interaction: naturalistic settings often blur the distinction of affect and cognition and demand the simultaneous processing of such different stimulus dimensions. Here, we investigate how empathy and ToM related brain networks interact in contexts wherein multiple cognitive and affective demands must be processed simultaneously. Building on the findings of a recent meta-analysis and hierarchical clustering analysis, we perform meta-analytic connectivity modeling to determine patterns of task-context specific network changes. We analyze 140 studies including classical empathy and ToM tasks, as well as complex social tasks. For studies at the intersection of empathy and ToM, neural co-activation patterns included areas typically associated with both empathy and ToM. Network integration is discussed as a means of combining mechanisms across unique behavioral domains. Such integration may enable adaptive behavior in complex, naturalistic social settings that require simultaneous processing of a multitude of different affective and cognitive information.

The gradient model of brain organization in decisions involving "empathy for pain".

Influential models of cortical organization propose a close relationship between heteromodal association areas and highly connected hubs in the default mode network. The "gradient model" of cortical organization proposes a close relationship between these areas and highly connected hubs in the default mode network, a set of cortical areas deactivated by demanding tasks. Here, we used a decision-making task and representational similarity analysis with classic "empathy for pain" stimuli to probe the relationship between high-level representations of imminent pain in others and these areas. High-level representations were colocalized with task deactivations or the transitions from activations to deactivations. These loci belonged to 2 groups: those that loaded on the high end of the principal cortical gradient and were associated by meta-analytic decoding with the default mode network, and those that appeared to accompany functional repurposing of somatosensory cortex in the presence of visual stimuli. These findings suggest that task deactivations may set out cortical areas that host high-level representations. We anticipate that an increased understanding of the cortical correlates of high-level representations may improve neurobiological models of social interactions and psychopathology.

A Short Functional Neuroimaging Assay Using Attachment Scenes to Recruit Neural Correlates of Social Cognition-A Replication Study.

Attachment theory provides a conceptual framework to understand the impact of early child-caregiver experiences, such as loss or separation, on adult functioning and psychopathology. In the current study, scenes from the Adult Attachment Projective Picture System (AAP), a validated, commonly used standardized diagnostic instrument to assess adult attachment representations, were used to develop a short fMRI assay eliciting the neural correlates of encoding of potentially hurtful and threatening social situations such as social losses, rejections or loneliness. Data from healthy participants (N = 19) showed activations in brain areas associated with social cognition and semantic knowledge during exposure to attachment-related scenes compared to control scenes. Extensive activation of the temporal poles was observed, suggesting the use of semantic knowledge for generating social concepts and scripts. This knowledge may underlie our ability to explain and predict social interactions, a specific aspect of theory of mind or mentalization. In this replication study, we verified the effectiveness of a modified fMRI assay to assess the external validity of a previously used imaging paradigm to investigate the processing of emotionally negatively valenced and painful social interactions. Our data confirm the recruitment of brain areas associated with social cognition with our very short neuroimaging assay.

Does the temporal cortex make us human? A review of structural and functional diversity of the primate temporal lobe.

Temporal cortex is a primate specialization that shows considerable variation in size, morphology, and connectivity across species. Human temporal cortex is involved in many behaviors that are considered especially well developed in humans, including semantic processing, language, and theory of mind. Here, we ask whether the involvement of temporal cortex in these behaviors can be explained in the context of the 'general' primate organization of the temporal lobe or whether the human temporal lobe contains unique specializations indicative of a 'step change' in the lineage leading to modern humans. We propose that many human behaviors can be explained as elaborations of temporal cortex functions observed in other primates. However, changes in temporal lobe white matter suggest increased integration of information within temporal cortex and between posterior temporal cortex and other association areas, which likely enable behaviors not possible in other species.

Social prediction modulates activity of macaque superior temporal cortex.

The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied in humans; however, its evolutionary origins have been challenged. Computationally, the basis of TOM has been interpreted within the predictive coding framework and associated with activity in the temporoparietal junction (TPJ). Here, we revealed, using a nonlinguistic task and functional magnetic resonance imaging, that activity in a region of the macaque middle superior temporal cortex was specifically modulated by the predictability of social situations. As in human TPJ, this region could be distinguished from other temporal regions involved in face processing. Our result suggests the existence of a precursor for the TOM ability in the last common ancestor of human and Old World monkeys.

Variability in Brain Structure and Function Reflects Lack of Peer Support.

Humans are a highly social species. Complex interactions for mutual support range from helping neighbors to building social welfare institutions. During times of distress or crisis, sharing life experiences within one's social circle is critical for well-being. By translating pattern-learning algorithms to the UK Biobank imaging-genetics cohort (n = ~40 000 participants), we have delineated manifestations of regular social support in multimodal whole-brain measurements. In structural brain variation, we identified characteristic volumetric signatures in the salience and limbic networks for high- versus low-social support individuals. In patterns derived from functional coupling, we also located interindividual differences in social support in action-perception circuits related to binding sensory cues and initiating behavioral responses. In line with our demographic profiling analysis, the uncovered neural substrates have potential implications for loneliness, substance misuse, and resilience to stress.

Toward a hierarchical model of social cognition: A neuroimaging meta-analysis and integrative review of empathy and theory of mind.

Along with the increased interest in and volume of social cognition research, there has been higher awareness of a lack of agreement on the concepts and taxonomy used to study social processes. Two central concepts in the field, empathy and Theory of Mind (ToM), have been identified as overlapping umbrella terms for different processes of limited convergence. Here, we review and integrate evidence of brain activation, brain organization, and behavior into a coherent model of social-cognitive processes. We start with a meta-analytic clustering of neuroimaging data across different social-cognitive tasks. Results show that understanding others' mental states can be described by a multilevel model of hierarchical structure, similar to models in intelligence and personality research. A higher level describes more broad and abstract classes of functioning, whereas a lower one explains how functions are applied to concrete contexts given by particular stimulus and task formats. Specifically, the higher level of our model suggests 3 groups of neurocognitive processes: (a) predominantly cognitive processes, which are engaged when mentalizing requires self-generated cognition decoupled from the physical world; (b) more affective processes, which are engaged when we witness emotions in others based on shared emotional, motor, and somatosensory representations; (c) combined processes, which engage cognitive and affective functions in parallel. We discuss how these processes are explained by an underlying principal gradient of structural brain organization. Finally, we validate the model by a review of empathy and ToM task interrelations found in behavioral studies. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cross-network interactions in social cognition: A review of findings on task related brain activation and connectivity.

Theory of Mind, empathy, and action observation are central themes in social neuroscience research. Meta-analyses of functional neuroimaging studies show substantial heterogeneity in brain activation for these cognitive abilities, depending on the type of experimental task used. We followed up on these findings by a comparison to basic connectivity networks of the brain. In particular, we evaluated to what extent brain activation for social cognition tasks draws on areas of different fMRI resting-state networks (e.g., Default Mode, Ventral Attention Network) in parallel. Our review illustrates high prevalence of such network co-recruitments across Theory of Mind, empathy, and action observation tasks. To characterize these observations in more detail, we additionally conducted a literature review of fMRI effective connectivity studies. Findings reveal two main types of cross-network interactions in social cognition tasks: Negative coupling (segregation) between Default Mode and Control Networks (Ventral Attention, Frontoparietal, and Dorsal Attention Network), and positive coupling (integration) between these networks. The two patterns reflect different types of brain network organization taking place in the context of social cognition tasks-segregation for specialized, versus integration for flexible processing. We discuss evidence from connectivity research in other research fields, suggesting that increased network integration indicates more effortful and controlled processing. Based on that, we consider how findings of network segregation versus integration can provide new perspectives on dual-system accounts of social cognition, which differentiate between automatic and controlled processes. Moreover, we discuss how the reviewed evidence relates to neural processes which are assumed to take place during naturalistic social cognition.

Principles of temporal association cortex organisation as revealed by connectivity gradients.

To establish the link between structure and function of any large area of the neocortex, it is helpful to identify its principles of organisation. One way to establish such principles is to investigate how differences in whole-brain connectivity are structured across the area. Here, we use Laplacian eigenmaps on diffusion MRI tractography data to investigate the organisational principles of the human temporal association cortex. We identify three overlapping gradients of connectivity that are, for the most part, consistent across hemispheres. The first gradient reveals an inferior-superior organisation of predominantly longitudinal tracts and separates visual and auditory unimodal and multimodal cortices. The second gradient radiates outward from the posterior middle temporal cortex with the arcuate fascicle as a distinguishing feature; the third gradient is concentrated in the anterior temporal lobe and emanates towards its posterior end. We describe the functional relevance of each of these gradients through the meta-analysis of data from the neuroimaging literature. Together, these results unravel the overlapping dimensions of structural organization of the human temporal cortex and provide a framework underlying its functional multiplicity.

The role of the IPL in person identification.

We investigate the brain activations when identifying a newly encountered individual as being the same as a person previously perceived, a fundamental but seldom acknowledged process. In an identity condition, two faces had to be identified as the same person in contrast to a control condition, in which two faces had to be recognised as belonging to similar looking twins. Our results demonstrate an increase of neural activation in frontal as well as in parietal areas including the left inferior parietal lobe and the precuneus during identification. We introduce mental files theory to model this process as a linking of co-referential files and identify important connections to other domains in neurological and cognitive science (e.g., delusional misidentification syndromes, theory of mind).

Measuring visual perspective taking in the brain with avatars and arrows: Which question are we asking?

There is an ongoing debate about the involvement of Theory of Mind (ToM) processes in Visual Perspective Taking (VPT). In an fMRI study (Schurz et al., 2015), we borrowed the positive features from a novel VPT task - which is widely used in behavioral research - to study previously overlooked experimental factors in neuroimaging studies. However, as Catmur et al. (2016) rightly argue in a comment on our work, our data do not speak strongly to questions discussed in the original behavioral studies, in particular the issue of implicit mentalizing. We appreciate the clarification of these interpretational limitations of our study, but would like to point out the differences between questions emerging from behavioral and neuroimaging research on VPT. Different from what Catmur et al. (2016) discuss, our study was not intended as a test of implicit mentalizing. In fact, the terms "automatic" and "implicit mentalizing" were never mentioned in our manuscript. Our study addressed a methodological gap between ToM and VPT research, which we identified in two previous meta-analyses on the topics (Schurz et al., 2013, 2014). With this difference in mind we show that the critical points levelled by Catmur et al. (2016) cease to apply.

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects.

Specifying the brain anatomy underlying temporo-parietal junction activations for theory of mind: A review using probabilistic atlases from different imaging modalities.

In this quantitative review, we specified the anatomical basis of brain activity reported in the Temporo-Parietal Junction (TPJ) in Theory of Mind (ToM) research. Using probabilistic brain atlases, we labeled TPJ peak coordinates reported in the literature. This was carried out for four different atlas modalities: (i) gyral-parcellation, (ii) sulco-gyral parcellation, (iii) cytoarchitectonic parcellation and (iv) connectivity-based parcellation. In addition, our review distinguished between two ToM task types (false belief and social animations) and a nonsocial task (attention reorienting). We estimated the mean probabilities of activation for each atlas label, and found that for all three task types part of TPJ activations fell into the same areas: (i) Angular Gyrus (AG) and Lateral Occpital Cortex (LOC) in terms of a gyral atlas, (ii) AG and Superior Temporal Sulcus (STS) in terms of a sulco-gyral atlas, (iii) areas PGa and PGp in terms of cytoarchitecture and (iv) area TPJp in terms of a connectivity-based parcellation atlas. Beside these commonalities, we also found that individual task types showed preferential activation for particular labels. Main findings for the right hemisphere were preferential activation for false belief tasks in AG/PGa, and in Supramarginal Gyrus (SMG)/PFm for attention reorienting. Social animations showed strongest selective activation in the left hemisphere, specifically in left Middle Temporal Gyrus (MTG). We discuss how our results (i.e., identified atlas structures) can provide a new reference for describing future findings, with the aim to integrate different labels and terminologies used for studying brain activity around the TPJ. Hum Brain Mapp 38:4788-4805, 2017. © 2017 Wiley Periodicals, Inc.

Systematic Comparison of Brain Imaging Meta-Analyses of ToM with vPT.

In visual perspective taking (vPT) one has to concern oneself with what other people see and how they see it. Since seeing is a mental state, developmental studies have discussed vPT within the domain of "theory of mind (ToM)" but imaging studies have not treated it as such. Based on earlier results from several meta-analyses, we tested for the overlap of visual perspective taking studies with 6 different kinds of ToM studies: false belief, trait judgments, strategic games, social animations, mind in the eyes, and rational actions. Joint activation was observed between the vPT task and some kinds of ToM tasks in regions involving the left temporoparietal junction (TPJ), anterior precuneus, left middle occipital gyrus/extrastriate body area (EBA), and the left inferior frontal and precentral gyrus. Importantly, no overlap activation was found for the vPT tasks with the joint core of all six kinds of ToM tasks. This raises the important question of what the common denominator of all tasks that fall under the label of "theory of mind" is supposed to be if visual perspective taking is not one of them.

The rTPJ's overarching cognitive function in networks for attention and theory of mind.

Cortical networks underpinning attentional control and mentalizing converge at the right temporoparietal junction (rTPJ). It is debated whether the rTPJ is fractionated in neighboring, but separate functional modules underpinning attentional control and mentalizing, or whether one overarching cognitive mechanism explains the rTPJ's role in both domains. Addressing this question, we combined attentional control and mentalizing in a factorial design within one task. We added a social context condition, in which another individual's mental states became apparently task-relevant, to a spatial cueing paradigm. This allowed for assessing cue validity- and context-dependent functional activity and effective connectivity of the rTPJ within corresponding cortical networks. We found two discriminable rTPJ subregions, an anterior and a posterior one. Yet, we did not observe a sharp functional dissociation between these two, as both regions responded to attention cueing and social context manipulation. The results suggest that the rTPJ is part of both the ventral attention and the ToM network and that its function is defined by context-dependent coupling with the respective network. We argue that the rTPJ as a functional unit underpins an overarching cognitive mechanism in attentional control and mentalizing and discuss how the present results help to further specify this mechanism.

White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults.

Cognitive reserve (CR) models posit that lifestyle factors such as education modulate the relationship between brain damage and cognition. However, the functional correlates of CR in healthy aging are still under investigation. White matter hyperintensities (WMHs) are a common age-associated finding that impacts cognition. In this study, we used functional magnetic resonance imaging to characterize the patterns of brain activation during a working memory task in older participants with high and low levels of education (as a proxy of CR) and high and low WMH volumes. Ninety older volunteers (aged 63-76 years) and 16 young adults (aged 21-27) completed the study. We found that older adults with higher education had better working memory performance than their less educated peers. Among the highly educated participants, those with WMH over-recruited areas engaged by young volunteers and showed activation in additional cortical and subcortical structures. However, those with low WMH differed little with respect to their younger counterparts. Our findings demonstrate that the functional mechanisms subtending the effects of education, as a proxy of CR, are modulated according to the WMH burden.

Left ventral occipitotemporal activation during orthographic and semantic processing of auditory words.

The present fMRI study investigated the hypothesis that activation of the left ventral occipitotemporal cortex (vOT) in response to auditory words can be attributed to lexical orthographic rather than lexico-semantic processing. To this end, we presented auditory words in both an orthographic ("three or four letter word?") and a semantic ("living or nonliving?") task. In addition, a auditory control condition presented tones in a pitch evaluation task. The results showed that the left vOT exhibited higher activation for orthographic relative to semantic processing of auditory words with a peak in the posterior part of vOT. Comparisons to the auditory control condition revealed that orthographic processing of auditory words elicited activation in a large vOT cluster. In contrast, activation for semantic processing was only weak and restricted to the middle part vOT. We interpret our findings as speaking for orthographic processing in left vOT. In particular, we suggest that activation in left middle vOT can be attributed to accessing orthographic whole-word representations. While activation of such representations was experimentally ascertained in the orthographic task, it might have also occurred automatically in the semantic task. Activation in the more posterior vOT region, on the other hand, may reflect the generation of explicit images of word-specific letter sequences required by the orthographic but not the semantic task. In addition, based on cross-modal suppression, the finding of marked deactivations in response to the auditory tones is taken to reflect the visual nature of representations and processes in left vOT.