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.

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.

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.

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.

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.

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.

Resting-State and Task-Based Functional Brain Connectivity in Developmental Dyslexia.

Reading requires the interaction between multiple cognitive processes situated in distant brain areas. This makes the study of functional brain connectivity highly relevant for understanding developmental dyslexia. We used seed-voxel correlation mapping to analyse connectivity in a left-hemispheric network for task-based and resting-state fMRI data. Our main finding was reduced connectivity in dyslexic readers between left posterior temporal areas (fusiform, inferior temporal, middle temporal, superior temporal) and the left inferior frontal gyrus. Reduced connectivity in these networks was consistently present for 2 reading-related tasks and for the resting state, showing a permanent disruption which is also present in the absence of explicit task demands and potential group differences in performance. Furthermore, we found that connectivity between multiple reading-related areas and areas of the default mode network, in particular the precuneus, was stronger in dyslexic compared with nonimpaired readers.

Clarifying the role of theory of mind areas during visual perspective taking: Issues of spontaneity and domain-specificity.

Visual perspective taking is a fundamental feature of the human social brain. Previous research has mainly focused on explicit visual perspective taking and contrasted brain activation for other- versus self-perspective judgements. This produced a conceptual gap to theory of mind studies, where researchers mainly compared activation for taking another's mental perspective to non-mental control conditions. We compared brain activation for visual perspective taking to activation for non-mental control conditions where the avatar was replaced by directional (arrow, lamp) or non-directional (brick-wall) objects. We found domain-specific activation linked to the avatar's visual perspective in right TPJ, ventral mPFC and ventral precuneus. Interestingly, we found that these areas are spontaneously processing information linked to the other's perspective during self-perspective judgements. Based on a review of the visual perspective taking literature, we discuss how these findings can explain some of the inconsistent/negative results found in previous studies comparing other- versus self-perspective judgements.

Impaired consciousness is linked to changes in effective connectivity of the posterior cingulate cortex within the default mode network.

The intrinsic connectivity of the default mode network has been associated with the level of consciousness in patients with severe brain injury. Especially medial parietal regions are considered to be highly involved in impaired consciousness. To better understand what aspect of this intrinsic architecture is linked to consciousness, we applied spectral dynamic causal modeling to assess effective connectivity within the default mode network in patients with disorders of consciousness. We included 12 controls, 12 patients in minimally conscious state and 13 in vegetative state in this study. For each subject, we first defined the four key regions of the default mode network employing a subject-specific independent component analysis approach. The resulting regions were then included as nodes in a spectral dynamic causal modeling analysis in order to assess how the causal interactions across these regions as well as the characteristics of neuronal fluctuations change with the level of consciousness. The resulting pattern of interaction in controls identified the posterior cingulate cortex as the main driven hub with positive afferent but negative efferent connections. In patients, this pattern appears to be disrupted. Moreover, the vegetative state patients exhibit significantly reduced self-inhibition and increased oscillations in the posterior cingulate cortex compared to minimally conscious state and controls. Finally, the degree of self-inhibition and strength of oscillation in this region is correlated with the level of consciousness. These findings indicate that the equilibrium between excitatory connectivity towards posterior cingulate cortex and its feedback projections is a key aspect of the relationship between alterations in consciousness after severe brain injury and the intrinsic functional architecture of the default mode network. This impairment might be principally due to the disruption of the mechanisms underlying self-inhibition and neuronal oscillations in the posterior cingulate cortex.

Reading in the brain of children and adults: a meta-analysis of 40 functional magnetic resonance imaging studies.

We used quantitative, coordinate-based meta-analysis to objectively synthesize age-related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23-34 years) were matched to 20 studies with children (age means: 7-12 years). The separate meta-analyses of these two sets showed a pattern of reading-related brain activation common to children and adults in left ventral occipito-temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta-analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading-related activation clusters in children and adults are provided.

Fixation-related FMRI analysis in the domain of reading research: using self-paced eye movements as markers for hemodynamic brain responses during visual letter string processing.

The present study investigated the feasibility of using self-paced eye movements during reading (measured by an eye tracker) as markers for calculating hemodynamic brain responses measured by functional magnetic resonance imaging (fMRI). Specifically, we were interested in whether the fixation-related fMRI analysis approach was sensitive enough to detect activation differences between reading material (words and pseudowords) and nonreading material (line and unfamiliar Hebrew strings). Reliable reading-related activation was identified in left hemisphere superior temporal, middle temporal, and occipito-temporal regions including the visual word form area (VWFA). The results of the present study are encouraging insofar as fixation-related analysis could be used in future fMRI studies to clarify some of the inconsistent findings in the literature regarding the VWFA. Our study is the first step in investigating specific visual word recognition processes during self-paced natural sentence reading via simultaneous eye tracking and fMRI, thus aiming at an ecologically valid measurement of reading processes. We provided the proof of concept and methodological framework for the analysis of fixation-related fMRI activation in the domain of reading research.

Top-down and bottom-up influences on the left ventral occipito-temporal cortex during visual word recognition: an analysis of effective connectivity.

The functional role of the left ventral occipito-temporal cortex (vOT) in visual word processing has been studied extensively. A prominent observation is higher activation for unfamiliar but pronounceable letter strings compared to regular words in this region. Some functional accounts have interpreted this finding as driven by top-down influences (e.g., Dehaene and Cohen [2011]: Trends Cogn Sci 15:254-262; Price and Devlin [2011]: Trends Cogn Sci 15:246-253), while others have suggested a difference in bottom-up processing (e.g., Glezer et al. [2009]: Neuron 62:199-204; Kronbichler et al. [2007]: J Cogn Neurosci 19:1584-1594). We used dynamic causal modeling for fMRI data to test bottom-up and top-down influences on the left vOT during visual processing of regular words and unfamiliar letter strings. Regular words (e.g., taxi) and unfamiliar letter strings of pseudohomophones (e.g., taksi) were presented in the context of a phonological lexical decision task (i.e., "Does the item sound like a word?"). We found no differences in top-down signaling, but a strong increase in bottom-up signaling from the occipital cortex to the left vOT for pseudohomophones compared to words. This finding can be linked to functional accounts which assume that the left vOT contains neurons tuned to complex orthographic features such as morphemes or words [e.g., Dehaene and Cohen [2011]: Trends Cogn Sci 15:254-262; Kronbichler et al. [2007]: J Cogn Neurosci 19:1584-1594]: For words, bottom-up signals converge onto a matching orthographic representation in the left vOT. For pseudohomophones, the propagated signals do not converge, but (partially) activate multiple orthographic word representations, reflected in increased effective connectivity.

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.

Processing counterfactual and hypothetical conditionals: an fMRI investigation.

Counterfactual thinking is ubiquitous in everyday life and an important aspect of cognition and emotion. Although counterfactual thought has been argued to differ from processing factual or hypothetical information, imaging data which elucidate these differences on a neural level are still scarce. We investigated the neural correlates of processing counterfactual sentences under visual and aural presentation. We compared conditionals in subjunctive mood which explicitly contradicted previously presented facts (i.e. counterfactuals) to conditionals framed in indicative mood which did not contradict factual world knowledge and thus conveyed a hypothetical supposition. Our results show activation in right occipital cortex (cuneus) and right basal ganglia (caudate nucleus) during counterfactual sentence processing. Importantly the occipital activation is not only present under visual presentation but also with purely auditory stimulus presentation, precluding a visual processing artifact. Thus our results can be interpreted as reflecting the fact that counterfactual conditionals pragmatically imply the relevance of keeping in mind both factual and supposed information whereas the hypothetical conditionals imply that real world information is irrelevant for processing the conditional and can be omitted. The need to sustain representations of factual and suppositional events during counterfactual sentence processing requires increased mental imagery and integration efforts. Our findings are compatible with predictions based on mental model theory.

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.

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.

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).

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.

A dual-route perspective on brain activation in response to visual words: evidence for a length by lexicality interaction in the visual word form area (VWFA).

Based on our previous work, we expected the Visual Word Form Area (VWFA) in the left ventral visual pathway to be engaged by both whole-word recognition and by serial sublexical coding of letter strings. To examine this double function, a phonological lexical decision task (i.e., "Does xxx sound like an existing word?") presented short and long letter strings of words, pseudohomophones, and pseudowords (e.g., Taxi, Taksi and Tazi). Main findings were that the length effect for words was limited to occipital regions and absent in the VWFA. In contrast, a marked length effect for pseudowords was found throughout the ventral visual pathway including the VWFA, as well as in regions presumably engaged by visual attention and silent-articulatory processes. The length by lexicality interaction on brain activation corresponds to well-established behavioral findings of a length by lexicality interaction on naming latencies and speaks for the engagement of the VWFA by both lexical and sublexical processes.