Using second-person neuroscience to elucidate the mechanisms of social interaction.

Although a large proportion of our lives are spent participating in social interactions, the investigation of the neural mechanisms supporting these interactions has largely been restricted to situations of social observation - that is, situations in which an individual observes a social stimulus without opportunity for interaction. In recent years, efforts have been made to develop a truly social, or 'second-person', neuroscientific approach to these investigations in which neural processes are examined within the context of a real-time reciprocal social interaction. These developments have helped to elucidate the behavioural and neural mechanisms of social interactions; however, further theoretical and methodological innovations are still needed. Findings to date suggest that the neural mechanisms supporting social interaction differ from those involved in social observation and highlight a role of the so-called 'mentalizing network' as important in this distinction. Taking social interaction seriously may also be particularly important for the advancement of the neuroscientific study of different psychiatric conditions.

When "more for others, less for self" leads to co-benefits: A tri-MRI dyad-hyperscanning study.

Unselfishness is admired, especially when collaborations between groups of various scales are urgently needed. However, its neural mechanisms remain elusive. In a tri-MRI dyad-hyperscanning experiment involving 26 groups, each containing 4 participants as two rotating pairs in a coordination game, we sought to achieve reciprocity, or "winning in turn by the two interacting players," as the precursor to unselfishness. Due to its critical role in social processing, the right temporal-parietal junction (rTPJ) was the seed for both time domain (connectivity) and frequency domain (i.e., coherence) analyses. For the former, negative connectivity between the rTPJ and the mentalizing network areas (e.g., the right inferior parietal lobule, rIPL) was identified, and such connectivity was further negatively correlated with the individual's final gain, supporting our task design that "rewarded" the reciprocal participants. For the latter, cerebral coherences of the rTPJs emerged between the interacting pairs (i.e., within-group interacting pairs), and the coupling between the rTPJ and the right superior temporal gyrus (rSTG) between the players who were not interacting with each other (i.e., within-group noninteracting pairs). These coherences reinforce the hypotheses that the rTPJ-rTPJ coupling tracks the collaboration processes and the rTPJ-rSTG coupling for the emergence of decontextualized shared meaning. Our results underpin two social roles (inferring others' behavior and interpreting social outcomes) subserved by the rTPJ-related network and highlight its interaction with other-self/other-concerning brain areas in reaching co-benefits among unselfish players.

Attachment, Mentalization, Emotion Dysregulation, and Empathy in Eating Disorders: Comparing Anorexic and Bulimic Patients.

ABSTRACT: Eating disorders (EDs) represent a wide range of clinical symptoms related to food intake, body image, and weight issues, and include anorexia nervosa-restricting type (AN-R), anorexia nervosa-binge-purge type (AN-BP), and bulimia nervosa (BN). The aim was to investigate the characteristics of attachment, mentalization, emotion dysregulation, and empathy in a sample of 102 patients with EDs. A sample of 102 patients and therapists completed a series of measures for the assessment of ED pathology, mentalization, empathy, and emotion dysregulation. Pearson correlations and analysis of variance were used to test the characteristics of the variables among the groups. In relation to attachment and emotion dysregulation, no significant differences were found. In relation to mentalization, significant difference in good mentalization was found in AN-R subtype compared with the BN subtype. In relation to empathy, results showed significantly lower scores in BN subtype on affective empathy compared with the AN-BP subtype, and in AN-R subtype on cognitive empathy. Finally, we used Z -scores for each item ranked by value (higher to lower) to develop different clinical prototypes for each group. Our results point toward the clinical need to address the assessed variables, specifically mentalization, emotion dysregulation, and empathy, in the diagnosis and treatment of EDs.

Live agent preference and social action monitoring in the macaque mid-superior temporal sulcus region.

Mentalizing, the ability to infer the mental states of others, is a cornerstone of adaptive social intelligence. While functional brain mapping of human mentalizing has progressed considerably, its evolutionary signature in nonhuman primates remains debated. The discovery that the middle part of the macaque superior temporal sulcus (mid-STS) region has a connectional fingerprint most similar to the human temporoparietal junction (TPJ)-a crucial node in the mentalizing network-raises the possibility that these cortical areas may also share basic functional properties associated with mentalizing. Here, we show that this is the case in aspects of a preference for live social interactions and in a theoretical framework of predictive coding. Macaque monkeys were trained to perform a turn-taking choice task with another real monkey partner sitting directly face-to-face or a filmed partner appearing in prerecorded videos. We found that about three-fourths of task-related mid-STS neurons exhibited agent-dependent activity, most responding selectively or preferentially to the partner's action. At the population level, activities of these partner-type neurons were significantly greater under live-partner compared to video-recorded-partner task conditions. Furthermore, a subset of the partner-type neurons responded proactively when predictions about the partner's action were violated. This prediction error coding was specific to the action domain; almost none of the neurons signaled error in the prediction of reward. The present findings highlight unique roles of the macaque mid-STS at the single-neuron level and further delineate its functional parallels with the human TPJ in social cognitive processes associated with mentalizing.

Social cognition in women with borderline personality disorder based on an exhaustive analysis of the Movie for Assessment of Social Cognition (MASC) categories.

A significant number of borderline personality disorder (BPD) symptoms are manifested in the interpersonal context. This can be explained by the difficulties in attributing the mental states of oneself and others, which constitutes social cognition. Errors in social cognition are interrelated with the affective, cognitive, impulsive, and interpersonal areas of the person with BPD. The aims of this study was to analyze social cognition in women with BPD compared with a control group and to analyze social cognition in BPD based on BPD symptoms and its severity. To assess social cognition, we used a full range of social cognition categories provided by the Movie for the Assessment of Social Cognition (MASC): correct theory of mind (ToM); attribution of mental states (thoughts, emotions, or intentions); errors of mentalization; types of ToM; and attribution of mental states through perceptive or cognitive cues and through hot or cold emotions. The MASC has high ecological validity and has been validated in Spanish. The sample comprised 79 women, including 47 women with BPD and 32 healthy women. Worse social cognition performance was observed in women with BPD. More severe borderline symptoms were related to worse functioning in the correct ToM and to errors of no mentalization. Involvement of the cognitive area in borderline symptoms was associated with worse functioning in correct ToM and worse social cognition in cognitive areas as well as with hypermentalization. This is the first study that uses all the MASC categories and considers BPD heterogeneity and its severity to study social cognition.

To Do or Not to Do: The cerebellum and neocortex contribute to predicting sequences of social intentions.

Humans read the minds of others to predict their actions and efficiently navigate social environments, a capacity called mentalizing. Accumulating evidence suggests that the cerebellum, especially Crus 1 and 2, and lobule IX are involved in identifying the sequence of others' actions. In the current study, we investigated the neural correlates that underly predicting others' intentions and how this plays out in the sequence of their actions. We developed a novel intention prediction task, which required participants to put protagonists' behaviors in the correct chronological order based on the protagonists' honest or deceitful intentions (i.e., inducing true or false beliefs in others). We found robust activation of cerebellar lobule IX and key mentalizing areas in the neocortex when participants ordered protagonists' intentional behaviors compared with not ordering behaviors or to ordering object scenarios. Unlike a previous task that involved prediction based on personality traits that recruited cerebellar Crus 1 and 2, and lobule IX (Haihambo et al., 2021), the present task recruited only the cerebellar lobule IX. These results suggest that cerebellar lobule IX may be generally involved in social action sequence prediction, and that different areas of the cerebellum are specialized for distinct mentalizing functions.

Two is company: The posterior cerebellum and sequencing for pairs versus individuals during social preference prediction.

Previous studies have identified that the posterior cerebellum, which plays a role in processing temporal sequences in social events, is consistently and robustly activated when we predict future action sequences based on personality traits (Haihambo Haihambo et al. Social Cognitive and Affective Neuroscience 17(2), 241-251, 2022) and intentions (Haihambo et al. Cognitive, Affective, and Behavioral Neuroscience 23(2), 323-339, 2023). In the current study, we investigated whether these cerebellar areas are selectively activated when we predict the sequences of (inter)actions based on protagonists' preferences. For the first time, we also compared predictions based on person-to-person interactions or single person activities. Participants were instructed to predict actions of one single or two interactive protagonists by selecting them and putting them in the correct chronological order after being informed about one of the protagonists' preferences. These conditions were contrasted against nonsocial (involving objects) and nonsequencing (prediction without generating a sequence) control conditions. Results showed that the posterior cerebellar Crus 1, Crus 2, and lobule IX, alongside the temporoparietal junction and dorsal medial prefrontal cortex were more robustly activated when predicting sequences of behavior of two interactive protagonists, compared to one single protagonist and nonsocial objects. Sequence predictions based on one single protagonist recruited lobule IX activation in the cerebellum and more ventral areas of the medial prefrontal cortex compared to a nonsocial object. These cerebellar activations were not found when making predictions without sequences. Together, these findings suggest that cerebellar mentalizing areas are involved in social mentalizing processes which require temporal sequencing, especially when they involve social interactions, rather than behaviors of single persons.

Personality and mentalization: A latent profile analysis of mentalizing problematics in adult patients.

BACKGROUND: The aim of this study was to investigate the relationship between patients' mentalizing problematics and their personality; specifically, it aimed to identify clusters of individuals characterized by specific patterns of mentalizing imbalances and to analyze the relationship between these and diagnosis of personality disorder (PD), nonmentalizing modes, emotion dysregulation, and interpersonal reactivity. METHODS: Four hundred therapeutic dyads were recruited. A part of these (n = 183) only completed clinician-report measures, Mentalization Imbalances Scale, and Modes of Mentalization Scale, while others (n = 217) also completed patients' self-report measures, which were Reflective Functioning Questionnaire, Difficulties in Emotion Regulation Scale, and Interpersonal Reactivity Index. RESULTS: A latent profile analysis enlightened the presence of four clusters with problematics in the dimensions of mentalization, indicated by cluster names: (1) Affective-self-automatic profile (ASA-P) (with higher percentage of PDs); (2) External profile (E-P) (with lower percentage of PDs); (3) Others-automatic-affective profile (OAA-P); (4) Cognitive-self-automatic profile (CSA-P). Multivariate analysis of variances confirmed that the four clusters differed in relation to the quality of mentalization, emotional dysregulation and interpersonal reactivity, with higher levels of nonmentalization modes, uncertainty about mental states and emotion dysregulation in ASA-P, higher levels of good mentalization in E-P, lower impulsivity in CSA-P, and greater empathic concern in OAA-P.

Constructing Others' Beliefs from One's Own Using Medial Frontal Cortex.

Many daily choices are based on one's own knowledge. However, when predicting other people's behavior, we need to consider the differences between our knowledge and other people's presumed knowledge. Social agents need a mechanism to use privileged information for their own behavior but exclude it from predictions of others. Using fMRI, we investigated the neural implementation of such social and personal predictions in healthy human volunteers of both sexes by manipulating privileged and shared information. The medial frontal cortex appeared to have an important role in flexibly making decisions using privileged information for oneself or predicting others' behavior. Specifically, we show that ventromedial PFC tracked the state of the world independent of the type of decision (personal, social), whereas dorsomedial regions adjusted their frame of reference to the use of privileged or shared information. Sampling privileged evidence not available to another person also relied on specific interactions between temporoparietal junction area and frontal pole.SIGNIFICANCE STATEMENT What we know about the minds of others and how we use that information is crucial to understanding social interaction. Mentalizing, or reading the minds of others, is argued to be particularly well developed in the human and crucially affected in some disorders. However, the intractable nature of human interactions makes it very difficult to study these processes. Here, we present a way to objectively quantify the information people have about others and to investigate how their brain deals with this information. This shows that people use similar areas in the brain related to nonsocial decision-making when making decisions in social situations and modify this information processing by the knowledge about others use these to modify their information processing according to the knowledge of others.

This is not who you are: The posterior cerebellum and stereotype-inconsistent action sequences.

Recent research has indicated that the posterior cerebellum plays a crucial role in social cognition by encoding sequences of social actions. This study investigates its role in learning sequences of stereotype-implying actions by group members. We presented a set of five sentences that each described a group member who performed either stereotype-consistent or inconsistent actions. Participants were instructed to memorize the temporal order of the sentences and infer a common stereotype of the group. As a comparison, we included control conditions where participants had to memorize sequences of nonsocial consistent events or simply read stereotype-consistent sentences without memorizing their order. The results showed that the posterior cerebellum was strongly activated when participants were memorizing the order of the social actions, as opposed to simply reading these social actions. More importantly, when the social actions were inconsistent as opposed to consistent with the stereotype of the group, the posterior cerebellum was activated more strongly. This activation occurred together with cortical recruitment of the mentalizing network involving the dorsomedial prefrontal cortex (dmPFC) during social actions, and additionally the conflict monitoring network involving the lateral prefrontal cortex (PFC) and posterior medial frontal cortex (pmFC) during stereotype-inconsistent actions. These findings suggest that the cerebellum supports not only learning of low-level action sequences, but also of their high-level social implications.

The Involvement of the Posterior Cerebellum in Reconstructing and Predicting Social Action Sequences.

Recent advances in social neuroscience have highlighted the critical role of the cerebellum and especially the posterior cerebellar Crus in social mentalizing (i.e., theory of mind). Research in the past 5 years has provided growing evidence supporting the view that the posterior cerebellum builds internal action models of our social interactions to predict how other people's actions will be executed, and what our most likely responses to these actions will be. This paper presents an overview of a series of fMRI experiments on novel tasks involving a combination of (a) the learning or generation of chronological sequences of social actions either in an explicit or implicit manner, which (b) require social mentalizing on another person's mental state such as goals, beliefs, and implied traits. Together, the results strongly confirm the central role of the posterior cerebellar Crus in identifying and automatizing action sequencing during social mentalizing, and in predicting future action sequences based on social mentalizing inferences about others. This research program has important implications: It provides for the first time (a) fruitful starting points for diagnosing and investigating social sequencing dysfunctions in a variety of mental disorders which have also been related to cerebellar dysfunctions, (b) provides the necessary tools for testing whether non-invasive neurostimulation targeting the posterior cerebellum has a causal effect on social functioning, and (c) whether these stimulation techniques and training programs guided by novel cerebellar social sequencing insights, can be exploited to increase posterior cerebellar plasticity in order to alleviate social impairments in mental disorders.

Investigation of the Factor Structure of the Reflective Functioning Questionnaire (RFQ-8): One or Two Dimensions?

There is a need to have reliable and accessible screening measures of mentalizing ability to investigate the role of this capacity in social functioning and its development, emergence of psychopathological conditions, as well as to understand its role in psychotherapeutic processes. The 8-itemed Reflective Functioning Questionnaire (RFQ-8) has been developed for this purpose, however its factor structure and psychometric properties are unclear. The aim of the current study was to further investigate the factor structure of the RFQ-8 and explore its psychometric properties in a Polish sample. 538 participants aged 17-50 (M = 21.44, SD = 2.92) took part in the study. They were asked to complete the RFQ-8, Difficulties in Emotion Regulation Scale (DERS), General Health Questionnaire (GHQ-28), the Relationship Structures (ECR-RS) questionnaire and the Borderline Personality Inventory (BPI). Results of both exploratory and confirmatory analysis indicated that the RFQ-8 may be regarded as a scale measuring a unidimensional construct. Our results confirmed good construct validity for the unidimensional RFQ-8, suggesting that the one-dimensional RFQ specifically assesses uncertainty concerning mental states. Our findings highlight the need for further studies investigating the factor structure and psychometric properties of the RFQ-8.

Psychometric Properties of the Italian Mentalization Questionnaire: Assessing Structural Invariance and Construct Validity.

Mentalization is an important interpersonal ability, necessary for adaptive interpersonal relationships and emotion regulation. Deficits in mentalization have been associated with poor psychological outcomes and have been observed in patients with Borderline Personality Disorder. The Mentalization Questionnaire (MZQ) has been developed as self-report measure of mentalization deficit. The aim of the study was to investigate the dimensionality of the MZQ in a nonclinical sample composed of Italian adults from the general population and to analyze its performance in categorizing individuals with higher risk of borderline symptoms. A non-clinical sample of 1,015 adults (709 women and 306 men) was administered the Italian versions of the MZQ, the Reflective Functioning Questionnaire (RFQ), and a measure of borderline psychopathology. A revised single-factor solution fitted the data well and demonstrated metric invariance across gender. The internal consistency (Ordinal α = 0.87) and stability (r = 0.84) were satisfactory. The MZQ was moderately associated with the RFQ dimensions. The ROC curve analysis showed that the MZQ was able to discriminate satisfactorily people with higher risk for borderline symptomatology from those with lower risk. The MZQ may, therefore, be considered a reliable and valid measure of mentalization for categorizing people at higher risk for borderline pathology.

Failure to resolve loss and compromised mentalizing in female inpatients with major depressive disorder.

Attachment and mentalizing are central concepts in research on the etiology, course, and treatment of depression. The goal of this cross-sectional study was to clarify the unique value of these constructs in characterizing the presence, severity, and chronicity of depression. We examined 50 female inpatients suffering from Major Depressive Disorder (MDD) in comparison to 47 matched healthy controls regarding their attachment states of mind, mentalizing capacities, and clinical variables indicating depression severity and chronicity (e.g. illness duration, number of hospitalizations). In the group of depressed patients, unresolved attachment with regard to loss was significantly overrepresented. Dimensionally, patients were more disorganized and more insecure, whereas there was no difference on the dismissing-preoccupied dimension between the two groups. Mentalizing was significantly lower in patients than in healthy controls. Logistic regression analysis revealed attachment insecurity, mentalizing deficits, and unresolved loss to be incrementally relevant to predict MDD. Correlations with clinical parameters in the group of depressed patients showed positive associations between mentalizing deficits, attachment insecurity, and variables indicating illness chronicity. Our findings highlight the relevance of the inability to resolve or reappraise loss experiences in depressive states.

Bifocalism is in the eye of the beholder: Social learning as a developmental response to the accuracy of others' mentalizing.

This commentary argues the case for developmental psychopathology in understanding social learning. Informed by work on "epistemic disruption," we have described difficulties with social learning associated with many forms of psychopathology. Epistemic disruption manifests in an inability to move between innovation and conformity, and arises from poor mentalizing, which generates difficulties in identifying social cues that trigger the correct stance.

Investigation of the neural correlates of mentalizing through the Dynamic Inference Task, a new naturalistic task of social cognition.

Understanding others' intentions requires both the identification of social cues (e.g., emotional facial expressions, gaze direction) and the attribution of a mental state to another. The neural substrates of these processes have often been studied separately, and results are heterogeneous, in part attributable to the variety of paradigms used. The aim of the present study was to explore the neural regions underlying these sociocognitive processes, using a novel naturalistic task in which participants engage with human protagonists featured in videos. A total of 51 right-handed volunteers underwent functional magnetic resonance imaging while performing the Dynamic Inference Task (DIT), manipulating the degree of inference (high vs. low), the presence of emotion (emotional vs. nonemotional), and gaze direction (direct vs. averted). High nonemotional inference elicited neural activation in temporal regions encompassing the right posterior superior temporal sulcus. The presence (vs. absence) of emotion in the high-inference condition elicited a bilateral pattern of activation in internal temporal areas around the amygdala and orbitofrontal structures, as well as activation in the right dorsomedial part of the superior frontal gyrus and the left precuneus. On account of its dynamic, naturalistic approach, the DIT seems a suitable task for exploring social interactions and the way we interact with others, both in nonclinical and clinical populations.

A large-scale structural and functional connectome of social mentalizing.

Humans have a remarkable ability to infer the mind of others. This mentalizing skill relies on a distributed network of brain regions but how these regions connect and interact is not well understood. Here we leveraged large-scale multimodal neuroimaging data to elucidate the brain-wide organization and mechanisms of mentalizing processing. Key connectomic features of the mentalizing network (MTN) have been delineated in exquisite detail. We found the structural architecture of MTN is organized by two parallel subsystems and constructed redundantly by local and long-range white matter fibers. We uncovered an intrinsic functional architecture that is synchronized according to the degree of mentalizing, and its hierarchy reflects the inherent information integration order. We also examined the correspondence between the structural and functional connectivity in the network and revealed their differences in network topology, individual variance, spatial specificity, and functional specificity. Finally, we scrutinized the connectome resemblance between the default mode network and MTN and elaborated their inherent differences in dynamic patterns, laterality, and homogeneity. Overall, our study demonstrates that mentalizing processing unfolds across functionally heterogeneous regions with highly structured fiber tracts and unique hierarchical functional architecture, which make it distinguishable from the default mode network and other vicinity brain networks supporting autobiographical memory, semantic memory, self-referential, moral reasoning, and mental time travel.

Seeing things differently: Gaze shapes neural signal during mentalizing according to emotional awareness.

Studies on social cognition often use complex visual stimuli to asses neural processes attributed to abilities like "mentalizing" or "Theory of Mind" (ToM). During the processing of these stimuli, eye gaze, however, shapes neural signal patterns. Individual differences in neural operations on social cognition may therefore be obscured if individuals' gaze behavior differs systematically. These obstacles can be overcome by the combined analysis of neural signal and natural viewing behavior. Here, we combined functional magnetic resonance imaging (fMRI) with eye-tracking to examine effects of unconstrained gaze on neural ToM processes in healthy individuals with differing levels of emotional awareness, i.e. alexithymia. First, as previously described for emotional tasks, people with higher alexithymia levels look less at eyes in both ToM and task-free viewing contexts. Further, we find that neural ToM processes are not affected by individual differences in alexithymia per se. Instead, depending on alexithymia levels, gaze on critical stimulus aspects reversely shapes the signal in medial prefrontal cortex (MPFC) and anterior temporoparietal junction (TPJ) as distinct nodes of the ToM system. These results emphasize that natural selective attention affects fMRI patterns well beyond the visual system. Our study implies that, whenever using a task with multiple degrees of freedom in scan paths, ignoring the latter might obscure important conclusions.

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.

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.