The social neuroscience of mentalizing: challenges and recommendations

Our ability to understand and think about the mental states of other people is referred to as “mentalizing” or “theory of mind”. It features prominently in all social behavior, is essential for maintaining relationships, and shows pronounced individual differences. Here we review new approaches to study the underlying psychological mechanisms and discuss how they could best be investigated using modern tools from social neuroscience. We list key desiderata for the field, such as validity, specificity, and reproducibility, and link them to specific recommendations for the future. We also discuss new computational modeling approaches, and the application to psychopathology

The social neuroscience of mentalizing: challenges and recommendations

Our ability to understand and think about the mental states of other people is referred to as “mentalizing” or “theory of mind”. It features prominently in all social behavior, is essential for maintaining relationships, and shows pronounced individual differences. Here we review new approaches to study the underlying psychological mechanisms and discuss how they could best be investigated using modern tools from social neuroscience. We list key desiderata for the field, such as validity, specificity, and reproducibility, and link them to specific recommendations for the future. We also discuss new computational modeling approaches, and the application to psychopathology

Approximating Implicit and Explicit Mentalizing with Two Naturalistic Video-Based Tasks in Typical Development and Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) have been proposed to show greater impairments in implicit than explicit mentalizing. To test this proposition, we developed two comparable naturalistic tasks for a performance-based approximation of implicit and explicit mentalizing in 28 individuals with ASD and 23 matched typically developed (TD) participants. Although both tasks were sensitive to the social impairments of individuals with ASD, implicit mentalizing was not more dysfunctional than explicit mentalizing. In TD participants, performance on the tasks did not correlate with each other, whereas in individuals with ASD they were highly correlated. These findings suggest that implicit and explicit mentalizing processes are separable in typical development. In contrast, in individuals with ASD implicit and explicit mentalizing processes are similarly impaired and closely linked suggesting a lack of developmental specification of these processes in ASD.German Research Foundation (Grant EXC 302

Increased hippocampal shape asymmetry and volumetric ventricular asymmetry in autism spectrum disorder

Autism spectrum disorder (ASD) is a prevalent and fast-growing pervasive neurodevelopmental disorder worldwide. Despite the increasing prevalence of ASD and the breadth of research conducted on the disorder, a conclusive etiology has yet to be established and controversy still exists surrounding the anatomical abnormalities in ASD. In particular, structural asymmetries have seldom been investigated in ASD, especially in subcortical regions. Additionally, the majority of studies for identifying structural biomarkers associated with ASD have focused on small sample sizes. Therefore, the present study utilizes a large-scale, multi-site database to investigate asymmetries in the amygdala, hippocampus, and lateral ventricles, given the potential involvement of these regions in ASD. Contrary to prior work, we are not only computing volumetric asymmetries, but also shape asymmetries, using a new measure of asymmetry based on spectral shape descriptors. This measure represents the magnitude of the asymmetry and therefore captures both directional and undirectional asymmetry. The asymmetry analysis is conducted on 437 individuals with ASD and 511 healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) database. Results reveal significant asymmetries in the hippocampus and the ventricles, but not in the amygdala, in individuals with ASD. We observe a significant increase in shape asymmetry in the hippocampus, as well as increased volumetric asymmetry in the lateral ventricles in individuals with ASD. Asymmetries in these regions have not previously been reported, likely due to the different characterization of neuroanatomical asymmetry and smaller sample sizes used in previous studies. Given that these results were demonstrated in a large cohort, such asymmetries may be worthy of consideration in the development of neurodiagnostic classification tools for ASD

Intrinsic Functional Connectivity of the Brain in Adults with a Single Cerebral Hemisphere

A reliable set of functional brain networks is found in healthy people and thought to underlie our cognition, emotion, and behavior. Here, we investigated these networks by quantifying intrinsic functional connectivity in six individuals who had undergone surgical removal of one hemisphere. Hemispherectomy subjects and healthy controls were scanned with identical parameters on the same scanner and compared to a large normative sample (n = 1,482). Surprisingly, hemispherectomy subjects and controls all showed strong and equivalent intrahemispheric connectivity between brain regions typically assigned to the same functional network. Connectivity between parts of different networks, however, was markedly increased for almost all hemispherectomy participants and across all networks. These results support the hypothesis of a shared set of functional networks that underlie cognition and suggest that between-network interactions may characterize functional reorganization in hemispherectomy

Atypical gaze patterns in autistic adults are heterogeneous across but reliable within individuals

Background: Across behavioral studies, autistic individuals show greater variability than typically developing individuals. However, it remains unknown to what extent this variability arises from heterogeneity across individuals, or from unreliability within individuals. Here, we focus on eye tracking, which provides rich dependent measures that have been used extensively in studies of autism. Autistic individuals have an atypical gaze onto both static visual images and dynamic videos that could be leveraged for diagnostic purposes if the above open question could be addressed. Methods: We tested three competing hypotheses: (1) that gaze patterns of autistic individuals are less reliable or noisier than those of controls, (2) that atypical gaze patterns are individually reliable but heterogeneous across autistic individuals, or (3) that atypical gaze patterns are individually reliable and also homogeneous among autistic individuals. We collected desktop-based eye tracking data from two different full-length television sitcom episodes, at two independent sites (Caltech and Indiana University), in a total of over 150 adult participants (N = 48 autistic individuals with IQ in the normal range, 105 controls) and quantified gaze onto features of the videos using automated computer vision-based feature extraction. Results: We found support for the second of these hypotheses. Autistic people and controls showed equivalently reliable gaze onto specific features of videos, such as faces, so much so that individuals could be identified significantly above chance using a fingerprinting approach from video epochs as short as 2 min. However, classification of participants into diagnostic groups based on their eye tracking data failed to produce clear group classifications, due to heterogeneity in the autistic group. Limitations: Three limitations are the relatively small sample size, assessment across only two videos (from the same television series), and the absence of other dependent measures (e.g., neuroimaging or genetics) that might have revealed individual-level variability that was not evident with eye tracking. Future studies should expand to larger samples across longer longitudinal epochs, an aim that is now becoming feasible with Internet- and phone-based eye tracking. Conclusions: These findings pave the way for the investigation of autism subtypes, and for elucidating the specific visual features that best discriminate gaze patterns—directions that will also combine with and inform neuroimaging and genetic studies of this complex disorder.publishedVersionPeer reviewe

Video-evoked fMRI BOLD responses are highly consistent across different data acquisition sites

Naturalistic imaging paradigms, in which participants view complex videos in the scanner, are increasingly used in human cognitive neuroscience. Videos evoke temporally synchronized brain responses that are similar across subjects as well as within subjects, but the reproducibility of these brain responses across different data acquisition sites has not yet been quantified. Here we characterize the consistency of brain responses across independent samples of participants viewing the same videos in fMRI scanners at different sites (Indiana University and Caltech). We compared brain responses collected at these different sites for two carefully matched datasets with identical scanner models, acquisition, and preprocessing details, along with a third unmatched dataset in which these details varied. Our overall conclusion is that for matched and unmatched datasets alike, video-evoked brain responses have high consistency across these different sites, both when compared across groups and across pairs of individuals. As one might expect, differences between sites were larger for unmatched datasets than matched datasets. Residual differences between datasets could in part reflect participant-level variability rather than scanner- or data-related effects. Altogether our results indicate promise for the development and, critically, generalization of video fMRI studies of individual differences in healthy and clinical populations alike

Erkenntnisse aus Verhalten, Blickbewegungen und Funktioneller Magnetresonanztomographi

Our social environment challenges us with a richness of social cues that need to be effectively recognized and processed in order to initiate adequate behavioral responses. Importantly, social information is not always presented obviously and respective demands towards the social agents are seldomly stated explicitly. Instead, a great portion of social information is reflected in subtle social signs. To successfully interact with others, we thus need to both implicitly and explicitly process aspects of our social world. Impairments in social cognitive functioning can have a severe impacton individual well-being and integration in society, such as in autism spectrum disorder (ASD). Individuals on the autism spectrum show impairments in implicit and explicit social functioning starting early in development, persisting into adulthood, crucially impactinglife of affected individuals, even of those at the higher functioning end of the spectrum. The relations of implicit and explicit socio-cognitive impairments, as well as specific mechanisms behind respective altered processes, remain unclear to date. This dissertation represents an empirical attempt towards advancing our understanding of implicit and explicit social cognitive impairments in ASD with a multi-method approach including behavioral, eye-tracking and neuroimaging methods. To this end, in this dissertation I focus on the behavioral and neural mechanisms underlying one of the most prominent features within the autistic social symptomatology: impairments in recognizing emotions from faces. In Study I we developed and evaluated two new video-based tasks for implicit and explicit facial emotion recognition to identify and define relations between respective impairments in ASD. In Study II, we assessed gaze on emotional faces in ASD, specifically the puzzle of reduced focus on the eye region, as an important aspect during implicit social processing. In Study III, we investigated the underlying neural basis of atypical reflexive gaze patterns in ASD as identified in Study II, in particular the role of the amygdala. Results of Study I of this dissertation underline the previously suggested greater impairments in implicit as compared to explicit processing in ASD, as shown by respective group differences and interaction regarding performance in the new Face Puzzle tasks. In fact, implicit and explicit aspects of facial emotion recognition processes seem to be more closely related in ASD as compared to healthy controls. In the context of impaired implicit processing, I show in Study II and III that a reduced eye focus in ASD seems to be characterized by an interaction of avoidance and reduced orientation related gaze,which is accompanied by specific blood-oxygen level dependent signal (BOLD) response patterns in the amygdala. Taking gaze behavior and brain function together, the findings suggest altered avoidance processing and impaired implicit reflexive orientation to salient social cues in ASD. Distinct increases and decreases in amygdala activity in response to emotional faces imply that the amygdala is a dysfunctional node in the neural network underlying emotional face recognition, leading to alterations in function and structure of the facial emotion recognition network, ultimately affecting effective social processing and thus the behavioral phenotype of ASD.Unsere soziale Umwelt enthält eine Vielzahl von sozialen Hinweisreizen, die erkannt und verarbeitet werden müssen damit eine adäquate Verhaltensantwort erfolgen kann. Soziale Information ist jedoch nicht immer offensichtlich erkennbar dargeboten und selten sind Interpretationsanforderungen explizit ausgewiesen. Im Gegenteil, ein Großteil der sozialen Information in unserer Umwelt ist in subtilen sozialen Hinweisen versteckt. Um erfolgreich mit unseren Mitmenschen zu interagieren müssen wir demnach sowohl implizite als auch explizite Aspekte unserer sozialen Umwelt verarbeiten. Beeinträchtigungen sozial-kognitiver Funktionen können zu schwerwiegenden Einschnitten im individuellen Wohlbefinden und mangelnder Integration in die Gesellschaft führen. Ein Beispiel dafür sind Autismus Spektrumsstörungen (ASD): Individuen aus dem Autismusspektrum weisen schon in früher Kindheit Beeinträchtigungen in impliziten und expliziten sozial-kognitiven Funktionen auf, die bis ins hohe Lebensalter bestehen bleiben und somit das Leben der Betroffenen stark beeinflussen. Diese Beeinträchtigungen betreffen auch Individuen, die am hoch- funktionalen Ende des Spektrums eingeordnet werden, also keine Intelligenzminderung aufweisen. Die Beziehung zwischen impliziten und expliziten sozialen Beeinträchtigungen, als auch die Mechanismen die zu diesen Beeinträchtigungen führen, bleiben jedoch bis heute unerklärt. Diese Dissertation stellt einen empirischen Versuch dar, unser Verständnis von impliziten und expliziten sozial-kognitiven Beeinträchtigungen in ASD mit einem multi-methodalen Ansatz, der Verhaltens-, Blickbewegungs- und Bildgebungsverfahren umfasst,voranzutreiben. Der Fokus liegt hierbei auf einem der prominentesten Merkmale autistischer sozialer Symptomatologie, sowie deren zugrunde liegenden Prozesse und Mechanismen auf Verhaltens- und neuronaler Ebene: Beeinträchtigungen im Erkennen von Emotionen anhand von Gesichtsausdrücken. In Studie I haben wir zwei neue Video-basierte Verhaltenstests für implizite und explizite faziale Emotionserkennung entwickelt und evaluiert um entsprechende Beeinträchtigungen in ASD besser zu definieren. Studie II untersuchte einen wichtigen Aspekt impliziter sozialer Kognition: Blickbewegungen auf emotionalen Gesichtern, im Besonderen den reduzierten Fokus auf die Augenregion in ASD. Darauf aufbauend haben wir in Studie III die zugrunde liegende neuronale Basis atypischen Blickverhaltens in ASD untersucht, wobei besonders die Rolle der Amygdala im Vordergrund stand. Die speziellen Gruppenunterschiede und Interaktionen der Performanzergebnisse von Studie I unterstreichen die Annahme dass implizite soziale Beeinträchtigungen in ASD prominenter sindals explizite. Die Ergebnisse legen nahe, dass implizite und explizite Prozesse in ASD stärker miteinander assoziiert sind als bei gesunden Kontrollprobanden. Ergebnisse von Studie II zeigen weiterhin, dass der reduzierte Fokus auf die Augenregion in ASD durch eine Interaktion von Vermeidungs- und verminderten Orientierungsprozessen auf Blickbewegungs- und auf neuronaler Ebene charakterisiert wird. Hypo- und hyperaktivierungen in der Amygdala implizieren weiterhin, dass diese Region einen wichtigen Knotenpunkt innerhalb des neuronalen Netzwerkes zur Verarbeitung sozialer Reize darstellt. Entsprechende Beeinträchtigungen führen demnach zu Veränderungen in der Funktion und Struktur des neuronalen Netzwerkes zur fazialen Emotionserkennung, die letzendlich effektive sozial- kognitive Funktionen beeinträchtigen und somit zum Phänotyp von ASD führen