Sofie L. Valk

Selective Disruption of Sociocognitive Structural Brain Networks in Autism and Alexithymia

Autism spectrum conditions (ASC) are neurodevelopmental disorders characterized by abnormal social cognition. A core feature of ASC is disrupted Theory of Mind (ToM), our ability to take the mental perspective of others. ASC is also associated with alexithymia, a trait characterized by altered emotional interoception and empathy. Here, we applied structural MRI covariance analysis to assess whether ASC and alexithymia differentially affect structural brain networks associated with sociocognitive and socioaffective functions. Based on previous functional MRI findings, we expected disrupted ToM networks (centered on dorsomedial prefontal cortex [dmPFC], and temporo-parietal junction [TPJ]) in ASC, while alexithymia would affect networks centered on fronto-insular cortex (FI), regions associated with interoception of emotion and empathy. Relative to controls, ASC indeed showed reduced covariance in networks centered on dmPFC and TPJ, but not within FI networks. Irrespective of ASC, covariance was negatively modulated by alexithymia in networks extending from FI to posterior regions. Network findings were complemented by self-reports, indicating decreased perspective taking but normal empathic concern in ASC. Our results show divergent effects of ASC and alexithymia on inter-regional structural networks, suggesting that networks mediating socioaffective processes may be separable from networks mediating sociocognitive processing.

Multicenter mapping of structural network alterations in autism

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions primarily characterized by abnormalities in social cognition. Abundant previous functional MRI studies have shown atypical activity in networks encompassing medial prefrontal cortex (mPFC) and medial parietal regions corresponding to posterior cingulate cortex and precuneus (PCC/PCU). Conversely, studies assessing structural brain anomalies in ASD have been rather inconsistent. The current work evaluated whether structural changes in ASD can be reliability detected in a large multicenter dataset. Our comprehensive structural MRI framework encompassed cortical thickness mapping and structural covariance analysis based on three independent samples comprising individuals with ASD and controls (n = 220), selected from the Autism Brain Imaging Data Exchange open‐access database. Surface‐based analysis revealed increased cortical thickness in ASD relative to controls in mPFC and lateral prefrontal cortex. Clusters encompassing mPFC were embedded in altered inter‐regional covariance networks, showing decreased covariance in ASD relative to controls primarily to PCC/PCU and inferior parietal regions. Cortical thickness increases and covariance reductions in ASD were consistent, yet of variable effect size, across the different sites evaluated and measurable both in children and adults. Our multisite study shows regional and network‐level structural alterations in mPFC in ASD that, possibly, relate to atypical socio‐cognitive functions in this condition. Hum Brain Mapp 36:2364–2373, 2015.

Structural plasticity of the social brain: Differential change after socio-affective and cognitive mental training

Training to understand the feelings and thoughts of others induces structural changes in two divergent social brain networks. Although neuroscientific research has revealed experience-dependent brain changes across the life span in sensory, motor, and cognitive domains, plasticity relating to social capacities remains largely unknown. To investigate whether the targeted mental training of different cognitive and social skills can induce specific changes in brain morphology, we collected longitudinal magnetic resonance imaging (MRI) data throughout a 9-month mental training intervention from a large sample of adults between 20 and 55 years of age. By means of various daily mental exercises and weekly instructed group sessions, training protocols specifically addressed three functional domains: (i) mindfulness-based attention and interoception, (ii) socio-affective skills (compassion, dealing with difficult emotions, and prosocial motivation), and (iii) socio-cognitive skills (cognitive perspective-taking on self and others and metacognition). MRI-based cortical thickness analyses, contrasting the different training modules against each other, indicated spatially diverging changes in cortical morphology. Training of present-moment focused attention mostly led to increases in cortical thickness in prefrontal regions, socio-affective training induced plasticity in frontoinsular regions, and socio-cognitive training included change in inferior frontal and lateral temporal cortices. Module-specific structural brain changes correlated with training-induced behavioral improvements in the same individuals in domain-specific measures of attention, compassion, and cognitive perspective-taking, respectively, and overlapped with task-relevant functional networks. Our longitudinal findings indicate structural plasticity in well-known socio-affective and socio-cognitive brain networks in healthy adults based on targeted short daily mental practices. These findings could promote the development of evidence-based mental training interventions in clinical, educational, and corporate settings aimed at cultivating social intelligence, prosocial motivation, and cooperation.

Socio-Cognitive Phenotypes Differentially Modulate Large-Scale Structural Covariance Networks

Abstract Functional neuroimaging studies have suggested the existence of 2 largely distinct social cognition networks, one for theory of mind (taking others’ cognitive perspective) and another for empathy (sharing others’ affective states). To address whether these networks can also be dissociated at the level of brain structure, we combined behavioral phenotyping across multiple socio‐cognitive tasks with 3‐Tesla MRI cortical thickness and structural covariance analysis in 270 healthy adults, recruited across 2 sites. Regional thickness mapping only provided partial support for divergent substrates, highlighting that individual differences in empathy relate to left insular‐opercular thickness while no correlation between thickness and mentalizing scores was found. Conversely, structural covariance analysis showed clearly divergent network modulations by socio‐cognitive and ‐affective phenotypes. Specifically, individual differences in theory of mind related to structural integration between temporo‐parietal and dorsomedial prefrontal regions while empathy modulated the strength of dorsal anterior insula networks. Findings were robust across both recruitment sites, suggesting generalizability. At the level of structural network embedding, our study provides a double dissociation between empathy and mentalizing. Moreover, our findings suggest that structural substrates of higher‐order social cognition are reflected rather in interregional networks than in the the local anatomical markup of specific regions per se.

Substrates of metacognition on perception and metacognition on higher-order cognition relate to different subsystems of the mentalizing network.

Humans have the ability to reflect upon their perception, thoughts, and actions, known as metacognition (MC). The brain basis of MC is incompletely understood, and it is debated whether MC on different processes is subserved by common or divergent networks. We combined behavioral phenotyping with multi‐modal neuroimaging to investigate whether structural substrates of individual differences in MC on higher‐order cognition (MC‐C) are dissociable from those underlying MC on perceptual accuracy (MC‐P). Motivated by conceptual work suggesting a link between MC and cognitive perspective taking, we furthermore tested for overlaps between MC substrates and mentalizing networks. In a large sample of healthy adults, individual differences in MC‐C and MC‐P did not correlate. MRI‐based cortical thickness mapping revealed a structural basis of this independence, by showing that individual differences in MC‐P related to right prefrontal cortical thickness, while MC‐C scores correlated with measures in lateral prefrontal, temporo‐parietal, and posterior midline regions. Surface‐based superficial white matter diffusivity analysis revealed substrates resembling those seen for cortical thickness, confirming the divergence of both MC faculties using an independent imaging marker. Despite their specificity, substrates of MC‐C and MC‐P fell clearly within networks known to participate in mentalizing, confirmed by task‐based fMRI in the same subjects, previous meta‐analytical findings, and ad‐hoc Neurosynth‐based meta‐analyses. Our integrative multi‐method approach indicates domain‐specific substrates of MC; despite their divergence, these nevertheless likely rely on component processes mediated by circuits also involved in mentalizing. Hum Brain Mapp 37:3388–3399, 2016.

Multidimensional Neuroanatomical Subtyping of Autism Spectrum Disorder

Abstract Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with multiple biological etiologies and highly variable symptoms. Using a novel analytical framework that integrates cortex‐wide MRI markers of vertical (i.e., thickness, tissue contrast) and horizontal (i.e., surface area, geodesic distance) cortical organization, we could show that a large multi‐centric cohort of individuals with ASD falls into 3 distinctive anatomical subtypes (ASD‐I: cortical thickening, increased surface area, tissue blurring; ASD‐II: cortical thinning, decreased distance; ASD‐III: increased distance). Bootstrap analysis indicated a high consistency of these biotypes across thousands of simulations, while analysis of behavioral phenotypes and resting‐state fMRI showed differential symptom load (i.e., Autism Diagnostic Observation Schedule; ADOS) and instrinsic connectivity anomalies in communication and social‐cognition networks. Notably, subtyping improved supervised learning approaches predicting ADOS score in single subjects, with significantly increased performance compared to a subtype‐blind approach. The existence of different subtypes may reconcile previous results so far not converging on a consistent pattern of anatomical anomalies in autism, and possibly relate the presence of diverging corticogenic and maturational anomalies. The high accuracy for symptom severity prediction indicates benefits of MRI biotyping for personalized diagnostics and may guide the development of targeted therapeutic strategies.

Change in emotional self-concept following socio-cognitive training relates to structural plasticity of the prefrontal cortex

Self‐referential processing is a key component of the emotional self‐concept. Previous studies have shown that emotional self‐referential processing is related to structure and function of cortical midline areas such as medial prefrontal cortex (mPFC), and that it can be altered on a behavioral level by specific mental training practices. However, it remains unknown how behavioral training‐related change in emotional self‐concept content relates to structural plasticity.