Corpus callosum size and homotopic connectivity in Autism spectrum disorder.

By examining how morphology of the corpus callosum (CC) in autism spectrum disorder (ASD) may affect functional communication across hemispheres, we hope to provide new insights into the structure-function relationship in the brain. We used a sample of 94 participants from the Autism Brain Imaging Data Exchange (ABIDE) database (55 typically-developing (TD) and 39 with ASD). The CC was segmented into five sub-regions (anterior, mid-anterior, central, mid-posterior, posterior) using FreeSurfer software, which were further examined for group differences. The total volume and specific sub-region volumes of the CC, and interhemispheric (homotopic) functional connectivity were calculated, along with the relationship between volume and connectivity. These measures were correlated with social ability assessed by the Social Responsiveness Scale (SRS). The central sub-region of CC was significantly smaller in ASD, although there was no group difference in total CC volume. ASD participants also showed stronger homotopic connectivity in the superior frontal gyrus. SRS scores were negatively correlated with the CC central sub-region volumes in ASD. The findings of this study add to the body of research showing morphological differences in the CC in ASD as well as connectivity differences. The absence of a significant relationship between structure and homotopic functional connectivity aligns with previous findings.

Neural responses to viewing human faces in autism spectrum disorder: A quantitative meta-analysis of two decades of research.

The human face communicates a wealth of socially relevant information such as person identity, emotion, and intention. A consistent behavioral finding in autism spectrum disorder (ASD) is reduced attention to or difficulty drawing meaning from faces. However, neuroimaging research into the neural correlates of face processing differences in ASD has returned mixed results. While many studies find hypo-activation or hypo-connectivity of core and extended face network regions, others show hyper-activation, equal activation, or even activation shifted to object-selective fusiform gyrus (FG) regions in ASD during face processing. This study consolidates two decades of literature to reveal common and consistent patterns of brain activation when viewing human faces in ASD. It also addresses whether face processing in ASD is routinely shifted to object-centric regions of the FG. To do so, we conducted an extensive search of the neuroimaging literature according to PRISMA guidelines. Peak activation coordinates from a final set of 23 studies, yielding a sample of 713 participants (338 ASD), were included for quantitative meta-analysis using Activation Likelihood Estimation (ALE). ASD within-group results across studies revealed a single activation cluster in the left FG, which presented laterally to the mid-fusiform sulcus (MFS). Typically developing groups displayed common activations across core and extended face network regions. Exploratory analysis of between group findings from the literature did not yield significant results. Overall, our results suggest that individuals with ASD consistently activate at least one typical face network region, the left FG, when processing faces and this activation is not routinely shifted to object-centric areas of the FG.

The Mid-Fusiform Sulcus in Autism Spectrum Disorder: Establishing a Novel Anatomical Landmark Related to Face Processing.

Despite decades of research, the brain basis of aberrant face processing in autism spectrum disorder (ASD) remains a topic of debate. The mid-fusiform sulcus (MFS), a minor feature of the ventral occipitotemporal cortex, provides new directions for studying face processing. The MFS closely aligns with face-selective cortical patches and other structural and functional divisions of the fusiform gyrus; however, it has received little attention in clinical populations. We collected structural MRI data from 54 individuals with ASD and 61 age-and-IQ-matched controls ages 8 to 40 years. The MFS was identified on cortical surface reconstructions via 4 trained raters and classified into known surface patterns. Mean MFS gray matter volume (GMV), cortical surface area (SA), cortical thickness (CT), and standard deviation of CT (CT SD) were extracted. Effects of diagnosis, age, and hemisphere on MFS surface presentation and morphometry were assessed via multinomial logistic regression and mixed effects general linear modeling, respectively. The MFS was reliably identified in 97% of hemispheres examined. Macroanatomical patterns and age-related decreases in MFS GMV and CT were similar between groups. CT SD was greater in the left hemisphere in ASD. Participants' ability to interpret emotions and mental states from facial features was significantly negatively correlated with MFS CT and CT SD. Overall, the MFS is a stable feature of the fusiform gyrus in ASD and CT related measures appear to be sensitive to diagnosis and behavior. These results can inform future investigations of face processing and structure-function relationships in populations with social deficits. LAY SUMMARY: A small structural feature of the brain related to seeing faces (the mid-fusiform sulcus; MFS) appears similar in autism spectrum disorder (ASD) and neurotypical development; however, the thickness of this structure on the left side of the brain is more variable in ASD. People who are better at judging mental states from another person's eyes tend to have thinner and less variable MFS. This feature may teach us more about face processing and how brain structure influences function in ASD.

Hyperconnectivity of social brain networks in autism during action-intention judgment.

Deficits in social communication in autism spectrum disorder (ASD) have been documented using neuroimaging techniques such as functional MRI over the past decade. More recently, functional connectivity MRI has revealed altered connectivity in face processing, mentalizing, and mirroring brain networks, networks involved in the social brain in ASD. However, to our knowledge, previous studies have not examined these three networks concurrently. The purpose of the current study was to investigate the functional connectivity of the face processing, mentalizing, and mirroring networks (within each network and across networks) in ASD during an action-intention task in which participants were asked to determine the means and intention of a model's actions. We examined: a) within-network connectivity of each network using an ROI-to-ROI analysis; b) connectivity of each network hub to the rest of the brain using a seed-to-voxel analysis; c) the between-network connectivity of each network hub using ROI-to-ROI analysis; and d) brain-behavior relationships by correlating autism symptoms with brain connectivity. Task-fMRI data were used from 21 participants with ASD and 20 typically developing participants. The ASD group consistently showed significantly greater connectivity between networks and between hub regions to the rest of the brain. Hyperconnectivity in ASD may entail more and widespread resource utilization for accomplishing action-intention judgment.

Differential recruitment of theory of mind brain network across three tasks: An independent component analysis.

Social neuroscience research has focused on an identified network of brain regions primarily associated with processing Theory of Mind (ToM). However, ToM is a broad cognitive process, which encompasses several sub-processes, such as mental state detection and intentional attribution, and the connectivity of brain regions underlying the broader ToM network in response to paradigms assessing these sub-processes requires further characterization. Standard fMRI analyses which focus only on brain activity cannot capture information about ToM processing at a network level. An alternative method, independent component analysis (ICA), is a data-driven technique used to isolate intrinsic connectivity networks, and this approach provides insight into network-level regional recruitment. In this fMRI study, three complementary, but distinct ToM tasks assessing mental state detection (e.g. RMIE: Reading the Mind in the Eyes; RMIV: Reading the Mind in the Voice) and intentional attribution (Causality task) were each analyzed using ICA in order to separately characterize the recruitment and functional connectivity of core nodes in the ToM network in response to the sub-processes of ToM. Based on visual comparison of the derived networks for each task, the spatiotemporal network patterns were similar between the RMIE and RMIV tasks, which elicited mentalizing about the mental states of others, and these networks differed from the network derived for the Causality task, which elicited mentalizing about goal-directed actions. The medial prefrontal cortex, precuneus, and right inferior frontal gyrus were seen in the components with the highest correlation with the task condition for each of the tasks highlighting the role of these regions in general ToM processing. Using a data-driven approach, the current study captured the differences in task-related brain response to ToM in three distinct ToM paradigms. The findings of this study further elucidate the neural mechanisms associated with mental state detection and causal attribution, which represent possible sub-processes of the complex construct of ToM processing.

Brain Responses Underlying Anthropomorphism, Agency, and Social Attribution in Autism Spectrum Disorder.

BACKGROUND: Theory of Mind (ToM), the ability to attribute mental states to oneself and others, is frequently impaired in Autism Spectrum Disorder (ASD) and may result from altered activation of social brain regions. Conversely, Typically Developing (TD) individuals overextend ToM and show a strong tendency to anthropomorphize and interpret biological motion in the environment. Less is known about how the degree of anthropomorphism influences intentional attribution and engagement of the social brain in ASD. OBJECTIVE: This fMRI study examines the extent of anthropomorphism, its role in social attribution, and the underlying neural responses in ASD and TD using a series of human stick figures and geometrical shapes. METHODS: 14 ASD and 14 TD adults watched videos of stick figures and triangles interacting in random or socially meaningful ways while in an fMRI scanner. In addition, they completed out-of-scanner measures of ToM skill and real-world social deficits. Whole brain statistical analysis was performed for regression and within and between group comparisons of all conditions using SPM12's implementation of the general linear model. RESULTS: ToM network regions were activated in response to social movement and human-like characters in ASD and TD. In addition, greater ToM ability was associated with increased TPJ and MPFC activity while watching stick figures; whereas more severe social symptoms were associated with reduced right TPJ activation in response to social movement. CONCLUSION: These results suggest that degree of anthropomorphism does not differentially affect social attribution in ASD and highlights the importance of TPJ in ToM and social attribution.

Hemispheric differences in language processing in autism spectrum disorders: A meta-analysis of neuroimaging studies.

Language impairments, a hallmark feature of autism spectrum disorders (ASD), have been related to neuroanatomical and functional abnormalities. Abnormal lateralization of the functional language network, increased reliance on visual processing areas, and increased posterior brain activation have all been reported in ASD and proposed as explanatory models of language difficulties. Nevertheless, inconsistent findings across studies have prevented a comprehensive characterization of the functional language network in ASD. The aim of this study was to quantify common and consistent patterns of brain activation during language processing in ASD and typically developing control (TD) participants using a meta-analytic approach. Activation likelihood estimation (ALE) meta-analysis was used to examine 22 previously published functional Magnetic Resonance Imaging (fMRI)/positron emission tomography studies of language processing (ASD: N = 328; TD: N = 324). Tasks included in this study addressed semantic processing, sentence comprehension, processing figurative language, and speech production. Within-group analysis showed largely overlapping patterns of language-related activation in ASD and TD groups. However, the ASD participants, relative to TD participants, showed: (1) more right hemisphere activity in core language areas (i.e., superior temporal gyrus and inferior frontal gyrus), particularly in tasks where they had poorer performance accuracy; (2) bilateral MTG hypo-activation across many different paradigms; and (3) increased activation of the left lingual gyrus in tasks where they had intact performance. These findings show that the hypotheses reviewed here address the neural and cognitive aspects of language difficulties in ASD across all tasks only in a limited way. Instead, our findings suggest the nuances of language and brain in ASD in terms of its context-dependency. Autism Res 2016, 9: 1046-1057. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Language and motor cortex response to comprehending accidental and intentional action sentences.

Understanding the meaning of others' actions involves mentally simulating those actions by oneself. Embodied theories of language espouse a prominent role for motor simulation in reading comprehension, especially when words, sentences, or narratives portray everyday actions. Inherent in these actions is the level of agency of the actor. Motor cortex activity in response to processing action verbs has been relatively well-established. What has been less explored, however, are: (1) the neural bases of determining whether an action is intentional or accidental (agency); and (2) whether agency influences level of motor simulation. This functional MRI study investigated how language and motor areas of the brain respond to sentences depicting intentional versus accidental action. 25 healthy adults read a series of sentences in the MRI scanner and determined whether the actions described were accidental or intentional. The main results include: (1) left hemisphere language areas (left inferior frontal gyrus, LIFG; left superior temporal gyrus, LSTG), premotor cortex (PM), and presupplementary motor area (pSMA) were strongly activated by both sentence types; (2) processing accidental action, relative to intentional action, elicited greater activity in LIFG, medial prefrontal cortex (MPFC), and left amygdala; no statistically significant activity was found in the opposite contrast; and (3) greater percent signal change was observed in LIFG while processing accidental action and in right precentral gyrus for intentional action. The results of this study support language and motor region involvement in action sentence comprehension in accordance with embodiment theories. Additionally, it provides new insight into the linguistic, integrative, and emotional demands of comprehending accidental action, its underlying neural circuitry, and its relationship to intentionality bias: the predisposition to ascribe purpose to action.