The neurobiological map of theory of mind and pragmatic communication in autism.

Children with autism often have difficulty with Theory of Mind (ToM), the ability to infer mental states, and pragmatic skills, the contextual use of language. Neuroimaging research suggests ToM and pragmatic skills overlap, as the ability to understand another's mental state is a prerequisite to interpersonal communication. To our knowledge, no study in the last decade has examined this overlap further. To assess the emerging consensus across neuroimaging studies of ToM and pragmatic skills in autism, we used coordinate-based activation likelihood estimation (ALE) analysis of 35 functional magnetic resonance imaging (MRI) studies (13 pragmatic skills, 22 ToM), resulting in a meta-analysis of 1,295 participants (647 autistic, 648 non-autistic) aged 7 to 49 years. Group difference analysis revealed decreased left inferior frontal gyrus (LIFG) activation in autistic participants during pragmatic skills tasks. For ToM tasks, we found reduced anterior cingulate cortex (ACC), medial prefrontal cortex (MPFC), and temporoparietal junction (TPJ) activation in autistic participants. Collectively, both ToM and pragmatic tasks showed activation in IFG and superior temporal gyrus (STG) and a reduction in left hemispheric activation in autistic participants. Overall, the findings underscore the cognitive and neural processing similarities between ToM and pragmatic skills, and their underlying neurobiological differences in autism.

Alterations of Functional Connectivity in Autism and Attention-Deficit/Hyperactivity Disorder Revealed by Multi-Voxel Pattern Analysis.

Background: Autism and attention-deficit/hyperactivity disorder (ADHD) are comorbid neurodevelopmental disorders that share common and distinct neurobiological mechanisms, with disrupted brain connectivity patterns being a hallmark feature of both conditions. It is challenging to gain a mechanistic understanding of the underlying disorder, because brain connectivity changes in autism and ADHD are heterogeneous. Objectives: The present resting state functional MRI (rs-fMRI) study focuses on investigating the shared and distinct resting state-fMRI connectivity (rsFC) patterns in autistic and ADHD adults using multi-voxel pattern analysis (MVPA). By identifying spatial patterns of fMRI activity across a given time course, MVPA is an innovative and powerful method for generating seed regions of interest (ROIs) without a priori hypotheses. Methods: We performed a data-driven, whole-brain, connectome-wide MVPA on rs-fMRI data collected from 15 autistic, 19 ADHD, and 15 neurotypical (NT) young adults. Results: MVPA identified cerebellar vermis 9, precuneus, and the right cerebellum VI for autistic versus NT, right inferior frontal gyrus and vermis 9 for ADHD versus NT, and right dorsolateral prefrontal cortex for autistic versus ADHD as significant clusters. Post hoc seed-to-voxel analyses using these clusters as seed ROIs were performed for further characterization of group differences. The cerebellum VI, vermis, and precuneus in autistic adults, and the vermis and frontal regions in ADHD showed different connectivity patterns in comparison with NT. Conclusions: The study characterizes the rsFC profile of cerebellum with key cortical areas in autism and ADHD, and it emphasizes the importance of studying the role of the functional connectivity of the cerebellum in neurodevelopmental disorders.

Psychopathic traits and social brain responses during moral evaluation in adolescence.

Brain functioning underlying moral decision-making in adolescents with psychopathic traits is relatively less understood. This fMRI study examined the neural correlates of moral decision-making in relation to psychopathic traits, as measured by the Youth Psychopathic Traits Inventory (YPI), in a sample of 16 community-recruited youth (mean age=13.94) with reported behavior problems. Participants viewed images that depicted a moral violation, a conflict with no moral violation, and a neutral scenario. We analyzed activation, seed-to-voxel, and seed-to-seed functional connectivity using a social brain mask during moral reasoning and decision-making. Results indicated: a) greater activity in social brain regions while assessing acts of moral, compared to nonmoral, violations; b) positive correlations between activation of several social brain regions and YPI subscale scores; c) a positive association between YPI and functional connectivity between the social brain network and the bilateral middle cingulate cortices; d) significant effects of YPI on connectivity between social brain regions and the rest of the brain; and e) decreased connectivity between several ROIs during moral reasoning: the left temporoparietal junction (lTPJ) and dorsomedial prefrontal cortex (DMPFC), the precuneus (PREC) and left amygdala (lAMYG), and the PREC and rAMYG. Clinical and developmental implications of these findings are discussed.

The role of the broader autism phenotype in anxiety and depression in college-aged adults.

The current study examines the relationship between the presence of autistic traits and anxiety and mood disorders in young adults from different racial groups. A representative sample from a predominately white university (2,791 non-Hispanic White (NHW) and 185 Black students) completed the broad autism phenotype questionnaire (BAPQ), a measure of depression (Patient Health Questionnaire, PHQ-9), and anxiety (Generalized Anxiety Disorder, GAD-7). Statistical Package for Social Sciences (SPSS) was used to perform two multiple regression analyses to determine the association between race, BAPQ score and anxiety and depression symptoms. The current study found a stronger association between autistic traits had depression and anxiety symptoms in Black participants than did NHW participants. These findings underscore the association between autistic traits and anxiety and depression in Black communities, and the need for further studies on this topic area. Additionally, it highlights the importance of improving access to mental health care for this population.

Amplitude of low frequency fluctuations during resting state fMRI in autistic children.

Resting state fMRI (rs-fMRI) provides an excellent platform for examining the amplitude of low frequency fluctuations (ALFF) and fractional amplitude of low frequency fluctuations (fALFF), which are key indices of brain functioning. However, ALFF and fALFF have been used only sporadically to study autism. rs-fMRI data from 69 children (40 autistic, mean age = 8.47 ± 2.20 years; age range: 5.2 to 13.2; and 29 non-autistic, mean age = 9.02 ± 1.97 years; age range 5.9 to 12.9) were obtained from the Autism Brain Imaging Data Exchange (ABIDE II). ALFF and fALFF were measured using CONN connectivity toolbox and SPM12, at whole-brain & network-levels. A two-sampled t-test and a 2 Group (autistic, non-autistic) × 7 Networks ANOVA were conducted to test group differences in ALFF and fALFF. The whole-brain analysis identified significantly reduced ALFF values for autistic participants in left parietal opercular cortex, precuneus, and right insula. At the network level, there was a significant effect of diagnostic group and brain network on ALFF values, and only significant effect of network, not group, on fALFF values. Regression analyses indicated a significant effect of age on ALFF values of certain networks in autistic participants. Such intrinsically different network-level responses in autistic participants may have implications for task-level recruitment and synchronization of brain areas, which may in turn impact optimal cognitive functioning. Moreover, differences in low frequency fluctuations of key networks, such as the DMN and SN, may underlie alterations in brain responses in autism that are frequently reported in the literature.

Thalamic functional connectivity and sensorimotor processing in neurodevelopmental disorders.

One of the earliest neurobiological findings in autism has been the differences in the thalamocortical pathway connectivity, suggesting the vital role thalamus plays in human experience. The present functional MRI study investigated resting-state functional connectivity of the thalamus in 49 (autistic, ADHD, and neurotypical) young adults. All participants underwent structural MRI and eyes-open resting state functional MRI scans. After preprocessing the imaging data using Conn's connectivity toolbox, a seed-based functional connectivity analysis was conducted using bilateral thalamus as primary seeds. Autistic participants showed stronger thalamic connectivity, relative to ADHD and neurotypical participants, between the right thalamus and right precentral gyrus, right pars opercularis-BA44, right postcentral gyrus, and the right superior parietal lobule (RSPL). Autistic participants also showed significantly increased connectivity between the left thalamus and the right precentral gyrus. Furthermore, regression analyses revealed a significant relationship between autistic traits and left thalamic-precentral connectivity (R2 = 0.1113), as well as between autistic traits and right postcentral gyrus and RSPL connectivity (R2 = 0.1204) in autistic participants compared to ADHD. These findings provide significant insights into the role of thalamus in coordinating neural information processing and its alterations in neurodevelopmental disorders.

Serving Individuals With Autism Spectrum Disorder in the Age of COVID-19: Special Considerations for Rural Families.

This position paper explores the needs of rural families of children, adolescents, and adults with autism spectrum disorder (ASD) during the COVID-19 pandemic. Prior to COVID-19, literature portrays elevated stress in families of individuals with ASD and health and socioeconomic disparities for rural and underserved populations. These disparities were exacerbated due to COVID-19 and subsequent lockdowns and economic turmoil. Academic and adaptive skills training were particularly impacted due to school closures, with parents tasked with taking some responsibility for training these skills. Our goals for this article focus on special considerations for rural families regarding (a) neurobiological and developmental impacts of stressful experiences like COVID-19, (b) delineation of the impacts on individuals with ASD and other comorbid and related conditions, and (c) education and intervention needs during these times. Finally, we offer suggestions for future care during pandemic events, including recommendations for improving service delivery under such conditions.

Behavioral and neurobiological evidence for the effects of reading interventions on autistic children: A systematic review.

This study systematically reviewed the literature on reading interventions for autistic children. Peer-reviewed articles that reported behavioral and/or neurobiological effects of reading intervention were identified in five online databases. After screening, 15 studies met the inclusion criteria for this review. These studies focus on interventions targeted towards improving specific reading skills: comprehension, vocabulary, fluency, and phonological awareness. Studied interventions included interactive and shared reading, visualization strategies, vocabulary and main idea instruction, video modeling, and interventions supported by tablet-based technology. Overall, the studies identified in this review reported improvements to each of the targeted reading skills and changes to neural activation and connectivity. In addition, changes at the brain level were associated with improvements in reading. Specifically, frontal, temporal, and occipital regions associated with visual and language processing showed increased activation and functional connectivity following intervention. This review provides important insights into the landscape of reading intervention studies in autism and into the neurobiological underpinnings of reading skills and how interventions affect those processes.

Executive Function Brain Network Activation Predicts Driving Hazard Detection in ADHD.

Drivers with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are at increased risk of experiencing driving difficulties. An important aspect of driving safety and skill involves hazard detection. This functional magnetic resonance imaging study examined the neural responses associated with driving hazard detection in drivers with ASD, ADHD, and typically developing (TD) drivers. Forty participants (12 ASD, 15 ADHD, 13 TD) ages 16-30 years completed a driving simulator task in which they encountered social and nonsocial hazards; reaction time (RT) for responding to hazards was measured. Participants then completed a similar hazard detection task in the MRI scanner so that neural response to hazards could be measured. Activation of regions of interest considered part of the executive function (EF) and theory of mind (ToM) networks were examined and related to driving simulator behavior. Results showed that stronger activation of the EF network during social hazard processing, including the bilateral dorsolateral prefrontal cortex and posterior parietal cortex, was associated with faster RT to social hazards among drivers with ADHD, but not among drivers with ASD. This provides the first evidence of a relationship between EF network brain activation and driving skills in ADHD and suggests that alterations in this network may underlie driving behavior. In comparison, the current study did not observe a relationship between ToM network activation and RT to social hazards in any group. This study lays the groundwork for relating neural activation to driving behavior among individuals with NDDs.

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.

Neuropsychological predictors of driving hazard detection in autism spectrum disorder and ADHD.

Driving is a neuropsychologically complex task; this can present challenges for individuals with neurodevelopmental disorders (NDDs) such asautism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Deficits in theory of mind (ToM) and executive function (EF) are common features of ASD and ADHD, respectively, and may influence driving processes such as hazard perception. No studies have directly examined the neuropsychological contributions to hazard detection among drivers with ASD compared to ADHD.In the current study, 48 participants ages 16-30 years (13 ASD, 17 ADHD, 18 typically developing (TD)) completed a driving simulator task in which they encountered hazards in the driving environment. Hazards varied in whether they were social (contained a human component) or nonsocial (were physical objects) to examine the contribution of ToM and social processing to hazard response. Additionally, participants completed a neuropsychological battery targeting ToM and EF/attention skills (cognitive tasks and self-report measures).Within the ASD group, participants responded relatively slower to social compared to nonsocial hazards; no effect of hazard type was observed in the ADHD or TD groups. Additionally, measures of ToM and EF were correlated with driving performanceamong ASD participants; within the ADHD group, only self-reported behavior regulation was associated with driving performance. Broadly, this suggests that cognitive factors such as ToM and EF impact driving hazard performance in ASD and ADHD. The results of the study have implications for developing driving intervention programs for individuals with NDDs.

"Unrest while Resting"? Brain entropy in autism spectrum disorder.

Biological systems typically exhibit complex behavior with nonlinear dynamic properties. Nonlinear signal processing techniques such as sample entropy is a novel approach to characterize the temporal dynamics of brain connectivity. Estimating entropy is especially important in clinical populations such as autism spectrum disorder (ASD) as differences in entropy may signal functional alterations in the brain. Considering the models of disrupted brain network connectivity in ASD, sample entropy would provide a novel direction to understand brain organization. Resting state fMRI data from 45 high-functioning children with ASD and 45 age-and-IQ-matched typically developing (TD) children were obtained from the Autism Brain Imaging Data Exchange (ABIDE-II) database. Data were preprocessed using the CONN toolbox. Sample entropy was then calculated using the complexity toolbox, in a whole-brain voxelwise manner as well as in regions of interests (ROIs) based methods. ASD participants demonstrated significantly increased entropy in left angular gyrus, superior parietal lobule, and right inferior temporal gyrus; and reduced sample entropy in superior frontal gyrus compared to TD participants. Positive correlations of average entropy in clusters of significant group differences scores across all subjects were found. Finally, ROI analysis revealed a main effect of lobes. Differences in entropy between the ASD and TD groups suggests that entropy may provide another important index of brain dysfunction in clinical populations like ASD. Further, the relationship between increased entropy and ASD symptoms in our study underscores the role of optimal brain synchronization in cognitive and behavioral functions.

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.

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.

Frontoparietal Network in Executive Functioning in Autism Spectrum Disorder.

Higher cognitive functions in autism spectrum disorder (ASD) are characterized by impairments in executive functions (EF). While some research attributes this to an overreliance of the prefrontal cortex (PFC), others demonstrate poor recruitment of the PFC in individuals with ASD. In order to assess the emerging consensus across neuroimaging studies of EF in ASD, the current study used a coordinate-based activation likelihood estimation (ALE) analysis of 16 functional magnetic resonance imaging (fMRI) studies, resulting in a meta-analysis of data from 739 participants (356 ASD, 383 typically developing [TD] individuals) ranging from 7 to 52 years of age. Within-group analysis of EF tasks revealed that both TD and ASD participants had significant activity in PFC regions. Analysis of group differences indicated greater activation in ASD, relative to TD participants, in the right middle frontal gyrus and the anterior cingulate cortex, and lesser activation in the bilateral middle frontal, left inferior frontal gyrus, right inferior parietal lobule, and precuneus. Although both ASD and TD participants showed similar PFC activation, there was differential recruitment of wider network of EF regions such as the IPL in ASD participants. The under-recruitment of parietal regions may be due to poor connectivity of the frontoparietal networks with other regions during EF tasks or a restricted executive network in ASD participants which is limited primarily to the PFC. These results support the executive dysfunction hypothesis of ASD and suggests that poor frontoparietal recruitment may underlie some of the EF difficulties individuals with ASD experience. LAY SUMMARY: This study reports a meta-analysis of 16 brain imaging studies of executive functions (EF) in individuals with autism spectrum disorder (ASD). While parts of the brain's EF network is activated in both ASD and control participants, the ASD group does not activate a wider network of EF regions such as the parietal cortex. This may be due to poor EF network connectivity, or a constrained EF network in ASD participants. These results may underlie some of the EF difficulties individuals with ASD experience. Autism Res 2020, 13: 1762-1777. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Metacognition and behavioral regulation predict distinct aspects of social functioning in autism spectrum disorder.

Executive function (EF) deficits are common in autism spectrum disorder (ASD), and previous studies suggest that EF may influence or predict social functioning. Thus, EF is a potential treatment target in this population. However, the nature of how specific metacognition and behavioral regulation components of EF may differentially impact social function remains unclear. The goal of the current study was to examine the relationships between sub-components of EF (e.g., working memory, shifting, inhibition, etc.) and social functioning as measured by parent ratings on the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Social Responsiveness Scale (SRS), while controlling for the influence of age, sex, and IQ. A second goal was to examine whether BRIEF scores were predictive of clinician-rated measures of ASD symptoms. Behavioral data were acquired from the Autism Brain Imaging Data Exchange-II database and included 106 children with ASD (ages 5-13). Based on analysis of parent ratings, self-monitoring skills predicted social awareness; shifting ability predicted social cognition; working memory and monitoring skills predicted social communication; initiation predicted social motivation; and shifting ability predicted restrictive and repetitive behaviors among children with ASD. Parent ratings on the BRIEF did not predict clinician-rated measures of ASD symptoms; this requires further study. Overall, the current findings indicate that metacognition and behavioral regulation both contribute to social functioning in ASD, although they each have distinct patterns of influence on different aspects of social functioning. These findings have promising implications for tailoring social interventions for ASD that target specific EF skills.

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.

Patterns of Cerebellar Connectivity with Intrinsic Connectivity Networks in Autism Spectrum Disorders.

There is growing evidence of altered connectivity in autism spectrum disorders (ASD) between the cerebellum and cortex. Three intrinsic connectivity networks (ICNs) are especially important to cognitive processing in ASD: the default mode network (DMN), executive control network (ECN), and salience networks (SNs). The goal of this study was to compare resting-state functional connectivity between the cerebellum and the DMN, ECN, and SN in ASD and typically developing children (n = 74, ages 7-12 years). Children with ASD showed stronger connectivity between the ventral DMN and left cerebellar lobules I-IV. No meaningful relationships were observed between ICN-cerebellar functional connectivity and ASD symptoms. These results suggest that the cerebellum contributes to altered network connectivity in ASD.

Aberrant "deep connectivity" in autism: A cortico-subcortical functional connectivity magnetic resonance imaging study.

The number of studies examining functional brain networks in Autism Spectrum Disorder (ASD) has risen over the last decade and has characterized ASD as a disorder of altered brain connectivity. However, these studies have focused largely on cortical structures, and only a few studies have examined cortico-subcortical connectivity in regions like thalamus and basal ganglia in ASD. The goal of this study was to characterize the functional connectivity between cortex and subcortical regions in ASD using the Autism Brain Imaging Data Exchange (ABIDE-II). Resting-state functional magnetic resonance imaging data were used from 168 typically developing (TD) and 138 ASD participants across different sites from the ABIDE II dataset. Functional connectivity of basal ganglia and thalamus to unimodal and supramodal networks was examined in this study. Overconnectivity (ASD > TD) was found between unimodal (except for medial visual network) and subcortical regions, and underconnectivity (TD > ASD) was found between supramodal (except for default mode and dorsal attention networks) and subcortical regions; positive correlations between ASD phenotype and unimodal-subcortical connectivity were found and negative ones with supramodal-subcortical connectivity. These findings suggest that brain networks heavily involved in sensory processing had higher connectivity with subcortical regions, whereas those involved in higher-order thinking showed decreased connectivity in ASD. In addition, brain-behavior correlations indicated a relationship between ASD phenotype and connectivity. Thus, differences in cortico-subcortical connectivity may have a significant impact on basic and higher-order cognitive processes in ASD. Autism Res 2019, 12: 384-400 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study focused on examining the functional connectivity (synchronization of brain activity across regions) of two types of brain networks (unimodal and supramodal) with subcortical areas (thalamus and basal ganglia) in children, adolescents, and adults with autism spectrum disorder (ASD) and how this relates to ASD phenotype. ASD participants showed overconnectivity in unimodal networks and underconnectivity in supramodal networks. These findings provide new insights into cortico-subcortical connections between basic sensory and high-order cognitive processes.