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.

Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder.

Social impairments in autism spectrum disorder (ASD), a hallmark feature of its diagnosis, may underlie specific neural signatures that can aid in differentiating between those with and without ASD. To assess common and consistent patterns of differences in brain responses underlying social cognition in ASD, this study applied an activation likelihood estimation (ALE) meta-analysis to results from 50 neuroimaging studies of social cognition in children and adults with ASD. In addition, the group ALE clusters of activation obtained from this was used as a social brain mask to perform surface-based cortical morphometry (SBM) in an empirical structural MRI dataset collected from 55 ASD and 60 typically developing (TD) control participants. Overall, the ALE meta-analysis revealed consistent differences in activation in the posterior superior temporal sulcus at the temporoparietal junction, middle frontal gyrus, fusiform face area (FFA), inferior frontal gyrus (IFG), amygdala, insula, and cingulate cortex between ASD and TD individuals. SBM analysis showed alterations in the thickness, volume, and surface area in individuals with ASD in STS, insula, and FFA. Increased cortical thickness was found in individuals with ASD, the IFG. The results of this study provide functional and anatomical bases of social cognition abnormalities in ASD by identifying common signatures from a large pool of neuroimaging studies. These findings provide new insights into the quest for a neuroimaging-based marker for ASD. Hum Brain Mapp 37:3957-3978, 2016. © 2016 Wiley Periodicals, Inc.

Changes in intrinsic connectivity of the brain's reading network following intervention in children with autism.

While task-based neuroimaging studies have identified alterations in neural circuitry underlying language processing in children with autism spectrum disorders [ASD], resting state functional magnetic resonance imaging [rsfMRI] is a promising alternative to the constraints posed by task-based fMRI. This study used rsfMRI, in a longitudinal design, to study the impact of a reading intervention on connectivity of the brain regions involved in reading comprehension in children with ASD. Functional connectivity was examined using group independent component analysis (GICA) and seed-based correlation analysis of Broca's and Wernicke's areas, in three groups of participants: an experimental group of ASD children (ASD-EXP), a wait list control group of ASD children (ASD-WLC), and a group of typically developing (TD) control children. Both GICA and seed-based analyses revealed stronger functional connectivity of Broca's and Wernicke's areas in the ASD-EXP group postintervention. Additionally, improvement in reading comprehension in the ASD-EXP group was correlated with greater connectivity in both Broca's and Wernicke's area in the GICA identified reading network component. In addition, increased connectivity between the Broca's area and right postcentral and right STG, and the Wernicke's area and LIFG, were also correlated with greater improvement in reading comprehension. Overall, this study revealed widespread changes in functional connectivity of the brain's reading network as a result of intervention in children with ASD. These novel findings provide valuable insights into the neuroplasticity of brain areas underlying reading and the impact of intensive intervention in modifying them in children with ASD.

Attribution of emotions to body postures: an independent component analysis study of functional connectivity in autism.

The ability to interpret others' body language is a vital skill that helps us infer their thoughts and emotions. However, individuals with autism spectrum disorder (ASD) have been found to have difficulty in understanding the meaning of people's body language, perhaps leading to an overarching deficit in processing emotions. The current fMRI study investigates the functional connectivity underlying emotion and action judgment in the context of processing body language in high-functioning adolescents and young adults with autism, using an independent components analysis (ICA) of the fMRI time series. While there were no reliable group differences in brain activity, the ICA revealed significant involvement of occipital and parietal regions in processing body actions; and inferior frontal gyrus, superior medial prefrontal cortex, and occipital cortex in body expressions of emotions. In a between-group analysis, participants with autism, relative to typical controls, demonstrated significantly reduced temporal coherence in left ventral premotor cortex and right superior parietal lobule while processing emotions. Participants with ASD, on the other hand, showed increased temporal coherence in left fusiform gyrus while inferring emotions from body postures. Finally, a positive predictive relationship was found between empathizing ability and the brain areas underlying emotion processing in ASD participants. These results underscore the differential role of frontal and parietal brain regions in processing emotional body language in autism.

The implications of brain connectivity in the neuropsychology of autism.

Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to the characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a neural marker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate.

An fMRI investigation of working memory and its relationship with cardiorespiratory fitness in pediatric posterior fossa tumor survivors who received cranial radiation therapy.

BACKGROUND: The present study investigated the relationship between cardiorespiratory fitness and executive functioning in pediatric brain tumor survivors who received cranial radiation. This population is known to show executive dysfunction and lower rates of aerobic exercise compared to peers. PROCEDURE: Nine adolescent survivors of pediatric posterior fossa tumor completed an n-back working memory task during a functional MRI scan, as well as cardiorespiratory fitness testing on a cycle ergometer. RESULTS: Neuroimaging findings indicated typical activation patterns associated with working memory, mainly in the frontal-parietal network. Higher cardiorespiratory fitness was related to better performance on a behavioral measure of working memory and more efficient neural functioning. CONCLUSIONS: This study provides preliminary evidence that cardiorespiratory fitness may be related to executive functioning, particularly working memory, in pediatric brain tumor survivors. Descriptions of the brain regions recruited for working memory by pediatric brain tumor survivors may be used to inform future interventions or indicators of treatment efficacy.

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.

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 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.

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.

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.

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.

"The archeologist's career ended in ruins": hemispheric differences in pun comprehension in autism.

Appropriate interpretation of figurative language involves inferring the speaker's intent by integrating word meaning with context. In disorders like autism, understanding intended and contextual meanings in language may pose a challenge. Such difficulties are prevalent even when individuals exhibit otherwise fluent language ability (Szatmari et al., 1990). A pun is a rhetorical technique in which a speaker deliberately invokes multiple meanings through a word or phrase likely resulting in a joke. Comprehending puns may involve identifying multiple meanings of a word, embedding it in right contexts, and understanding the underlying humor. This fMRI study investigated the brain responses associated with figures of speech like puns. In the fMRI scanner, participants read sentences containing puns (e.g. To write with a broken pencil is pointless) and control sentences (literal meaning) presented in a blocked design format. The participants' task was to silently read and understand one meaning (in the literal condition) or two meanings (in the pun condition). Participants with autism, relative to typical controls, showed an increase in overall activation while comprehending sentences containing puns, particularly within the right hemisphere as well as in relatively posterior brain areas. Overall, there was reduced response in left hemisphere areas, reduced response to humor, and more distributed recruitment of regions in autism relative to control participants. We also examined the relationship between symptom severity in autism and verbal ability with brain responses to pun comprehension finding negative and positive correlations respectively. Overall, the results from the present study suggest that individuals with autism resort to altered neural routes in comprehending language in general, and figurative language in particular.

Cardiorespiratory fitness in survivors of pediatric posterior fossa tumor.

Advances in medical therapies have greatly improved survivorship rates in children diagnosed with brain tumor; as a result, morbidities associated with survivorship have become increasingly important to identify and address. In general, pediatric posterior fossa tumor survivors tend to be less physically active than peers. This may be related to late effects of diagnosis and treatment, including cardiovascular, endocrine, psychological, and neurocognitive difficulties. Exercise has been shown to be effective in improving physical functioning, mood, and even cognitive functioning. Consequently, the benefits of physical exercise need to be explored and incorporated into the daily lives of pediatric posterior fossa tumor survivors. The primary aim of the present study was to establish the feasibility and safety of cardiorespiratory fitness testing in pediatric posterior fossa tumor survivors who had received cranial radiation therapy. In addition, comparing our cohort with previously published data, we found that pediatric posterior fossa tumor survivors tended to be less fit than children with pulmonary disease and healthy controls and approximately as fit as children with chronic heart disease and survivors of other types of childhood cancer. The importance of cardiorespiratory fitness in pediatric posterior fossa tumor survivors is discussed along with implications for future directions.

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.

"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.

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.

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.

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.