scholarly journals Autism Spectrum Disorder Symptoms are Associated with Connectivity Between Large-Scale Neural Networks and Brain Regions Involved in Social Processing

2020 ◽  
Vol 50 (8) ◽  
pp. 2765-2778
Author(s):  
Korey P. Wylie ◽  
Jason R. Tregellas ◽  
Joshua J. Bear ◽  
Kristina T. Legget
Keyword(s):  
Neural Networks ◽  
Autism Spectrum Disorder ◽  
Large Scale ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Social Processing

scholarly journals Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Merel C. Postema ◽  
Daan van Rooij ◽  
Evdokia Anagnostou ◽  
Celso Arango ◽  
Guillaume Auzias ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Cortical Thickness ◽  
Large Scale ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Brain Asymmetry ◽  
Spectrum Disorder ◽  
Data Sets ◽  
Control Effect ◽  
Structural Brain

Abstract Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

scholarly journals Graph Ricci Curvatures Reveal Disease-related Changes in Autism Spectrum Disorder

2021 ◽  
Author(s):  
Pavithra Elumalai ◽  
Yasharth Yadav ◽  
Nitin Williams ◽  
Emil Saucan ◽  
Jürgen Jost ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Resting State ◽  
Neurodevelopmental Disorders ◽  
Data Exchange ◽  
Meta Analysis ◽  
Resting State Fmri ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
The Brain

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders that pose a significant global health burden. Measures from graph theory have been used to characterise ASD-related changes in resting-state fMRI functional connectivity networks (FCNs), but recently developed geometry-inspired measures have not been applied so far. In this study, we applied geometry-inspired graph Ricci curvatures to investigate ASD-related changes in resting-state fMRI FCNs. To do this, we applied Forman-Ricci and Ollivier-Ricci curvatures to compare networks of ASD and healthy controls (N = 1112) from the Autism Brain Imaging Data Exchange I (ABIDE-I) dataset. We performed these comparisons at the brain-wide level as well as at the level of individual brain regions, and further, determined the behavioral relevance of region-specific differences with Neurosynth meta-analysis decoding. We found brain-wide ASD-related differences for both Forman-Ricci and Ollivier-Ricci curvatures. For Forman-Ricci curvature, these differences were distributed across 83 of the 200 brain regions studied, and concentrated within the Default Mode, Somatomotor and Ventral Attention Network. Meta-analysis decoding identified the brain regions showing curvature differences as involved in social cognition, memory, language and movement. Notably, comparison with results from previous non-invasive stimulation (TMS/tDCS) experiments revealed that the set of brain regions showing curvature differences overlapped with the set of brain regions whose stimulation resulted in positive cognitive or behavioural outcomes in ASD patients. These results underscore the utility of geometry-inspired graph Ricci curvatures in characterising disease-related changes in ASD, and possibly, other neurodevelopmental disorders.

scholarly journals Increased burden of deleterious variants in essential genes in autism spectrum disorder

2016 ◽  
Vol 113 (52) ◽  
pp. 15054-15059 ◽  
Author(s):  
Xiao Ji ◽  
Rachel L. Kember ◽  
Christopher D. Brown ◽  
Maja Bućan
Keyword(s):  
Autism Spectrum Disorder ◽  
Large Scale ◽  
De Novo ◽  
Autism Spectrum ◽  
Essential Genes ◽  
Spectrum Disorder ◽  
Model Organisms ◽  
Disease Genes ◽  
Priority List ◽  
Human Orthologs

Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.

Executive Functions in Adolescents with Autism Spectrum Disorder

2017 ◽  
pp. 67-90
Author(s):  
Yael Dai ◽  
Inge-Marie Eigsti
Keyword(s):  
Autism Spectrum Disorder ◽  
Working Memory ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Clinical Implications ◽  
Future Directions ◽  
Adolescents With Autism ◽  
Memory Flexibility ◽  
The Brain

This chapter reviews strengths and weaknesses in executive function (EF) domains, including inhibition, working memory, flexibility, fluency, and planning, in adolescents (age 13–19) with autism spectrum disorder (ASD). Given the dramatic developmental changes in the brain regions that support EF during the period of adolescence, it is critical to evaluate which EF abilities show a distinct profile during this period. As this chapter will demonstrate, youth with ASD show deficits across all domains of EF, particularly in complex tasks that include arbitrary instructions. We describe the fundamental measures for assessing skills in each domain and discuss limitations and future directions for research, as well as clinical implications of these findings for working with youth with ASD.

scholarly journals Neural features of sustained emotional information processing in autism spectrum disorder

Autism ◽  
2020 ◽  
Vol 24 (4) ◽  
pp. 941-953 ◽  
Author(s):  
Carla A Mazefsky ◽  
Amanda Collier ◽  
Josh Golt ◽  
Greg J Siegle
Keyword(s):  
Autism Spectrum Disorder ◽  
Emotion Dysregulation ◽  
Emotional Processing ◽  
Brain Activity ◽  
A Priori ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typically Developing ◽  
Autism Spectrum Disorder Group

Emotion dysregulation is common in autism spectrum disorder; a better understanding of the underlying neural mechanisms could inform treatment development. The tendency toward repetitive cognition in autism spectrum disorder may also increase susceptibility to perseverate on distressing stimuli, which may then increase emotion dysregulation. Therefore, this study investigated the mechanisms of sustained processing of negative information in brain activity using functional magnetic resonance imaging. We used an event-related task that alternated between emotional processing of personally relevant negative words, neutral words, and a non-emotional task. A priori criteria were developed to define heightened and sustained emotional processing, and feature conjunction analysis was conducted to identify all regions satisfying these criteria. Participants included 25 adolescents with autism spectrum disorder and 23 IQ-, age-, and gender-matched typically developing controls. Regions satisfying all a priori criteria included areas in the salience network and the prefrontal dorsolateral cortex, which are areas implicated in emotion regulation outside of autism spectrum disorder. Collectively, activity in the identified regions accounted for a significant amount of variance in emotion dysregulation in the autism spectrum disorder group. Overall, these results may provide a potential neural mechanism to explain emotion dysregulation in autism spectrum disorder, which is a significant risk factor for poor mental health. Lay abstract Many individuals with autism spectrum disorder struggle with emotions that are intense and interfering, which is referred to as emotion dysregulation. Prior research has established that individuals with autism may be more likely than individuals who are not autistic to have repetitive thoughts. It is possible that persistent thoughts about negative or distressing stimuli may contribute to emotion dysregulation in autism spectrum disorder. This study aimed to identify areas of the brain with evidence of persistent processing of negative information via functional magnetic resonance neuroimaging. We used a task that alternated between emotional processing of personally relevant negative words, neutral words, and a non-emotional task. Criteria were developed to define heightened and persistent emotional processing, and analyses were conducted to identify all brain regions satisfying these criteria. Participants included 25 adolescents with autism spectrum disorder and 23 typically developing adolescents who were similar to the autism spectrum disorder group in IQ, age, and gender ratios. Brain regions identified as having greater and continued processing following negative stimuli in the autism spectrum disorder group as compared with the typically developing group included the salience network and the prefrontal dorsolateral cortex. These areas have been previously implicated in emotion dysregulation outside of autism spectrum disorder. Collectively, brain activity in the identified regions was associated with parent-reported emotion dysregulation in the autism spectrum disorder group. These results help to identify a potential process in the brain associated with emotion dysregulation in autism spectrum disorder. This information may be useful for the development of treatments to decrease emotion dysregulation in autism spectrum disorder.

scholarly journals Sex-dependent and sex-independent brain resting-state functional connectivity in children with autism spectrum disorder

2016 ◽  
Author(s):  
Xin Di ◽  
Bharat B Biswal
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Resting State ◽  
Data Exchange ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Imaging Data ◽  
Resting State Functional Connectivity ◽  
Main Effects

Background: Males are more likely to suffer from autism spectrum disorder (ASD) than females. As to whether females with ASD have similar brain alterations remain an open question. The current study aimed to examine sex-dependent as well as sex-independent alterations in resting-state functional connectivity in individuals with ASD compared with typically developing (TD) individuals. Method: Resting-state functional MRI data were acquired from the Autism Brain Imaging Data Exchange (ABIDE). Subjects between 6 to 20 years of age were included for analysis. After matching the intelligence quotient between groups for each dataset, and removing subjects due to excessive head motion, the resulting effective sample contained 28 females with ASD, 49 TD females, 129 males with ASD, and 141 TD males, with a two (diagnosis) by two (sex) design. Functional connectivity among 153 regions of interest (ROIs) comprising the whole brain was computed. Two by two analysis of variance was used to identify connectivity that showed diagnosis by sex interaction or main effects of diagnosis. Results: The main effects of diagnosis were found mainly between visual cortex and other brain regions, indicating sex-independent connectivity alterations. We also observed two connections whose connectivity showed diagnosis by sex interaction between the precuneus and medial cerebellum as well as the precunes and dorsal frontal cortex. While males with ASD showed higher connectivity in these connections compared with TD males, females with ASD had lower connectivity than their counterparts. Conclusions: Both sex-dependent and sex-independent functional connectivity alterations are present in ASD.

scholarly journals Reproducible functional connectivity alterations are associated with autism spectrum disorder

2018 ◽  
Author(s):  
Štefan Holiga ◽  
Joerg F. Hipp ◽  
Christopher H. Chatham ◽  
Pilar Garces ◽  
Will Spooren ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Large Scale ◽  
Clinical Symptoms ◽  
Brain Activity ◽  
Network Connectivity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Replication Procedure ◽  
Medication Status

AbstractDespite the high clinical burden little is known about pathophysiology underlying autism spectrum disorder (ASD). Recent resting state functional magnetic resonance imaging (rs-fMRI) studies have found atypical synchronization of brain activity in ASD. However, no consensus has been reached on the nature and clinical relevance of these alterations. Here we address these questions in the most comprehensive, large-scale effort to date comprising evaluation of four large ASD cohorts. We followed a strict exploration and replication procedure to identify core rs-fMRI functional connectivity (degree centrality) alterations associated with ASD as compared to typically developing (TD) controls (ASD: N=841, TD: N=984). We then tested for associations of these imaging phenotypes with clinical and demographic factors such as age, sex, medication status and clinical symptom severity. We find reproducible patterns of ASD-associated functional hyper- and hypo-connectivity with hypo-connectivity being primarily restricted to sensory-motor regions and hyper-connectivity hubs being predominately located in prefrontal and parietal cortices. We establish shifts in between-network connectivity from outside to within the identified regions as a key driver of these abnormalities. The magnitude of these alterations is linked to core ASD symptoms related to communication and social interaction and is not affected by age, sex or medication status. The identified brain functional alterations provide a reproducible pathophysiological phenotype underlying the diagnosis of ASD reconciling previous divergent findings. The large effect sizes in standardized cohorts and the link to clinical symptoms emphasize the importance of the identified imaging alterations as potential treatment and stratification biomarkers for ASD.

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