scholarly journals A normative modelling approach reveals age-atypical cortical thickness in a subgroup of males with autism spectrum disorder

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Richard A. I. Bethlehem ◽  
Jakob Seidlitz ◽  
Rafael Romero-Garcia ◽  
Stavros Trakoshis ◽  
Guillaume Dumas ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Autism Spectrum ◽  
Case Control ◽  
Small Subset ◽  
Typically Developing ◽  
Average Case ◽  
Age Related ◽  
Small Subgroup ◽  
Individualized Approach ◽  
Age Range

AbstractUnderstanding heterogeneity is an important goal on the path to precision medicine for autism spectrum disorders (ASD). We examined how cortical thickness (CT) in ASD can be parameterized as an individualized metric of atypicality relative to typically-developing (TD) age-related norms. Across a large sample (n = 870 per group) and wide age range (5–40 years), we applied normative modelling resulting in individualized whole-brain maps of age-related CT atypicality in ASD and isolating a small subgroup with highly age-atypical CT. Age-normed CT scores also highlights on-average differentiation, and associations with behavioural symptomatology that is separate from insights gleaned from traditional case-control approaches. This work showcases an individualized approach for understanding ASD heterogeneity that could potentially further prioritize work on a subset of individuals with cortical pathophysiology represented in age-related CT atypicality. Only a small subset of ASD individuals are actually highly atypical relative to age-norms. driving small on-average case-control differences.

scholarly journals Normative age modelling of cortical thickness in autistic males

2018 ◽  
Author(s):  
Richard A. I Bethlehem ◽  
Jakob Seidlitz ◽  
Rafael Romero-Garcia ◽  
Guillaume Dumas ◽  
Michael V. Lombardo
Keyword(s):  
Cortical Thickness ◽  
Structural Features ◽  
Brain Regions ◽  
Autism Spectrum ◽  
Important Variable ◽  
Future Research ◽  
Small Subset ◽  
Age Related ◽  
Individualized Approach ◽  
Underlying Mechanisms

AbstractUnderstanding heterogeneity in neural phenotypes is an important goal on the path to precision medicine for autism spectrum disorders (ASD). Age is a critically important variable in normal structural brain development and examining structural features with respect to age-related norms could help to explain ASD heterogeneity in neural phenotypes. Here we examined how cortical thickness (CT) in ASD can be parameterized as an individualized metric of deviance relative to typically-developing (TD) age-related norms. Across a large sample (n=870 per group) and wide age range (5-40 years), we applied a normative modelling approach that provides individualized whole-brain maps of age-related CT deviance in ASD. This approach isolates a subgroup of ASD individuals with highly age-deviant CT. The median prevalence of this ASD subgroup across all brain regions is 7.6%, and can reach as high as 10% for some brain regions. This work showcases an individualized approach for understanding ASD heterogeneity that could potentially further prioritize work on a subset of individuals with significant cortical pathophysiology represented in age-related CT deviance. Rather than cortical thickness pathology being a widespread characteristic of most ASD patients, only a small subset of ASD individuals are actually highly deviant relative to age-norms. These individuals drive small on-average effects from case-control comparisons. Rather than sticking to the diagnostic label of autism, future research should pivot to focus on isolating subsets of autism patients with highly deviant phenotypes and better understand the underlying mechanisms that drive those phenotypes.

scholarly journals Gray matter covariations and core symptoms of autism: the EU-AIMS Longitudinal European Autism Project

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting Mei ◽  
◽  
Alberto Llera ◽  
Dorothea L. Floris ◽  
Natalie J. Forde ◽  
...  
Keyword(s):  
Gray Matter ◽  
Inferior Frontal Gyrus ◽  
Autism Spectrum ◽  
Case Control ◽  
Precentral Gyrus ◽  
Typically Developing ◽  
Autism Symptoms ◽  
Independent Components ◽  
Autism Group ◽  
Occipital Lobes

Abstract Background Voxel-based morphometry (VBM) studies in autism spectrum disorder (autism) have yielded diverging results. This might partly be attributed to structural alterations being associating with the combined influence of several regions rather than with a single region. Further, these structural covariation differences may relate to continuous measures of autism rather than with categorical case–control contrasts. The current study aimed to identify structural covariation alterations in autism, and assessed canonical correlations between brain covariation patterns and core autism symptoms. Methods We studied 347 individuals with autism and 252 typically developing individuals, aged between 6 and 30 years, who have been deeply phenotyped in the Longitudinal European Autism Project. All participants’ VBM maps were decomposed into spatially independent components using independent component analysis. A generalized linear model (GLM) was used to examine case–control differences. Next, canonical correlation analysis (CCA) was performed to separately explore the integrated effects between all the brain sources of gray matter variation and two sets of core autism symptoms. Results GLM analyses showed significant case–control differences for two independent components. The first component was primarily associated with decreased density of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and increased density of caudate nucleus in the autism group relative to typically developing individuals. The second component was related to decreased densities of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to typically developing individuals. The CCA results showed significant correlations between components that involved variation of thalamus, putamen, precentral gyrus, frontal, parietal, and occipital lobes, and the cerebellum, and repetitive, rigid and stereotyped behaviors and abnormal sensory behaviors in autism individuals. Limitations Only 55.9% of the participants with autism had complete questionnaire data on continuous parent-reported symptom measures. Conclusions Covaried areas associated with autism diagnosis and/or symptoms are scattered across the whole brain and include the limbic system, basal ganglia, thalamus, cerebellum, precentral gyrus, and parts of the frontal, parietal, and occipital lobes. Some of these areas potentially subserve social-communicative behavior, whereas others may underpin sensory processing and integration, and motor behavior.

scholarly journals Atypical age-related changes in cortical thickness in autism spectrum disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Adonay S. Nunes ◽  
Vasily A. Vakorin ◽  
Nataliia Kozhemiako ◽  
Nicholas Peatfield ◽  
Urs Ribary ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Cortical Thickness ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Age Related ◽  
Age Related Changes

Children's referential understanding of novel words and parent labeling behaviors: similarities across children with and without autism spectrum disorders

2012 ◽  
Vol 40 (5) ◽  
pp. 971-1002 ◽  
Author(s):  
HANADY BANI HANI ◽  
ANA MARIA GONZALEZ-BARRERO ◽  
APARNA S. NADIG
Keyword(s):  
Autism Spectrum Disorder ◽  
Word Learning ◽  
Autism Spectrum ◽  
Social Cues ◽  
Language Ability ◽  
Typically Developing ◽  
Typically Developing Children ◽  
Children With Asd ◽  
Spectrum Disorders ◽  
Age Range

ABSTRACTThis study examined two facets of the use of social cues for early word learning in parent–child dyads, where children had an Autism Spectrum Disorder (ASD) or were typically developing. In Experiment 1, we investigated word learning and generalization by children with ASD (age range: 3;01–6;02) and typically developing children (age range: 1;02–4;09) who were matched on language ability. In Experiment 2, we examined verbal and non-verbal parental labeling behaviors. First, we found that both groups were similarly able to learn a novel label using social cues alone, and to generalize this label to other representations of the object. Children who utilized social cues for word learning had higher language levels. Second, we found that parental cues used to introduce object labels were strikingly similar across groups. Moreover, parents in both groups adapted labeling behavior to their child's language level, though this surfaced in different ways across groups.

scholarly journals Comparison of the Metabolic Profiles in the Plasma and Urine Samples Between Autistic and Typically Developing Boys: A Preliminary Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Xin-Jie Xu ◽  
Xiao-E Cai ◽  
Fan-Chao Meng ◽  
Tian-Jia Song ◽  
Xiao-Xi Wang ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Urine Samples ◽  
Metabolic Profiles ◽  
Plasma Samples ◽  
Typically Developing ◽  
Children With Asd ◽  
Full Picture ◽  
Plasma And Urine Samples ◽  
Healthy Control ◽  
Age Range

Background: Autism spectrum disorder (ASD) is defined as a pervasive developmental disorder which is caused by genetic and environmental risk factors. Besides the core behavioral symptoms, accumulated results indicate children with ASD also share some metabolic abnormalities.Objectives: To analyze the comprehensive metabolic profiles in both of the first-morning urine and plasma samples collected from the same cohort of autistic boys.Methods: In this study, 30 autistic boys and 30 tightly matched healthy control (HC) boys (age range: 2.4~6.7 years) were recruited. First-morning urine and plasma samples were collected and the liquid chromatography–mass spectrometry (LC-MS) was applied to obtain the untargeted metabolic profiles. The acquired data were processed by multivariate analysis and the screened metabolites were grouped by metabolic pathway.Results: Different discriminating metabolites were found in plasma and urine samples. Notably, taurine and catechol levels were decreased in urine but increased in plasma in the same cohort of ASD children. Enriched pathway analysis revealed that perturbations in taurine and hypotaurine metabolism, phenylalanine metabolism, and arginine and proline metabolism could be found in both of the plasma and urine samples.Conclusion: These preliminary results suggest that a series of common metabolic perturbations exist in children with ASD, and confirmed the importance to have a comprehensive analysis of the metabolites in different biological samples to reveal the full picture of the complex metabolic patterns associated with ASD. Further targeted analyses are needed to validate these results in a larger cohort.

Atypicalities in the developmental trajectory of cortico-striatal functional connectivity in autism spectrum disorder

Autism ◽  
2021 ◽  
pp. 136236132110419
Author(s):  
Zeng-Hui Ma ◽  
Bin Lu ◽  
Xue Li ◽  
Ting Mei ◽  
Yan-Qing Guo ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Brain Connectivity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Typically Developing ◽  
Sensorimotor Network ◽  
Intrinsic Functional Connectivity ◽  
Age Related ◽  
Atypical Development

The last decades of neuroimaging research has revealed atypical development of intrinsic functional connectivity within and between large-scale cortical networks in autism spectrum disorder, but much remains unknown about cortico-subcortical developmental connectivity atypicalities. This study examined cortico-striatal developmental intrinsic functional connectivity changes in autism spectrum disorder and explored how those changes may be correlated with autistic traits. We studied 49 individuals with autism spectrum disorder and 52 age-, sex-, and head motion–matched typically developing individuals (5–30 years old (14.0 ± 5.6)) using resting-state functional magnetic resonance imaging. Age-related differences in striatal intrinsic functional connectivity were compared between the two groups by adopting functional network–based parcellations of the striatum as seeds. Relative to typically developing individuals, autism spectrum disorder individuals showed atypical developmental changes in intrinsic functional connectivities between almost all striatal networks and sensorimotor network/default network, with connectivity increasing with age in the autism spectrum disorder group and decreasing or constant in typically developing individuals. Age-related degree centrality and voxel-mirrored homotopic connectivity atypicalities in sensorimotor network/default network and voxel-mirrored homotopic connectivity disruptions in striatal regions were also observed in autism spectrum disorder. Significant correlations were found between cortico-striatal intrinsic functional connectivities and Autism Diagnostic Observation Schedule communication/repetitive and restricted-behavior subscores in autism spectrum disorder. Our results indicated that developmental atypicalities of cortico-striatal intrinsic functional connectivities might contribute to the neuropathology of autism spectrum disorder. Lay abstract Autism spectrum disorder has long been conceptualized as a disorder of “atypical development of functional brain connectivity (which refers to correlations in activity levels of distant brain regions).” However, most of the research has focused on the connectivity between cortical regions, and much remains unknown about the developmental changes of functional connectivity between subcortical and cortical areas in autism spectrum disorder. We used the technique of resting-state functional magnetic resonance imaging to explore the developmental characteristics of intrinsic functional connectivity (functional brain connectivity when people are asked not to do anything) between subcortical and cortical regions in individuals with and without autism spectrum disorder aged 6–30 years. We focused on one important subcortical structure called striatum, which has roles in motor, cognitive, and affective processes. We found that cortico-striatal intrinsic functional connectivities showed opposite developmental trajectories in autism spectrum disorder and typically developing individuals, with connectivity increasing with age in autism spectrum disorder and decreasing or constant in typically developing individuals. We also found significant negative behavioral correlations between those atypical cortico-striatal intrinsic functional connectivities and autistic symptoms, such as social-communication deficits, and restricted/repetitive behaviors and interests. Taken together, this work highlights that the atypical development of cortico-subcortical functional connectivity might be largely involved in the neuropathological mechanisms of autism spectrum disorder.

scholarly journals Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

2021 ◽  
Author(s):  
Matthias Kirschner ◽  
Casey Paquola ◽  
Budhachandra Khundrakpam ◽  
Uku Vainik ◽  
Neha Bhutani ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
Neurodevelopmental Disorder ◽  
Disease Onset ◽  
Case Control ◽  
Imaging Genetics ◽  
Typically Developing ◽  
Typically Developing Children ◽  
Polygenic Risk ◽  
Cortical Organization ◽  
Risk Scoring

Schizophrenia is widely recognized as a neurodevelopmental disorder, but determining neurodevelopmental features of schizophrenia requires a departure from classic case-control designs. Polygenic risk scoring for schizophrenia (PRS-SCZ) enables investigation of the influence of genetic risk for schizophrenia on cortical anatomy during neurodevelopment and prior to disease onset. PRS-SCZ and cortical morphometry were assessed in typically developing children (3-21 years) using T1-weighted MRI and whole genome genotyping (n=390) from the Pediatric Imaging, Neurocognition and Genetics (PING) cohort. Then, we sought to contextualise the findings using (i) age-matched transcriptomics, (ii) gradients of cortical differentiation and (iii) case-control differences of major psychiatric disorders. Higher PRS-SCZ was associated with greater cortical thickness in typically developing children, while surface area and cortical volume showed only subtle associations. Greater cortical thickness was most prominent in areas with heightened gene expression for dendrites and synapses. The pattern of PRS-SCZ associations with cortical thickness reflected functional specialisation in the cortex and was spatially related to cortical abnormalities of patient populations of schizophrenia, bipolar disorder, and major depression. Finally, age interaction models indicated PRS-SCZ effects on cortical thickness were most pronounced between ages 3 and 6, suggesting an influence of PRS-SCZ on cortical maturation early in life. Integrating imaging-genetics with multi-scale mapping of cortical organization, our work contributes to an emerging understanding of how risk for schizophrenia and related disorders manifest in early life.

scholarly journals Connectivity alterations in autism reflect functional idiosyncrasy

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Oualid Benkarim ◽  
Casey Paquola ◽  
Bo-yong Park ◽  
Seok-Jun Hong ◽  
Jessica Royer ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Autism Spectrum ◽  
Case Control ◽  
Individual Variability ◽  
Typically Developing ◽  
Attention Networks ◽  
Novel Approach ◽  
Variable Nature ◽  
Research Findings ◽  
Novel Biomarkers

AbstractAutism spectrum disorder (ASD) is commonly understood as an alteration of brain networks, yet case-control analyses against typically-developing controls (TD) have yielded inconsistent results. Here, we devised a novel approach to profile the inter-individual variability in functional network organization and tested whether such idiosyncrasy contributes to connectivity alterations in ASD. Studying a multi-centric dataset with 157 ASD and 172 TD, we obtained robust evidence for increased idiosyncrasy in ASD relative to TD in default mode, somatomotor and attention networks, but also reduced idiosyncrasy in lateral temporal cortices. Idiosyncrasy increased with age and significantly correlated with symptom severity in ASD. Furthermore, while patterns of functional idiosyncrasy were not correlated with ASD-related cortical thickness alterations, they co-localized with the expression patterns of ASD risk genes. Notably, we could demonstrate that patterns of atypical idiosyncrasy in ASD closely overlapped with connectivity alterations that are measurable with conventional case-control designs and may, thus, be a principal driver of inconsistency in the autism connectomics literature. These findings support important interactions between inter-individual heterogeneity in autism and functional signatures. Our findings provide novel biomarkers to study atypical brain development and may consolidate prior research findings on the variable nature of connectome level anomalies in autism.

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