Cited by 110Functional Brain Connectivity StudiesAutism Spectrum Disorder ResearchGenetics and Neurodevelopmental Disorders

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Atypical Flexibility in Dynamic Functional Connectivity Quantifies the Severity in Autism Spectrum Disorder

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Harlalka, Vatika, Bapi, Raju S., Vinod, P. K., Roy, Dipanjan·2019·Frontiers in Human Neuroscience

Published version of a preprint

Abstract

Resting-state functional connectivity (FC) analyses have shown atypical connectivity in autism spectrum disorder (ASD) as compared to typically developing (TD). However, this view emerges from investigating static FC overlooking the whole brain transient connectivity patterns. In our study, we investigated how age and disease influence the dynamic changes in functional connectivity of TD and ASD. We used resting-state functional magnetic resonance imaging (rs-fMRI) data stratified into three cohorts: children (7-11 years), adolescents (12-17 years), and adults (18+ years) for the analysis. The dynamic variability in the connection strength and the modular organization in terms of measures such as flexiblity, cohesion strength, and disjointness were explored for each subject to characterize the differences between ASD and TD. In ASD, we observed significantly higher inter-subject dynamic variability in connection strength as compared to TD. This hyper-variability relates to the symptom severity in ASD. We also found that whole-brain flexibility correlates with static modularity only in TD. Further, we observed a core-periphery organization in the resting-state, with Sensorimotor and Visual regions in the rigid core; and DMN and attention areas in the flexible periphery. TD also develops a more cohesive organization of sensorimotor areas. However, in ASD we found a strong positive correlation of symptom severity with flexibility of rigid areas and with disjointness of sensorimotor areas. The regions of the brain showing high predictive power of symptom severity were distributed across the cortex, with stronger bearings in the frontal, motor, and occipital cortices. Our study demonstrates that the dynamic framework best characterizes the variability in ASD.

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Crossref · 10.3389/fnhum.2019.00006

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Figures

Figure 1 Pipeline of the analysis: resting-state fMRI data used to analyze varying temporal dynamics in ASD and TD.
Figure 1 Pipeline of the analysis: resting-state fMRI data used to analyze varying temporal dynamics in ASD and TD.CC BY · PubMed Central
Figure 2 Hypervariant ASD connections in the dFCvar matrix. Majority of connections in children and adults are long-range while adolescents are seen to have majority short-range connections.
Figure 2 Hypervariant ASD connections in the dFCvar matrix. Majority of connections in children and adults are long-range while adolescents are seen to have majority short-range connections.CC BY · PubMed Central
Figure 3 Plot of regional flexibility values for TD and ASD groups where the data is stratified into three groups: Children, adolescents, and adults.
Figure 3 Plot of regional flexibility values for TD and ASD groups where the data is stratified into three groups: Children, adolescents, and adults.CC BY · PubMed Central
Figure 4 (A) Correlation between whole-brain mean flexibility score and modularity. A significant weak negative correlation is observed only in TD group. (B) Areas showing a significant negative correlation between local flexibility score and modularity in TD adults. None of these are significant in the ASD group.
Figure 4 (A) Correlation between whole-brain mean flexibility score and modularity. A significant weak negative correlation is observed only in TD group. (B) Areas showing a significant negative correlation between local flexibility score and modularity in TD adults. None of these are significant in the ASD group.CC BY · PubMed Central
Figure 5 (A) correlation between ADOS total score and modularity (B) correlation between ADOS score and visual/auditory system flexibility (p < 0.05).
Figure 5 (A) correlation between ADOS total score and modularity (B) correlation between ADOS score and visual/auditory system flexibility (p < 0.05).CC BY · PubMed Central
Figure 6 Brain plot of areas showing significant effect of age and disease on (A) flexibility, (B) cohesion strength, and (C) disjointness.
Figure 6 Brain plot of areas showing significant effect of age and disease on (A) flexibility, (B) cohesion strength, and (C) disjointness.CC BY · PubMed Central

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  1. Harlalka, Atypical flexibility in dynamic functional connectivity quantifies the severity in autism spectrum disorder, bioXriv, 10.1101/387886 · DOI

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Metadata

Authors
Harlalka, V., Bapi, R. S., Vinod, P. K., & Roy, D.
Affiliations
  • International Institute of Information Technology, Hyderabad (IN)
  • University of Hyderabad (IN)
  • National Brain Research Centre (IN)
Corresponding author
  • Vinod, P. K.
  • Roy, Dipanjan
Venue
Frontiers in Human Neuroscience
Published
2019-02-01
Volume
13
Pages
6-6
ISSN
1662-5161 (ISSN-L)
OpenAlex
W2952965410
Cited by
110
References
51
Citations by year
2026: 7 · 2025: 18 · 2024: 18 · 2023: 14 · 2022: 13 · 2021: 20 · 2020: 14 · 2019: 5
FWCI
7.56
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Human Neuroscience (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Department of Science and Technology, Ministry of Science and Technology, India (SR/CSRI/21/2016)
  • Science and Engineering Research Board (ECR/2016/000488)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
autism spectrum disorder, dynamic functional connectivity, network flexibility, symptom severity, brain modularity, dynamic variability, resting-state functional connectivity, sensorimotor regions, default mode network, age differences

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