Dataset Information

Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

ABSTRACT: Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize these confounds and examine primary vulnerability mechanisms, we need to investigate very early brain development. Here, we tested the hypothesis that brain functional connectivity is altered in neonates who are vulnerable to this condition due to a family history of ASD. We acquired high temporal resolution multiband resting state functional magnetic resonance imaging (fMRI) in newborn infants with and without a first-degree relative with ASD. Differences in local functional connectivity were quantified using regional homogeneity (ReHo) analysis and long-range connectivity was assessed using distance correlation analysis. Neonates who have a first-degree relative with ASD had significantly higher ReHo within multiple resting state networks in comparison to age matched controls; there were no differences in long range connectivity. Atypical local functional activity may constitute a biomarker of vulnerability, that might precede disruptions in long range connectivity reported in older individuals diagnosed with ASD.

SUBMITTER: Ciarrusta J

PROVIDER: S-EPMC7203016 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

Ciarrusta Judit J Dimitrova Ralica R Batalle Dafnis D O'Muircheartaigh Jonathan J Cordero-Grande Lucilio L Price Anthony A Hughes Emer E Kangas Johanna J Perry Emily E Javed Ayesha A Demilew Jill J Hajnal Joseph J Edwards Anthony David AD Murphy Declan D Arichi Tomoki T McAlonan Grainne G

Translational psychiatry 20200506 1

Studies in animal models of autism spectrum disorders (ASD) suggest atypical early neural activity is a core vulnerability mechanism which alters functional connectivity and predisposes to dysmaturation of neural circuits. However, underlying biological changes associated to ASD in humans remain unclear. Results from functional connectivity studies of individuals diagnosed with ASD are highly heterogeneous, in part because of complex life-long secondary and/or compensatory events. To minimize th ...[more]

PMID: 32376820

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Project description:Autism spectrum disorders (ASDs) are a group of heterogeneous neurodevelopmental disorders that are highly heritable and are associated with impaired dynamic functional connectivity (DFC). However, the molecular mechanisms behind DFC alterations remain largely unknown. Eighty-eight patients with ASDs and 87 demographically matched typical controls (TCs) from the Autism Brain Imaging Data Exchange II database were included in this study. A seed-based sliding window approach was then performed to investigate the DFC changes in each of the 29 seeds in 10 classic resting-state functional networks and the whole brain. Subsequently, the relationships between DFC alterations in patients with ASDs and their symptom severity were assessed. Finally, transcription-neuroimaging association analyses were conducted to explore the molecular mechanisms of DFC disruptions in patients with ASDs. Compared with TCs, patients with ASDs showed significantly increased DFC between the right dorsolateral prefrontal cortex (DLPFC) and left fusiform/lingual gyrus, between the DLPFC and the superior temporal gyrus, between the right frontal eye field (FEF) and left middle frontal gyrus, between the FEF and the right angular gyrus, and between the left intraparietal sulcus and the right middle temporal gyrus. Moreover, significant relationships between DFC alterations and symptom severity were observed. Furthermore, the genes associated with DFC changes in ASDs were identified by performing gene-wise across-sample spatial correlation analysis between gene expression extracted from six donors' brain of the Allen Human Brain Atlas and case-control DFC difference. In enrichment analysis, these genes were enriched for processes associated with synaptic signaling and voltage-gated ion channels and calcium pathways; also, these genes were highly expressed in autistic disorder, chronic alcoholic intoxication and several disorders related to depression. These results not only demonstrated higher DFC in patients with ASDs but also provided novel insight into the molecular mechanisms underlying these alterations.

Dataset Information

Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

Publications

Emerging functional connectivity differences in newborn infants vulnerable to autism spectrum disorders.

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