Brain Connectomics In Autism Spectrum Disorder Based On Magnetic Resonance Imaging

Autism spectrum disorder(ASD)is a heterogeneous neurodevelopmental disorder manifested as behavioral difficulties in social interaction and communication,and repetitive and stereotypic behavioral patterns.Clinical characteristics among individuals with ASD can vary widely,such as variable degrees of communication ability,motor deficits,intellectual impairments,and multiple comorbidities.Prominent social impairments are common symptoms in individuals with ASD.Despite genetic and neuroimaging studies of ASD have been growing rapidly,its pathophysiological mechanism remains unclear,and there is no effective drug or treatment strategy for ASD.Nevertheless,genetic,electrophysiological and neuroimaging studies have demonstrated that abnormal patterns of neural connections in the brain may be the neurobiological basis of ASD.In recent years,magnetic resonance imaging technology,as a safe and non-invasive neuroimaging technology,has provided an important way for us to explore the structure and function of the healthy developing brain and the brain under the condition of disease.The development of brain network analysis methods based on magnetic resonance imaging has shaped our understanding of the brain network organization of neuropsychiatric diseases.Therefore,the current study will use the brain network analyses approaches,focused on the developmental changes and connectivity dynamics of the brain networks,to investigate the brain structural and functional networks in ASD,aimed at exploring the neuropathological mechanisms underlying ASD.The main research contents include the following five parts.1.Resting-state amplitude of low-frequency fluctuations(ALFF)analysis was used to explore the developmental trajectory of spontaneous brain activity in individuals with ASD from childhood to adulthood.Compared with typically developing control group,individuals with ASD showed decreased ALFF in the right precuneus and left middle occipital gyrus in all developmental stages.We also observed abnormal developmental changes of ALFF in the medial prefrontal cortex in ASD.In addition,abnormal local spontaneous brain activity in individuals with ASD was related to the symptom severity in the social domain.The findings indicate aberrant developmental patterns of spontaneous brain activity associated with social deficits in ASD and highlight the crucial role of the default mode network in the development of ASD.2.The indirect functional connectivity analysis based on shortest path length was used to explore the indirect functional connectivity abnormalities in adults with ASD from multiple spatial scales.Compared with control group,adults with ASD showed higher indirect functional connectivity percentages at the whole brain,hemispheres,networks and nodes levels,similar to previous reports in adolescents with ASD.Differences were primarily in weaker,longer-distance edges in the majority between networks.These findings suggest enhanced indirect functional connections in ASD is persistent from adolescence to adulthood and is indicative of reduced functional network integration.3.Dynamic functional connectivity approach seeded at the right anterior insula was utilized to explore the dynamic functional connectivity states of this region in ASD.Compared with control group,individuals with ASD showed significantly reduced connectivity in the default mode network regions,including the ventral medial prefrontal cortex and posterior cingulate cortex.States in which ASD showed decreased connectivity between the right anterior insula and these regions were those more relevant to socio-cognitive processing.From a dynamic perspective,these findings demonstrate partially impaired resting-state functional connectivity patterns between the right anterior insula and default mode network across states in ASD,and provide novel insights into the neural mechanisms underlying social impairments in individuals with ASD.4.Dynamic functional connectivity density analysis was used to explore the temporal variability of intra-and inter-hemispheric functional integration in children with ASD by dividing the whole brain functional connection patterns into intra-and inter-hemispheric connections.Compared with typically developing children,children with ASD showed higher intra-and inter-hemispheric dynamic functional connectivity density variability in the anterior cingulate cortex/medial prefrontal cortex and lower variability in the fusiform gyrus/inferior temporal gyrus.Autistic children additionally showed decreased intra-hemispheric dynamic functional connectivity density variability in the sensorimotor regions.Moreover,aberrant temporal variability of the inter-hemispheric dynamic functional connectivity density predicted the severity of social communication impairments in autistic children.These findings demonstrate altered temporal dynamics of the intra-and inter-hemispheric functional connectivity in brain regions incorporating social brain network of ASD,and highlight the potential role of abnormal inter-hemispheric communication dynamics in neural substrates underlying impaired social processing in ASD.5.Voxel-based morphometry analysis and causal structural covariance network analysis were used to explore the structural development and causal structural covariance networks in autistic brain during early childhood.Compared with control group,abnormal developmental trajectory of gray matter was observed in the cerebellum/vermis and fusiform face area in children with ASD.Autistic children also displayed different causal changes of the structural brain network seeded at the fusiform face area,particularly in social brain regions.These findings indicate aberrant neurodevelopment of the fusiform face area in the autistic brain during early childhood,and highlight altered developmental influences of this region on the social brain network.