Reduced Inter-hemispheric Resting State Functional Connectivity and Its Association With Social Deficits in Autism

Abstract

Autism spectrum disorder (ASD) is an early onset developmental disorder which persists throughout life and is increasing in prevalence over the last few decades. Given its early onset and variable cognitive and emotional functional impairments, it is generally challenging to assess ASD individuals using task-based behavioral and functional MRI paradigms. Consequently, resting state functional MRI (rs-fMRI) has become a key approach for examining ASD-associated neural alterations and revealed functional alterations in large-scale brain networks relative to typically developing (TD) individuals, particularly those involved in social-cognitive and affective processes. Recent progress suggests that alterations in inter-hemispheric resting state functional connectivity (rsFC) between regions in the 2 brain hemispheres, particularly homotopic ones, may be of great importance. Here we have reviewed neuroimaging studies examining inter-hemispheric rsFC abnormities in ASD and its associations with symptom severity. As an index of inter-hemispheric functional connectivity, we have additionally reviewed previous studies on corpus callosum (CC) volumetric and fiber changes in ASD. There are converging findings on reduced inter-hemispheric (including homotopic) rsFC in large-scale brain networks particularly in posterior hubs of the default mode network, reduced volumes in the anterior and posterior CC, and on decreased FA and increased MD or RD across CC subregions. Associations between the strength of inter-hemispheric rsFC and social impairments in ASD together with their classification performance in distinguishing ASD subjects from TD controls across ages suggest that the strength of inter-hemispheric rsFC may be a more promising biomarker for assisting in ASD diagnosis than abnormalities in either brain wide rsFC or brain structure.

Experience-dependent weakening of callosal synaptic connections in the absence of postsynaptic FMRP

“…Reduced interhemispheric connectivity, observed both structurally and functionally, is a hallmark of ASD in humans and correlated with symptoms (Dimond et al, 2019;Holiga et al, 2019;Li et al, 2019;O'Reilly et al, 2017;Rane et al, 2015;Yao et al, 2021). However, little is known of the cellular, synaptic, and molecular mechanisms by which this occurs in ASD and any direct role of ASD-risk genes.…”

“…Disrupted structural and functional brain connectivity has been widely observed in patients with autism spectrum disorder (ASD) (Dimond et al, 2019;Holiga et al, 2019;Rane et al, 2015). A common finding in ASD is reduced corpus callosum integrity and interhemispheric functional connectivity, the latter of which correlates with autistic symptoms (Li et al, 2019;O'Reilly et al, 2017;Yao et al, 2021).…”

Experience-dependent weakening of callosal synaptic connections in the absence of postsynaptic FMRP

“…Reduced interhemispheric connectivity, observed both structurally and functionally, is a hallmark of ASD in humans and correlated with symptoms (Dimond et al ., 2019; Holiga et al ., 2019; Li et al ., 2019; O’Reilly et al ., 2017; Rane et al ., 2015; Yao et al ., 2021). However, little is known of the cellular, synaptic, and molecular mechanisms by which this occurs in ASD and any direct role of ASD-risk genes.…”

“…Disrupted structural and functional brain connectivity has been widely observed in patients with autism spectrum disorder (ASD) (Dimond et al, 2019; Holiga et al, 2019; Rane et al, 2015). A common finding in ASD is reduced corpus callosum integrity and interhemispheric functional connectivity, the latter of which correlates with autistic symptoms (Li et al, 2019; O’Reilly et al, 2017; Yao et al, 2021). The corpus callosum connects bilateral hemispheres and functions to synchronize cortical circuits necessary for sensory-motor processing, attention, perception and higher cognitive functions (Schulte and Müller-Oehring, 2010).…”

Non-Oscillatory Connectivity Approach for Classification of Autism Spectrum Disorder Subtypes Using Resting-State fMRI

“…Several studies have revealed that brain connectivity can be a substantial biomarker for ASD classification. It can reveal patterns that distinguish ASD from healthy controls [14]- [16]. Resting-state functional Magnetic Resonance Imaging (rs-fMRI) is a powerful method to examine brain connectivity patterns.…”