Local brain connectivity across development in autism spectrum disorder: A cross‐sectional investigation

Abstract

Lay Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with ASD. Here we investigated the development of local connectivity across three age cohorts of individuals with ASD and typically developing (TD) individuals. We find that in typical development, children exhibit high levels of local connectivity across the brain, while adolescents exhibit lower levels of local connectivity, similar to adult levels. On the other hand, children with ASD exhibit marginally lower local connectivity than TD children, and adolescents and adults with ASD exhibit levels of local connectivity comparable to that observed in neurotypical individuals. During all developmental stages -- childhood, adolescence, and adulthood -- individuals with ASD exhibited lower local connectivity in brain regions involved in sensory processing and higher local connectivity in brain regions involved in complex information processing. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. Thus we demonstrate that local connectivity is disrupted in autism across development, with the most pronounced differences occurring in childhood. Scientific Abstract There is a general consensus that autism spectrum disorder (ASD) is accompanied by alterations in brain connectivity. Much of the neuroimaging work has focused on assessing long-range connectivity disruptions in ASD. However, evidence from both animal models and postmortem examination of the human brain suggests that local connections may also be disrupted in individuals with the disorder. Here we investigated how regional homogeneity (ReHo), a measure of similarity of a voxel’s timeseries to its nearest neighbors, varies across age in individuals with ASD and typically developing (TD) individuals using a cross-sectional design. Resting-state fMRI data obtained from a publicly available database were analyzed to determine group differences in ReHo between three age cohorts: children, adolescents, and adults. In typical development, ReHo across the entire brain was higher in children than in adolescents and adults. In contrast, children with ASD exhibited marginally lower ReHo than TD children, while adolescents and adults with ASD exhibited similar levels of local connectivity as age-matched neurotypical individuals. During all developmental stages, individuals with ASD exhibited lower local connectivity in sensory processing brain regions and higher local connectivity in complex information processing regions. Further, higher local connectivity in ASD corresponded to more severe ASD symptomatology. These results demonstrate that local connectivity is disrupted in ASD across development, with the most pronounced differences occurring in ch...

Principles of connectivity among morphologically defined cell types in adult neocortex

“…The finding that the complex functional cortical architecture can be broken down into a small number of connectivity motifs may lead to breakthroughs in our understanding of cortical computation at the circuit level. Given that numerous neuropsychiatric and neurological diseases–such as autism spectrum disorders and epilepsy–may be associated with cell type-specific connectivity change in cortical microcircuits (18, 38, 39), such a detailed blueprint of cortical microcircuits could serve as an invaluable platform for screening and pinpointing specific circuit abnormalities in animal models of disease, thus providing a path to the development of comprehensive circuit-based, cell type-specific interventions that are otherwise not addressable with current treatments.…”

What can autism teach us about the role of sensorimotor systems in higher cognition? New clues from studies on language, action semantics, and abstract emotional concept processing

“…Functional connectivity, at least, seems to trend from hyperactivity in childhood towards normalization or hypoactivity in older age (Dajani & Uddin, 2016;Nomi & Uddin, 2015). Anatomically, the increased grey matter seen in primary motor cortex by Mahajan et al in autistic children is contradicted by a relationship between reduced grey matter and poorer finger-tapping in autistic adults (Duffield et al, 2013).…”

Short-range connections in the developmental connectome during typical and atypical brain maturation

“…Short-range FC, quantified as regional homogeneity (ReHo) (Zang et al, 2004), has also been defined as the connectivity of a given voxel to those of its nearest neighboring voxels, ranging from 6 voxels (Shukla et al, 2010) to 26 voxels (e.g. Anderson et al, 2014; Dajani and Uddin, 2016; Lopez-Larson et al, 2011). In addition, short-range FC has been defined as the connectivity within the same lobe (e.g.…”

“…In studies that incorporated ReHo analyses of fMRI data, there was an increase in short-range connectivity in default-mode network (DMN), visual, motor resting-state networks in individuals with ASD (6–17 years) (Washington et al, 2014) while other studies found more mixed results such as both hypo- and hyperconnectivity of short-range connections (e.g. Dajani and Uddin, 2016; Maximo et al 2013; Shukla et al, 2010). Specifically, individuals with ASD showed decreased short-range FC in superior parietal and prefrontal regions (Shukla et al, 2010), middle/posterior cingulate and medial frontal regions (Maximo et al, 2013), sensory processing brain regions (Dajani and Uddin, 2016) and increased short-range FC in lateral and medial temporal regions (Shukla et al, 2010), occipital and posterior temporal regions (Maximo et al, 2013) and complex information processing regions (Dajani and Uddin, 2016).…”

“…Dajani and Uddin, 2016; Maximo et al 2013; Shukla et al, 2010). Specifically, individuals with ASD showed decreased short-range FC in superior parietal and prefrontal regions (Shukla et al, 2010), middle/posterior cingulate and medial frontal regions (Maximo et al, 2013), sensory processing brain regions (Dajani and Uddin, 2016) and increased short-range FC in lateral and medial temporal regions (Shukla et al, 2010), occipital and posterior temporal regions (Maximo et al, 2013) and complex information processing regions (Dajani and Uddin, 2016). In general, short-range “hyperconnectivity” was suggested for children with ASD.…”