Shared and Distinct Intrinsic Functional Network Centrality in Autism and Attention-Deficit/Hyperactivity Disorder

Abstract

Background Individuals with autism spectrum disorders (ASD) often exhibit symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Across both disorders, observations of distributed functional abnormalities suggest aberrant large-scale brain network connectivity. Yet, common and distinct network correlates of ASD and ADHD remain unidentified. Here, we aimed to examine patterns of dysconnection in school-age children with ASD, ADHD and typically developing children (TDC) who completed a resting state fMRI (R-fMRI) scan. Methods We measured voxel-wise network centrality, functional connectivity metrics indexing local (degree centrality; DC) and global (eigenvector centrality; EC) functional relationships across the entire brain connectome, in R-fMRI data from 56 children with ASD, 45 children with ADHD and 50 TDC. A one-way ANCOVA, with group as fixed factor (whole-brain corrected), was followed by post-hoc pair-wise comparisons. Results Cortical and subcortical areas exhibited centrality abnormalities; some common to both ADHD and ASD, such as in precuneus. Others were disorder-specific and included ADHD-related increases in DC in right striatum/pallidum, in contrast with ASD-related increases in bilateral temporolimbic areas. Secondary analyses differentiating children with ASD into those with or without ADHD-like comorbidity (ASD+ and ASD−, respectively) revealed that the ASD+ group shared ADHD-specific abnormalities in basal ganglia. By contrast, centrality increases in temporolimbic areas characterized children with ASD regardless of ADHD-like comorbidity. At the cluster level eignevector centrality group patterns were similar to DC. Conclusions ADHD and ASD are neurodevelopmental disorders with distinct and overlapping clinical presentations. This work provides evidence for both shared and distinct underlying mechanisms at the large-scale network level.

A Diffusion Tensor Imaging Study in Children With ADHD, Autism Spectrum Disorder, OCD, and Matched Controls: Distinct and Non-Distinct White Matter Disruption and Dimensional Brain-Behavior Relationships

“…It is also consistent with evidence of enrichment for rare genetic variants that encode cell-adhesion and neuronal synapse scaffolding in both conditions (7). Although we did not find disease-specific fractional anisotropy alterations in ASD or ADHD in the present sample, two previous studies found differences between these disorders in terms of network topology (35,36). In contrast to the absence of significant differences between ADHD and ASD, we found differences in white matter structure in both the ASD group and the ADHD group, compared with the OCD group.…”

“…However, no fractional anisotropy differences were found in the ADHD group compared with the ASD group, and fractional anisotropy differences did not extend beyond the splenium in the OCD group compared with the control group. Our results in ADHD and ASD are consistent with two recent imaging studies that directly compared connectivity patterns in children and adolescents with ASD or ADHD and controls (35,36). These studies indicated that both ASD and ADHD are disorders involving large-scale connectivity impairments based on the diffuse nature of structural and functional connectivity differences found across the brain in each NDD compared with controls.…”

Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults

“…The DMN as the hallmark of resting state has been found altered in many neurological and psychiatric disorders, such as, among all, schizophrenia (Stephan et al, 2009;Woodward et al, 2011;Guo et al, 2014), mild cognitive impairment (Sinanaj et al, 2015) and ADHD (Sonuga-Barke and Castellanos, 2007;Castellanos et al, 2008;Fair et al, 2010;Tomasi and Volkow, 2012;Di Martino et al, 2013). Based on previous reports of abnormal laterality of the ADHD brain (Dennis and Thompson, 2013;Shang et al, 2013;Cao et al, 2014;Hale et al, 2014Hale et al, , 2015Keune et al, 2015;Silk et al, 2015), we could postulate that the asymmetric expression of neurodevelopmental genes might be at the origin of structural and functional changes in this disorder.…”

“…From a neuroimaging viewpoint, compelling evidence points to rather large-scale abnormalities in network organization in ADHD (Sergeant et al, 2006;Konrad and Eickhoff, 2010;Cao et al, 2013), affecting both functional (Cocchi et al, 2012;Colby et al, 2012;Fair et al, 2012;Tomasi and Volkow, 2012;Cao et al, 2013;Di Martino et al, 2013) and structural (Cao et al, 2013;Hong et al, 2014) connectivity. Moreover, an abnormal hemispheric asymmetry of brain structure and function was also consistently reported in ADHD (Dennis and Thompson, 2013;Shang et al, 2013;Cao et al, 2014;Hale et al, 2014Hale et al, , 2015Keune et al, 2015;Silk et al, 2015), suggesting a possible neurodevelopmental scenario for this disorder.…”

“…In terms of neural networks, whole brain resting-state functional imaging studies have reported abnormalities in the well-known Default Mode Network (DMN) (Sonuga-Barke and Castellanos, 2007;Castellanos et al, 2008;Fair et al, 2010;Tomasi and Volkow, 2012;Di Martino et al, 2013;Hale et al, 2014), a "task-negative" network including cortical areas that show temporally-coherent activity during the resting condition (i.e., posterior cingulate cortex (PCC), retrosplenial cortex, inferior parietal lobule, lateral temporal cortex, medial prefrontal cortex and hippocampal formation) (Buckner et al, 2008). These abnormalities included a decreased DMN functional activation (Hale et al, 2014), a delayed DMN maturation (Fair et al, 2010) and a structural/functional right-biased DMN asymmetry (Hale et al, 2014).…”