Developmental Meta-Analysis of the Functional Neural Correlates of Autism Spectrum Disorders

Abstract

Objective There is a pressing need to elucidate the brain–behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted a developmental analysis of activation likelihood estimation (ALE) meta-analysis to compare child versus adult ASD fMRI studies. We hypothesized that children and adolescents with ASD (<18 years old) would rely less on prefrontal cortex structures than adults (≥18 years old). Method PubMed and PsycInfo literature searches were conducted to identify task-dependent fMRI studies of children or adults with ASD. Then recent GingerALE software improvements were leveraged to perform direct comparisons of child (n =18) versus adult (n =24) studies. Results ALE meta-analyses of social tasks showed that children and adolescents with ASD versus adults had significantly greater hyperactivation in the left post-central gyrus, and greater hypoactivation in the right hippocampus and right superior temporal gyrus. ALE meta-analyses of nonsocial tasks showed that children with ASD versus adults had significantly greater hyperactivation in the right insula and left cingulate gyrus, and hypoactivation in the right middle frontal gyrus. Conclusion Our data suggest that the neural alterations associated with ASD are not static, occurring only in early childhood. Instead, children with ASD have altered neural activity compared to adults during both social and nonsocial tasks, especially in fronto-temporal structures. Longitudinal neuroimaging studies are required to examine these changes prospectively, as potential targets for brain-based treatments for ASD.

Salience processing and insular cortical function and dysfunction

“…A recent study found that in children with ASD (aged 7-12 years old) there was a hyperconnectivity of the insula-based salience network 27 . The shift from the hyperconnectivity seen in younger children to hypoconnectivity seen in adolescents and adults in these studies suggests that developmental changes in insular functional connectivity might accompany the disorder 89,90 .…”

Face processing in autism spectrum disorders: From brain regions to brain networks

“…Recent meta-analyses investigating social dysfunction in ASD have implicated atypical activation patterns related to a broad range of social tasks. For example, Di Martino et al (2008) found that the ACC and the right anterior insula showed hypo-activation in ASD across a number of studies of social processing, while Dickstein et al (2013) found hypo-activation of the right STG across a number of social studies. Finally, a recent metaanalysis of the ASD face perception literature by Nickl-Jockschat et al (2014) reported hypo-activation of the left FG that was functionally hypo-connected with the IFG and temporo-occipital cortex across a number of studies.…”

Advancing our understanding of the brain in autism: contribution of functional MRI and diffusion tensor imaging

“…In particular, the study found greater reductions in activation in the parahippo campal gyrus, hippocampus and superior temporal gyrus in children with ASD compared with adults with ASD for social tasks, and increased hyperactivation in the right insula, right middle frontal gyrus and left cingulate for nonsocial tasks [113]. Thus, there are greater activation differences in children with ASD compared with their normal developing peers, and, with age, these differences seem to abate [113].…”

“…Advancing our understanding of the brain in autism REVIEW Nevertheless, a recent meta-analysis specifically comparing fMRI studies of children and adults showed greater hyper-and hypo-activation in children with ASD compared with adults with ASD [113]. In particular, the study found greater reductions in activation in the parahippo campal gyrus, hippocampus and superior temporal gyrus in children with ASD compared with adults with ASD for social tasks, and increased hyperactivation in the right insula, right middle frontal gyrus and left cingulate for nonsocial tasks [113].…”