Atypical local brain connectivity in pediatric autism spectrum disorder? A coordinate-based meta-analysis of regional homogeneity studies

Abstract

Despite decades of massive neuroimaging research, the comprehensive characterization of short-range functional connectivity in autism spectrum disorder (ASD) remains a major challenge for scientific advances and clinical translation. From the theoretical point of view, it has been suggested a generalized local over-connectivity that would characterize ASD. This stance is known as the general local over-connectivity theory. However, there is little empirical evidence supporting such hypothesis, especially with regard to pediatric individuals with ASD (age ≤\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\le$$\\end{document} 18 years old). To explore this issue, we performed a coordinate-based meta-analysis of regional homogeneity studies to identify significant changes of local connectivity. Our analyses revealed local functional under-connectivity patterns in the bilateral posterior cingulate cortex and superior frontal gyrus (key components of the default mode network) and in the bilateral paracentral lobule (a part of the sensorimotor network). We also performed a functional association analysis of the identified areas, whose dysfunction is clinically consistent with the well-known deficits affecting individuals with ASD. Importantly, we did not find relevant clusters of local hyper-connectivity, which is contrary to the hypothesis that ASD may be characterized by generalized local over-connectivity. If confirmed, our result will provide a valuable insight into the understanding of the complex ASD pathophysiology.