Characteristics of Brains in Autism Spectrum Disorder: Structure, Function and Connectivity across the Lifespan

Abstract

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterized by impaired social communication and restricted and repetitive behaviors (RRBs). Over the past decade, neuroimaging studies have provided considerable insights underlying neurobiological mechanisms of ASD. In this review, we introduce recent findings from brain imaging studies to characterize the brains of ASD across the human lifespan. Results of structural Magnetic Resonance Imaging (MRI) studies dealing with total brain volume, regional brain structure and cortical area are summarized. Using task-based functional MRI (fMRI), many studies have shown dysfunctional activation in critical areas of social communication and RRBs. We also describe several data to show abnormal connectivity in the ASD brains. Finally, we suggest the possible strategies to study ASD brains in the future.

Keywords: Autism spectrum disorder (ASD); Diffusion tensor image (DTI); Functional MRI (fMRI); Magnetic resonance image (MRI); Neuroimaging.

Fig. 1. Whole brain volume by age and group. ASD: autism spectrum disorder, TDC: typically developing control, For more information, see [7] (From Nicholas Lange et al., Autism Research (2015) by permission of John Wiley & Sons).

Fig. 2. Main effect of emotional face perception (A and B: fearful stimuli, C and D: happy stimuli, E and F: neutral stimuli). Reduced activities were observed in several parts of the social brain network in the ASD group compared with the TDC group while pictures of emotional faces were shown (uncorrected, p<0.01). Brain regions indicated are right superior temporal sulcus (STS) (A), right inferior frontal gyrus (IFG) (B); left insular cortex (C); right IFG (D); left superior insular sulcus (E); left superior insular sulcus (F). ASD: autism spectrum disorder, TDC: typically developing children, A: anterior, P: posterior, R: right, L: left. For more information, see [39] (From Kim et al., Psychiatry Investig (2015), open access article).

Fig. 3. Anterior thalamic radiation (ATR) showing reduced fractional anisotropy (FA, red) and increased mean diffusivity (MD, blue) in ASD group compared to control boys. Between-group analysis using FMRIB Software Library (FSL, Oxford, United Kingdom) after correction for multiple comparisons at p<.05. R: right, L: left, MNI: Montreal Neurological Institute coordinates. Right ATR cluster size: 477 1 mm³ voxels. For more information, see [78] (From Cheon K-A et al., Brain Research (2011) by permission of Elsevier).

Fig. 4. Whole-brain intrinsic functional connectivity analyses. (a) Significant group differences (that is, autism spectrum disorder [ASD] vs typical control [TC]) for intrinsic functional connectivity between each of the 112 parcellation units (56 per hemisphere) included in the structural Harvard-Oxford Atlas. Parcellations are represented with their center of mass overlaid as spheres on glass brains. The upper panel shows the intrinsic functional connections (blue lines) that were significantly weaker in ASD vs TC. The lower panel shows the intrinsic functional connections that were significantly stronger in ASD relative to TC (red lines). Each Harvard-Oxford Atlas unit is colored based on its membership in the six functional divisions. (yellow: primary sensorimotor (SM); green: unimodal association; Blue: heteromodal association; orange: paralimbic; red: limbic; pink: subcortical). Displayed results are corrected for multiple comparisons using false discovery rate at p<0.05. (b) The table summarizes the absolute number and percentage of node-to-node intrinsic functional connectivity surviving statistical threshold for group comparisons within and between functional divisions. Gray cells represent the absence of significant intrinsic functional connectivity, blue cells represent ASD-related hypoconnectivity (Hypo: ASDTC). Blue and red shadings decrease proportionally from the highest percentage (37%) to the lowest (~0%). For more information, see [87] (From Di Martino et al., Molecular Psychiatry (2014) by permission of Nature Publishing Group).