Abnormalities of Inter- and Intra-Hemispheric Functional Connectivity in Autism Spectrum Disorders: A Study Using the Autism Brain Imaging Data Exchange Database

Abstract

Recently, the Autism Brain Imaging Data Exchange (ABIDE) project revealed decreased functional connectivity in individuals with Autism Spectrum Disorders (ASD) relative to the typically developing controls (TDCs). However, it is still questionable whether the source of functional under-connectivity in subjects with ASD is equally contributed by the ipsilateral and contralateral parts of the brain. In this study, we decomposed the inter- and intra-hemispheric regions and compared the functional connectivity density (FCD) between 458 subjects with ASD and 517 TDCs from the ABIDE database. We quantified the inter- and intra-hemispheric FCDs in the brain by counting the number of functional connectivity with all voxels in the opposite and same hemispheric brain regions, respectively. Relative to TDCs, both inter- and intra-hemispheric FCDs in the posterior cingulate cortex, lingual/parahippocampal gyrus, and postcentral gyrus were significantly decreased in subjects with ASD. Moreover, in the ASD group, the restricted and repetitive behavior subscore of the Autism Diagnostic Observation Schedule (ADOS-RRB) score showed significant negative correlations with the average inter-hemispheric FCD and contralateral FCD in the lingual/parahippocampal gyrus cluster. Also, the ADOS-RRB score showed significant negative correlations with the average contralateral FCD in the default mode network regions such as the posterior cingulate cortex and precuneus. Taken together, our findings imply that a deficit of non-social functioning processing in ASD such as restricted and repetitive behaviors and sensory hypersensitivity could be determined via both inter- and intra-hemispheric functional disconnections.

Keywords: Autism Spectrum Disorder (ASD); functional connectivity; inter-hemisphere; intra-hemisphere; resting state fMRI.

Figure 1

Calculating three measures of functional connectivity density. cFCD (contralateral functional connectivity density) is the number of functional connectivity from the opposite hemisphere; iFCD (ipsilateral functional connectivity density) is from the same hemisphere; gFCD (global functional connectivity density) is computed as the sum of cFCD and iFCD.

Figure 2

Average maps of functional connectivity densities for the typically developing controls (TDCs) and autism spectrum disorders (ASDs). Distribution of gFCD, cFCD, and iFCD are averaged over 458 patients with ASDs and 517 TDCs. The color bar represents the number of functional connectivities.

Figure 3

Decreased functional connectivity density (FCD) in autism spectrum disorder (ASD) group. Group differences in the normalized global, contralateral, and ipsilateral FCDs were visualized with the statistical significance at corrected P < 0.05. Detailed information on each cluster is written in Table 2.

Figure 4

The extent of regional overlaps for functional underconnectivities in the normalized global, contralateral, and ipsilateral FCDs (gFCD, cFCD, and iFCD). Yellow color represents the overlapping areas for functional underconnectivities observed in gFCD, cFCD, and iFCD. Orange color represents the overlapping areas of functional underconnectivities observed in any pairs of FCDs: gFCD and cFCD, gFCD and iFCD, or cFCD and iFCD. Purple color represents functional underconnectivities observed in gFCD, cFCD, or iFCD without overlapping areas.

Figure 5

Scatter plots of functional connectivity density (FCD) vs. clinical variable. (A) gFCD in the Lingual/PHG and ADOS-RRB score; (B) iFCD in the Lingual/PHG and ADOS-RRB score; (C) cFCD in the Lingual/PHG and ADOS-RRB score; (D) cFCD in the PCC and ADOS-RRB score; and (E) cFCD in the precuneus and ADOS-RRB score.