Abnormal functional connectivity of default mode sub-networks in autism spectrum disorder patients

Abstract

Autism spectrum disorders (ASDs) are characterized by deficits in social and communication processes. Recent data suggest that altered functional connectivity (FC), i.e. synchronous brain activity, might contribute to these deficits. Of specific interest is the FC integrity of the default mode network (DMN), a network active during passive resting states and cognitive processes related to social deficits seen in ASD, e.g. Theory of Mind. We investigated the role of altered FC of default mode sub-networks (DM-SNs) in 16 patients with high-functioning ASD compared to 16 matched healthy controls of short resting fMRI scans using independent component analysis (ICA). ICA is a multivariate data-driven approach that identifies temporally coherent networks, providing a natural measure of FC. Results show that compared to controls, patients showed decreased FC between the precuneus and medial prefrontal cortex/anterior cingulate cortex, DMN core areas, and other DM-SNs areas. FC magnitude in these regions inversely correlated with the severity of patients' social and communication deficits as measured by the Autism Diagnostic Observational Schedule and the Social Responsiveness Scale. Importantly, supplemental analyses suggest that these results were independent of treatment status. These results support the hypothesis that DM-SNs under-connectivity contributes to the core deficits seen in ASD. Moreover, these data provide further support for the use of data-driven analysis with resting-state data for illuminating neural systems that differ between groups. This approach seems especially well suited for populations where compliance with and performance of active tasks might be a challenge, as it requires minimal cooperation.

Fig. 1

The upper panel depicts the 3 ICA components that represent the Default Mode sub-networks. These maps were identified by GIFT (http://icatb.sourceforge.net/, version 1.3e) using resting scans data from all 32 participants (patients and controls) and thresholded at p <0.05 corrected for family-wise errors. The lower panel shows all 3 components concurrently.

Fig. 2

Group differences in the Default Mode sub-networks. Only the PrC in Component A and MPFC in component C showed significant group differences, such that patients had decreased strength of connectivity. Each map is masked with the corresponding component mask generated from all participants (black outline, see Fig. 1) and threshold at p_FDR <0.05.

Fig. 3

Correlations between the functional connectivity strength of the Default Mode sub-networks and ADOS and SRS scores in patients with ASD. Patients receiving treatment at the time of the scan are depicted as filled white circles, patients without drug treatment at the time of the scan are depicted as blue circles, and patients with unknown treatment status are shown as unfilled white circles. Each map is masked with the corresponding component mask generated from all participants (black outline, see Fig. 1) and threshold at p_FDR <0.05. Note that the graph for the ACC cluster (shown in the two lower panels) correlation with SRS total scores is not displayed. Also, no significant correlation was found for component (comp.) A. ACC, anterior cingulate cortex; MPFC, medial prefrontal cortex; PrC, precuneus.