Distinctive Developmental Pattern of Functional and Structural Connectivities within Default Mode Network in ASD

Background:  Literature documents aberrant brain connectivity in individuals with autism spectrum disorder (ASD). Among the brain networks, the default mode network (DMN) has been widely reported to be atypical in ASD based on both the functional connectivity (FC) and structural connectivity (SC) neuroimaging studies. However, the developmental differences in the FC and SC of the DMN between individuals with ASD and typically developing individuals (TD) remain underinvestigated. 

Objectives:   We used the resting-state fMRI (rs-fMRI) and diffusion spectrum imaging (DSI) to clarify, respectively, the atypical FC and SC in boys and adolescents with ASD and their TD counterparts. We also examined the age effect on the FC-SC correlations in the two groups.

Methods:   The final sample recruited 80 individuals with ASD and 75 TD with age and PIQ matched after the rs-fMRI and DSI imaging preprocessing (Table1). Rs-fMRI data (3-Tesla Siemens Tim Trio system, 6-minute scan with eyes closed, TR=2sec) were preprocessed using the DPARSF toolbox (http://rfmri.org/DPARSF) with SPM8. Motion artifact was corrected by nuisance regression against 24-autoregressive motion parameters at an individual level. The DMN FCmap with significant activation of posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC) was constructed with the seed-based approach.

DSI data were acquired by a twice-refocused balanced echo diffusion echo planar imaging sequence, TR/TE = 9600/130 ms, imaging matrix size = 80 x 80, spatial resolution = 2.5 x 2.5 mm², and slice thickness = 2.5 mm. 102 diffusion encoding gradients with the maximum diffusion sensitivity bmax = 4000 s/mm² sampled on the grid points in a half sphere of the 3D q-space with |q| ≤ 3.6 units. The bilateral cingulum tracts were reconstructed on the DSI standard template by an expert using cingulate cortex as ROIs defined in the Automatic Anatomical Labeling system and the individual generalized fractional anisotropy values were sampled as SC indices. (Figure 1)

The effects of age (younger/elder) and group (ASD/TD) on the FC between PCC and mPFC and the SC of the cingulum were analyzed with two-way ANOVA analysis. The FC-SC correlations were investigated using multiple regression analysis with age as an independent factor in the two groups. 

Results:  The results showed that all the SC and FC indices were significantly higher in the elder group than the younger group (left cingulum: F (1,153)=10.833, p=0.001; right cingulum: F (1,153)=5.156, p=0.025; left_FC: F(1,153)=6.150, p=0.014; right_FC: F(1,153)=5.088, p=0.026), and the SC of right cingulum was significantly higher in the TD than ASD (F (1,153)=7.113, p=0.008). No group-by-age interaction was found. Multiple regression results showed a significant positive FC-SC correlation regarding age as an independent variable in ASD group (Right: beta=0.325, p=.004, Left:beta=0.270, p=.016), while there was no such correlation in the TD group.

Conclusions:   Despite the same age effect on the SC and FC in both ASD and TD, significant age-dependent SC-FC correlation was noted only in ASD. This implies that the developmental patterns of FC-SC interaction differ between the ASD and TD groups and such finding warrants further investigation across different ages.