Structural White Matter Abnormalities in Children and Adolescents with High-Functioning Autism Spectrum Disorders

Background: The etiopathogenesis of autism spectrum disorders (ASD) still remains to be clarified, but imaging studies indicate that brain structure anomalies play an important role (Brambilla et al, 2003; Courchesne et al, 2007; Minshew et al, 2007). Previous studies yielded abnormalities in different white matter (WM) regions (Bonilla et al, 2008; Waiter et al, 2005) but others failed to found structural differences in ASD children or adolescents compared to neurotypically developing children (Mengotti et al, 2011; Poutska et al, 2011). So, decreased and increased WM volumes have been reported in some VBM studies (analysis corrected) in high-functioning ASD children. More recently, a wide meta-analysis provided also evidence for deficits of WM in this region, among others, and most significantly increases in WM in different regions (Radua et al, 2011). But there is still a lack of knowledge about the meaning of those changes. Preliminary results of a large structural and functional study in HF-ASD children are presented.

Objectives: The aim of the present study is analyzed the nature of structural differences in HF-ASD patients.

Methods: Subjects: Participants were 22 HF-ASD children (mean age=13.00, SD=3.05; 21 male, 1 girl) and 12 healthy comparison controls (mean age=10.81, SD=2.72; 11 male, 1 girl). Both samples were balanced for age, gender and IQ. All patients fulfilled ASD criteria on DSM-IV and ICD-10 and ASD diagnosis were confirmed with the Autism Disorder Interview (ADI-R). Inclusion criteria included an IQ above 70 in all participants. Procedures: The MRI scannig protocol consisted of a 3D structural using a T1-weighted MPRAGE sequence (acquisition plane:sagital, TR:2300ms, TE:2.98ms, voxel size: 1x1x1mm3 ) New segmentation, DARTEL normalisation, smooth (10mm gaussian kernel) and whole-brain voxelwise analyses of GM and WM were carried out using SPM8. Age, gender and total intracranial volume were used as nuisance variables, and statistical threshold criteria was set at p<0.05 corrected for multiple comparison FWE (Family Wise Error correction).

Results: Compared to controls, HF-ASD participants showed decreased WM volume in Cingulate Gyrus in Right Frontal Lobe (MNI space coordinates (mm)=[15 20 40], p(FWE)=0.040 peak-level, T=5.25 and cluster size=741). These coordinates were quoted in Talairach Daemon Labels atlas and JHU White-Matter Tractography Atlas using FSL (FMRIB Software Library, Oxford, UK). No areas of significantly increased white matter volume were found and there were no significant differences in GM volume between controls and ASD patients.

Conclusions: In our study, HF-ASD children showed WM decreased volume in the medial right frontal lobe, in cingulated gyrus. These results are consistent with those reported in previous studies. Abnormalities of WM in HF-ASD are probably responsible for some of the clinical features of ASD. Moreover, medial regions of the right frontal lobe have been consistently linked to neuropsychological deficits in ASD. Our results failed to find differences in GM, but our sample could be small enough to detect such differences.