The Diffusion Tensor Imaging (DTI) is an innovative technique that reports several data of white matter (WM) integrity, analyzing different indexes as a Fractional Anisotropy (FA), Mean Diffusivity (MD), Radial Diffusivity (RD) and Axial Diffusivity (AD). Previous studies found reduced FA and increased MD and RD in several areas of WM in ASD children, as the anterior thalamic radiation (ATR), the corpus callosum, the uncinate fasciculus, the corticospinal tract, the internal capsule, the pedunculi cerebri, the inferior longitudinal fasciculus, the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus and the cingulum (Brito, 2009; Cheon, 2011; Ameis, 2011; Shukla, 2011). Barnea-Goraly (2010) also reported aberrancies of WM in healthy siblings of ASD children, but their findings have been not replicated in similar samples.
The aim of the present study is to analyze the nature of WM structural connectivity in high functioning ASD (HF-ASD) patients and in their unaffected siblings.
Subjects: Participants were 35 HF-ASD children and adolescents (mean age=12.31, SD=3.10; 31 male, 4 girl), 18 healthy comparison (HC) controls (mean age=11.53, SD=3.07; 17 male, 1 girl) and 17 ASD siblings (mean age=14.07, SD=4.75; 9 male, 8 girl). There were differences in sex, IQ and socioeconomic status (SES) within groups, but these variables were included as additional covariates. All patients fulfilled ASD criteria on DSM-IV and ASD diagnosis were confirmed with the ADI-R. Inclusion criteria included an IQ > 70 in all participants.
Procedures: DTI maps were acquired using 3 Tesla Siemens MAGNETOM TIM Trio by employing a DTI sequence using echo planar imaging (EPI) pulse sequence with diffusion-weighted (acquisition plane: sagital, TR:9300ms, TE:94ms, b:1000s/mm, n of diffusion gradients:30, slice thickness:2mm, voxel size:2x2x2mm3). FA, MD, L1 and RD maps were generated using FSL. Diffusion images were corrected for eddy current distortion, corrected for motion and registered to 3D T1 using FLIRT. New segmentation of GM and WM were employed to calculate the flow fields using DARTEL that were applied to DTI maps to normalize to MNI space, smooth (4 mm Gaussian kernel) and Voxel Base Analysis was done using SPM8. Intracranial volume, age, gender, SES and IQ were used as covariates, and statistical threshold criteria was set at p<0.05 corrected for multiple comparison FWE (Family Wise Error correction) at cluster level.
Compared to controls, HF-ASD participants showed decreased FA in the left ATR (MNI space coordinates (mm)=[-16 -26 10], p(FWE)=0.012 cluster-level and cluster size=83). These coordinates were quoted in JHU White-Matter Tractography Atlas using FSL (FMRIB Software Library, Oxford, UK). In ASD siblings, we found increased MD values in the left area that involves the ATR, the cingulum, the forceps major, the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculus (MNI space coordinates (mm)=[-26 -54 6], p(FWE)=0.000 cluster-level and cluster size=148). There were no significant differences in WM structure between the ASD and siblings groups.
Our finding of similar abnormalities of WM in ASD children and their unaffected siblings, could contribute to the investigation of the meaning of WM alterations in the families of children with ASD.
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