Computational protocol: Large-scale structural alteration of brain in epileptic children with SCN1A mutation

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Protocol publication

[…] All measurements, including cortical thickness, surface area, and volume were obtained from T1 MRI scans using FreeSurfer (version 5.3.0,, a fully automated surface-based analysis. The technical details of the procedures have been previously described (, , , ). Briefly, the processing pipeline included correcting of intensity variation, removal of non-brain tissue, segmentation of the gray matter/white matter (GM/WM) tissue, tessellation of the cortical GM/WM boundary, inflation of the folded surfaces, and automatic correction of topological defects to detect GM/WM and GM/cerebrospinal fluid (CSF) boundaries. Cortical thickness was quantified as the closest distance from the GM/WM boundary to the GM/CSF boundary at each vertex. Subcortical volumes were calculated with FreeSurfer's automated procedure for volumetric measures. Each voxel in the normalized brain volumes were assigned to one of 40 labels, including cerebellum and brain stem (). Cortical volume, cortical thickness, and surface area were estimated for 34 regions per hemisphere according to the Desikan FreeSurfer atlas (). To improve accuracy of imaging analysis, key intermediate processing outputs (skull stripping, segmentation, parcellation) of FreeSurfer were visually inspected and, if needed, brain masks and inaccurate definitions of white matters were manually corrected by a trained researcher (WH Shim) as described in FreeSurfer website. [...] We compared age and gender distributions between groups using t-tests and chi-square tests. FreeSurfer's built-in general linear model tool, QDEC, was performed to compare regional cortical thickness between groups, controlling for age and gender. Cortical thickness data were smoothed with a 10 mm full width at half maximum (FWHM) Gaussian kernel. To correct for multiple comparisons, the false discovery rate (FDR) was implemented using a cluster-wise correction method with an initial cluster-forming threshold set at p < 0.01. Only clusters with a corrected value of p < 0.05 were considered to be significant. Analysis of covariance (ANCOVA) was performed using SPSS version 18.0 (SPSS, Chicago, IL) to compare group differences in the mean cortical thickness, mean surface area, and volume (global volume and regional volume) with age and gender as covariates. In surface area and volumetric analysis, total intracranial volume (TIV) was included as a covariate to control the total brain size. Bonferroni correction for multiple comparisons was applied, and a p < 0.0015 was considered to be significant for both the cortical volume and surface area analysis for 34 regions (p < 0.05/34) as well as the analysis of 35 subcortical structural volumes (p < 0.05/35). We also assessed age-related group differences using QDEC (cortical thickness) and ANCOVA in SPSS (volume, surface area) after adjusting age and gender. The measurements in whole-brain analysis and age-related group differences were considered as significant with a value of p < 0.05. […]

Pipeline specifications

Software tools FreeSurfer, SPSS
Applications Miscellaneous, Magnetic resonance imaging
Organisms Homo sapiens
Chemicals Sodium