Supplementary material Data processing and analyses Image analyses and tensor calculations were done using the “Oxford Centre for Functional Magnetic Resonance Imaging of the Brain Software Library” (FSL 5.0; www.fmrib.ox.ac.uk/fsl/index.html)(Smith et al 2004; Woolrich et al 2009). First, each of the 35 DTI volumes was affine registered to the T2-weighted b=0 volume using FLIRT (FMRIB's Linear Image Registration Tool)(Jenkinson and Smith 2001). These images were then corrected for motion between scans and residual eddy–current distortions present in the diffusion- weighted images. After removal of nonbrain tissue(Smith 2002), least-square fits were performed to estimate the FA, eigenvector, and eigenvalue maps. Next, all individuals' volumes were skeletonized and transformed into a common space as used in Tract- Based Spatial Statistics(Smith et al 2006; Smith et al 2007). All volumes were nonlinearly warped to the FMRIB58_FA template supplied with FSL (http://www.fmrib.ox.ac.uk/fsl/tbss/FMRIB58_FA.html) and normalized to the Montreal Neurological Institute (MNI) space, by use of local deformation procedures performed by FMRIB's Non-Linear Image Registration Tool (FNIRT) (www.fmrib.ox.ac.uk/fsl/fnirt/index.html), a nonlinear registration toolkit using a b-spline representation of the registration warp field(Rueckert et al 1999). Next, a mean FA volume of all subjects was generated and thinned to create a mean FA skeleton representing the centres of all common tracts. We thresholded and binarized the mean skeleton at FA>0.20 to reduce the likelihood of partial voluming in the borders between tissue classes, yielding a mask of 137,833 WM voxels. Individual FA values were warped onto this mean skeleton mask by searching perpendicular from the skeleton for maximum FA values(Smith et al 2006). The resulting tract invariant skeletons for each participant were fed into voxelwise permutation-based cross- subject statistics. Similar warping and analyses were used on MD, AD, and RD data sampled from voxels with FA>0.20. Cognitive functions associate with DTI measures of WM microstructure in Val/Val subjects Table S1. Correlation of attention and speed of information processing (symbol coding) scores with DTI measures in Val/Val subjects. In the first column, values of the DTI measures of MD (means±SD) are given for regions showing maximal effects on TBSS values (signal peaks). The second column shows dimensions of clusters (number of voxels, mm3) and localization of signal peaks (MNI coordinates). The third column lists the WM tracts significantly associated to attention and speed of information processing in the clusters. N. Voxels & Signal Peaks Fractional Anisotropy White Matter Tracts (x, y, z) R Superior longitudinal fasciculus R Inferior fronto-occipital fasciculus R Superior longitudinal fasciculus 1890 R Anterior thalamic radiation Forceps major 29 -59 25 R cingulate gyrus (R Superior longitudinal fasciculus) Splenium of corpus callosum R hippocampus R Posterior corona radiata R Corticospinal tract L Superior corona radiata L Posterior corona radiata 988 L Anterior corona radiata L Superior longitudinal fasciculus -24 -4 34 L Corticospinal tract (L Superior corona radiata) L Anterior thalamic radiation 0.469 ± 0.083 L cingulate gyrus Body of corpus callosum 608 R Superior longitudinal fasciculus R Corticospinal tract 38 -13 28 R Superior corona radiata (R Superior longitudinal fasciculus) 285 L Superior longitudinal fasciculus L Corticospinal tract -37 -13 30 L Superior corona radiata ( Superior longitudinal fasciculus) 224 Body of corpus callosum L Cingulum -15 -22 31 L Superior longitudinal fasciculus (Body of corpus callosum) N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z) L Superior longitudinal fasciculus 6565 L Inferior longitudinal fasciculus 1.208 ± 0.198 L Inferior fronto-occipital fasciculus -40 -22 30 Forceps major (L Superior longitudinal fasciculus) L cingulate gyrus Splenium of corpus callosum L Superior corona radiata L Uncinate fasciculus L Anterior thalamic radiation L Posterior thalamic radiation L Anterior corona radiata L Posterior corona radiata R Superior longitudinal fasciculus R Inferior longitudinal fasciculus R Inferior fronto-occipital fasciculus 5848 Body of corpus callosum R Anterior thalamic radiation 46 -7 25 R cingulate gyrus (R Superior longitudinal fasciculus) R hippocampus R Superior corona radiata R Corticospinal tract N. Voxels & Signal Peaks Radial Diffusivity White Matter Tracts (x, y, z) R Superior longitudinal fasciculus R Inferior fronto-occipital fasciculus Forceps major Forceps minor R Inferior longitudinal fasciculus 5930 R cingulate gyrus Body of corpus callosum 28 -58 25 Splenium of corpus callosum (R Superior longitudinal fasciculus) R Anterior thalamic radiation R Anterior corona radiata R Superior corona radiata R Corticospinal tract 0.543 ± 0.066 L Superior corona radiata L Anterior thalamic radiation L Inferior longitudinal fasciculus L Inferior fronto-occipital fasciculus 4803 L Superior longitudinal fasciculus L Posterior corona radiata -24 -4 34 L Superior corona radiata (L Superior corona radiata) Body of corpus callosum L cingulate gyrus L Anterior thalamic radiation Forceps major N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z) Bilateral Superior longitudinal fasciculus Bilateral Inferior longitudinal fasciculus Bilateral Inferior fronto-occipital fasciculus R Corticospinal tract R Superior corona radiata 19950 L Anterior corona radiata Bilateral Posterior corona radiata 50 -8 23 Splenium of corpus callosum (R Superior longitudinal fasciculus) Bilateral Anterior thalamic radiation Forceps major Forceps minor Bilateral cingulate gyrus 0.756 ±0.045 Bilateral hippocampus R Inferior fronto-occipital fasciculus 463 R Uncinate fasciculus R Anterior thalamic radiation 35 33 -4 R Uncinate fasciculus (R Inferior fronto-occipital fasciculus) R Anterior corona radiata 248 R External capsule R Uncinate fasciculus 26 16 -8 R Inferior fronto-occipital fasciculus (R External capsule) R Anterior corona radiata FigureS1. WM areas where better performances in attention and speed of information processing significantly correlated with lower fractional anisotropy in Val/Val subjects. Voxels of significant positive correlation are mapped on the mean FA template of the studied sample, and are shown in glass-brain images. The colorbar refers to 1-p values for the observed differences. Numbers are z coordinates in the standard Montreal Neurological Institute (MNI) space. FigureS2. WM areas where better performances in attention and speed of information processing significantly correlated with higher axial diffusivity in Val/Val subjects. Voxels of significant positive correlation are mapped on the mean FA template of the studied sample, and are shown in glass-brain images. The colorbar refers to 1-p values for the observed differences. Numbers are z coordinates in the standard Montreal Neurological Institute (MNI) space. FigureS3. WM areas where better performances in attention and speed of information processing significantly correlated with higher radial diffusivity in Val/Val subjects. Voxels of significant positive correlation are mapped on the mean FA template of the studied sample, and are shown in glass-brain images. The colorbar refers to 1-p values for the observed differences. Numbers are z coordinates in the standard Montreal Neurological Institute (MNI) space. FigureS4. WM areas where better performances in attention and speed of information processing significantly correlated with higher mean diffusivity in Val/Val subjects. Voxels of significant positive correlation are mapped on the mean FA template of the studied sample, and are shown in glass-brain images. The colorbar refers to 1-p values for the observed differences. Numbers are z coordinates in the standard Montreal Neurological Institute (MNI) space. Table S2. Correlation of executive functions (Tower of London) scores with DTI measures in Val/Val subjects. In the first column, values of the DTI measures of MD (means±SD) are given for regions showing maximal effects on TBSS values (signal peaks). The second column shows dimensions of clusters (number of voxels, mm3) and localization of signal peaks (MNI coordinates). The third column lists the WM tracts significantly associated to executive functions in the clusters. N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z) R Superior longitudinal fasciculus R Inferior longitudinal fasciculus R Inferior fronto-occipital fasciculus Forceps major 14906 R cingulate gyrus Body of corpus callosum 38 2 24 R Posterior corona radiata (R Superior longitudinal fasciculus) R Superior corona radiata R Anterior thalamic radiation R Corticospinal tract R internal capsule R Uncinate fasciculus Body of corpus callosum Forceps major 1.186±0.170 Forceps minor L Inferior longitudinal fasciculus L Inferior fronto-occipital fasciculus L Superior longitudinal fasciculus L hippocampus 14769 L cingulate gyrus L Anterior thalamic radiation -10 11 25 (Body of corpus callosum) L Posterior corona radiata L Superior corona radiata L Anterior corona radiata L Corticospinal tract Splenium of corpus callosum L Posterior limb of internal capsule L Anterior limb of internal capsule L Uncinate fasciculus N. Voxels & Signal Peaks Radial Diffusivity White Matter Tracts (x, y, z) L Superior longitudinal fasciculus Forceps minor L Anterior thalamic radiation L Inferior fronto-occipital fasciculus 4488 L Inferior longitudinal fasciculus L Anterior