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 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 -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 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 corona radiata 0.546±0.051 -32 7 25 L Posterior corona radiata (L Superior longitudinal fasciculus) L Superior corona radiata L cingulate gyrus L Uncinate fasciculus L Corticospinal tract Body of corpus callosum R Superior corona radiata R Superior longitudinal fasciculus R Inferior fronto-occipital fasciculus 3988 R Inferior longitudinal fasciculus R cingulate gyrus 26 2 34 R hippocampus (R Superior corona radiata) R Corticospinal tract R Anterior thalamic radiation Body of corpus callosum Forceps major N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z) Bilateral Anterior thalamic radiation Bilateral Posterior thalamic radiation Bilateral Uncinate fasciculus Bilateral Inferior fronto-occipital fasciculus Bilateral Inferior longitudinal fasciculus Bilateral Superior longitudinal fasciculus Bilateral cingulate gyrus 18710 Bilateral hippocampus

0.748±0.040 Bilateral Superior corona radiata -40 19 17 Bilateral Poserior corona radiata (L Anterior thalamic radiation) L External capsule Bilateral Corticospinal tract L Anterior limb of internal capsule L internal capsule Splenium of corpus callosum Forceps major Forceps minor

FigureS5. WM areas where better performances in executive functions 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.

FigureS6. WM areas where better performances in executive functions 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.

FigureS7. WM areas where better performances in executive functions 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 S3. Correlation of working memory (digit sequencing) 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 working memory in the clusters.

Fractional N. Voxels & Signal Peaks White Matter Tracts Anisotropy (x, y, z) L cingulate gyrus L Superior longitudinal fasciculus L Superior corona radiata L Posterior corona radiata 5075 L Inferior longitudinal fasciculus L Inferior fronto-occipital fasciculus -18 22 26 L Corticospinal tract L Anterior coro na radiata (L Anterior corona radiata) L Anterior thalamic radiation Body of corpus callosum Splenium of corpus callosum Forceps minor L Uncinate fasciculus 0.452±0.083 R Superior longitudinal fasciculus R Inferior longitudinal fasciculus R Inferior fronto-occipital fasciculus R Corticospinal tract 4635 R Posterior corona radiata R Anterior corona radiata 35 -14 29 R cingulate gyrus R hippocampus (R Superior longitudinal fasciculus) R Anterior thalamic radiation Right Corticospinal tract Splenium of corpus callosum Body of corpus callosum Forceps major 363 -43 -40 33 L Superior longitudinal fasciculus L Inferior longitudinal fasciculus (L Superior longitudinal fasciculus) L Inferior fronto-occipital fasciculus

247 L Superior longitudinal fasciculus L Inferior longitudinal fasciculus

-46 -45 24 L Inferior fronto-occipital fasciculus (L Superior longitudinal fasciculus) L Anterior thalamic radiation N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z) Bilateral Superior longitudinal fasciculus Bilateral Inferior fronto-occipital fasciculus Bilateral Inferior longitudinal fasciculus Bilateral Anterior thalamic radiation 20751 Body of corpus callosum Splenium of corpus callosum 1.197±0.203 49 -15 28 Bilateral cingulate gyrus Bilateral hippocampus (R Superior longitudinal fasciculus) Bilateral Posterior corona radiata L Uncinate fasciculus Bilateral Anterior corona radiata Bilateral Superior corona radiata Forceps major Forceps minor

N. Voxels & Signal Peaks Radial Diffusivity White Matter Tracts (x, y, z) Forceps minor L cingulate gyrus L Uncinate fasciculus L Superior longitudinal fasciculus L Inferior longitudinal fasciculus 7784 L Inferior fronto-occipital fasciculus

L Superior corona radiata -24 14 31 L Anterior corona radiata (L Superior longitudinal fasciculus) L Posterior corona radiata L Corticospinal tract L Anterior thalamic radiation Splenium of corpus callosum 0.552±0.058 Body of corpus callosum R Superior longitudinal fasciculus R Inferior longitudinal fasciculus R Inferior fronto-occipital fasciculus R Anterior thalamic radiation 7256 R Superior corona radiata

Splenium of corpus callosum 42 1 23 Body of corpus callosum (R Superior longitudinal fasciculus) cingulate gyrus R hippocampus R Corticospinal tract Forceps major N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z) Bilateral Superior longitudinal fasciculus Bilateral Anterior thalamic radiation Bilateral Superior corona radiata Bilateral Anterior corona radiata Bilateral Posterior corona radiata Bilateral Corticospinal tract 20860 Forceps major

0.755±0.047 Forceps minor 46 -3 25 Splenium of corpus callosum (R Superior longitudinal fasciculus) Body of corpus callosum Bilateral Inferior fronto-occipital fasciculus Bilateral Inferior longitudinal fasciculus Bilateral cingulate gyrus Bilateral hippocampus L Uncinate fasciculus

FigureS8. WM areas where better performances in working memory 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.

FigureS9. WM areas where better performances in working memory 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.

FigureS10. WM areas where better performances in working memory significantly correlated with higher radial diffusivity in Val/Val subject. 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.

FigureS11. WM areas where better performances in working memory 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.

Cognitive functions associate with DTI measures of WM microstructure

- Attention and speed of information processing

A positive correlation was observed between attention and speed of information processing and AD and

MD (TableS4; FigureS12 and S13).

Three clusters of significance were found for AD showing signal peaks in the corticospinal tract, the right superior longitudinal fasciculus and the left corticospinal tract and encompassing tracts both in the right

(corpus callosum, anterior corona radiata, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, cosrticospinal tract, inferior fronto-occipital fasciculus, anterior and posterior thalamic radiation and inferior longitudinal fasciculus) and in the left hemisphere (superior longitudinal fasciculus and anterior thalamic radiation).

Two clusters of significance were individuated for MD, showing signal peaks in the bilateral superior corona radiata and encompassing tracts in both right (superior longitudinal fasciculus, corticospinal tract, body of corpus callosum, retrolenticular part of internal capsule, inferior fronto-occipital fasciculus) and left hemisphere (cingulate gyrus, superior longitudinal fasciculus, anterior thalamic radiation, corticospinal tract).

Table S4. Correlation of attention and speed of information processing (symbol coding) scores with DTI measures. In the first column, values of the DTI measures of AD and 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 Axial Diffusivity White Matter Tracts (x, y, z) R Corpus Callosum 2989 R Anterior Corona Radiata R Superior Longitudinal Fasciculy 20 -27 50 (R Corticol Spinal Tract) R Inferior fronto-occipital Fasciculus R Cosrticospinal tract 1.21±0.15 1750 R Inferior fronto-occipital fasciculus R Inferior Longitudinal Fasciculus 48 -37 16 (R Superior Longitudinal Fasciculus) R Anterior and Posterior Thalamic Radiation 301 L Superior Longitudinal fasciculus

L Anterior Thalamic Radiation -22 -23 37 (L Corticospinal Tract) N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z) R Superior Longitudinal Fasciculus 4966 R Corticospinal Tract Body of Corpus Callosum 28 -8 21 (R Superior Corona radiata) R Retrolenticular part of internal Capsule 0.769±0.041 R Inferior fronto-occipital fasciculus L Cingulate Gyrus 1181 L Superior Longitudinal Fasciculus

L Anterior Thalamic Radiation -21 -29 41(L Superior Corona Radiata) L Corticospinal Tract

Figure S12. WM areas where better performances in attention and speed of information processing significantly correlated with higher axial diffusivity. 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.

FigureS13 . WM areas where better performances in attention and speed of information processing significantly correlated with higher mean diffusivity. 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.

- Executive functions

A positive correlation was observed between executive functions and AD, RD and MD (TableS5; FigureS14,

S15; and S16).

Three clusters of significance were found for AD showing signal peaks in the right superior corona radiata, the body of corpus callosum, and the left inferior longitudinal fasciculus, and encompassing tracts both in the right (superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, forceps major) and in the left hemisphere (anterior corona radiata, superior longitudinal fasciculus, forceps major, forceps minor and anterior thalamic radiation, inferior fronto-occipital fasciculus).

RD analysis individuated two clusters of significance, showing signal peaks in the bilateral superior corona radiata, and encompassing tracts in both right (splenium of corpus callosum, cingulated gyrus, superior longitudinal fasciculus, and body of corpus callosum) and left hemisphere (body of corpus callosum, cingulum, superior longitudinal fasciculus, forceps minor, forceps major, posterior corona radiata).

MD analysis individuated one clusters of significance, showing signal peaks in the left superior corona radiata and encompassing splenium of corpus callosum, superior and inferior longitudinal fasciculus and inferior fronto-occipital fasciculus.

Table S5. Correlation of executive functions (WCST) scores with DTI measures. In the first column, values of the DTI measures of AD, RD and 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 with executive functions in the clusters.

N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z) R Superior Longitudinal Fasciculus 15915 R Inferior fronto-occipital fasciculus 1.187±0.17 R Inferior Longitudinal Fasciculus 28 5 28 (R Superior Corona Radiata) R Forceps Major L Anterior Corona Radiata 9256 L Superior Longitudinal Fasciculus

L Forceps Major -10 -10 29 (Body of Corpus Callosum) L Forceps Minor L Anterior Thalamic Radiation 152

L Inferior fronto-occipital Fasciculus -23 -81 3 (Inferior Longitudinal Fasciculus) N. Voxels & Signal Peaks Radial Diffusivity White Matter Tracts (x, y, z) Body of Corpus Callosum L Cingulum 9247 L Superior Longitudinal Fasciculus 0.528 ± 0.072 Forceps Minor -27 -4 28 (L Superior Corona Radiata) Forceps Major Posterior Corona Radiata

R Splenium of Corpus Callosum 8633 Body of Corpus Callosum

R Cingulum (Cingulate Gyrus) 27 -2 28 (R Superior Corona Radiata) R Superior Longitudinal Fascisulus

N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z) Splenium of Corpus Callosum 32091 Superior Longitudinal Fasciculus 0.753±0.44 Inferior Longitudinal Fasciculus 27 5 27 (L Superior Corona Radiata) Inferior fronto-occipital Fasciculus

FigureS14. WM areas where better performances in executive functions significantly correlated with higher axial diffusivity. 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.

FigureS15. WM areas where better performances in executive functions significantly correlated with higher radial diffusivity. 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.

FigureS16. WM areas where better performances in executive functions significantly correlated with higher mean diffusivity. 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.

- Working memory

A positive correlation was observed between working memory and AD, RD and MD (TableS6; FigureS17,

S18, and S19).

Two clusters of significance were found for AD showing signal peaks in the right splenium of corpus callosum and the left superior longitudinal fasciculus and encompassing tracts both in the right (splenium of corpus callosum, superior corona radiata, forceps major, corticospinal tract, inferior fronto-occipital fasciculus, cingulum) and in the left hemisphere (superior longitudinal fasciculus, body of corpus callosum, inferior longitudinal fasciculum and cingulum).

RD analysis individuated two clusters of significance, showing signal peaks in the left portion of the anterior corona radiata and in the right portion of the superior corona radiata; this clusters encompass tracts in both right (body of corpus callosum, superior longitudinal fasciculus, cyngulate gyrus, anterior thalamic radiation) and left hemisphere (superior longitudinal fasciculus).

MD analysis individuated two clusters of significance, showing signal peaks in the right superior longitudinal fasciculus, and the left part of the body of corpus callosum; and encompassing tracts in both right (superior corona radiata, corticospinal tract, body of corpus callosum, cingulate gyrus) and left hemisphere (superior longitudinal fasciculum, inferior fronto-occipital fasciculum, anterior thalamic radiation).

TableS6. Correlation of the working memory (digit sequencing task) scores with DTI measures. In the first column, values of the DTI measures of AD, RD and 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, mm 3) and localization of signal peaks (MNI coordinates). The third column lists the WM tracts significantly associated with working memory in the clusters.

N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z) R Splenium of Corpus Callosum R Superior Corona Radiata 10023 R Forceps Major 1.203±0.171 R Corticospinal Tract 20 -37 31 (R Splenium of Corpus Callosum) R Inferior fronto-occipital Fasciculus R Cingulum

L Superior Longitudinal Fasciculus 5893 L Body of Corpus Callosum

L Inferior Longitudinal fasciculum -47 -16 28 (L Superior Longitudinal Fasciculus) L Cingulum

N. Voxels & Signal Peak Radial Diffusivity White Matter Tracts (x, y, z)

Body of Corpus Callosum 3393 0.556 ± 0.056 R Superior Longitudinal Fasciculus

R Cyngulate Gyrus 26 0 32 (R Superior Corona radiata) R Anterior Thalamic Radiation

148 L Superior Longitudinal Fasciculus -25 14 31 (L Anterior Corona radiata)

N. Voxels & Signal Peak Mean Diffusivity White Matter Tracts (x, y, z)

R Superior Corona Radiata 7832 R Corticospinal Tract 0.758±0.041 R Body of Corpus Callosum 26 -35 26 (R Superior Longitudinal Fasciculus) R Cingulate Gyrus 5165 L Superior Longitudinal Fasciculum L Inferior Fronto-occipital Fasciculum -13 -8 31 (L Body of Corpus Callosum) L Anterior Thalamic Radiation

FigureS17. WM areas where better performances in working memory significantly correlated with higher axial diffusivity. 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.

FigureS18. WM areas where better performances in working memory significantly correlated with higher radial diffusivity. 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.

FigureS19. WM areas where better performances in working memory significantly correlated with higher mean diffusivity. 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.

COMT polymorphism associate with DTI measures of WM microstructure

Table S7. Correlation of COMT polymorphism with DTI measures. In the first column, values of the DTI measures of axial diffusivity (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 COMT polymorphism, in the clusters.

N. Voxels & Signal Peaks Axial Diffusivity White Matter Tracts (x, y, z)

834 R Superior Longitudinal Fasciculus

38 -7 31 (R Superior longitudinal fasciculus) Splenium of corpus callosum Body of corpus callosum 800 L Anterior thalamic radiation

Forceps major 6 -26 24 (R Anterior thalamic radiation) 1.36±0.29 R Inferior longitudinal fasciculus

R Cingulum Inferior fronto-occipital fasciculus R 210 R Superior longitudinal fasciculus 29 9 28 (R Superior longitudinal fasciculus) 107 R Inferior longitudinal fasciculus

R Superior longitudinal fasciculus 31 -46 29 (R Superior longitudinal fasciculus)

FigureS20. WM areas where COMT polymorphism significantly correlated with higher axial diffusivity. 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.

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