fMRI-guided tractography method: group analysis.

<p>Steps A–F described in the text (Materials and Methods section) are here graphically explained (A: Registration, B: Masking, C: Dilation, D: Individual fMRI-guided tractography, E: fMRI-guided probabilistic map, F: fMRI-guided <i>ensemble</i> tract). The final result is the <i>ensemble</i> tract, i.e. a tractographic template of the activated tracts in the considered population.</p

fMRI activation maps and fMRI-guided <i>ensemble</i> tracts for a) HC, b) aMCI and c) AD.

<p>From left to right, <u>PANEL 1</u>: second level fMRI group activation map resulting from one sample t-tests performed separately for each group, verbal fluency task, axial views; <u>PANELS 2/4</u>: anterior (A), left lateral (L) and right lateral (R) views of the <i>ensemble</i> tract based on the activation of the first panel. The yellow circles highlight the left CB (anterior view) and the left AF (left view), observable with different portions in all the three groups.</p

Demographic data of the study groups.

<p>Chi square was used for gender comparison. One-way ANOVA test with Bonferroni correction for multiple comparisons was used for age and MMSE score comparisons (significance level: pcorr<0.05).</p><p>Abbreviations: HC  =  healthy controls; aMCI  =  amnestic mild cognitive impairment; AD =  Alzheimer's disease; M/F =  males/females; CDR =  clinical dementia rating scale; MMSE =  mini-mental state examination; SD =  standard deviation.</p><p>*All differences resulted significant between the groups.</p

The main effect of verbal fluency task in HC (n = 14), subjects with aMCI (n = 15) and AD (n = 14), who completed the fMRI assessments.

<p>One sample t-test with cluster correction (Z>2.3), significance threshold of p = 0.05. X, Y, Z coordinates expressed in millimiters.</p><p>Abbreviations: Sup  =  superior; Inf  =  inferior; Mid  =  middle; R  =  right; L  =  left; Gy  =  gyrus; SMA  =  supplementary motor area; BA  =  Brodmann area; HC  =  healthy controls; aMCI  =  amnestic mild cognitive impairment; AD  =  Alzheimer's disease.</p

Measure of integrity and percentages of involvement in the activation of WM bundles for the three groups.

<p>The percentages over 5% in at least one group are reported. For each group, the percentages of involvement were computed superimposing the <i>ensemble</i> tract to the atlases of the WM fiber bundles and represent the number of overlapping voxels between the two, with respect to the number of voxels of the atlas. Abbreviations: WM  =  white matter; HC  =  healthy controls; aMCI  =  amnestic mild cognitive impairment; AD  =  Alzheimer's disease; FA  =  fractional anisotropy; SD  =  standard deviation; CB  =  cingulum bundle; AF  =  arcuate fasciculus; CC  =  corpus callosum; sup  =  superior; par  =  parietal; post  =  posterior; temp  =  temporal.</p><p>(*)The average FA was found to be significantly different between AD and HC (p<0.05 corrected for multiple comparisons).</p><p>(#)The average FA was found to be significantly different between aMCI and AD (p<0.05 corrected for multiple comparisons).</p

Probability of occurrence of the observed number of DNVs in genes recurrently hit by non-synonymous de novo SNVs.

<p>Probability of occurrence of the observed number of DNVs in genes recurrently hit by non-synonymous de novo SNVs.</p

List of the 49 validated <i>de novo</i> variants.

<p>List of the 49 validated <i>de novo</i> variants.</p