Fig. 1

Schematic flow-chart of the iterative stereotaxic normalization during preprocessing of DTI data. a After transformation into a 50 μm isogrid (i), scanner- and sequence specific b₀- and FA-templates were created in a first step by arithmetically averaging data sets of all mice after linear transformation according to manually set landmarks (ii, iii). After non-linear normalization (iv) and further arithmetic averaging (v), the template for optimized fiber tracking (FT) was use for normalization of DTI data. These FT results (xii) were used for calculating tractwise fractional anisotropy statistics (TFAS). b Whole brain-based spatial statistics was performed on FA maps (vii) after quality check (vi). FA maps of each data set were were smoothed with a Gaussian filter of 200 μm full-width-at-half-maximum (viii). Statistical comparisons of FA were performed voxelwise (ix). Statistical results were corrected for multiple comparisons by use of the false-discovery-rate (FDR) algorithm at p <  0.05 (x); further reduction of the alpha error was performed by a spatial correction algorithm (xi) to finally obtain cross-sectional and longitudinal differences at the cohort level. Illustration of quality of the DTI-based templates and tract and ROI identifications. c b0 and color coded FA templates. d FT connecting left and right motor areas M1,M2 via the corpus callosum (CC) and in the corticospinal tract (CST)