The DARTEL approach performs an iterative but highly integrated spatial normalization scheme, in that all images in a population initially contribute to a straight mean to which then again all images are iteratively registered to. The images resulting from this first round are then again used to create a second average image, to which the images are again registered, and so on. Hence, in a first step, the standard DARTEL procedure (SPM12 batch module “DARTEL, create template”) was applied to the full dataset, yielding an initial set of six conventional templates for GM and WM each. In a second step (SPM12 batch module “Run DARTEL with existing template”), all images were then iteratively registered to these initial templates. However, the intermediate steps (reflecting the registration of each individual image to the first, second, third… template from the first step) are only computed internally, iteratively building on the results from the previous step. In order to obtain these intermediate images, the second processing job was therefore split into six successive jobs. The settings used correspond to the defaults and are listed in Table 2. After completing each iteration, the resulting intermediate deformation fields were copied before they were updated in the next iteration. See Fig. 1 for an overview. This ensures that each iteration builds upon the results from the previous step, in line with the original DARTEL approach. These twelve sets of deformation fields (two tissue classes per subject, times six iterations) were then used to write out corresponding sets of increasingly crisp tissue probability maps, six sets for GM and six sets for WM. These twelve sets of 1919 images each were then submitted for data analysis.Table 2DARTEL processing options used for each iteration. The penalizing energy term (linear elastic energy), the number of inner iterations (3), the Levenberg-Marquardt regularization (0.01), the number of cycles for the full multi-grid matrix solver (3) and the number of relaxations in each multi-grid cycle (3) as well as the third regularization parameter id (0.000001) were kept constant over iterations.Table 2Time stepsRegularization parameter [µ]Regularization parameter [λ]Iteration 1141Iteration 2121Iteration 321.5Iteration 44.5.25Iteration 516.25.125Iteration 664.25.125