Clusters surviving FWE correction in each voxel-wise analysis at FWE p < 0.05. (a) Main effect of group: The Wolfram group has lower volume (yellow clusters) in multiple regions (e.g. brainstem, cerebellum, thalamus) and greater volume (blue) in relatively small portions of cortex compared to the control group. (b) Group × time interaction: Clusters where groups differed over time in volume (green) largely fell within the regions where the Wolfram group had lower volume than controls (yellow in a). (c) Main effect of time within the control group: Volume increased in most white matter regions (yellow and red clusters) and decreased in cortical gray matter regions (turquoise and blue) over time, as expected. (d) Main effect of time within the Wolfram group: Volume decreased over time (turquoise) in many white and gray matter regions, and no increased volume was seen anywhere in the brain. Expansion = increase in volume over time; Contraction = decrease in volume over time.