(A) This pattern was identified by spatial covariance analysis of ¹⁸F-Fluorodeoxyglucose (FDG) PET scans at baseline from 12 premanifest HD gene carriers and 12 age-matched healthy control subjects (115). This pattern is characterized by metabolic decreases in the striatum and cingulate cortex, with relative increases in the ventral thalamus, primary motor cortex (Brodmann areas [BA] 4), and occipital cortex (BA 17, 18). The covariance map was overlaid on T1-weighted magnetic resonance–template images. Voxel weights for the pattern were thresholded at P = 0.005. Voxels with positive region weights (increases) are shown in red, and voxels with negative region weights (decreases) are shown in blue. (B) Time course of HDRP expression in the 12 premanifest gene carriers scanned at baseline and at 18 and 44 months. Mean subject scores are displayed for the 8 premanifest subjects who subsequently phenoconverted (red), the 4 subjects who did not phenoconvert during the period of follow-up (blue), and all 12 subjects (black). Subject scores, reflecting the expression of this pattern, separate the premanifest from the control groups (P < 0.01). (The mean value [± 1 SD] for the healthy control group is represented by dotted lines. Error bars represent 1 SEM at each time point). Reprinted with permission from Brain (88).