The individual growth curve model (114) was applied to the longitudinal imaging data (88) to estimate the time course of these imaging measures in the period prior to clinical diagnosis. The decline in striatal D₂ receptor binding (black) begins approximately 25 years before diagnosis (year 0). About 5 years later, striatal metabolism (green) begins to decline. Thalamic metabolic activity (blue) is likely elevated early on (exactly when is not known), but declines to normal levels as clinical signs (Unified HD Rating Scale [UHDRS] score, purple) become evident. HDRP activity is estimated to increase beginning approximately 15 years before diagnosis. This network measure likely increases for a number of years, then declines prior to symptom onset (see text). The horizontal dashed line represents the normal mean. Reprinted with permission from Brain (88).