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Abstract:
Non-linear effects of age on white matter integrity are ubiquitous in the brain and indicate that these effects are more pronounced in certain brain regions at specific ages. Box–Cox analysis is a technique to increase the log-likelihood of linear relationships between variables by means of monotonic non-linear transformations. Here we employ Box–Cox transformations to flexibly and parsimoniously determine the degree of non-linearity of age-related effects on white matter integrity by means of model comparisons using a voxel-wise approach. Analysis of white matter integrity in a sample of adults between 20 and 89 years of age (n = 88) revealed that considerable portions of the white matter in the corpus callosum, cerebellum, pallidum, brainstem, superior occipito-frontal fascicle and optic radiation show non-linear effects of age. Global analyses revealed an increase in the average non-linearity from fractional anisotropy to radial diffusivity, axial diffusivity, and mean diffusivity. These results suggest that Box–Cox transformations are a useful and flexible tool to investigate more complex non-linear effects of age on white matter integrity and extend the functionality of the Box–Cox analysis in neuroimaging.
