No MD differences between groups were seen in any of the 8 clusters that showed between-group FA differences, or anywhere else in the brain, suggesting the potential mechanism of white matter change in this sample may be alterations in the highly organized fiber structure, as compared to tissue loss or demyelination, although this remains uncertain [7,11,54]. Although the pathological relationship between these diffusion indices (e.g., FA and MD) is not entirely understood due to the complicated geometry of white matter tracts in the brain, correlations between MD and FA may point to contributions to the breakdown in microstructural integrity of white matter (e.g., changes in intra/extra cellular fluid, axonal density, disorganization of fiber structure) [72]. Our results propose a relationship between both adolescent binge drinking and marijuana use and subtle white matter tissue microstructural abnormalities in varying projection and association fiber pathways (e.g. superior longitudinal fasciculus) that are important for healthy adolescent neural and cognitive development [19,63,64,87].
