did not hold in very heavy substance users, suggesting that differences in white matter composition may be dependent on the extent of use. Among heavy MJ+ALC users, greater lifetime alcohol use was linked to higher FA in the anterior limb of the internal capsule, where users showed greater FA than controls (i.e., greater divergence from controls for the heaviest drinkers). We speculate that these changes may reflect compensatory responses that are more likely to occur with increasing use, as also observed in studies of functional activation (Tapert et al., 2004; Tapert et al., 2007). Although further examination is needed, these findings highlight the complex interaction between neurotoxic substance effects and concomitant neurodevelopmental changes that take place across brain regions.
