Changes in FA reflect maturational increase in cell packing density, fiber diameter, directional coherence and myelination195. Accordingly, FA within the white matter tracts increases with age in children and adolescents, and correlates with cognitive abilities196, 197. Using DTI, evidence for WM microstructural alterations has been reported in subjects with and without PEMCS, which were interactive with adolescent exposure (i.e., current smokers versus non-smokers)194. PEMCS alone was found to increase FA in right and left frontal regions and the genu of the CC. Adolescent smoking alone, in absence of PEMCS, was associated with increased FA in a larger number of frontal regions, the genu and splenium of the CC, the left inferior longitudinal fasciculus, and the anterior limb of right internal capsule (IC). However, PEMCS combined with adolescent smoking was associated with increased FA in an even larger number of regions relative to the other two exposure groups and included the genu of CC, left frontal WM, right superior longitudinal fasciculus, and the anterior limb of the right IC. Direct comparison of adolescent smokers with no PEMCS to prenatally exposed non-smokers