Across a one-to-two-year period of active use, initiators demonstrated a greater-than-expected decline in cortical thickness in the right hemisphere middle frontal gyral region. The expected pattern is for this area to show evidence of pruning (operationalized as loss of gray matter volume or decreasing cortical thickness) with increasing age. The middle frontal gyrus is part of the cognitive control network that subserves inhibitory control (69), working memory, particularly for spatial information (70), and episodic memory retrieval (71). Indeed, it is a region with numerous links to executive processing, particularly under conditions of high demand (72). The middle frontal gyrus shows both structural (73) and functional (74) changes as a consequence of fetal alcohol exposure in human children, adolescents and young adults as well as in adolescents with positive family histories of alcohol abuse (75). The relative decline in cortical thickness observed in the current study is consistent with these findings as well as with the observed correlation between decreased prefrontal gray matter volumes and heightened drinking behavior in adolescents with substance use disorders (76). Similarly, Medina et al. (30) reported
