Our third set of findings relates to sex differences in the PLX4720 coordination of cortical maturation, and has two principal implications. First, by replicating our earlier report of sexually dimorphic CT change within the left FPC (Raznahan et al., 2010)—despite using a different methodology within a largely independent sample of scans—our data firmly establishes the FPC as key a region of interest for researchers seeking to delineate human brain systems that mature differently in males and females. Second, our findings stress the need to move beyond localization when seeking to understand how factors such as sex might impact brain development,

and to explicitly model relationships between different brain regions. By modeling these relationships, we found that while female adolescents show a very close relationship between FPC and

DLPFC maturation, male adolescents do not. The FPC and DLPFC are known to be structurally interconnected in nonhuman primates (Petrides and Pandya, 1999), and have been implicated in both flexible cognitive control and decision-making in humans (Badre and Wagner, 2004). Notably, FPC and DLPFC are most reliably engaged together by tasks that place high demands on working memory (Badre and Wagner, 2004) in open-ended, ill-defined, or reward-laden TSA HDAC chemical structure (Pochon et al., 2002) contexts and require the coordination

of multiple higher cognitive processes Thymidine kinase for successful completion (Ramnani and Owen, 2004). We tentatively speculate therefore that sex differences in the tempo of adolescent FPC maturation and its coupling with DLPFC change may be relevant for developmental sex differences in the neural bases of cognitive control (Christakou et al., 2009), and the real-world sex differences in risk-taking and motivational control they may contribute to (Steinberg, 2010). There have been no published studies examining developmental influences on sex differences in FPC-DLPFC interactions during problem solving, and this will be an important area for future research, as will studies that directly test how sex and prefrontal maturational coupling interact to predict behavior. Our methodology for characterizing sex differences in maturational coupling could easily be extended to contrasts between disease groups and healthy controls. The findings of our study should be considered in light of several caveats and limitations. First, CT development is known to follow a nonlinear trajectory from early childhood to early adulthood, but longitudinal neuroimaging data sets required to model these nonlinear trajectories within individuals are not yet available.