While many studies have now characterized the pattern of

While many studies have now characterized the pattern of white T0901317 cost changes over the course of development using age, very few have considered examining changes that coalesce with pubertal changes, rather than chronological age. One study (Asato et al., 2010) found that the vast majority of white matter tracts, including the uncinate, are still immature during mid-puberty, as measured by RD. Their findings suggest that the UF is still immature during adolescence when measured using both chronological age and pubertal status. Another recent study (Menzies et al., 2015) demonstrated significant decreases in MD from early puberty to late puberty in a number of tracts, including the UF. All participants were male, and the study demonstrated a significant negative relationship between testosterone levels and MD averaged across the white matter regions that showed a pubertal status effect during early and late puberty. There is some evidence suggesting asymmetry of the left and right uncinate; however, inconsistencies exist with respect to the direction of the asymmetry (i.e. left hemisphere greater than right vs. right hemisphere greater than left) depending on the specific measure examined. Studies using post-mortem dissection techniques, a method that measures white matter macrostructure and is believed to be more reliable than DTI, have reported that the right uncinate is larger than the left uncinate in approximately 80% of the brains studied (Highley et al., 2002; Park et al., 2004). In contrast, DTI studies, which measure white matter microstructure, have reported inconsistent results with some studies reporting relatively higher FA values in the left UF (e.g., Diehl et al., 2008; Eluvathingal et al., 2007; K. Hasan et al., 2009) while other studies have reported relatively higher FA values in the right UF (Rodrigo et al., 2007) or no asymmetry in FA values at all (Lebel et al., 2008; Rodrigo et al., 2007; Taoka et al., 2006). It should be noted that although many assume that the relationship between macrostructure and microstructure is straightforward, the small number of studies that have explicitly looked at this have reported only weak correlations (Fjell et al., 2008). In regards to developmental changes in asymmetry, evidence is scant due to the fact that participants in DTI studies are usually over 6 years in age. The data that does exist also conflicts (Geng et al., 2012; Johnson et al., 2014).
Clinical disorders In this section, we review evidence for the involvement of the uncinate in three disorders: social deprivation and maltreatment, autism spectrum disorders, and conduct disorder. These disorders were chosen because our earlier review of the diffusion imaging literature revealed that the UF is frequently mentioned in the contexts of these developmental disorders (Von Der Heide et al., 2013). When possible, we ground these findings in basic research on the functionality of the UF.
Conclusions There is growing interest in understanding developmental changes in structural connectivity and the implications for behavior. Our review of the literature revealed several limitations and issues to consider that are important for conducting this type of research (see Box 1). The focus of this review was the development of the limbic white matter structure, the uncinate fasciculus. The UF exhibits a very late maturational profile, with microstructural development spanning into the 30s, thus it is plausible that aberrations in its developmental trajectory could underlie certain psychopathologies. Although the literature is sprinkled with inconsistent findings, there is evidence linking uncinate abnormalities to child maltreatment, ASD, and conduct disorder and psychopathic traits. However, our review of the DTI literature revealed the disappointing conclusion that the traditional approach of using DSM-V categories generally had low levels of reproducibility. It is unclear whether these inconsistent findings are due to technical and statistical problems (see Box 1) or variability in the sample population. The one exception to this was antisocial personality disorder and conduct disorder, which have shown consistent correlations with UF microstructure (see Fig. 3).