White matter connectivity of uncinate fasciculus and inferior fronto-occipital fasciculus: A possible early biomarker for callous-unemotional behaviors in young children with ADHD

Abstract Background Callous-unemotional (CU) behaviors are important for identifying severe patterns of conduct problems (CP). One major fiber tract implicated in the development of CP is the uncinate fasciculus (UF), which connects amygdala and orbitofrontal cortex (OFC). The goals of the current study were to 1) explore differences in the white matter microstructure in the UF and other major fiber tracks (inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], cingulum, and corticospinal tract [CST]) between young typically developing (TD) children and those with Attention-Deficit/Hyperactivity Disorder (ADHD), and 2) explore, within the ADHD group, whether individual differences in these white matter microstructures relate to co-occurring CP and CU behaviors, respectively. Methods Participants included 198 young children (78% boys, M age = 4.95 years; 80% Latinx; 49% TD). CU behaviors and CP were measured via a combination of teacher/parent ratings. Non-invasive diffusion-weighted imaging (DWI) was used to measure fractional anisotropy (FA), an indirect indicator of white matter properties. Results Relative to TD children, children with ADHD had reduced FA on four out of the five fiber tracks we examined (except for cingulum). Within the ADHD group, no associations were found between CP and reduced white matter integrity across any of the fiber tracks examined. However, we found that even after accounting for CP and a host of covariates including whole brain FA, CU behaviors were independently related to reduced FA in bilateral UF and left IFOF. Conclusions The bilateral UF and IFOF may be a biomarker of CU behaviors, even in very young children.