Sex differences in atypical fronto-subcortical structural connectivity among children with attention-deficit/hyperactivity disorder: Associations with delay discounting

Atypical fronto-subcortical neural circuitry has been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD), including connections between prefrontal cortical regions involved in top-down cognitive control and subcortical limbic structures (striatum and amygdala) involved in bottom-up reward and emotional processing. The integrity of fronto-subcortical connections may also relate to interindividual variability in delay discounting, or a preference for smaller, immediate over larger, delayed rewards, which is associated with ADHD, with recent evidence of ADHD-related sex differences.We applied diffusion tensor imaging to compare the integrity of the white matter connections within fronto-subcortical tracts among 187 8-12 year-old children either with ADHD ((n = 106; 29 girls) or typically developing (TD) controls ((n = 81; 28 girls). Analyses focused on diagnostic group differences in fractional anisotropy (FA) within fronto-subcortical circuitry implicated in delay discounting, connecting subregions of the striatum (dorsal executive and ventral limbic areas) and amygdala with prefrontal regions of interest (dorsolateral [dlPFC], orbitofrontal [OFC] and anterior cingulate cortex [ACC]), and associations with two behavioral assessments of delay discounting.Children with ADHD showed reduced FA in tracts connecting OFC with ventral striatum, regardless of sex, whereas reduced FA in the OFC-amygdala and ventral ACC-amygdala tracts were specific to boys with ADHD. Across diagnostic groups and sex, reduced FA in the dorsal ACC-executive striatum tract correlated with greater game time delay discounting.These results suggest a potential neurobiological substrate of heightened delay discounting in children with ADHD and support the need for additional studies including larger sample sizes of girls with ADHD to further elucidate ADHD-related sex differences in these relationships.