White matter microstructural integrity correlates of emotion dysregulation in children with ADHD: A diffusion imaging tractography study

Background: Emotion dysregulation (ED) is prevalent in youths with attention-deficit hyperactivity disorder (ADHD) and causes more social impairment and poor adaptive function. Alterations in the integrity of white matter (WM) tracts might have important implications for affective processing related to ED. However, little is known about the WM correlates underpinning ED in ADHD. Methods: Using diffusion spectrum image tractography, we obtained generalized fractional anisotropy (GFA) values of 76 WM tracts in 77 children with ADHD and 105 typically developing controls (TDC). ED severity was defined by the dysregulation profile from the child behavior checklist. Canonical correlation analysis (CCA) was performed to identify modes that relate WM microstructural property to ED severity and cognitive measures. Results: The application of CCA identified one significant mode (r = 0.638, FWE-corrected p = 0.046) of interdependencies between WM property patterns and diagnosis, ADHD total symptom levels, dysregulation by diagnosis interaction, and full-scale intellectual quotient (FIQ). GFA values of 19 WM tracts that were linked to affective-processing, sensory-processing and integration, and cognitive control circuitry were positively correlated with ED severity in TDC but negatively correlated with ED severity in ADHD. ADHD symptom severity and diagnosis were negatively associated with the GFA patterns of this set of tract bundles. In contrast, FIQ was positively correlated with this set of tract bundles. Conclusions: This study used the CCA to show that children with ADHD and TDC had distinct multivariate associations between ED severity (diagnosis by ED interaction) and microstructural property in a set of WM tracts. These tracts interconnect the cortical regions that are principally involved in emotion processing, integration, and cognitive control in multiple brain systems. The WM microstructure integrity impairment might be an essential correlate of emotion dysregulation in ADHD.