Fixel-based diffusion MRI reveals novel associations between white matter microstructure and childhood aggressive behavior

Abstract Background Childhood aggression has been linked to white matter abnormalities, but research has been inconsistent in both regions of alterations and directionality of the associations. We examined white matter microstructure correlates of aggression using a novel diffusion imaging analysis technique, fixel-based analysis, which leverages connectivity and crossing-fiber information to assess fiber bundle density. Method The sample included 70 children with aggressive behavior and 25 healthy controls without aggressive behavior. Aggression was measured by the parent-rated Aggressive Behavior scale of the Child Behavior Checklist (CBCL). Fixel-based analysis was conducted at the whole-brain and region-of-interest (ROI) levels including uncinate fasciculus, inferior longitudinal fasciculus, fornix, cingulate bundle, and genu, body, isthmus, and splenium of the corpus callosum. Results Whole-brain analysis of covariance revealed that children with aggressive behavior, relative to controls, had lower fiber density in a cluster of limbic and cortical pathways including inferior fronto-occipital fasciculus, fornix, middle cerebellar peduncle, and superior thalamic radiations (FWE-corrected p Conclusions Diminished white matter density in pathways connecting limbic and cortical regions are associated with childhood aggression. Abnormal interhemispheric connectivity via corpus callosum may also reflect a potential neural mechanism involved in aggression.