Linking Limbic-Prefrontal White Matter Microstructure to Behavioral Problems Following Pediatric Traumatic Brain Injury

Diffusion tensor imaging studies in children suggest a link between abnormal white matter in limbic-prefrontal circuitry and behavioral problems. However, in children with traumatic injury, links between atypical limbic-prefrontal circuitry and new behavioral problems remain largely unexamined. In a prospective longitudinal study of children ages 8-15 years, we examined white matter microstructure 7 weeks following a traumatic brain injury (TBI) or extracranial injury (EI) relative to typically developing children (TDC). Internalizing and externalizing behavioral problems were assessed via the Child Behavior Checklist; ratings estimated preinjury and 7-month postinjury status. Limbic-prefrontal white matter fiber tracts were estimated using seed-to-seed analysis originating in each amygdala and hippocampus; fractional anisotropy (FA) was calculated along with the tracts. Controlling for preinjury behavior problems, general linear models examined the effect of injury type on behavioral outcomes and pathway FA, including group (TBI+EI vs. TDC; TBI vs. EI), age, sex, and their interactions. Injured children had higher postinjury internalizing problem scores than TDC, and FA was lower in several pathways connecting hippocampi with nucleus accumbens and parahippocampal cingulate. Internalizing and/or externalizing problems were associated with FA of pathways connecting hippocampi to amygdalae, medial orbitalfrontal cortex, and parahippocampal cingulate, as well as pathways connecting amygdale to thalami. The relation between FA and behavioral problems was negative for the TBI group but neutral to positive for the EI and TDC groups. Together, these findings suggest disrupted microstructural organization of the limbic-prefrontal circuitry as a neurobiological predictor of behavioral problems following TBI.