Rachael Grazioplene1, Wan-Ling Tseng2, Kimberly Cimino2, Carla Kalvin2, Karim Ibrahim2, Kevin A Pelphrey3, Denis G Sukhodolsky4. 1. Department of Psychology, Yale University, New Haven, Connecticut. 2. Child Study Center, Yale University School of Medicine, New Haven, Connecticut. 3. Department of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia. 4. Child Study Center, Yale University School of Medicine, New Haven, Connecticut. Electronic address: denis.sukhodolsky@yale.edu.
Abstract
BACKGROUND: Childhood aggression has been linked to white matter abnormalities, but research has been inconsistent with regard to 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. METHODS: The sample included 70 children with aggressive behavior and 25 healthy control children without aggressive behavior. Aggression was measured by the parent-rated Aggressive Behavior scale of the Child Behavior Checklist. Fixel-based analysis was conducted at the whole-brain and region-of-interest levels, including the uncinate fasciculus, inferior longitudinal fasciculus, fornix, cingulum 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 control children, had lower fiber density in a cluster of limbic and cortical pathways, including the inferior fronto-occipital fasciculus, fornix, middle cerebellar peduncle, and superior thalamic radiations (familywise error-corrected p < .01), and had higher fiber density in the corpus callosum (body and splenium) (familywise error-corrected p < .05). Region-of-interest analyses showed decreased fiber density in cingulum bundles associated with aggression. These effects were independent of age, sex, IQ, symptoms of attention-deficit/hyperactivity disorder, medications, and head motion. In children with aggressive behavior, co-occurring callous-unemotional traits and anxiety did not moderate the association between aggression and white matter density. CONCLUSIONS: Diminished white matter density in pathways connecting limbic and cortical regions is associated with childhood aggression. Abnormal interhemispheric connectivity via corpus callosum may also reflect a potential neural mechanism involved in aggression.
BACKGROUND: Childhood aggression has been linked to white matter abnormalities, but research has been inconsistent with regard to 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. METHODS: The sample included 70 children with aggressive behavior and 25 healthy control children without aggressive behavior. Aggression was measured by the parent-rated Aggressive Behavior scale of the Child Behavior Checklist. Fixel-based analysis was conducted at the whole-brain and region-of-interest levels, including the uncinate fasciculus, inferior longitudinal fasciculus, fornix, cingulum 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 control children, had lower fiber density in a cluster of limbic and cortical pathways, including the inferior fronto-occipital fasciculus, fornix, middle cerebellar peduncle, and superior thalamic radiations (familywise error-corrected p < .01), and had higher fiber density in the corpus callosum (body and splenium) (familywise error-corrected p < .05). Region-of-interest analyses showed decreased fiber density in cingulum bundles associated with aggression. These effects were independent of age, sex, IQ, symptoms of attention-deficit/hyperactivity disorder, medications, and head motion. In children with aggressive behavior, co-occurring callous-unemotional traits and anxiety did not moderate the association between aggression and white matter density. CONCLUSIONS: Diminished white matter density in pathways connecting limbic and cortical regions is associated with childhood aggression. Abnormal interhemispheric connectivity via corpus callosum may also reflect a potential neural mechanism involved in aggression.
Authors: Daniel F Connor; Jeffrey H Newcorn; Keith E Saylor; Birgit H Amann; Lawrence Scahill; Adelaide S Robb; Peter S Jensen; Benedetto Vitiello; Robert L Findling; Jan K Buitelaar Journal: J Child Adolesc Psychopharmacol Date: 2019-08-27 Impact factor: 2.576