Multimodal imaging biomarkers of cognitive control network deficits in youths with disruptive behavior

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Project Summary The goal of the proposed project is to investigate functional and structural brain networks that predict disruptive behavior in children. Disruptive behavior disorders (DBD) affect over 113 million youths worldwide and are characterized by irritability/anger, aggression, noncompliance, and/or antisocial behavior. These disorders are of great interest because they are highly predictive of delinquency, criminality, and substance abuse in later adolescence and adulthood. DBD also co-occur in over 50% of children with autism spectrum disorder (ASD). A large body of evidence links DBD with perturbations in frontoparietal circuitry that support the cognitive control of emotion (i.e., emotion regulation), particularly connections between regions of the dorsal and ventral prefrontal cortex (d/vPFC) and amygdala. However, it is unclear if dysregulation in emotion regulation circuitry can contribute to a biomarker of DBD in children with and without ASD. With a focus on the amygdala-d/vPFC circuit, this study will be the first to examine disruptions in brain-wide connectivity and structure in emotion regulation networks as a transdiagnostic biomarker of DBD and disruptive behavior problems more broadly in children. First, we will develop and test a multimodal imaging biomarker of DBD in the Adolescent Brain Cognitive Development study dataset, which contains clinical and fMRI data for 11,878 9-12 year olds in the first and second releases. Next, we will test the hypothesized disruptions in emotion regulation circuitry using a fMRI task of cognitive reappraisal in a new, transdiagnostic sample of children with disruptive behavior with and without ASD. This study will leverage cutting-edge neuroimaging analytics that resonate with several NIMH research priorities: network neuroscience or connectomics, multimodal imaging, computational modeling (machine learning), big data analytics, and the RDoC domain of cognitive control. The proposed research will push forward the development of brain-based biomarkers of disruptive behavior that could guide development of targeted interventions, refinement of existing treatments, or identify children likely to respond to a particular treatment. The proposed project will prepare Dr. Karim Ibrahim to become an independent clinical researcher with a unique niche and expertise in transdiagnostic brain biomarkers of emotion regulation in childhood-onset psychiatric disorders using connectomics, multimodal imaging, and predictive modeling approaches. To accomplish this, the proposed training will provide Dr. Karim Ibrahim with multidisciplinary training in network neuroscience/connectomics, machine learning/predictive modeling, biostatistical approaches for the analysis of large imaging datasets, and emotion regulation circuitry. The training and research are enhanced by the intellectually rigorous environment at the Yale Child Study Center and Department of Psychology. The mentorship of a multidisciplinary team with complementary expertise in fMRI, connectomics, and child psychopathology ensures achievement of the research and training aims.