Concussion and Attention-Deficit/Hyperactivity Disorder: Investigating the relationship between cognitive outcome, prescription stimulants, and functional MRI biomarkers in the ABCD study.

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Project Summary/Abstract Traumatic brain injury (TBI) is the most common cause of acquired neurological deficits in children. Mild TBI, or concussion, is highly prevalent in adolescence, and is linked with short- and long-term cognitive deficits, chiefly inattention. Attention-deficit hyperactivity disorder (ADHD) is similarly prevalent in children and represents a primary form of inattention that occurs even without a history of head injury. The phenotypic similarity between primary ADHD vs long-term symptoms of inattention subsequent to concussion is both a diagnostic dilemma and clinical window of opportunity into the mechanisms by which brain injury affects cognition. In line with this framework, the goal of this K23 award is to provide the applicant with training necessary to identify distinct signatures of brain activity in children with primary ADHD vs ADHD with a history of concussion, which will motivate mechanism-specific treatments for these inattention symptoms. The proposed research leverages the Adolescent Brain Cognitive Development study, which is the largest ever cohort of children with concussion paired with detailed cognitive and functional MRI data, to achieve this goal. It capitalizes on the the superb cognitive neuroscience and imaging expertise of the applicant's mentors and collaborators to achieve the applicant’s short-term goals of training in cognitive assessment (Dr. Barch), TBI research (Dr. Brody), ADHD research (Dr. Fair), task-based (stop signal, n-back) fMRI (Dr. Barch), resting state fMRI (Dr. Dosenbach), and multivariate imaging statistics (Dr. Thompson). The proposed training will facilitate the applicant’s long-term goal of becoming an independent physician-scientist in the field of cognitive neuroimaging. These training goals will be advanced through the proposed research. First, the applicant will use multivariate fMRI methods to detect distinct patterns of task-related brain activation (Aim 1a) and resting-state connectivity (1b) in children with ADHD and a history of concussion, compared to controls and either condition alone. Then the applicant will investigate the fMRI correlates of time since last concussion (Aim 2) using task-related and resting-state fMRI. Finally, the applicant will perform exploratory analysis on the effects of prescription stimulant medications on brain activity in these groups (Aim 3). Notably, the proposed methods and techniques can be extended to answer many other outstanding questions about the intersection between neurological and cognitive disorders in the ABCD and future imaging studies. With a research program that employs multiple converging techiques to interrogate neural signatures related to concussion and its cognitive sequelae, the applicant will continue to address research questions relevant to the NINDS throughout his independent career.