Identifying Developmental Changes in Functional Brain Connectivity Associated with Cognitive Functioning in Children and Adolescents with ADHD

Children and adolescents diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) often show deficits in various measures of higher-level cognition, such as, memory and executive functioning. Poorer high-level cognitive functioning in children with ADDH has been associated with differences in functional connectivity across the brain, including the frontoparietal network. However, little is known about the developmental changes to cortical functional connectivity profiles associated with higher-order cognitive abilities in this cohort. To characterize changes in the functional brain connectivity profiles related to higher-order cognitive functioning, we analyzed a large dataset(n=479) from the publicly available Healthy Brain Network which included fMRI data collected while children and adolescents between the ages of 6 and 16 watched a short movie-clip. The cohort was divided into two groups, neurotypical youth (n=106), and children and adolescents with ADHD (n=373). We applied machine learning models to functional connectivity profiles generated from the fMRI data to identify patterns of network connectivity that differentially predict cognitive abilities in our cohort of interest. We found, using out-of-sample cross validation, models using functional connectivity profiles in response to movie-watching successfully predicted IQ, visual spatial, verbal comprehension, and fluid reasoning in children ages 6 to 11, but not in adolescents with ADHD. The models identified connections with the default mode, memory retrieval, and dorsal attention networks as driving prediction during early and middle childhood, but connections with the somatomotor, cingulo-opercular, and frontoparietal networks were more important in middle childhood. This work demonstrated that computational models applied to neuroimaging data in response to naturalistic stimuli can identify distinct neural mechanisms associated with cognitive abilities at different developmental stages in children and adolescents with ADHD.