Real-world goal-directed behavior reveals aberrant functional brain connectivity in children with ADHD

Functional connectomics is a popular approach to investigate the neural underpinnings of developmental disorders of which attention deficit hyperactivity disorder (ADHD) is one of the most prevalent. Nonetheless, neuronal mechanisms driving the aberrant functional connectivity resulting in ADHD symptoms remain largely unclear. Whereas resting state activity reflecting intrinsic tonic background activity is only vaguely connected to behavioral effects, naturalistic neuroscience has provided means to measure phasic brain dynamics associated with overt manifestation of the symptoms. Here we collected functional magnetic resonance imaging (fMRI) data in three experimental conditions, an active virtual reality (VR) task where the participants execute goal-directed behaviors, a passive naturalistic Video Viewing task, and a standard Resting State condition. Thirty-nine children with ADHD and thirty-seven typically developing (TD) children participated in this preregistered study. Functional connectivity was examined with network-based statistics (NBS) and graph theoretical metrics. During the naturalistic VR task, the ADHD group showed weaker task performance and stronger functional connectivity than the TD group. Group differences in functional connectivity were observed in widespread brain networks: particularly subcortical areas showed hyperconnectivity in ADHD. More restricted group differences in functional connectivity were observed during the Video Viewing, and there were no group differences in functional connectivity in the Resting State condition. These observations were consistent across NBS and graph theoretical analyses, although NBS revealed more pronounced group differences. Furthermore, during the VR task and Video Viewing, functional connectivity in TD controls was associated with task performance during the measurement, while Resting State activity in TD controls was correlated with ADHD symptoms rated over six months. We conclude that overt expression of the symptoms is correlated with aberrant brain connectivity in ADHD. Furthermore, naturalistic paradigms where clinical markers can be coupled with simultaneously occurring brain activity may further increase the interpretability of psychiatric neuroimaging findings.