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

Abstract

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 to ADHD symptoms remain largely unclear. Whereas resting state activity reflecting inherent ’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 freely execute goal-directed actions, a passive naturalistic Video Viewing task, and a standard Resting State condition. Thirty-nine children with ADHD and thirty-seven typically developing (TD) children matching in age and gender participated in this preregistered study. Functional connectivity was examined with network-based statistics (NBS) and graph theoretical metrics. During the VR task that has been developed for precision diagnostics, 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 as subcortical rewiring 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. In a similar vein, only during the VR task and Video Viewing, functional connectivity in TD controls was associated with attention-related behavioral performance. These observations were consistent across NBS and graph theoretical analyses, although NBS revealed more pronounced group differences. We conclude that overt expression of the symptoms has a key role in driving the 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.