Abstract
Background Multiple cognitive theories have been proposed to explain the cognitive impairments observed in Attention-deficit/Hyperactivity Disorder (ADHD). Functional imaging studies building on these theories reveal a heterogeneous pattern of neuronal dysfunction and fail to provide an overarching perspective on the pathophysiology of ADHD. Going beyond single task analyses, we here apply a biotyping strategy that integrates results across multiple task domains and assess common neuronal alteration.
Method We integrated across multiple functional magnetic resonance imaging acquisitions: resting-state, and working memory, monetary incentive delay, and stop signal tasks collected in 96 participants with ADHD, 78 unaffected siblings, and 156 controls (total N=330, age range=8-27 years). We indexed whether connections were modulated away from the resting-state baseline, across all tasks or specific to individual task paradigms and we then assessed their group membership.
Results Participants with ADHD and unaffected siblings exhibited a reduced number of connections that were modulated regardless of task, compared to control, but an increased number of task-specific connections. However, siblings over-modulated connections also modulated by the other groups, while participants with ADHD relied on over-modulating task-specific patterns of connectivity. Finally, task common connections were reproducible in controls, yet highly variable in both ADHD and siblings.
Conclusions Participants with ADHD and unaffected siblings exhibit a similar neurobiological profile characterized by a lack of across task connections and an increase in task-tailored connections. Although showing a similar functional brain fingerprint, siblings might compensate through increasing the amount of modulation. The absence of common connections is a potential predictive biomarker of an at-risk ADHD profile.
