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An integrated analysis across separate task domains reveals a lack of common processing in the ADHD brain

By Roselyne J. Chauvin, Jan Buitelaar, Marianne Oldehinkel, Barbara Franke, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian Beckmann, Maarten Mennes

Posted 05 Sep 2019
bioRxiv DOI: 10.1101/755603

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.

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