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Task-generic and task-specific connectivity modulations in the ADHD brain: An integrated analysis across multiple tasks

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

Posted 05 Sep 2019
bioRxiv DOI: 10.1101/755603

Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with altered functioning in multiple cognitive domains and neural networks. This paper offers an overarching biological perspective across these. We applied a novel strategy that extracts functional connectivity modulations in the brain across one (Psingle), two (Pmix) or three (Pall) cognitive tasks and compared the pattern of modulations between participants with ADHD (n-89), unaffected siblings (n=93) and controls (n=84; total N=266; age range=8-27 years). Participants with ADHD had significantly fewer Pall connections (modulated regardless of task), but significantly more task-specific (Psingle) connectivity modulations than the other groups. The amplitude of these Psingle modulations was significantly higher in ADHD. Unaffected siblings showed a similar degree of Pall connectivity modulation as controls but a similar degree of Psingle connectivity modulation as ADHD probands. Pall connections were strongly reproducible at the individual level in controls, but showed marked heterogeneity in both participants with ADHD and unaffected siblings. The pattern of reduced task-generic and increased task-specific connectivity modulations in ADHD may be interpreted as reflecting a less efficient functional brain architecture due to a reduction in the ability to generalise processing pathways across multiple cognitive domains. The higher amplitude of unique task-specific connectivity modulations in ADHD may index a more -effortful- coping strategy. Unaffected siblings displayed a task connectivity profile in between that of controls and ADHD probands, supporting an endophenotype view. Our approach provides a new perspective on the core neural underpinnings of ADHD. ### Competing Interest Statement Jan K Buitelaar has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Shire, Roche, Medice, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. Barbara Franke has received educational speaking fees from Medice and Shire. Roselyne J. Chauvin, Marianne Oldehinkel, Catharina Hartman, Dirk J. Heslenfeld, Pieter J. Hoekstra, Jaap Oosterlaan, Christian F. Beckmann, Maarten Mennes reported no financial interests or potential conflicts of interest.

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