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

R.J. Chauvin, J.K. Buitelaar, E. Sprooten, M. Oldehinkel, B. Franke, C. Hartman, D.J. Heslenfeld, P.J. Hoekstra, J. Oosterlaan, C.F. Beckmann, M. Mennes

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

© 2021, The Author(s).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.
Original languageEnglish
Article number159
JournalTranslational Psychiatry
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jun 2021

Funding

This work was supported by a Marie Curie International Incoming Fellowship under the European Union\u2019s Seventh Framework Programme (FP7/ 2007\u20132013), Grant 327340 (Brain Fingerprint) to MM; The Netherlands Organization for Scientific Research (NWO) Grant NWO-Vidi 864-12-003 to CFB; and Wellcome Trust UK Strategic Award [098369/Z/12/Z] to CFB. Additional support was received from the European Community\u2019s Horizon 2020 Programme (H2020/2014\u20132020) under grant agreements 667302 (CoCA) and 728018 (Eat2beNICE). BF is supported by a personal Vici grant of the Netherlands Organization for Scientific Research (NWO; grant 016-130-669). The NeuroIMAGE study was supported by NIH Grant R01MH62873, NWO Large Investment Grant 1750102007010 (to JB), ZonMW grant 60-60600-97-193, NWO grants 056-13-015 and 433-09-242, and matching grants from Radboud University Medical Center, University Medical Center Groningen and Accare, and Vrije Universiteit Amsterdam. The research leading to these results also received support from the European Community\u2019s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 278948 (TACTICS) and 603016 (MATRICS) and the Innovation Medicine Initiative grants 115300 (EU-AIMS) and 777394 (AIMS-2-TRIALS).

FundersFunder number
National Institute of Mental HealthR01MH062873

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