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

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

doi:10.1038/s41398-021-01284-z

Abstract

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.

Highlights

Attention-deficit/hyperactivity disorder (ADHD) is a mostly early onset neurodevelopmental disorder characterised by symptoms of inattention and/or hyperactivity-impulsivity that are associated with impairments in multiple functional domains[1]
Establishing an ADHD connectivity profile Starting from the set of connections that yielded significant connectivity modulations across all participants, we compared the diagnostic groups in terms of the sensitivity and specificity of their connectome to task modulations
We used a novel framework to provide an overarching perspective on the neurobiology of ADHD by inferring the nature of connectivity modulations in ADHD under the demands of working memory, reward processing, and response inhibition tasks

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is a mostly early onset neurodevelopmental disorder characterised by symptoms of inattention and/or hyperactivity-impulsivity that are associated with impairments in multiple functional domains[1]. Theories suggesting inefficient management of resources in participants with ADHD would be supported by observing, for example, a pattern of modulations that is highly specific to each task, while an overall cognitive core in support of task-general processes remains under-modulated[16,17]. Both theories are not incompatible: an alteration in one function network may induce coping strategies involving other functional networks. In light of these possibilities we hypothesized that, in ADHD, the brain’s functional core interacts differently with more specialized network modulations, which could reflect inefficient use of the brain’s resources in ADHD

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