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

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 (P single ), two (P mix ) or three (P all ) 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 P all connections (modulated regardless of task), but significantly more task-specific (P single ) connectivity modulations than the other groups. The amplitude of these P single modulations was significantly higher in ADHD. Unaffected siblings showed a similar degree of P all connectivity modulation as controls but a similar degree of P single connectivity modulation as ADHD probands. P all 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.