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

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.