Aberrant Development of Functional Connectivity among Resting State-Related Functional Networks in Medication-Naive ADHD Children

Objective: The aim of this study was to investigate the compromised developmental trajectory of the functional connectivity among resting-state-related functional networks (RSFNs) in medication-naive children with attention-deficit/hyperactivity disorder (ADHD). Subjects and Methods: Using both independent component analysis and dual regression, subject-specific time courses of 12 RSFNs were extracted from both 20 medication-naive children with ADHD, and 20 age and gender-matched control children showing typical development (TDC). Both partial correlation coefficients among the 12 RSFNs and a resting-state resource allocation index (rsRAI) of the salience network (SN) were entered into multiple linear regression analysis to investigate the compromised, age-related change in medication-naive ADHD children. Finally, correlation analyses were performed between the compromised RSFN connections showing significant group-by-age interaction and rsRAI of SN or clinical variables. Results: Medication-naive ADHD subjects failed to show age-related increment of functional connectivity in both rsRAI of SN and two RSFN connections, SN-Sensory/motor and posterior default mode/precuneus network (pDMN/prec) - anterior DMN. Lower SN-Sensory/motor connectivity was related with higher scores on the ADHD Rating Scale, and with poor scores on the continuous performance test. The pDMN/prec-aDMN connectivity was positively related with rsRAI of SN. Conclusions: Our results suggest that medication-naive ADHD subjects may have delayed maturation of the two functional connections, SN-Sensory/Motor and aDMN-pDMN/prec. Interventions that enhance the functional connectivity of these two connections may merit attention as potential therapeutic or preventive options in both ADHD and TDC.