Differential structure-function network coupling in the inattentive and combined types of attention deficit hyperactivity disorder

Abstract

The heterogeneous presentation of inattentive and hyperactive-impulsive core symptoms in attention deficit hyperactivity disorder (ADHD) warrants further investigation into brain network connectivity as a basis for subtype divisions in this prevalent disorder. With diffusion and resting-state functional magnetic resonance imaging data from the Healthy Brain Network database, we analyzed both structural and functional network efficiency and structure-functional network (SC-FC) coupling at the default mode (DMN), executive control (ECN), and salience (SAN) intrinsic networks in 201 children diagnosed with the inattentive subtype (ADHD-I), the combined subtype (ADHD-C), and typically developing children (TDC) to characterize ADHD symptoms relative to TDC and to test differences between ADHD subtypes. Relative to TDC, children with ADHD had lower structural connectivity and network efficiency in the DMN, without significant group differences in functional networks. Children with ADHD-C had higher SC-FC coupling, a finding consistent with diminished cognitive flexibility, for all subnetworks compared to TDC. The ADHD-C group also demonstrated increased SC-FC coupling in the DMN compared to the ADHD-I group. The correlation between SC-FC coupling and hyperactivity scores was negative in the ADHD-I, but not in the ADHD-C group. The current study suggests that ADHD-C and ADHD-I may differ with respect to their underlying neuronal connectivity and that the added dimensionality of hyperactivity may not explain this distinction.

Fig 1. ADHD-related brain networks for subnetwork analysis—The default mode network (12 regions), executive control network (12 regions), and salience network (12 regions).

Abbreviations: ANG, angular gyrus; PRCU, precuneus; ACC, anterior cingulate cortex; MCC, middle cingulate cortex; OFGmed, orbitofrontal cortex (medial part); MTG, middle temporal gyrus; SFGdor, superior frontal gyrus (dorsal part); MFG, middle frontal gyrus; IFGop, inferior frontal gyrus (pars orbitalis); IFGtr, inferior frontal gyrus (triangular part); IPL, inferior parietal lobe; CAU, caudate; INS, insular; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; SMA, supplementary motor area.

Fig 2. (A) Statistical group differences in structural connectivity between regions of the subnetworks (B) Because functional connectivity measures did not distinguish either ADHD subtype from TDC, only the difference in functional connectivity between the ADHD-I and ADHD-C subtypes are displayed (FDR < 0.05).

Fig 3. Group comparisons of global structural efficiency (A) and global functional efficiency (B) in the default mode, executive control, and salience networks.

*p<0.05, **p<0.01 (two-sample t-tests).

Fig 4. Structure-function coupling results for the ADHD-related subnetworks.

*p<0.05. **p<0.01 (two-sample t-tests).

Fig 5. Relationship between inattention and hyperactivity (A), between SC-FC coupling in the DMN and hyperactivity score (B) between SC-FC coupling in the DMN and inattention score (C) in ADHD-I and ADHD-C.

Diff: statistical significance of the two different correlation coefficients.

Fig 6. Summary of the global efficiency of both structural connectivity (SC) and functional connectivity (FC), and the SC-FC couplings in ADHD-related subnetworks.

The solid arrow indicates significant group differences and the dotted arrow indicates a tendency of differences (if not significant) between groups. The colors indicate the group means of each feature relative to the TDC. Red indicates higher mean value while blue indicates lower mean value than TDC. DMN: default mode network, ECN: executive control network, and SAN: salience network.