Resting state dynamic functional connectivity in children with attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder (ADHD) is characterized by inattention, hyperactivity and impulsivity. In this study, we investigated group differences in dynamic functional connectivity (dFC) between 113 children with inattentive (46 ADHD_I) and combined (67 ADHD_C) ADHD and 76 typically developing (TD) children using resting-state functional MRI data. For dynamic connectivity analysis, the data were first decomposed into 100 independent components, among which 88 were classified into eight well-known resting-state networks (RSNs). Three discrete FC states were then identified using k-means clustering and used to estimate transition probabilities between states in both patient and control groups using a hidden Markov model. Our results showed state-dependent alterations in intra and inter-network connectivity in both ADHD subtypes in comparison with TD. Spending less time than healthy controls in state 1, both ADHD_Iand ADHD_Cwere characterized with weaker intra-hemispheric connectivity with functional asymmetries. In this state, ADHD_Ifurther showed weaker inter-hemispheric connectivity. The patients spent more time in state 2, exhibiting characteristic abnormalities in corticosubcortical and corticocerebellar connectivity. In state 3, a less frequently state observed across the ADHD and TD children, ADHD_Cwas differentiated from ADHD_Iby significant alterations in FC between bilateral temporal regions and other brain areas in comparison with TD. Across all three states, several strategic brain regions, mostly bilateral, exhibited significant alterations in both static functional connectivity (sFC) and dFC in the ADHD groups compared to TD, including inferior, middle and superior temporal gyri, middle frontal gyri, insula, anterior cingulum cortex, precuneus, calcarine, fusiform, superior motor area, and cerebellum. Our results show distributed abnormalities in sFC and dFC between different large-scale RSNs including cortical and subcortical regions in both ADHD subtypes compared to TD. Our findings show that the dynamic changes in brain FC can better explain the underlying pathophysiology of ADHD such as deficits in visual cognition, attention, memory and emotion processing, and cognitive and motor control.