Disrupted Brain Functional Networks in Drug-Naïve Children with ADHD Assessed Using Graph Theory Analysis

Abstract

Background: Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in childhood characterized by multiple behavioral problems and executive dysfunctions. Neuroimaging studies revealed a variety of abnormalities, but the results were inconsistent, partly owing to confounding medication effects and psychiatric comorbidities. Thus, studies of drug- naive ADHD with limited comorbidities is needed to better define disorder-related abnormalities in brain networks. Methods: Resting state functional magnetic resonance imaging was performed on 51 drug-naive ADHD patients (age 6 to 16) and 55 age-matched healthy controls. Brain functional networks were constructed by thresholding partial correlation matrices of 90 brain regions, and graph theory was used to analyze the network topological properties. The Stroop test was used to assess the cognitive inhibitory abilities in the subjects. The non-parametric permutation tests were used to compare the topological architectures in the two groups. Results: Compared with the healthy subjects, the brain networks in the ADHD patients demonstrated altered topological characteristics including lower global and local efficiency ( p=.002,.026), and longer path length (p=.002). Lower nodal efficiencies were found in the left inferior frontal gyrus and anterior cingulate cortex in the ADHD group (p<.05, corrected for the FDR). Altered global and nodal topological efficiency were associated with severity of inhibitory cognitive control deficits and hyperactivity symptoms in ADHD (p<.05). Conclusions: Alterations in network typologies in drug-naive ADHD indicate a weaker small-worldization with decreased segregation and integration of functional brain networks, notably involving a dysfunction of the cingulo-fronto-parietal attention network that was associated with inhibitory control deficits. Funding Statement: This study was supported by the National Natural Science Foundation (Grant Nos. 81621003，81761128023, 81220108013, 81227002, 81030027, 81671669, 81371536 and 81801358), the Humboldt Foundation, and the Program for Changjiang Scholars and Innovative Research Teams in Universities of China (PCSIRT, Grant No. IRT16R52). Dr. Gong would also like to acknowledge the support from his Changjiang Scholar Professorship Award of China (Award No. T2014190) and American CMB Distinguished Professorship Award (Award No. F510000/ G16916411) administered by the Institute of International Education, USA Declaration of Interests: None of the authors has conflicts of interests to report with regard to this manuscript. Ethics Approval Statement: This study was approved by the research ethics committee of West China Hospital of Sichuan University, written informed consent was obtained from the parents/guardians of all participants, and the assents were obtained from study participants prior to participation.