Abnormalities Of Neural Network In Children With Attention Deficit Hyperactivity Disorder:a Functional Magnetic Resonance Imaging Study

Objective:Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood. It is characterized by impairing levels of inattention, disorganization, and hyperactivity-impulsivity while its etiology is still unclear. In this study, we utilized resting-state functional magnetic resonance imaging (RS-fMRI) and task fMRI to investigate the abnormalities of neural networks in children with attention deficit hyperactivity disorder as the frequency-dependent changes in the amplitude of low-frequency oscillations (LFOs), Granger causality correlation between dorsal attention network and ventral attention network, altered neral circuits related to sustained attention and executive control. Methods:29medication-naive children with ADHD-combined type and33healthy control aged from7to12years participated in the RS-fMRI scanning. The amplitude of low-frequency fluctuations of four different frequency bands, slow-5(0.01-0.027Hz), slow-4(0.027-0.073Hz), slow-3(0.073-0.198Hz) and slow-2(0.198-0.25Hz) was analyzed in children with and without ADHD. Furthermore, voxel-wise Granger causality strength (GCS) was used to analyze the spontaneous neural activities and to explore the causal interaction between dorsal attention network (DAN) and ventral attention network (VAN) in ADHD. Event-related functional magnetic resonance imaging (fMRI) was used to examine the brain activation of28medication-naive children with ADHD aged from7to12years and31healthy controls during a cued continuous performance task (AX-CPT) in three stimulus context conditions (Go, NoGo, Lure). Results:Comparet to controls, the ADHD children had increasd LFOs amplitude in the right medial frontal gyrus and bilateral postcentral gyri at four bands. Significant interaction between frequency band and group was observed in the cerebellum, right middle frontal gyrus/superior frontal gyrus, left medial frontal gyrus and left precuneus. Additionally, children with ADHD had increased GCS in bilateral precentral gyri and right inferior frontal gyrus relative to healthy control. Furthermore, the over-recruited of DAN and VAN in children with ADHD were caused by right inferior parietal lobe, right superior temporal gyrus, and right supramarginal gyrus (SMG). Besides, GCS of SMG exhibits a positive correlation with the ADHD symptom rating scores. In task fMRI, the children with ADHD showed increased activation in the left middle frontal gyrus, bilateral middle temporal gyrus, left precuneus and right cerebellum posterior lobe under the Lure condition compared to the controls. In the Lure condition, in contrast to the NoGo condition, an increased activation in the left inferior frontal gyrus, right medial frontal gyrus and right inferior parietal gyrus was observed in ADHD children.Conclusion:The children with ADHD have widespread abnormalities in intrinsic brain activity. And the abnormalities of LFOs is dependent on the frequency band. The increased effective connectivity in children with ADHD may indicate that the abnormal interaction between DAN and VAN may underlie the pathophysiology of inattention and hyperactivity in ADHD and a potential biomarker for ADHD. These findings show that there are alternations in neural circuits related to sustained attention and executive control in children with ADHD, and further improve our understanding of the neural substrates of cognitive impairment in children with ADHD.