Structural and Functional Abnormalities in Children with Attention-Deficit/Hyperactivity Disorder: A Focus on Subgenual Anterior Cingulate Cortex

Abstract

Attention-deficit/hyperactivity disorder (ADHD), characterized by developmentally inappropriate inattention, hyperactivity/impulsivity, or a combination of both, is a major public health problem. Neuroimaging studies have revealed associations of these cognitive impairments with structural and functional deficits all over the brain. Existing findings are not fully consistent because of the heterogeneity of study samples and diversity of research techniques. In this study, we propose to utilize a multimodal magnetic resonance imaging (MRI) approach to study the structural and functional brain networks in children with ADHD-combined type (ADHD-C) with a focus on the subgenual anterior cingulate cortex (sgACC). Diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI) data from 32 children with ADHD-C and 32 group-matched controls were involved. Network-based statistic analysis of the rs-fMRI data revealed a disconnected functional network between the sgACC and multiple regions in the occipital lobe and cerebellum, whereas the DTI data showed disrupted white matter integrity in the subgenual cingulum bundle (sgCB). Post hoc region of interest (ROI)-based analyses showed significantly increased fluctuation of the spontaneous brain activity in the sgACC and higher radial diffusivity in the sgCB in the ADHD group. Both the rs-fMRI and DTI ROI-based measures were significantly correlated with clinical measures that examine behavioral capacities of attention and inhibitory control. Findings of this study suggest that functional alterations in the sgACC and white matter under development in the sgCB may impact each other, and together contribute to impaired attention and inhibitory control function in children with ADHD.

Keywords: ADHD; DTI; resting-state fMRI; subgenual anterior cingulate cortex; subgenual cingulum bundle.

FIG. 1.

A disconnected functional network in ADHD revealed by the network-based statistics analysis in resting-state fMRI data (nodes of the disconnected network are represented by spheres in sagittal (A), axial (B), and coronal (C) views. Regions in the sgACC, occipital lobe, and cerebellum are in red, blue, and magenta, respectively. 1, left sgACC; 2, right sgACC; 3, left cerebellum lobule VI; 4, right cerebellum lobule VI; 5, left superior occipital gyrus; 6, left cuneus gyrus; 7, right cuneus gyrus; 8, right calcarine gyrus; 9, right lingual gyrus). ADHD, attention-deficit/hyperactivity disorder; fMRI, functional magnetic resonance imaging; sgACC, subgenual anterior cingulate cortex. Color images available online at www.liebertpub.com/brain

FIG. 2.

White matter abnormalities in ADHD (RD was significantly increased in the sgCB (red in A) and PMC (red in B) in the ADHD group). For demonstration, the sgCC (Fig. 1) is displayed as a blue spot in (A). PMC, premotor cortex; RD, radial diffusivity; sgCB, subgenual cingulum bundle; sgCC, subgenual cingulate cortex. Color images available online at www.liebertpub.com/brain

FIG. 3.

Increased fluctuation of the spontaneous functional activation in the left sgACC was significantly correlated with increased clinical symptom severity in ADHD (average t value of a spherical ROI in sgACC was plotted with the parent hyperactive-impulsive T score (A), parent inattentive T score (B), and T score for sum of total raw scores (C). ADHD patients and normal controls are represented by orange diamonds (♦) and blue squares (■), respectively. ROI, region of interest. Color images available online at www.liebertpub.com/brain

FIG. 4.

Increased RD in sgCB and PMC was significantly correlated with the ADHD-associated symptom severity scores in the whole study sample (the average RD of the spherical ROIs in sgCB (A–C) and PMC (D–F) is plotted with the parent inattentive T score (A, D), parent hyperactive-impulsive T score (B, E), and T score for sum of total raw scores (C, F). The ADHD patients and normal controls are represented by red square (■) and green triangle (▲), respectively. Correlation coefficient (R) and p value for each correlation analysis are displayed in the subplot. Color images available online at www.liebertpub.com/brain