Intrinsic Brain Abnormalities in Attention Deficit Hyperactivity Disorder: A Resting-State Functional MR Imaging Study

Fei Li, PhD, Ning He, MD, Yuanyuan Li, MD, Lizhou Chen, MD, Xiaoqi Huang, PhD, Su Lui, PhD, Lanting Guo, MD, Graham J. Kemp, MA, DM, Qiyong Gong, MD, PhD


Attention deficit hyperactivity disorder (ADHD), characterized by age-inappropriate degrees of inattention, hyperactivity, and impulsivity, affects about 5% of children and adolescents worldwide (1). Researchers who have performed functional magnetic resonance (MR) imaging studies exploiting blood oxygen level -dependent signal contrast have detected abnormalities in specific brain areas in ADHD, leading to the suggestion that frontostriatal dysfunction is important in the pathophysiologic functional changes of the disorder (2). However, reported results have been inconsistent: For example, in functional MR imaging with a response inhibition task, patients with ADHD have been reported as showing both decreased (3) and increased (4) activation in prefrontal regions. In view of this complexity, rather than focus on the dysregulation of particular areas in particular tasks, a better approach to the pathophysiologic functional changes of ADHD may be to consider the whole set of brain systems (5).

A task-independent approach to assessing regional and network-level brain function is resting-state functional MR imaging, in which spontaneous blood oxygen level-dependent fluctuations are thought to reflect spontaneous neural function in the resting state (6,7). Two derived measurement indexes, regional amplitude low frequency fluctuation (ALFF) and functional connectivity (FC), provide information on regional activity and network-level brain function, respectively (8,9). In contrast to the task-based approach, resting-state functional MR imaging is not susceptible to potential performance confounds and is relatively easy to implement in a clinical setting (10). Evidence from resting-state functional MR imaging has underpinned the development of models of ADHD that encompass a number of large-scale resting-state networks, suggesting that aberrant frontosubcortical circuits are not a sufficient explanation (5).

However, the specific neuropsychological dysfunction underlying such atypical brain network profiles remains poorly understood (11). Patients with ADHD often exhibit deficiencies in cognitive function, particularly in executive functions such as strategic planning, set switching, cognitive flexibility, and interference inhibition (12), which can be defined by neuropsychological tests such as the Wisconsin Card Sorting Test (WCST) (13) and the Stroop Color-Word Test (14). A link to executive dysfunction is central to models involving aberrant frontosubcortical circuits; however, there has been much debate about what core deficit of brain function might cause the impairments of ADHD (2).

The aims of the present study were to explore alterations of regional and network-level neural function by using resting-state functional MR imaging in children and adolescents with ADHD and to assess the association between these alterations of intrinsic neural activity and executive dysfunction in ADHD.