Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered.

Methods: In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset.

Results: As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset.

Conclusion: Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.