Systematic Review and Meta-analysis: Resting-State Functional Magnetic Resonance Imaging Studies of Attention-Deficit/Hyperactivity Disorder

Objective: To conduct a meta-analysis of resting-state functional magnetic resonance imaging (R-fMRI) studies in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and in adults with ADHD to assess spatial convergence of findings from available studies. Method: Based on a preregistered protocol in PROSPERO (CRD42019119553), a large set of databases were searched up to April 9, 2019, with no language or article type restrictions. Study authors were systematically contacted for additional unpublished information/data. Resting-state functional magnetic resonance imaging studies using seed-based connectivity (SBC) or any other method (non-SBC) reporting whole-brain results of group comparisons between participants with ADHD and typically developing controls were eligible. Voxelwise meta-analysis via activation likelihood estimation with cluster-level familywise error (voxel-level: p < .001; cluster-level: p < .05) was used. Results: Thirty studies (18 SBC and 12 non-SBC), comprising 1,978 participants (1,094 with ADHD; 884 controls) were retained. The meta-analysis focused on SBC studies found no significant spatial convergence of ADHD-related hyperconnectivity or hypoconnectivity across studies. This nonsignificant finding remained after integrating 12 non-SBC studies into the main analysis and in sensitivity analyses limited to studies including only children or only non-medication-naive patients. Conclusion: The lack of significant spatial convergence may be accounted for by heterogeneity in study participants, experimental procedures, and analytic flexibility as well as in ADHD pathophysiology. Alongside other neuroimaging meta-analyses in other psychiatric conditions, the present results should inform the conduct and publication of future neuroimaging studies of psychiatric disorders.