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

Abstract

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. 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 Study authors were systematically contacted for additional unpublished information/data.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. 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-naïve patients. 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.