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

OBJECTIVE We conducted a meta-analysis of resting state functional magnetic resonance imaging (R-fMRI) studies in children/adolescents and 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 9th, 2019, with no language/type-of-document restrictions. Study authors were systematically contacted for additional unpublished information/data. R-fMRI studies using seed-based connectivity (SBC) or any other method (non-SBC) reporting whole-brain results of group comparisons between individuals with ADHD and typically developing controls were eligible. Voxel-wise meta-analysis via activation likelihood estimation with cluster-level Family Wise Error (FWE) (voxel-level: p < 0.001; cluster-level: p < 0.05) was used. The full dataset used for analyses will be freely available online in an open source platform (http://anima.fz-juelich.de/). RESULTS 30 studies (18 SBC and 12 non-SBC), including a total of 1978 participants (1094 ADHD; 884 controls) were retained. The meta-analysis focused on SBC studies found no significant spatial convergence of ADHD-related hyper- or hypo-connectivity across studies. This non-significant 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, our results should inform the conduct and publication of future neuroimaging studies of psychiatric disorders.