Abnormal hemispheric asymmetry of both brain function and structure in attention deficit/hyperactivity disorder: a meta-analysis of individual participant data.

Aberration in the asymmetric nature of the human brain is associated with several mental disorders, including attention deficit/hyperactivity disorder (ADHD). In ADHD, these aberrations are thought to reflect key hemispheric differences in the functioning of attention, although the structural and functional bases of these defects are yet to be fully characterized. In this study, we applied a comprehensive meta-analysis to multimodal imaging datasets from 627 subjects (303 typically developing control [TDCs] and 324 patients with ADHD) with both resting-state functional and structural magnetic resonance imaging (MRI), from seven independent publicly available datasets of the ADHD-200 sample. We performed lateralization analysis and calculated the combined effects of ADHD on each of three cortical regional measures (grey matter volume - GMV, fractional amplitude of low frequency fluctuations at rest -fALFF, and regional homogeneity -ReHo). We found that compared with TDC, 68%,73% and 66% of regions showed statistically significant ADHD disorder effects on the asymmetry of GMV, fALFF, and ReHo, respectively, (false discovery rate corrected, q = 0.05). Forty-one percent (41%) of regions had both structural and functional abnormalities in asymmetry, located in the prefrontal, frontal, and subcortical cortices, and the cerebellum. Furthermore, brain asymmetry indices in these regions were higher in children with more severe ADHD symptoms, indicating a crucial pathoplastic role for asymmetry. Our findings highlight the functional asymmetry in ADHD which has (1) a strong structural basis, and thus is likely to be developmental in nature; and (2) is strongly linked to symptom burden and IQ and may carry a possible prognostic value for grading the severity of ADHD.