Large-scale network abnormality in bipolar disorder: A multimodal meta-analysis of resting-state functional and structural magnetic resonance imaging studies

Bipolar disorder (BD) has been linked to abnormalities in the communication and gray matter volume (GMV) of large-scale brain networks, as reflected by impaired resting-state functional connectivity (rs-FC) and aberrant voxel-based morphometry (VBM). However, identifying patterns of large-scale network abnormality in BD has been elusive. Whole-brain seed-based rs-FC and VBM studies comparing individuals with BD and healthy controls (HCs) were retrieved from multiple databases. Multilevel kernel density analysis was used to identify brain networks in which BD was linked to hyper-connectivity or hypo-connectivity with each prior network and the overlap between dysconnectivity and GMV changes. Thirty-six seed-based rs-FC publications (1526 individuals with BD and 1578 HCs) and 70 VBM publications (2715 BD and 3044 HCs) were included in the meta-analysis. Our results showed that BD was characterized by hypo-connectivity within the default network (DN), hyper-connectivity within the affective network (AN), and ventral attention network (VAN) and hypo- and hyper-connectivity within the frontoparietal network (FN). Hyper-connectivity between-network of AN-DN, AN-FN, AN-VAN, AN-thalamus network (TN), VAN-TN, VAN-DN, VAN-FN, and TN-sensorimotor network were found. Hypo-connectivity between-network of FN and DN was observed. Decreased GMV was found in the insula, inferior frontal gyrus, and anterior cingulate cortex. Differential weights in the number of included studies and sample size of FC and VBM might have a disproportionate influence on the meta-analytic results. These results suggest that BD is characterized by both structural and functional abnormalities of large-scale neurocognitive networks, especially in the DN, AN, VAN, FN, and TN. • This is the first meta-analysis to comprehensively illustrate disconnection and structure perturbations in large-scale brain networks in bipolar disorder. • Multimodal conjunction analysis found dysconnectivity in bipolar disorder converged with reduced gray matter volume. • Bipolar disorder is characterized by both structural and functional abnormalities of large-scale neurocognitive networks, especially in the default mode network, affective network, ventral attention network, fronto-parietal network, and thalamus network.