Altered resting-state functional connectivity in bipolar disorder: a systematic review.

Bipolar disorder (BD) is a chronic psychiatric illness characterized by recurrent episodes of mania and depression with intervening euthymic periods and persistent cognitive and affective dysfunction. Resting-state functional magnetic resonance imaging (rs-fMRI) may provide insights into intrinsic brain network alterations underlying mood dysregulation in BD, but findings remain heterogeneous across analytic approaches. Our study aims to systematically synthesize rs-fMRI evidence on FC alterations in adults with BD across all major analytic methods. A systematic review and meta-analytic synthesis were conducted following PRISMA guidelines and Cochrane recommendations (PROSPERO: CRD420251041135). PubMed/MEDLINE, Embase, and Scopus were searched from inception to February 25, 2025. Eligible studies included adult BD patients diagnosed by DSM criteria, healthy controls, rs-fMRI acquisition, and any FC analytic approach. Two reviewers independently performed screening, data extraction, and quality assessment using the Newcastle–Ottawa Scale. Seventeen studies comprising 1,899 participants (978 BD) met inclusion criteria. Methods included independent component analysis, seed-based, ROI-to-ROI, graph-theory, ALFF, and ReHo approaches. Convergent evidence demonstrated FC alterations predominantly within and between the Default Mode Network (DMN), Central Executive Network (CEN), and Ventral Attention Network (VAN). Frequently affected regions included the prefrontal cortex, inferior frontal gyrus, posterior cingulate cortex/precuneus, and supramarginal gyrus. Patterns included mixed hyper- and hypoconnectivity in prefrontal and inferior frontal regions, consistent DMN hub hypoconnectivity, and variable VAN alterations. Study quality was moderate to high overall, though methodological heterogeneity and clinical variability were common. Consistent FC alteration in BD demonstrate large-scale network dysconnectivity centered on DMN, CEN, and VAN hubs, supporting a triple-network model of disrupted cognitive-affective regulation. Despite analytic and clinical heterogeneity, convergent regional patterns suggest distributed network level pathology. Longitudinal multimodal studies are needed to clarify state versus trait effects and advance FC measures toward clinical utility.