Unraveling the neurochemical basis of structure-function coupling in bipolar disorder: A multimodal data fusion analysis.
OBJECTIVES To characterize coupled structural-functional alterations and their spatial associations with normative neurotransmitter receptor/transporter maps in bipolar disorder (BD) using multimodal magnetic resonance imaging (MRI) data fusion. METHODS Structural MRI (gray matter volume, GMV) and resting-state functional MRI (fractional amplitude of low-frequency fluctuations, fALFF) data were acquired from 51 BD patients and 51 demographically matched healthy controls (HCs). Parallel independent component analysis (P-ICA) was used to identify covarying GMV-fALFF components. Significant component maps were then compared with 12 normative positron emission tomography/single photon emission computed tomography (PET/SPECT) neurotransmitter receptor/transporter maps using the JuSpace toolbox. RESULTS P-ICA identified one significantly correlated GMV-fALFF component pair that showed lower loading coefficients in BD patients (p < 0.001). These alterations primarily involved key nodes of the frontoparietal, default-mode, and salience networks, as well as the cerebellar-thalamic-prefrontal circuit. Spatial correlation analysis showed that the fALFF component was positively associated with normative dopaminergic (DAT, FDOPA) and opioid (μ-receptor) maps and negatively associated with serotonergic (5-HT1b, 5-HT2a), dopaminergic (D2), GABAergic (GABAa), and glutamatergic (mGluR5) maps. The GMV component showed negative spatial associations with serotonergic (5-HT2a, SERT), dopaminergic (D1, DAT), opioid (μ-receptor) and glutamatergic (mGluR5) maps. CONCLUSION These findings identify significantly covarying structure-function components in BD and suggest their links to large-scale brain network abnormalities. The integration of multimodal MRI with normative molecular atlases provides a scalable framework for linking macroscopic imaging phenotypes to molecular architecture, generating testable hypotheses for future validation with patient-specific PET/SPECT and multi-center studies.