Parallel multilink group joint ICA (pmg-jICA): Fusion of 3D structural and 4D functional data across multiple resting fMRI networks

Abstract Integrating neuroimaging data enhances our understanding of the brain. Structural magnetic resonance imaging (sMRI) offers high-resolution anatomical detail, while functional MRI (fMRI) captures dynamic neural activity. Combining these modalities can reveal significant structure–function relationships in the brain. However, existing approaches typically link sMRI to only a single fMRI network, overlooking the spatial complexity of multiple networks and thereby missing distributed structure–function relationships. To address this limitation, we present parallel multilink group joint ICA (pmg-jICA), a data-driven framework that fuses gray matter images from sMRI with multiple intrinsic fMRI networks within a single model. pmg-jICA captures cross-network structure–function coupling, preserves subject-specific variability, and enables robust group-level statistical analyses. To demonstrate the approach, we applied pmg-jICA to an Alzheimer’s disease (AD) dataset, recovering linked structural and functional components for 53 brain networks. Notably, patients with AD exhibited alterations in subcortical, cognitive control and visual regions. Importantly, the subject loadings enabled the computation of functional network connectivity (FNC), revealing additional alterations in subcortical, visual, and cognitive control systems. Overall, our results demonstrate that pmg-jICA overcomes key limitations of existing multimodal fusion techniques, yielding deeper insights into structure–function disruptions in AD and potentially offering a flexible framework for studying other neurological and psychiatric disorders.