Beyond tractography in brain connectivity mapping with dMRI morphometry and functional networks

Abstract

Traditional brain connectivity studies have focused mainly on structural connectivity, often relying on tractography with diffusion MRI (dMRI) to reconstruct white matter pathways. In parallel, studies of functional connectivity have examined correlations in brain activity using fMRI. However, emerging methodologies are advancing our understanding of brain networks. Here we explore advanced connectivity approaches beyond conventional tractography, focusing on dMRI morphometry and the integration of structural and functional connectivity analysis. dMRI morphometry enables quantitative assessment of white matter pathway volumes through statistical comparison with normative populations, while functional connectivity reveals network organization that is not restricted to direct anatomical connections. More recently, approaches that combine diffusion tensor imaging (DTI) with functional correlation tensor (FCT) analysis have been introduced, and these complementary methods provide new perspectives into brain structure-function relationships. Together, such approaches have important implications for neurodevelopmental and neurological disorders as well as brain plasticity. The integration of these methods with artificial intelligence techniques have the potential to support both basic neuroscience research and clinical applications.

Keywords: Functional MRI; Functional correlation tensor; Microstructure; Structure-function coupling; White matter.

Fig. 1

Conceptual schematic of modalities, methods, connectivity domains, and integration. The schematic illustrates a flow from imaging modalities to integration. At the top, diffusion MRI (dMRI) and functional MRI (fMRI) serve as complementary inputs. From dMRI, two analyses are highlighted: morphometry, which employs deformation fields to enhance sensitivity for detecting morphological abnormalities in specific white matter pathways, and fiber orientation, which supports tractography. From fMRI, neuroactivation measures contribute to functional analyses. These methods converge into two connectivity domains: tractography-based structural connectivity on the dMRI side, and correlation-based functional connectivity on the fMRI side. Finally, both domains merge at the bottom into structure–function coupling, providing a conceptual framework to relate microstructural features with large-scale functional networks and to inform both neuroscience research and potential clinical applications

Fig. 2

Structure-function connectivity relationships and clinical implications. Brain networks can be characterized through both structural and functional approaches that provide complementary information. Structural connectivity (SC) maps direct white matter pathways, while functional connectivity (FC) identifies temporal correlations in neural activity. The moderate correlation between SC and FC (0.3–0.6) reveals that functional networks can operate beyond anatomical constraints, enabling brain plasticity and compensatory mechanisms. This dissociation has important implications for understanding healthy brain function, injury recovery, and neurodevelopmental disorders