General Microstructure Factor Analysis of Diffusion MRI in Gray-Matter Predicts Cognitive Scores

Diffusion MRI has revealed important insights into white matter microstructure, but its application to gray matter remains comparatively less explored. Here, we investigate whether global patterns of gray-matter microstructure can be captured through neurite orientation dispersion and density imaging (NODDI) and whether such patterns are predictive of cognitive performance. Our findings demonstrate that PCA-based global indicators of gray-matter microstructure provide complementary markers of structure-function relationships, extending beyond region-specific analyses. Our results suggest that general microstructure factors may serve as robust, interpretable biomarkers for studying cognition and cortical organization at the population level. Using diffusion MRI and behavioral data from the Human Connectome Project Young Adult study, we derived region-averaged NODDI parameters and applied principal component analysis (PCA) to construct general gray-matter microstructure factors. We found that the factor derived from isotropic volume fraction explained substantial inter-individual variability and was significantly correlated with specific cognitive scores collected from the NIH Toolbox. In particular, the isotropic volume fraction factor was linked to reading and vocabulary performance and to cognitive fluidity.