The shape of the brain's connections is predictive of cognitive performance: an explainable machine learning study.

The shape of the brain's white matter connections is relatively unexplored in diffusion MRI tractography analysis. While it is known that tract shape varies in populations and across the human lifespan, it is unknown if the variability in dMRI tractography-derived shape may relate to the brain's functional variability across individuals. This work explores the potential of leveraging tractography fiber cluster shape measures to predict subject-specific cognitive performance. We implement machine learning models to predict individual cognitive performance scores. We study a large-scale database from the HCP-YA study. We apply an atlas-based fiber cluster parcellation to the dMRI tractography of each individual. We compute 15 shape, microstructure, and connectivity features for each fiber cluster. Using these features as input, we train a total of 210 models to predict 7 different NIH Toolbox cognitive performance assessments. We apply an explainable AI technique, SHAP, to assess the importance of each fiber cluster for prediction. Our results demonstrate that shape measures are predictive of individual cognitive performance. The studied shape measures, such as irregularity, diameter, total surface area, volume, and branch volume, are as effective for prediction as microstructure and connectivity measures. The overall best-performing feature is a shape feature, irregularity, which describes how different a cluster's shape is from an idealized cylinder. Further interpretation using SHAP values suggest that fiber clusters with features highly predictive of cognitive ability are widespread throughout the brain, including fiber clusters from the superficial association, deep association, cerebellar, striatal, and projection pathways. This study demonstrates the strong potential of shape descriptors to enhance the study of the brain's white matter and its relationship to cognitive function.