GAMing the Brain: Investigating the Cross-Modal Relationships Between Functional Connectivity and Structural Features Using Generalized Additive Models

Functional connectivity, reflecting synchronized brain activity across distinct regions, is crucial for understanding cognitive processes. Despite the recent interest in exploring the relationship between functional connectivity and structural brain features, understanding the precise link remains challenging. We propose a novel analysis method that integrates structural factors-such as anatomical morphology summaries, voxel intensity, diffusion-weighted information, and geographic distance to explain variation in functional connectivity. Our method employs generalized additive model (GAM), leveraging region-pair or vertex-pair information, while accommodating individual subject differences in both template and subject spaces. Furthermore, we assess repeatability via the so called discriminability of subjects under our approach, quantifying the probability of similarities between measurements for the same subject versus different subjects. Utilizing data from the Human Connectome Project, we analyze brain connectivity in twin pairs and non-twin pairs to evaluate the repeatability of model-based connectivity patterns estimated via GAMs. Our findings suggest that direct structure/function regression models enhances our understanding of functional connectivity variation, providing insights into underlying mechanisms and discriminability of brain connections.