Partial correlation as a tool for mapping functional-structural correspondence in human brain connectivity

• Published in: Network neuroscience (Cambridge, Mass.) pp. 1 - 22
• Main Authors: Santucci, Francesca, Jimenez-Marin, Antonio, Gabrielli, Andrea, Bonifazi, Paolo, Ibáñez-Berganza, Miguel, Gili, Tommaso, Cortes, Jesus M.
• Format: Journal Article
• Language: English
• Published: 12.08.2025
• DOI: 10.1162/netn.a.22
• ISSN: 2472-1751

Brain structure-function coupling has been studied in health and disease by many different researchers in recent years. Most of the studies have estimated functional connectivity matrices as correlation coefficients between different brain areas, despite well-known disadvantages compared with partial correlation connectivity matrices. Indeed, partial correlation represents a more sensible model for structural connectivity since, under a Gaussian approximation, it accounts only for direct dependencies between brain areas. Motivated by this and following previous results by different authors, we investigate structure-function coupling using partial correlation matrices of functional magnetic resonance imaging brain activity time series under various regularization (also known as noise-cleaning) algorithms. We find that, across different algorithms and conditions, partial correlation provides a higher match with structural connectivity retrieved from density-weighted imaging data than standard correlation, and this occurs at both subject and population levels. Importantly, we also show that regularization and thresholding are crucial for this match to emerge. Finally, we assess neurogenetic associations in relation to structure-function coupling, which presents promising opportunities to further advance research in the field of network neuroscience, particularly concerning brain disorders.