Multi-faceted Neuroimaging Data Integration via Analysis of Subspaces

TL;DR

This paper introduces the DIVAS method for comprehensive multi-block neuroimaging data integration, revealing key insights into how genetics and substance use relate to brain connectivity and providing new statistical tools for analysis.

Contribution

The study develops the DIVAS framework with novel hypothesis tests for multi-block neuroimaging data, enabling exhaustive analysis of complex interactions among brain, genetics, and behavior.

Findings

Genetics is the most predictive modality of brain connectivity.

Shared spaces explain 12-14% of connectivity variation.

Negative connections suggest brain responses to substance use.

Abstract

Neuroimaging studies, such as the Human Connectome Project (HCP), often collect multi-faceted and multi-block data to study the complex human brain. However, these data are often analyzed in a pairwise fashion, which can hinder our understanding of how different brain-related measures interact with each other. In this study, we comprehensively analyze the multi-block HCP data using the Data Integration via Analysis of Subspaces (DIVAS) method. We integrate structural and functional brain connectivity, substance use, cognition, and genetics in an exhaustive five-block analysis. This gives rise to the important finding that genetics is the single data modality most predictive of brain connectivity, outside of brain connectivity itself. Nearly 14\% of the variation in functional connectivity (FC) and roughly 12\% of the variation in structural connectivity (SC) is attributed to shared spaces with genetics. Moreover, investigations of shared space loadings provide interpretable associations between particular brain regions and drivers of variability, such as alcohol consumption in the substance-use data block. Novel Jackstraw hypothesis tests are developed for the DIVAS framework to establish statistically significant loadings. For example, in the (FC, SC, and Substance Use) shared space, these novel hypothesis tests highlight largely negative functional and structural connections suggesting the brain's role in physiological responses to increased substance use. Furthermore, our findings have been validated using a subset of genetically relevant siblings or twins not studied in the main analysis.