Covariance Regression with High-Dimensional Predictors

In the high-dimensional landscape, addressing the challenges of covariance regression with high-dimensional covariates has posed difficulties for conventional methodologies. This paper addresses these hurdles by presenting a novel approach for high-dimensional inference with covariance matrix outcomes. The proposed methodology is illustrated through its application in elucidating brain coactivation patterns observed in functional magnetic resonance imaging (fMRI) experiments and unraveling complex associations within anatomical connections between brain regions identified through diffusion tensor imaging (DTI). In the pursuit of dependable statistical inference, we introduce an integrative approach based on penalized estimation. This approach combines data splitting, variable selection, aggregation of low-dimensional estimators, and robust variance estimation. It enables the construction of reliable confidence intervals for covariate coefficients, supported by theoretical confidence levels under specified conditions, where asymptotic distributions are provided. Through various types of simulation studies, the proposed approach performs well for covariance regression in the presence of high-dimensional covariates. This innovative approach is applied to the Lifespan Human Connectome Project (HCP) Aging Study, which aims to uncover a typical aging trajectory and variations in the brain connectome among mature and older adults. The proposed approach effectively identifies brain networks and associated predictors of white matter integrity, aligning with established knowledge of the human brain.