SVR-based Multimodal Active Subspace Analysis for the Brain using Neuroimaging Data

Understanding the patterns of changes in brain function and structure due to various disorders and diseases is of utmost importance. There have been numerous efforts toward successful biomarker discovery for complex brain disorders by evaluating neuroimaging datasets with novel analytical frameworks. However, due to the multi-faceted nature of the disorders involving a wide and overlapping range of symptoms as well as complex changes in structural and functional brain networks, it is increasingly important to devise computational frameworks that can consider the underlying patterns of heterogeneous changes with specific target assessments, at the same time producing a summarizing output from the high-dimensional neuroimaging data. While various machine learning approaches focus on diagnostic prediction, many learning frameworks analyze important features at the level of brain regions involved in prediction using supervised methods. Unsupervised learning methods have also been utilized to break down the neuroimaging features into lower dimensional components. However, most learning frameworks either do not consider the target assessment information while extracting brain subspaces, or can extract only higher dimensional importance associations as an ordered list of involved features, making manual interpretation at the level of subspaces difficult. We present a novel multimodal active subspace learning framework to understand various subspaces within the brain that are associated with changes in particular biological and cognitive traits. For a given cognitive or biological trait, our framework performs a decomposition of the feature importances to extract robust multimodal subspaces that define the most significant change in the given trait. Through a rigorous cross-validation procedure on an Alzheimers disease (AD) dataset, we show that our framework can extract subspaces covering both functional and structural modalities, which are specific to a given clinical assessment (like memory and other cognitive skills) and also retain predictive performance in standard machine learning algorithms. We show that our framework not only uncovers AD-related brain regions (e.g., hippocampus, entorhinal cortex) in the associated brain subspaces, but also enables an automated identification of multiple underlying structural and functional sub-systems of the brain that collectively characterize changes in memory and cognitive skill proficiency related to brain disorders like AD.