A Method for Multimodal <scp>IVA</scp> Fusion Within a <scp>MISA</scp> Unified Model Reveals Markers of Age, Sex, Cognition, and Schizophrenia in Large Neuroimaging Studies

With the increasing availability of large-scale multimodal neuroimaging datasets, it is necessary to develop data fusion methods which can extract cross-modal features. A general framework, multidataset independent subspace analysis (MISA), has been developed to encompass multiple blind source separation approaches and identify linked cross-modal sources in multiple datasets. In this work, we utilized the multimodal independent vector analysis (MMIVA) model in MISA to directly identify meaningful linked features across three neuroimaging modalities-structural magnetic resonance imaging (MRI), resting state functional MRI and diffusion MRI-in two large independent datasets, one comprising of control subjects and the other including patients with schizophrenia. Results show several linked subject profiles (sources) that capture age-associated decline, schizophrenia-related biomarkers, sex effects, and cognitive performance. For sources associated with age, both shared and modality-specific brain-age deltas were evaluated for association with non-imaging variables. In addition, each set of linked sources reveals a corresponding set of cross-modal spatial patterns that can be studied jointly. We demonstrate that the MMIVA fusion model can identify linked sources across multiple modalities, and that at least one set of linked, age-related sources replicates across two independent and separately analyzed datasets. The same set also presented age-adjusted group differences, with schizophrenia patients indicating lower multimodal source levels. Linked sets associated with sex and cognition are also reported for the UK Biobank dataset.