The extraction of common and distinct biomedical signatures among different populations allows for a more detailed study of the group-specific as well as distinct information of different populations. A number of subspace analysis algorithms have been developed and successfully applied to data fusion, however they are limited to joint analysis of only a couple of datasets. Since subspace analysis is very promising for analysis of multi-subject medical imaging data as well, we focus on this problem and propose a new method based on independent vector analysis (IVA) for common subspace extraction (IVA-CS) for multi-subject data analysis. IVA-CS leverages the strength of IVA in identification of a complete subspace structure across multiple datasets along with an efficient solution that uses only second-order statistics. We propose a subset analysis approach within IVA-CS to mitigate issues in estimation in IVA due to high dimensionality, both in terms of components estimated and the number of datasets. We introduce a scheme to determine a desirable size for the subset that is high enough to exploit the dependence across datasets and is not affected by the high dimensionality issue. We demonstrate the success of IVA-CS in extracting complex subset structures and apply the method to analysis of functional magnetic resonance imaging data from 179 subjects and show that it successfully identifies shared and complementary brain patterns from patients with schizophrenia (SZ) and healthy controls group. Two components with linked resting-state networks are identified to be unique to the SZ group providing evidence of functional dysconnectivity. IVA-CS also identifies subgroups of SZs that show significant differences in terms of their brain networks and clinical symptoms.

Data‐driven methods have been widely used in functional magnetic resonance imaging (fMRI) data analysis. They extract latent factors, generally, through the use of a simple generative model. Independent component analysis (ICA) and dictionary learning (DL) are two popular data‐driven methods that are based on two different forms of diversity—statistical properties of the data—statistical independence for ICA and sparsity for DL. Despite their popularity, the comparative advantage of emphasizing one property over another in the decomposition of fMRI data is not well understood. Such a comparison is made harder due to the differences in the modeling assumptions between ICA and DL, as well as within different ICA algorithms where each algorithm exploits a different form of diversity. In this paper, we propose the use of objective global measures, such as time course frequency power ratio, network connection summary, and graph theoretical metrics, to gain insight into the role that different types of diversity have on the analysis of fMRI data. Four ICA algorithms that account for different types of diversity and one DL algorithm are studied. We apply these algorithms to real fMRI data collected from patients with schizophrenia and healthy controls. Our results suggest that no one particular method has the best performance using all metrics, implying that the optimal method will change depending on the goal of the analysis. However, we note that in none of the scenarios we test the highly popular Infomax provides the best performance, demonstrating the cost of exploiting limited form of diversity.

The existence of complementary information across multiple sensors has driven the proliferation of multivariate datasets. Exploitation of this common information, while minimizing the assumptions imposed on the data has led to the popularity of data-driven methods. Independent vector analysis (IVA), in particular, provides a flexible and effective approach for the fusion of multivariate data. In many practical applications, important prior information about the data exists and incorporating this information into the IVA model is expected to yield improved separation performance. In this paper, we propose a general formulation for non-orthogonal constrained IVA (C-IVA) framework that can incorporate prior information about either the sources or the mixing coefficients into the IVA cost function. A powerful decoupling method is the major enabling factor in this task. We demonstrate the improved performance of C-IVA over the unconstrained IVA model using both simulated as well as real medical imaging data.

The identification of homogeneous subgroups of patients with psychiatric disorders can play an important role in achieving personalized medicine and is essential to provide insights for understanding neuropsychological mechanisms of various mental disorders. The functional connectivity profiles obtained from functional magnetic resonance imaging (fMRI) data have been shown to be unique to each individual, similar to fingerprints; however, their use in characterizing psychiatric disorders in a clinically useful way is still being studied. In this work, we propose a framework that makes use of functional activity maps for subgroup identification using the Gershgorin disc theorem. The proposed pipeline is designed to analyze a large-scale multi-subject fMRI dataset with a fully data-driven method, a new constrained independent component analysis algorithm based on entropy bound minimization (c-EBM), followed by an eigenspectrum analysis approach. A set of resting-state network (RSN) templates is generated from an independent dataset and used as constraints for c-EBM. The constraints present a foundation for subgroup identification by establishing a connection across the subjects and aligning subject-wise separate ICA analyses. The proposed pipeline was applied to a dataset comprising 464 psychiatric patients and discovered meaningful subgroups. Subjects within the identified subgroups share similar activation patterns in certain brain areas. The identified subgroups show significant group differences in multiple meaningful brain areas including dorsolateral prefrontal cortex and anterior cingulate cortex. Three sets of cognitive test scores were used to verify the identified subgroups, and most of them showed significant differences across subgroups, which provides further confirmation of the identified subgroups. In summary, this work represents an important step forward in using neuroimaging data to characterize mental disorders.

Aim: In this work, we propose the novel use of adaptively constrained independent vector analysis (acIVA) to effectively capture the temporal and spatial properties of dynamic blood-oxygen-level-dependent (BOLD) activity (dBA), and we efficiently quantify the spatial property of dBA (sdBA). We also propose to incorporate dBA into the study of brain dynamics to gain insight into activity-connectivity co-evolution patterns. Introduction: Studies of the dynamics of the human brain using functional magnetic resonance imaging (fMRI) have enabled the identification of unique functional network connectivity (FNC) states and provided new insights into mental disorders. There is evidence showing that both BOLD activity, which is captured by fMRI, and FNC are related to mental and cognitive processes. However, a few studies have evaluated the inter-relationships of these two domains of function. Moreover, the identification of subgroups of schizophrenia has gained significant clinical importance due to a need to study the heterogeneity of schizophrenia. Methods: We design a simulation study to verify the effectiveness of acIVA and apply acIVA to the dynamic study of resting-state fMRI data collected from individuals with schizophrenia and healthy controls (HCs) to investigate the relationship between dBA and dynamic FNC (dFNC). Results: The simulation study demonstrates that acIVA accurately captures the spatial variability and provides an efficient quantification of sdBA. The fMRI analysis yields synchronized sdBA-temporal property of dBA (tdBA) patterns and shows that the dBA and dFNC are significantly correlated in the spatial domain. Using these dynamic features, we identify schizophrenia subgroups with significant differences in terms of their clinical symptoms. Conclusion: We find that brain function is abnormally organized in schizophrenia compared with HCs since there are less synchronized sdBA-tdBA patterns in schizophrenia and schizophrenia prefers a component that merges multiple brain regions. Identification of schizophrenia subgroups using dynamic features inspires the use of neuroimaging in studying the heterogeneity of disorders. Impact statement: This work introduces the use of joint blind source separation for the study of brain dynamics to enable efficient quantification of the spatial property of dynamic blood-oxygen-level-dependent (BOLD) activity to provide insight into the relationship of dynamic BOLD activity and dynamic functional network connectivity. The identification of subgroups of schizophrenia using dynamic features allows the study of heterogeneity of schizophrenia, emphasizing the importance of functional magnetic resonance imaging analysis in the study of brain activity and functional connectivity to gain a better understanding of the human brain, especially the brain with a mental disorder.