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.

Joint blind source separation (JBSS) has wide applications in modeling latent structures across multiple related datasets. However, JBSS is computationally prohibitive with high-dimensional data, limiting the number of datasets that can be included in a tractable analysis. Furthermore, JBSS may not be effective if the data’s true latent dimensionality is not adequately modeled, where severe overparameterization may lead to poor separation and time performance. In this paper, we propose a scalable JBSS method by modeling and separating the “shared” subspace from the data. The shared subspace is defined as the subset of latent sources that exists across all datasets, represented by groups of sources that collectively form a low-rank structure. Our method first provides the efficient initialization of the independent vector analysis (IVA) with a multivariate Gaussian source prior (IVA-G) specifically designed to estimate the shared sources. Estimated sources are then evaluated regarding whether they are shared, upon which further JBSS is applied separately to the shared and non-shared sources. This provides an effective means to reduce the dimensionality of the problem, improving analyses with larger numbers of datasets. We apply our method to resting-state fMRI datasets, demonstrating that our method can achieve an excellent estimation performance with significantly reduced computational costs.

Independent vector analysis (IVA) has emerged as a powerful tool for fusing and analyzing functional magnetic resonance imaging (fMRI) data. Applying IVA to multi-task fMRI data enhances analytical power by capturing the relationships across different tasks in order to discover their underlying multivariate relationship to one another. Incorporation of prior information into IVA enhances the separability and interpretability of estimated components. In this paper, we demonstrate successful fusion of multi-task fMRI feature data under two settings: constrained IVA and constrained transposed IVA (tIVA). We show that using these methods for fusing multi-task fMRI feature data offers novel ways to improve the quality and interpretability of the analysis. While constrained IVA extracts components linked to distinct brain networks, tIVA reverses the roles of spatial components and subject profiles, enabling flexible analysis of behavioral effects. We apply both methods to a multi-task fMRI dataset of 247 subjects. We demonstrate that for task-based fMRI, structural MRI (sMRI) references provide a better match for task data than resting-state fMRI (rs-fMRI) references, and using sMRI priors improves identification of group differences in task-related networks, such as the sensory-motor network during the Auditory Oddball (AOD) task. Additionally, constrained tIVA allows for targeted investigation of the effects of behavioral variables by applying them individually during the analysis. For instance, by using the letter number sequence subtest, a measure of working memory, as a behavioral constraint in tIVA, we observed significant group differences in the auditory and sensory-motor networks during the AOD task. Results show that the use of two constrained approaches, guided by well-aligned structural and behavioral references, enables a more comprehensive analysis of underlying brain function as modulated by task.