Identification of homogeneous subgroups of subjects plays a key role in the study of precision medicine. While there are a number of approaches based on the clustering of low-level features such as behavioral variables, work that makes use of fully multivariate nature of medical imaging data is very limited. Given that the individual variability in brain functional networks obtained from functional magnetic resonance imaging (fMRI) data is noted as being both significant and consistent like fingerprints, its use provides a particularly appealing approach to this challenging problem. We present a completely data-driven approach, subgroup identification using independent vector analysis (SI-IVA), which leverages the desirable properties of IVA to uncover the relationship across subjects along with the discovery of subgroup structures revealed by Gershgorin disc theorem. We show that SI-IVA outperforms an eigenanalysisbased approach by simulations. We then apply the method to real fMRI data obtained from patients of during resting state to identify group differences in multiple relevant brain regions including primary somatosensory and motor cortex, which demonstrates that SI-IVA provides interpretable and meaningful results.
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.
Independent component analysis (ICA) of multi-subject functional magnetic resonance imaging (fMRI) data has proven useful in providing a fully multivariate summary that can be used for multiple purposes. ICA can identify patterns that can discriminate between healthy controls (HC) and patients with various mental disorders such as schizophrenia (Sz). Temporal functional network connectivity (tFNC) obtained from ICA can effectively explain the interactions between brain networks. On the other hand, dictionary learning (DL) enables the discovery of hidden information in data using learnable basis signals through the use of sparsity. In this paper, we present a new method that leverages ICA and DL for the identification of directly interpretable patterns to discriminate between the HC and Sz groups. We use multi-subject resting-state fMRI data from 358 subjects and form subject-specific tFNC feature vectors from ICA results. Then, we learn sparse representations of the tFNCs and introduce a new set of sparse features as well as new interpretable patterns from the learned atoms. Our experimental results show that the new representation not only leads to effective classification between HC and Sz groups using sparse features, but can also identify new interpretable patterns from the learned atoms that can help understand the complexities of mental diseases such as schizophrenia.
Identification of subgroups of subjects homogeneous functional networks is a key step for precision medicine. Independent vector analysis (IVA) is shown to be effective for this task, however, it has a substantial computing cost. We propose a constrained independent component analysis algorithm based on minimizing the entropy bound (c-EBM) to overcome the computational complexity limitation of IVA. A set of spatial maps used as constraints provides a connection across the datasets, provides alignment across subjectwise ICA analyses and serves as a foundation for subgroup identification. The approach makes use of the available prior knowledge while allowing flexible density modeling without an orthogonality requirement for the demixing matrix. Synthetic data and large scale multi-subject resting state fMRI data have both been used to evaluate the performance of the new algorithm, c-EBM. The findings demonstrate that c-EBM is adaptable in terms of various settings for the constraint parameter on the synthetic data. With multi-subject resting state fMRI data, c-EBM can effectively identify subgroups and discover meaningful brain networks that show significant group differences between subgroups.
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.
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