A spatially constrained independent component analysis jointly informed by structural and functional network connectivity.

There are a growing number of neuroimaging studies motivating joint structural and functional brain connectivity. Brain connectivity of different modalities provides insight into brain functional organization by leveraging complementary information, especially for brain disorders such as schizophrenia. In this paper, we propose a multi-modal independent component analysis (ICA) model that utilizes information from both structural and functional brain connectivity guided by spatial maps to estimate intrinsic connectivity networks (ICNs). Structural connectivity is estimated through whole-brain tractography on diffusion-weighted MRI (dMRI), while functional connectivity is derived from resting-state functional MRI (rs-fMRI). The proposed structural-functional connectivity and spatially constrained ICA (sfCICA) model estimates ICNs at the subject level using a multi-objective optimization framework. We evaluated our model using synthetic and real datasets (including dMRI and rs-fMRI from 149 schizophrenia patients and 162 controls). Multi-modal ICNs revealed enhanced functional coupling between ICNs with higher structural connectivity, improved modularity, and network distinction, particularly in schizophrenia. Statistical analysis of group differences showed more significant differences in the proposed model compared to the unimodal model. In summary, the sfCICA model showed benefits from being jointly informed by structural and functional connectivity. These findings suggest advantages in simultaneously learning effectively and enhancing connectivity estimates using structural connectivity.

Multi-spatial-scale dynamic interactions between functional sources reveal sex-specific changes in schizophrenia.

We introduce an extension of independent component analysis (ICA), called multiscale ICA, and design an approach to capture dynamic functional source interactions within and between multiple spatial scales. Multiscale ICA estimates functional sources at multiple spatial scales without imposing direct constraints on the size of functional sources, overcomes the limitation of using fixed anatomical locations, and eliminates the need for model-order selection in ICA analysis. We leveraged this approach to study sex-specific and sex-common connectivity patterns in schizophrenia. Results show dynamic reconfiguration and interaction within and between multi-spatial scales. Sex-specific differences occur (a) within the subcortical domain, (b) between the somatomotor and cerebellum domains, and (c) between the temporal domain and several others, including the subcortical, visual, and default mode domains. Most of the sex-specific differences belong to between-spatial-scale functional interactions and are associated with a dynamic state with strong functional interactions between the visual, somatomotor, and temporal domains and their anticorrelation patterns with the rest of the brain. We observed significant correlations between multi-spatial-scale functional interactions and symptom scores, highlighting the importance of multiscale analyses to identify potential biomarkers for schizophrenia. As such, we recommend such analyses as an important option for future functional connectivity studies.