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 multispatial 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 multispatial-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.

Brain function can be modeled as the dynamic interactions between functional sources (e.g., intrinsic connectivity networks, ICNs) at different spatial scales. Each spatial scale contains its own functional sources with unique information. For example, the default mode (DM)-ICNs from lower order independent component analysis (ICA) are not a simple union of DM-ICNs from a higher order. Furthermore, dynamic functional interactions occur both within and between different spatial scales, which has been underrepresented. Here, we introduce multiscale ICA to capture functional sources and their interactions across multiple spatial scales. We leveraged this approach to study sex-specific changes in schizophrenia. Most sex-specific differences occur in between-model order, highlighting the benefit of multispatial-scale analysis. In sum, studying multispatial-scale functional sources provides us with a wealth of information to better characterize brain function.

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Author notes

Competing Interests: The authors have declared that no competing interests exist.

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