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For successful biomarker discovery, it is essential to develop computational frameworks that summarize high-dimensional neuroimaging data in terms of involved sub-systems of the brain, while also revealing underlying heterogeneous functional and structural changes covarying with specific cognitive and biological traits. However, unsupervised decompositions do not inculcate clinical assessment information, while supervised approaches extract only individual feature importance, thereby impeding qualitative interpretation at the level of subspaces. We present a novel framework to extract robust multimodal brain subspaces associated with changes in a given cognitive or biological trait. Our approach involves active subspace learning on the gradients of a trained machine learning model followed by clustering to extract and summarize the most salient and consistent subspaces associated with the target variable. Through a rigorous cross-validation procedure on an Alzheimer's disease (AD) dataset, our framework successfully extracts multimodal subspaces specific to a given clinical assessment (e.g., memory and other cognitive skills), and also retains predictive performance in standard machine learning algorithms. We also show that the salient active subspace directions occur consistently across randomly sub-sampled repetitions of the analysis. Compared to existing unsupervised decompositions based on principle component analysis, the subspace components in our framework retain higher predictive information. As an important step towards biomarker discovery, our framework not only uncovers AD-related brain regions in the associated brain subspaces, but also enables automated identification of multiple underlying structural and functional sub-systems of the brain that collectively characterize changes in memory and proficiency in cognitive skills related to brain disorders like AD. • A method to detect multiple underlying subspaces in the brain associated with a trait. • Multimodal active subspaces fuse structural and functional features of the brain. • Active subspaces retain predictive information for brain disorders. • Experiments with Alzheimer's related scores show successful subspace detection. [ABSTRACT FROM AUTHOR]

• NeuroMark combines templates with data-driven methods for biomarker extraction. • This study developed spatiotemporal functional templates throughout the lifespan. • The unique and shared networks across age populations were investigated. • Templates for other modalities were constructed using T1w and diffusion scans. • The reproducibility of network templates was evaluated across large-scale data. A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations. [ABSTRACT FROM AUTHOR]

Understanding hierarchy and modularity in natural as well as technological networks is of utmost importance. A major aspect of such analysis involves identifying the nodes that are crucial to the overall processing structure of the network. More recently, the approach of hourglass analysis has been developed for the purpose of quantitatively analyzing whether only a few intermediate nodes mediate the information processing between a large number of inputs and outputs of a network. We develop a new framework for hourglass analysis that takes network weights into account while identifying the core nodes and the extent of hourglass effect in a given weighted network. We use this framework to study the structural connectome of the C. elegans and identify intermediate neurons that form the core of sensori-motor pathways in the organism. Our results show that the neurons forming the core of the connectome show significant differences across the male and hermaphrodite sexes, with most core nodes in the male concentrated in sex-organs while they are located in the head for the hermaphrodite. Our work demonstrates that taking weights into account for network analysis framework leads to emergence of different network patterns in terms of identification of core nodes and hourglass structure in the network, which otherwise would be missed by unweighted approaches. [ABSTRACT FROM AUTHOR]

Previous studies of the association between parity and long-term cognitive changes have primarily focused on women and have shown conflicting results. We investigated this association by analyzing data collected on 303,196 subjects from the UK Biobank. We found that in both females and males, having offspring was associated with a faster response time and fewer mistakes made in the visual memory task. Subjects with two or three children had the largest differences relative to those who were childless, with greater effects observed in men. We further analyzed the association between parity and relative brain age (n = 13,584), a brain image-based biomarker indicating how old one's brain structure appears relative to peers. We found that in both sexes, subjects with two or three offspring had significantly reduced brain age compared to those without offspring, corroborating our cognitive function results. Our findings suggest that lifestyle factors accompanying having offspring, rather than the physical process of pregnancy experienced only by females, contribute to these associations and underscore the importance of studying such factors, particularly in the context of sex. [ABSTRACT FROM AUTHOR]