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Resting-state functional magnetic resonance imaging (rs-fMRI) is a noninvasive technique pivotal for understanding human neural mechanisms of intricate cognitive processes. Most rs-fMRI studies compute a single static functional connectivity matrix across brain regions of interest, or dynamic functional connectivity matrices with a sliding window approach. These approaches are at risk of oversimplifying brain dynamics and lack proper consideration of the goal at hand. While deep learning has gained substantial popularity for modeling complex relational data, its application to uncovering the spatiotemporal dynamics of the brain is still limited. In this study we propose a novel interpretable deep learning framework that learns goal-specific functional connectivity matrix directly from time series and employs a specialized graph neural network for the final classification. Our model, DSAM, leverages temporal causal convolutional networks to capture the temporal dynamics in both low- and high-level feature representations, a temporal attention unit to identify important time points, a self-attention unit to construct the goal-specific connectivity matrix, and a novel variant of graph neural network to capture the spatial dynamics for downstream classification. To validate our approach, we conducted experiments on the Human Connectome Project dataset with 1075 samples to build and interpret the model for the classification of sex group, and the Adolescent Brain Cognitive Development Dataset with 8520 samples for independent testing. Compared our proposed framework with other state-of-art models, results suggested this novel approach goes beyond the assumption of a fixed connectivity matrix, and provides evidence of goal-specific brain connectivity patterns, which opens up potential to gain deeper insights into how the human brain adapts its functional connectivity specific to the task at hand. 

IntroductionTypical adolescent neurodevelopment is marked by decreases in grey matter (GM) volume, increases in myelination, measured by fractional anisotropy (FA), and improvement in cognitive performance. MethodsTo understand how epigenetic changes, methylation (DNAm) in particular, may be involved during this phase of development, we studied cognitive assessments, DNAm from saliva, and neuroimaging data from a longitudinal cohort of normally developing adolescents, aged nine to fourteen. We extracted networks of methylation with patterns of correlated change using a weighted gene correlation network analysis (WCGNA). Modules from these analyses, consisting of co-methylation networks, were then used in multivariate analyses with GM, FA, and cognitive measures to assess the nature of their relationships with cognitive improvement and brain development in adolescence. ResultsThis longitudinal exploration of co-methylated networks revealed an increase in correlated epigenetic changes as subjects progressed into adolescence. Co-methylation networks enriched for pathways involved in neuronal systems, potassium channels, neurexins and neuroligins were both conserved across time as well as associated with maturation patterns in GM, FA, and cognition. DiscussionOur research shows that correlated changes in the DNAm of genes in neuronal processes involved in adolescent brain development that were both conserved across time and related to typical cognitive and brain maturation, revealing possible epigenetic mechanisms driving this stage of development. 

Human adolescence marks a crucial phase of extensive brain development, highly susceptible to environmental influences. Employing brain age estimation to assess individual brain aging, we categorized individuals (N= 7,435, aged 9–10 years old) from the Adolescent Brain and Cognitive Development (ABCD) cohort into groups exhibiting either accelerated or delayed brain maturation, where the accelerated group also displayed increased cognitive performance compared to their delayed counterparts. A 4-way multi-set canonical correlation analysis integrating three modalities of brain metrics (gray matter density, brain morphological measures, and functional network connectivity) with nine environmental factors unveiled a significant 4-way canonical correlation between linked patterns of neural features, air pollution, area crime, and population density. Correlations among the three brain modalities were notably strong (ranging from 0.65 to 0.77), linking reduced gray matter density in the middle temporal gyrus and precuneus to decreased volumes in the left medial orbitofrontal cortex paired with increased cortical thickness in the right supramarginal and bilateral occipital regions, as well as increased functional connectivity in occipital sub-regions. These specific brain characteristics were significantly more pronounced in the accelerated brain aging group compared to the delayed group. Additionally, these brain regions exhibited significant associations with air pollution, area crime, and population density, where lower air pollution and higher area crime and population density were correlated to brain variations more prominently in the accelerated brain aging group. 

Over the past decade and a half, dynamic functional imaging has revealed low-dimensional brain connectivity measures, identified potential common human spatial connectivity states, tracked the transition patterns of these states, and demonstrated meaningful transition alterations in disorders and over the course of development. Recently, researchers have begun to analyze these data from the perspective of dynamic systems and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Little attention has been paid to the effects of psychiatric disease on these measures, however. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, the results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.