Association of gene expression and brain connectivity in human cerebral cortex development and adulthood

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ABSTRACT The cell-to-cell connections that comprise the functional circuitry and global network organization of the human brain have at their root precise spatiotemporal patterns of gene expression that differentiate brain regions, cell types, and developmental periods. Recent discoveries have revealed highly dynamic spatiotemporal patterns of gene expression throughout development and in several regions of the brain, but elucidating the neural connectome – the comprehensive map of all neural connections – at multiple ages of human development has, until recently, not been practical. Consequently, although we now have a strong understanding of transcriptional reorganizations in the developing and adult human brain, how these dynamics mediate other key phenomena essential for brain function, such as neural connectivity, is not well understood. As region-specific disruptions to neural connectivity may underlie neuropsychiatric disorders including schizophrenia and autism spectrum disorder, the association of transcriptome information with connectivity is a critical next frontier for analysis. We therefore propose to integrate human brain connectome based on neural MRI and transcriptome data collected across multiple timepoints in human postnatal development with unprecedented spatial resolution to implicate candidate genes, gene expression modules, brain regions, developmental periods, and connectivity patterns with human brain development. To accomplish this, we will develop a high-resolution connectome atlas established with unique existing developmental and adult data as well as next-generation connectome data from early and late childhood being acquired with other sources. This atlas will be paired with transcriptomic atlas from the postnatal human neocortex consisting of 25 neocortical areas and will be integrated with publicly available, less comprehensive transcriptomic data generated at the level of the single cell. Finally, we will validate gene expression patterns and the associations we reveal, and freely disseminate atlases and datasets through an integrated web portal.