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    Area of Science:

    • Neuroscience
    • Developmental Neuroscience
    • Computational Neuroscience

    Background:

    • Brain organization is increasingly characterized by macroscale connectivity gradients.
    • The developmental trajectory and biological underpinnings of structural-functional gradient coupling are not well understood.

    Purpose of the Study:

    • To investigate the developmental evolution of structural-functional gradient coupling.
    • To explore the relationship between gradient coupling, behavior, and molecular features.
    • To determine the genetic and cellular basis of gradient coupling.

    Main Methods:

    • Analysis of high-resolution structural and functional connectivity data from large child and adult cohorts (ABCD and HCP studies).
    • Examination of gradient coupling across multiple metrics and spatial scales.
    • Application of cognitive and mental health assessments.
    • Heritability and transcriptomic analyses.

    Main Results:

    • Structural-functional gradient coupling shows significant developmental refinement from childhood to adulthood.
    • Distinct sex-specific patterns in gradient coupling were observed.
    • Gradient coupling metrics correlate with cognitive abilities and mental health outcomes, enabling predictive modeling.
    • Strong genetic influence on gradient coupling was identified.
    • Heritable coupling patterns are enriched for genes in deep-layer excitatory neurons.

    Conclusions:

    • Structural-functional gradient coupling is a key feature of brain organization that matures during development.
    • Gradient coupling links macroscale brain connectivity to cognitive, behavioral, and molecular levels.
    • This coupling reflects underlying cell-type-specific transcriptional architecture and genetic influences.