image: This schematic outlines their analytical framework. The approach involves creating a validated developmental atlas of the dorsal prefrontal cortex from structural connectivity, then using these regionalization patterns to analyze how brain networks mature and to identify the genetic mechanisms guiding their development.
Credit: ©Science China Press
Researchers analyzed neuroimaging data from over 650 individuals aged 8 to 21 from two large-scale datasets (HCP-D and IMAGEN). Using diffusion MRI, which maps the brain's structural wiring, they discovered a key organizational shift during development. In pre- and early adolescence, the dorsal prefrontal cortex is best described by a six-cluster pattern. However, as individuals transition into late adolescence and young adulthood, a seventh subregion emerges, indicating a more refined and specialized architecture.
“We found that this crucial step in brain maturation is not a uniform process but is driven by highly specific changes in the medial part of the prefrontal cortex, a region known as A9m,” said Professor Jiang, a lead author of the study. “While the neighboring lateral region remained relatively stable, the A9m underwent significant changes in its structural and functional connectivity. It’s a bit like watching a general-purpose tool being honed into a set of specialized instruments.”
The team validated this 6–7 cluster transition using multiple analytical methods and datasets. They further showed that these structural changes were associated with functional consequences. When analyzing brain activity during a reward-processing task, the researchers observed that the A9m region became significantly more active in older adolescents, while the A9l region did not, demonstrating a clear functional divergence between the two areas over time.
To uncover the biological underpinnings of this developmental timeline, the study correlated the imaging findings with gene expression data. The analysis revealed that the age-related connectivity changes in the A9m region were strongly associated with genes involved in critical neurodevelopmental processes, including axon regeneration and epigenetic control of gene expression.
“By integrating brain imaging with genetics, our findings provide further evidence for a proposed mechanism where genetically influenced patterns lay the groundwork for cortical organization early on, and this foundation is then refined by activity-dependent changes in brain wiring during the teen years,” explained Dr. Li, the study's senior author. “This provides a powerful framework for understanding not only normal brain development but also what might go wrong in neurodevelopmental disorders.”
The study's findings carry significant implications for clinical neuroscience. Many disorders, like ADHD and autism, are characterized by atypical prefrontal cortex development. However, research into these conditions often relies on adult brain atlases, which may fail to capture the unique developmental state of an adolescent brain.
“Using an adult brain map to study a teenager is like using a modern city map to navigate an ancient one—the fundamental layout is different,” added Dr. Jiang. “Our work emphasizes the urgent need for age-appropriate developmental brain atlases to improve our understanding and, eventually, treatment of these conditions.”
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Science Bulletin