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Heterochronous laminar maturation in the human prefrontal cortex

Sydnor, V. J.; Petrie, D.; McKeon, S. D.; Famalette, A.; Foran, W.; Calabro, F. J.; Luna, B.

2025-01-30 neuroscience
10.1101/2025.01.30.635751 bioRxiv
Show abstract

The human prefrontal cortex (PFC) exhibits markedly protracted developmental plasticity, yet whether reductions in plasticity occur synchronously across prefrontal cortical layers is unclear. Animal studies have shown that intracortical myelin consolidates developing circuits by restricting ongoing neuronal plasticity. Here, we use longitudinal myelin-sensitive imaging collected at ultra-high field to investigate whether superficial and deep PFC layers exhibit different timeframes of malleability. We find that myelin matures earlier in deep than in superficial compartments of the cortical ribbon; this laminar divergence in maturational timing is differentially expressed across cytoarchitecturally and functionally distinct frontal regions. By integrating myelin mapping with EEG and behavioral phenotyping, we provide evidence that prefrontal myelin impacts timescales of neural activity, task learning rates, and cognitive processing speed. Heterochronous myelination across deep and superficial layers is an underrecognized mechanism through which human association cortex balances cognitively-relevant increases in circuit stability and efficiency with extended neuroplasticity.

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