The average does not represent the individual: White matter variability across the brain, across the population, and across the lifespan

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Abstract

Inter-individual differences in brain anatomy are often treated as noise, yet may encode meaningful principles of organisation. Using >2,800 diffusion MRI scans spanning 0–100 years, we quantified spatial, microstructural and macrostructural variability across 64 major white-matter pathways. Variability is not random: spatial organisation follows a deep-to-superficial gradient, and variability across individuals shows a convergence–divergence profile, decreasing in early development and increasing in ageing. Microstructural and macrostructural features exhibit distinct trajectories and hemispheric asymmetries. Importantly, tract variability relates to individual differences in behaviour, most strongly during development. These results redefine white-matter variability as a structured, developmentally dynamic, lifespan-dependent feature of brain organisation and provide a foundation for normative modelling and precision neuroscience.

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