Bethlehem · Nature 2022 · Multi-cohort observational aggregation and normative modeling study · n=101,457 participants (123,984 scans across >100 studies)

Brain charts for the human lifespan.

Cited 1861 times in the scientific literature.

Level 3 - non-randomized controlled study

Aggregated observational cohort and cross-sectional neuroimaging datasets (design analogy for normative modeling)

PubMed 35388223 · doi:10.1038/s41586-022-04554-y · record verified 2026-08-27

What was done

Researchers aggregated 123,984 MRI scans from 101,457 human participants spanning 115 days post-conception to 100 years of age across more than 100 primary studies. Using this dataset, they modeled non-linear lifespan trajectories of structural brain metrics to generate standardized centile reference charts and an open interactive benchmarking tool.

What was found

The brain charts identified previously unreported neurodevelopmental milestones, showed high longitudinal stability across individual assessments, and maintained robustness to technical differences between studies. Centile scores demonstrated higher heritability than non-centiled raw MRI phenotypes and provided standardized measures to identify atypical neuroanatomical patterns in neurological and psychiatric disorders. Specific numerical metrics and effect sizes were not reported in the abstract.

Why it matters

This study provides the first comprehensive, lifespan-wide normative growth charts for human brain morphology, establishing a standardized framework to quantify individual structural brain differences and disease-related deviations analogous to pediatric growth charts.

Limits

The abstract explicitly acknowledges known representation biases in existing MRI studies relative to global population diversity. Detailed scanner specifications, cohort-specific demographics, attrition rates, and exact statistical estimates are omitted from the abstract.

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