Mapping human brain charts cross-sectionally and longitudinally

Significance

Charting how the brain develops is key to understanding abnormal brain changes in common psychiatric and neurological disorders. Pooling brain scans from large cohorts of individuals at a specific point in time—i.e., cross-sectionally—has allowed researchers to indirectly infer dynamic brain changes across the human lifespan. However, it is unknown whether this inference is accurate—do brain growth charts estimated from cross-sectional snapshots accurately mirror true brain changes observed in the same individuals scanned at multiple timepoints? Here, we demonstrate that brain charts inferred from cross-sectional data underestimate brain changes directly observed in longitudinal data. As we endeavor to accurately map human brain development, we must also incorporate longitudinal measurements of the brain.

Abstract

Brain scans acquired across large, age-diverse cohorts have facilitated recent progress in establishing normative brain aging charts. Here, we ask the critical question of whether cross-sectional estimates of age-related brain trajectories resemble those directly measured from longitudinal data. We show that age-related brain changes inferred from cross-sectionally mapped brain charts can substantially underestimate actual changes measured longitudinally. We further find that brain aging trajectories vary markedly between individuals and are difficult to predict with population-level age trends estimated cross-sectionally. Prediction errors relate modestly to neuroimaging confounds and lifestyle factors. Our findings provide explicit evidence for the importance of longitudinal measurements in ascertaining brain development and aging trajectories.