Brain age prediction: Cortical and subcortical shape covariation in the developing human brain

Yihong Zhao, Arno Klein, F. Xavier Castellanos, Michael P. Milham

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Cortical development is characterized by distinct spatial and temporal patterns of maturational changes across various cortical shape measures. There is a growing interest in summarizing complex developmental patterns into a single index, which can be used to characterize an individual's brain age. We conducted this study with two primary aims. First, we sought to quantify covariation patterns for a variety of cortical shape measures, including cortical thickness, gray matter volume, surface area, mean curvature, and travel depth, as well as white matter volume, and subcortical gray matter volume. We examined these measures in a sample of 869 participants aged 5–18 from the Healthy Brain Network (HBN) neurodevelopmental cohort using the Joint and Individual Variation Explained (Lock et al., 2013) method. We validated our results in an independent dataset from the Nathan Kline Institute - Rockland Sample (NKI-RS; N = 210) and found remarkable consistency for some covariation patterns. Second, we assessed whether covariation patterns in the brain can be used to accurately predict a person's chronological age. Using ridge regression, we showed that covariation patterns can predict chronological age with high accuracy, reflected by our ability to cross-validate our model in an independent sample with a correlation coefficient of 0.84 between chronologic and predicted age. These covariation patterns also predicted sex with high accuracy (AUC = 0.85), and explained a substantial portion of variation in full scale intelligence quotient (R2 = 0.10). In summary, we found significant covariation across different cortical shape measures and subcortical gray matter volumes. In addition, each shape measure exhibited distinct covariations that could not be accounted for by other shape measures. These covariation patterns accurately predicted chronological age, sex and general cognitive ability. In a subset of NKI-RS, test-retest (<1 month apart, N = 120) and longitudinal scans (1.22 ± 0.29 years apart, N = 77) were available, allowing us to demonstrate high reliability for the prediction models obtained and the ability to detect subtle differences in the longitudinal scan interval among participants (median and median absolute deviation of absolute differences between predicted age difference and real age difference = 0.53 ± 0.47 years, r = 0.24, p-value = 0.04).

Original languageEnglish (US)
Article number116149
StatePublished - Nov 15 2019

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cognitive Neuroscience


  • Brain age prediction
  • Brain developmental pattern
  • Cortical covariation pattern
  • Individual and joint analysis


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