Morphological integration of the human brain across adolescence and adulthood

Abstract

Significance Attaining correct anatomical proportions is an important developmental goal. Although the patterning of individual deviations from such proportions has been well-studied in nonhuman animals and various human body measurements, this theoretical framework has not been applied to human brain morphology. We analyze individual deviations from proportionality norms (“anatomical imbalance”) in a collection of over 20,000 brain MRI scans to reveal that individuals grow closer to proportionality norms in development and further from proportionality norms in aging. This effect is greatest in brain networks that support higher-order cognition and least in brain networks that support sensorimotor functions. We demonstrate that deviation from proportionality norms—a measure of neurodevelopmental coordination—is associated with cognitive function and sensitive to variation in prenatal stress. Brain structural covariance norms capture the coordination of neurodevelopmental programs between different brain regions. We develop and apply anatomical imbalance mapping (AIM), a method to measure and model individual deviations from these norms, to provide a lifespan map of morphological integration in the human cortex. In cross-sectional and longitudinal data, analysis of whole-brain average anatomical imbalance reveals a reproducible tightening of structural covariance by age 25 y, which loosens after the seventh decade of life. Anatomical imbalance change in development and in aging is greatest in the association cortex and least in the sensorimotor cortex. Finally, we show that interindividual variation in whole-brain average anatomical imbalance is positively correlated with a marker of human prenatal stress (birthweight disparity between monozygotic twins) and negatively correlated with general cognitive ability. This work provides methods and empirical insights to advance our understanding of coordinated anatomical organization of the human brain and its interindividual variation.