Differences in the way human cerebral cortices fold have been correlated to health, disease, development, and aging. However, to obtain a deeper understanding of the mechanisms that generate such differences, it is useful to derive one's morphometric variables from the first principles. This study explores one such set of variables that arise naturally from a model for universal self-similar cortical folding that was validated on comparative neuroanatomical data. We aim to establish a baseline for these variables across the human lifespan using a heterogeneous compilation of cross-sectional datasets as the first step to extending the model to incorporate the time evolution of brain morphology. We extracted the morphological features from structural MRI of 3,650 subjects: 3,095 healthy controls (CTL) and 555 patients with Alzheimer's Disease (AD) from 9 datasets, which were harmonized with a straightforward procedure to reduce the uncertainty due to heterogeneous acquisition and processing. The unprecedented possibility of analyzing such a large number of subjects in this framework allowed us to compare CTL and AD subjects' lifespan trajectories, testing if AD is a form of accelerated aging at the brain structural level. After validating this baseline from development to aging, we estimate the variables' uncertainties and show that Alzheimer's Disease is similar to premature aging when measuring global and local degeneration. This new methodology may allow future studies to explore the structural transition between healthy and pathological aging and may be essential to generate data for the cortical folding process simulations.

The generating mechanism for the gyrification of the mammalian cerebral cortex remains a central open question in neuroscience. Although many models have been proposed over the years, very few were able to provide empirically testable predictions. In this paper, we assume a model in which the cortex folds for all species of mammals according to a simple mechanism of effective free energy minimization of a growing self-avoiding surface subjected to inhomogeneous bulk stresses to derive a new set of morphological variables to express cortical morphology. In terms of these new variables, we seek to understand the variance present in two morphometric datasets: a human MRI harmonized multi-site dataset comprised by 3324 healthy controls (CTL) from 4 to 96 years old and a collection of different mammalian cortices with morphological measurements extracted manually. This is done using a standard Principal Component Analysis (PCA) of the cortical morphometric space. We prove there is a remarkable coincidence (typically less than 8 degrees) between the resulting principal components vectors in each datasets and the directions corresponding to the new variables. This shows that the new, theoretically-derived variables are a set of natural and independent morphometrics with which to express cortical shape and size.

Differences in the way human cerebral cortices fold have been correlated to health, disease, development, and aging. But to obtain a deeper understating of the mechanisms that generate such differences it is useful to derive one's morphometric variables from first principles. This work explores one such set of variables that arise naturally from a model for universal self-similar cortical folding that was validated on comparative neuroanatomical data. We aim to establish a baseline for these variables across the human lifespan using a heterogeneous compilation of cross-sectional datasets, as the first step to extend the model to incorporate the time evolution of brain morphology. We extracted the morphological features from structural MRI of 3650 subjects: 3095 healthy controls (CTL) and 555 Alzheimer's Disease (AD) patients from 9 datasets, which were harmonized with a straightforward procedure to reduce the uncertainty due to heterogeneous acquisition and processing. The unprecedented possibility of analyzing such a large number of subjects in this framework allowed us to compare CTL and AD subjects' lifespan trajectories, testing if AD is a form of accelerated aging at the brain structural level. After validating this baseline from development to aging, we estimate the variables' uncertainties and show that Alzheimer's Disease is similar to premature aging when measuring global and local degeneration. This new methodology may allow future studies to explore the structural transition between healthy and pathological aging and may be essential to generate data for the cortical folding process simulations.