Scaling patterns of cortical folding and thickness in early human brain development in comparison with primates.

Across mammalia, brain morphology follows specific scaling patterns. Bigger bodies have bigger brains, with surface area outpacing volume growth, resulting in increased foldedness. We have recently studied scaling rules of cortical thickness, both local and global, finding that the cortical thickness difference between thick gyri and thin sulci also increases with brain size and foldedness. Here, we investigate early brain development in humans, using subjects from the Developing Human Connectome Project, scanned shortly after pre-term or full-term birth, yielding magnetic resonance images of the brain from 29 to 43 postmenstrual weeks. While the global cortical thickness does not change significantly during this development period, its distribution does, with sulci thinning, while gyri thickening. By comparing our results with our recent work on humans and 11 non-human primate species, we also compare the trajectories of primate evolution with human development, noticing that the 2 trends are distinct for volume, surface area, cortical thickness, and gyrification index. Finally, we introduce the global shape index as a proxy for gyrification index; while correlating very strongly with gyrification index, it offers the advantage of being calculated only from local quantities without generating a convex hull or alpha surface.

Systematic cortical thickness and curvature patterns in primates.

Humans are known to have significant and consistent differences in thickness throughout the cortex, with thick outer gyral folds and thin inner sulcal folds. Our previous work has suggested a mechanical basis for this thickness pattern, with the forces generated during cortical folding leading to thick gyri and thin sulci, and shown that cortical thickness varies along a gyral-sulcal spectrum in humans. While other primate species are expected to exhibit similar patterns of cortical thickness, it is currently unknown how these patterns scale across different sizes, forms, and foldedness. Among primates, brains vary enormously from roughly the size of a grape to the size of a grapefruit, and from nearly smooth to dramatically folded; of these, human brains are the largest and most folded. These variations in size and form make comparative neuroanatomy a rich resource for investigating common trends that transcend differences between species. In this study, we examine 12 primate species in order to cover a wide range of sizes and forms, and investigate the scaling of their cortical thickness relative to the surface geometry. The 12 species were selected due to the public availability of either reconstructed surfaces and/or population templates. After obtaining or reconstructing 3D surfaces from publicly available neuroimaging data, we used our surface-based computational pipeline (https://github.com/mholla/curveball) to analyze patterns of cortical thickness and folding with respect to size (total surface area), geometry (i.e. curvature, shape, and sulcal depth), and foldedness (gyrification). In all 12 species, we found consistent cortical thickness variations along a gyral-sulcal spectrum, with convex shapes thicker than concave shapes and saddle shapes in between. Furthermore, we saw an increasing thickness difference between gyri and sulci as brain size increases. Our results suggest a systematic folding mechanism relating local cortical thickness to geometry. Finally, all of our reconstructed surfaces and morphometry data are available for future research in comparative neuroanatomy.

Cortical thickness systematically varies with curvature and depth in healthy human brains.

Cortical thickness varies throughout the cortex in a systematic way. However, it is challenging to investigate the patterns of cortical thickness due to the intricate geometry of the cortex. The cortex has a folded nature both in radial and tangential directions which forms not only gyri and sulci but also tangential folds and intersections. In this article, cortical curvature and depth are used to characterize the spatial distribution of the cortical thickness with much higher resolution than conventional regional atlases. To do this, a computational pipeline was developed that is capable of calculating a variety of quantitative measures such as surface area, cortical thickness, curvature (mean curvature, Gaussian curvature, shape index, intrinsic curvature index, and folding index), and sulcal depth. By analyzing 501 neurotypical adult human subjects from the ABIDE-I dataset, we show that cortex has a very organized structure and cortical thickness is strongly correlated with local shape. Our results indicate that cortical thickness consistently increases along the gyral-sulcal spectrum from concave to convex shape, encompassing the saddle shape along the way. Additionally, tangential folds influence cortical thickness in a similar way as gyral and sulcal folds; outer folds are consistently thicker than inner.

Computational models of cortical folding: A review of common approaches.

The process of gyrification, by which the brain develops the intricate pattern of gyral hills and sulcal valleys, is the result of interactions between biological and mechanical processes during brain development. Researchers have developed a vast array of computational models in order to investigate cortical folding. This review aims to summarize these studies, focusing on five essential elements of the brain that affect development and gyrification and how they are represented in computational models: (i) the constraints of skull, meninges, and cerebrospinal fluid; (ii) heterogeneity of cortical layers and regions; (iii) anisotropic behavior of subcortical fiber tracts; (iv) material properties of brain tissue; and (v) the complex geometry of the brain. Finally, we highlight areas of need for future simulations of brain development.

Numerical investigation of biomechanically coupled growth in cortical folding.

Cortical folding-the process of forming the characteristic gyri (hills) and sulci (valleys) of the cortex-is a highly dynamic process that results from the interaction between gene expression, cellular mechanisms, and mechanical forces. Like many other cells, neurons are sensitive to their mechanical environment. Because of this, cortical growth may not happen uniformly throughout gyri and sulci after the onset of cortical folding, which is accompanied by patterns of tension and compression in the surrounding tissue. Here, as an extension of our previous work, we introduce a biomechanically coupled growth model to investigate the importance of interaction between biological growth and mechanical cues during brain development. Our earlier simulations of cortical growth consisted of a homogeneous growing cortex attached to an elastic subcortex. Here, we let the evolution of cortical growth depend on a geometrical quantity-the mean curvature of the cortex-to achieve preferential growth in either gyri or sulci. As opposed to the popular pre-patterning hypothesis, our model treats inhomogeneous cortical growth as the result of folding rather than the cause. The model is implemented numerically in a commercial finite element software Abaqus/Explicit in Abaqus reference manuals, Dassault Systemes Simulia, Providence (2019) by writing user-defined material subroutine (VUMAT). Our simulations show that gyral-sulcal thickness variations are a phenomenon particular to low stiffness ratios. In comparison with cortical thickness measurements of [Formula: see text] human brains via a consistent sampling scheme, our simulations with similar cortical and subcortical stiffnesses suggest that cortical growth is higher in gyri than in sulci.

Non-integer viscoelastic constitutive law to model soft biological tissues to in-vivo indentation.

PURPOSE: During the last decades, derivatives and integrals of non-integer orders are being more commonly used for the description of constitutive behavior of various viscoelastic materials including soft biological tissues. Compared to integer order constitutive relations, non-integer order viscoelastic material models of soft biological tissues are capable of capturing a wider range of viscoelastic behavior obtained from experiments. Although integer order models may yield comparably accurate results, non-integer order material models have less number of parameters to be identified in addition to description of an intermediate material that can monotonically and continuously be adjusted in between an ideal elastic solid and an ideal viscous fluid. METHODS: In this work, starting with some preliminaries on non-integer (fractional) calculus, the "spring-pot", (intermediate mechanical element between a solid and a fluid), non-integer order three element (Zener) solid model, finally a user-defined large strain non-integer order viscoelastic constitutive model was constructed to be used in finite element simulations. Using the constitutive equation developed, by utilizing inverse finite element method and in vivo indentation experiments, soft tissue material identification was performed. RESULTS: The results indicate that material coefficients obtained from relaxation experiments, when optimized with creep experimental data could simulate relaxation, creep and cyclic loading and unloading experiments accurately. CONCLUSIONS: Non-integer calculus viscoelastic constitutive models, having physical interpretation and modeling experimental data accurately is a good alternative to classical phenomenological viscoelastic constitutive equations.