Exploring the role of the outer subventricular zone during cortical folding through a physics-based model

Abstract

The human brain has a highly complex structure both on the microscopic and macroscopic scales. Increasing evidence has emphasized the role of mechanical forces for cortical folding – a classical hallmark of the human brain. However, the link between cellular processes at the microscale and mechanical forces at the macroscale remains insufficiently understood. Recent findings suggest that an additional proliferating zone, the outer subventricular zone (OSVZ), is decisive for the particular size and complexity of the human cortex. To better understand how the OSVZ affects cortical folding, we establish a multifield computational model that couples cell proliferation and migration at the cell scale with growth and cortical folding at the organ scale by combining an advection-diffusion model with the theory of finite growth. We validate our model based on data from histologically stained sections of the human fetal brain. Finally, we address open questions regarding the role of the OSVZ for the formation of cortical folds. The presented framework not only improves our understanding of human brain development, but could eventually help diagnose and treat neuronal disorders arising from disruptions in cellular development and associated malformations of cortical development.

Multifield computational model for human brain development: Explicit numerical stabilization

“…Table 1 summarizes the most relevant used parameters. For more details about model parameters, we refer to [8, 9].…”

“…Table 1 summarizes the most relevant used parameters. For more details about model parameters, we refer to [8,9]. Figure 3 illustrates the comparison of the final folding pattern in the 2D case at gestational week 36 before and after applying the stabilization scheme as well as for different 𝛽 values.…”

“…On the other hand, the diffusion flux term $$\text{div}({d}^{cc}(\bm{x}) \bm{\nabla }_{\bm{x}} \,c )$$ mathematically mimics the neuronal connectivity occurring in the cortical layer in the third trimester of gestation, where $$d^{cc}$$ is the diffusivity. Since our recent work has emphasized the effect of the two brain proliferation zones on the resulting folding pattern [9], we introduce two source terms $$r_1^{c}(\bm{x}), \, r_2^{c} (\bm{x})$$ that describe the proliferation in the ventricular zone and outer subventricular zone, respectively.…”

“…Indeed, neither the biological nor the mechanical perspective alone are sufficient to understand the folding mechanism. To fill this knowledge gap, we have established a two-field computational model considering both perspectives [8,9]. Our model couples a cell density field kinematically with deformation generated on the tissue scale.…”

A bipolar taxonomy of adult human brain sulcal morphology related to timing of fetal sulcation and trans-sulcal gene expression gradients

“…Complementary to taxonomic studies, biomechanical models have focused on predicting what regions of cortex become sulcus versus gyrus during development as opposed to their prospective primary versus tertiary sulcal patterning [15][16][17] . These models have identified genes whose mutations are thought to play a causal role in cortical malformation disorders 18,19 .…”