Do human brain white matter and brain stem structures show direction-dependent mechanical behavior?

Since the corpus callosum and the brain stem are both vulnerable to diffuse axonal injury during head impacts, there is a high interest in modeling the mechanical behavior of these brain structures. In recent years, different versions of fiber-reinforced material models have been proposed for the corpus callosum and other white matter regions, as well as for the brain stem, even though there is currently no consensus on whether those structures exhibit a significant direction-dependent behavior during mechanical loading. Here, we present the first large-strain, multimodal experimental study on human brain tissue that includes the corpus callosum and the lower brain stem (medulla oblongata) tested along two different directions. Additionally, we compare those two structures with other white matter (corona radiata, cerebellar white matter) and brain stem structures (pons, midbrain) to highlight differences in their material response. Cyclic compression-tension and shear tests reveal statistically significant direction-dependent material behavior in the corpus callosum. Directional differences in the brain stem are not statistically significant and do not indicate a clear directionality. Combined with histological findings, our results suggest that the mechanical behavior of white matter structures is influenced not only by axon caliber, orientation and density, but also by the architectural organization, i.e., clustering versus even distribution, of cells and tracts, and possibly vascular density. These findings highlight the need for micromechanical constitutive models for brain white matter that do not merely include axons embedded in a matrix. Statement of significance Mechanical head injuries often result in insults like diffuse axonal injury in white matter regions of the human brain. Therefore, there is a high interest in understanding and predicting the mechanical properties of those regions in order to prevent injury and advance diagnosis and treatment strategies of neurological disorders. There has been a long controversy regarding the question whether human brain white matter regions show an anisotropic, direction-dependent mechanical response. With the goal of providing experimental evidence to conclusively answer this question, we here present large-strain, multimodal experimental data and representative histological analyses of different human brain white matter regions and brain stem structures, including directional investigations for both the corpus callosum and the medulla oblongata (lower brain stem).