Subsequent projects
Prof. Dr. Paul Steinmann
Friedrich-Alexander-University of
Erlangen-Nuremberg
Technische Mechanik
Prof. Dr. Ellen Kuhl
Stanford University
Department of Mechanical Engineering
Mechanical Characterization of Brain Development
Disclosing the origin of convolutions in the mammalian brain remains a scientific challenge. Malformations originating from early stages of development are associated with neurological disorders such as schizophrenia and autism. Recent evidence suggests that mechanics play a crucial role during brain development. The establishment of an effective mechanical model requires experimentally determined material parameters. Controversies regarding both the underlying mechanism of brain folding and the material properties of brain tissue have caused ongoing debate. Reported stiffness values vary by an order of magnitude or more. Furthermore, mechanical testing of brain tissue has so far been limited to fully developed brains, whose cellular microstructure differs significantly from that of brains in the immature developmental stage. We will combine continuum modeling and simulation with mechanical testing of brain tissue to clarify the role of mechanics during brain development and improves our understanding of normal and abnormal brain structure with its associated neurological disorders.
Primary project: Multi-Scale Modelling and Simulation of Higher Order Continuum Models of Diffusion
Final Report
The characteristically folded surface morphology is a classical hallmark of the mammalian brain. During development, the initially smooth surface evolves into an elaborately convoluted pattern, which closely correlates with brain function. More and more evidence suggests that mechanics play an important role in pattern selection. However, controversies regarding the material properties of brain tissue have caused ongoing debate and criticism.
During the funding period, as the result of a vivid and fruitful collaboration between the Chair of Applied Mechanics at Friedrich-Alexander University Erlangen-Nürnberg and the Living Matter Lab at Stanford University, we could eliminate some of these contradictions and comprehensively characterize the mechanical behavior of brain tissue. We have provided preliminary insights into the microstructural origin of the time-independent and time-dependent contributions to the macroscopic behavior of brain tissue [1]. Our results suggest that the purely ‘elastic’, time-independent stiffness closely correlates with the degree of interconnectivity between different cells or capillaries, and is thus also associated with brain activity [2]. The time-dependent contribution seems to be characterized by at least two different time scales, one related to the viscoelastic nature of the solid skeleton itself, and one associated with the poroelastic interaction of the solid and fluid phases within the tissue [3]. Importantly, we could also rule out the possibility of permanent softening or irreversible damage as a possible interpretation for the observed time-dependent effects [2].
Our results suggest that for the slow growth processes occurring during early stages of development, gray matter is stiffer than white matter, which, supported by our numerical simulations of brain growth, clearly strengthens the notion that mechanical instabilities evoked by differential growth between different layers in the brain control cortical folding.
[1] J. Weickenmeier, R. de Rooij, S. Budday, P. Steinmann, T. Ovaert, and E. Kuhl. Brain stiffness increases with myelin content. Acta Biomater., 42:265–272, 2016.
[2] S. Budday, G. Sommer, C. Birkl, C. Langkammer, J. Haybaeck, J. Kohnert, M. Bauer, F. Paulsen, P. Steinmann, E. Kuhl, and G. A. Holzapfel. Mechanical characterization of human brain tissue. Acta Biomater., 48:319–340, 2017.
[3] S. Budday, G. Sommer, J. Haybaeck, P. Steinmann, G. A. Holzapfel, and E. Kuhl. Rheological characterization of human brain tissue. Acta Biomater., 2017.