The Role of Mechanics during Brain Development

Abschlussarbeit
(Dissertation)


Details zur Publikation

Autor(en): Budday S
Verlag: FAU University Press
Verlagsort: Erlangen
Jahr der Veröffentlichung: 2018


Abstract

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. The surface pattern serves as a clinical indicator for physiological and pathological conditions. Despite its importance, however, the regulators of brain folding in evolution and development remain poorly understood. Recent evidence suggests that physical forces play an important role in pattern selection. This work combines analytical, computational, and experimental analyses to explore the role of mechanics during brain development. After thouroughly characterizing the time-independent and time-dependent, region-specific mechanical response of brain tissue under multiple loading conditions, a mechanical model of brain growth is established using the nonlinear field theories of continuum mechanics, supplemented by the theory of finite growth. The model consists of a morphogenetically growing outer cortex and a stretch-induced growing inner core, and thus combines the two popular but competing hypotheses that cortical folding is either driven by axonal tension or differential growth. Analytical analyses quantify the critical conditions at the onset of folding, and computational analyses additionally predict the highly nonlinear post-buckling behavior. They allow us to carefully investigate both growth-induced primary and secondary instabilities and to provide new evidence towards the emergence of advanced, higher order wrinkling modes. The analytical and computational predictions are experimentally validated using a model system comprised of an elastomeric bilayer. Taken together, the current work emphasizes that the key regulators of pattern selection in the developing brain include cortical thickness, brain geometry, stiffness, and growth. The presented results suggest that an interplay of the inwards folding of mechanically weak spots and growth-induced instabilities shape the developing brain with primary folds that are consistent between individuals and highly variable secondary and tertiary folds. The mechanical model explains why larger mammalian brains tend to be more convoluted than smaller brains. Numerical predictions agree well with the classical pathologies of lissencephaly and polymicrogyria. Thus, the model is capable of bridging the scales from cellular events on the microscopic level towards form and function on the organ level. Combining physics and biology holds promise to further advance our understanding of human brain development and to enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders such as epilepsy, autism spectrum disorder, and schizophrenia.


FAU-Autoren / FAU-Herausgeber

Budday, Silvia Dr.-Ing.
Lehrstuhl für Technische Mechanik


Zitierweisen

APA:
Budday, S. (2018). The Role of Mechanics during Brain Development (Dissertation).

MLA:
Budday, Silvia. The Role of Mechanics during Brain Development. Dissertation, Erlangen: FAU University Press, 2018.

BibTeX: 

Zuletzt aktualisiert 2018-31-07 um 09:38