A01 In silico modelling of brain malformations

Recent evidence suggests that mechanical forces drive cortical folding during brain development. While analytical, computational, and experimental models have significantly advanced our understanding of the mechanisms underlying the folding process, such models have so far not been used to tackle specific clinical challenges. For example, folding patterns are an important clinical hallmark of cortical development and brain malformations, such as those related to epilepsy. Assisting clinicians in the diagnosis and treatment of brain folding-related neurological disorders, e.g., by reverse-engineering the cellular processes that could have led to the macroscopic malformation, requires the close collaboration between clinicians, who define open clinical questions, and engineers, who develop targeted simulation tools to address them. To tackle some of the open questions concerning malformations associated with epilepsy analyzed in A02, we plan to use mechanical modelling approaches. A01 aims to develop a computational framework to numerically predict the mechanisms underlying abnormal brain development. Based on qualitative and quantitative insights into the interplay between mechanics, cell migration, cell differentiation, and brain malformations obtained through projects A02 through A05, we will establish a multifield theoretical framework to predict brain development under physiological and pathological conditions. For model calibration and validation, we will use the various human data sets generated in project A02 supplemented by mechanical tests under compression, tension, and torsional shear on fresh human brain tissue obtained from neurosurgical procedures. We will incorporate data from patients into the modelling framework to lay the foundation for later use in clinical practice – to advance from benchmark problems to disease-specific predictions and eventually assist the diagnosis and treatment of neurological diseases such as epilepsy.

Project leader: Dr.-Ing. Silvia Budday

Positions: 1 doctoral researcher