Modeling brain malformations: from ferrets to FCD II epilepsies
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Neurosurgical resection of the precisely localized seizure onset zone offers effective treatment for drug-resistant focal epilepsy that minimizes additional comorbidity. Here, we focus on focal cortical dysplasia ILAE Type 2 (FCD2), a prevalent pathology in pediatric focal epilepsy patients. FCD2 exhibits histopathological hallmarks including cytoarchitectonic disruption of the human neocortex and genetic mutations affecting the MTOR signaling pathway. Our goal is to develop a model capable of explaining patient-specific cortical folding patterns by incorporating variations in cell proliferation and migration dynamics. To this end, we conducted mechanical testing on fresh surgical tissue specimens and identified constitutive parameters using inverse parameter identification. We further performed histological analysis and neural network-based cell density estimation. We integrated these data into a finite element model that characterizes cortical folding as a finite growth process coupled with a cell density evolution, described by an advection-diffusion equation [1]. As a first use case, we applied our model to capture brain malformations in the ferret brain induced by an overexpression of the transcription factor Cux2, as described in an experimental study by Singh et al. [2]. Our results demonstrate that this model successfully explains how alterations in cell proliferation and migration give rise to cortical malformations.
