PT  - JOURNAL ARTICLE
AU  - Scott Rich
AU  - Homeira Moradi Chameh
AU  - Jeremie Lefebvre
AU  - Taufik A Valiante
TI  - Resilience through diversity: Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony
AID  - 10.1101/2021.03.02.433627
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.02.433627
4099  - http://biorxiv.org/content/early/2021/10/21/2021.03.02.433627.short
4100  - http://biorxiv.org/content/early/2021/10/21/2021.03.02.433627.full
AB  - A myriad of pathological changes associated with epilepsy can be recast as decreases in cell and circuit heterogeneity. We thus propose recontextualizing epileptogenesis as a process where reduction in cellular heterogeneity renders neural circuits less resilient to seizure. By comparing patch clamp recordings from human layer 5 (L5) cortical pyramidal neurons from epileptogenic and non-epileptogenic tissue, we demonstrate significantly decreased biophysical heterogeneity in seizure generating areas. Implemented computationally, this decreased heterogeneity renders model neural circuits prone to sudden transitions into synchronous states with increased firing activity, paralleling ictogenesis. This computational work also explains the surprising finding of significantly decreased excitability in the population activation functions of neurons from epileptogenic tissue. Finally, mathematical analyses reveal a unique bifurcation structure arising only with low heterogeneity and associated with seizure-like dynamics. Taken together, this work provides experimental, computational, and mathematical support for the theory that ictogenic dynamics accompany a reduction in biophysical heterogeneity.Competing Interest StatementThe authors have declared no competing interest.