Multiscale modeling and simulation of neuronal processes in the context of medical applications

Dr Gillian Queisser (Temple University)

Thursday 3rd November, 2022 14:00-15:00 Maths 311B / ZOOM (ID: 894 1122 8633)

Abstract

Repetitive transcranial magnetic stimulation (rTMS) is a treatment modality for neurological disorders, such as schizophrenia and depression. A coil is positioned close to the patient’s skull, through which a time-varying magnetic field induces an electric field which penetrates brain tissue. By this extracellular stimulation neurons are activated and ideally promote long-term cellular changes that improve the neurological condition. Although rTMS has been in clinical use for over a decade, the mechanisms by which a specific treatment protocol operates are far from understood. The complexity of understanding and optimizing rTMS lies in the multiscale nature of the biophysical problem, where macroscopic electric fields affect individual neurons and these in turn translate electrical signals into biochemical responses. We therefore developed a multiscale framework with which rTMS parameters, such as coil position and stimulation frequency, can be modified and effects of rTMS can be measured at the cellular level. The novelty of this framework is the incorporation of cellular calcium dynamics, which are critical for inducing long-term responses using a short rTMS window. In this talk, we will introduce the general problem and the calcium problem, in particular. Numerical analysis of the calcium problem shows existence and uniqueness, and careful linearization of the nonlinear problem gives rise to fast, efficient, and scalable time-stepping methods for solving the calcium problem on complex three-dimensional cellular domains. As examples we will show simulation results of calcium dynamics in human dendritic spines and on full 3D neurons, which are synaptically activated in concert with rTMS stimuli. These results demonstrate how different rTMS protocols and the spatial organization of neurons control intracellular calcium signaling and they pave the way for patient-specific rTMS optimization. Additionally, a similar framework can be used to study calcium dynamics under neuropathological states, such as Alzheimer’s disease. Here we show the effect of Alzheimer’s disease on intracellular calcium dynamics.

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