A large-scale detailed neuronal model of electrical stimulation of the dentate gyrus and perforant path as a platform for electrode design and optimization.

Owing to the dramatic rise in treatment of neurological disorders with electrical micro-stimulation it has become apparent that the major technological limitation in deploying effective devices lies in the process of designing efficient, safe, and outcome specific electrode arrays. The time-consuming and low-fidelity nature of gathering test data using experimental means and the immense control and flexibility of computational models, has prompted us and others to build models of electrical stimulation of neural networks that can be simulated in a computer. Because prior work has been focused on single cells, very small networks, or non-biological models of neural tissue, it was expedient that we take advantage of our, 4,040 processor, computing cluster to construct a large-scale 3-dimensional emulation of hippocampal tissue using detailed neuronal models with explicit and unique morphologies. This model, when paired with an equivalent circuit method of estimating voltage signal attenuation throughout anisotropic resistive tissue, can be used to predict tissue response to an exhaustive set of stimulation and tissue conditions: electrode geometry, array geometry, static dielectric properties of tissue, stimulation pulse features, etc. Preliminary experiments demonstrate that this system is capable of yielding neuronal responses with striking similarities to experimental results. This work provides an avenue to qualitative evaluation of electrode arrays, and more meaningful modeling of local field potentials in terms of their contributing sources and sinks.