Flexible modeling of large-scale neural network stimulation: electrical and optical extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX).

Computational models that predict effects of neural stimulation can be used as a preliminary tool to inform in-vivo research, reducing the costs, time, and ethical considerations involved. However, current models do not support the diverse neural stimulation techniques used in-vivo , including the expanding selection of electrodes, stimulation modalities, and stimulation paradigms. To develop a more comprehensive software, we created several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool from Newcastle University. VERTEX simulates input currents in a large population of multi-compartment neurons within a small cortical slice to model electric field stimulation, while recording local field potentials (LFPs) and spiking activity. Our extensions to its existing electric field stimulation framework include multiple pairs of parametrically defined electrodes and biphasic, bipolar stimulation delivered at programmable delays. To support the growing use of optogenetic approaches for targeted neural stimulation, we introduced a feature that models optogenetic stimulation through an additional VERTEX input function that converts irradiance to currents at optogenetically responsive neurons. Finally, we added extensions to allow complex stimulation protocols including paired-pulse, spatiotemporal patterned, and closed-loop stimulation. We demonstrated our novel features using VERTEX's built-in functionalities, illustrating how these extensions can be used to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.