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

Background: Computational models that predict effects of neural stimulation can be used as a preliminary tool to inform New Method: 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 allowing 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. Results: We demonstrated our novel features using VERTEX's built-in functionalities, with results in alignment with other models and experimental work. Conclusions: Our extensions provide an all in one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.