Flexible modeling of large-scale neural network stimulation: Electrical and optical extensions to The Virtual...

Computational models that predict effects of neural stimulation can serve as a preliminary tool to inform in-vivo research, reducing costs, time, and ethical considerations. However, current models do not support the diverse neural stimulation techniques used in-vivo, including the expanding selection of electrodes, stimulation modalities, and stimulation protocols.

We developed several extensions to The Virtual Electrode Recording Tool for EXtracellular Potentials (VERTEX), the MATLAB-based neural stimulation tool. 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 enhance this framework with support for 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 these novel features using VERTEX's built-in functionalities, with results consistent with other models and experimental work.

Unlike other tools, our extensions enable both electric field and optogenetic stimulation, provide a range of open- and closed-loop protocols, and offer flexible settings within a large-scale cortical network of neurons with realistic biophysical properties.

Our extensions provide an all-in-one platform to efficiently and systematically test diverse, targeted, and individualized stimulation patterns.