Extracellular neural microstimulation may activate much larger regions than expected by simulations: a combined experimental and modeling study.

Electrical stimulation of the central nervous system has been widely used for decades for either fundamental research purposes or clinical treatment applications. Yet, very little is known regarding the spatial extent of an electrical stimulation. If pioneering experimental studies reported that activation threshold currents (TCs) increase with the square of the neuron-to-electrode distance over a few hundreds of microns, there is no evidence that this quadratic law remains valid for larger distances. Moreover, nowadays, numerical simulation approaches have supplanted experimental studies for estimating TCs. However, model predictions have not yet been validated directly with experiments within a common paradigm. Here, we present a direct comparison between experimental determination and modeling prediction of TCs up to distances of several millimeters. First, we combined patch-clamp recording and microelectrode array stimulation in whole embryonic mouse spinal cords to determine TCs. Experimental thresholds did not follow a quadratic law beyond 1 millimeter, but rather tended to remain constant for distances larger than 1 millimeter. We next built a combined finite element--compartment model of the same experimental paradigm to predict TCs. While theoretical TCs closely matched experimental TCs for distances