Selective recruitment of cortical neurons by electrical stimulation.

Despite its critical importance in experimental and clinical neuroscience, at present there is no systematic method to predict which neural elements will be activated by a given stimulation regime. Here we develop a novel approach to model the effect of cortical stimulation on spiking probability of neurons in a volume of tissue, by applying an analytical estimate of stimulation-induced activation of different cell types across cortical layers. We utilize the morphology and properties of axonal arborization profiles obtained from publicly available anatomical reconstructions of the twelve main categories of neocortical neurons to derive the dependence of activation probability on cell type, layer and distance from the source. We then propagate this activity through the local network incorporating connectivity, synaptic and cellular properties. Our work predicts that (a) intracranial cortical stimulation induces selective activation across cell types and layers; (b) superficial anodal stimulation is more effective than cathodal at cell activation; (c) cortical surface stimulation focally activates layer I axons, and (d) there is an optimal stimulation intensity capable of eliciting cell activation lasting beyond the end of stimulation. We conclude that selective effects of cortical electrical stimulation across cell types and cortical layers are largely driven by their different axonal arborization and myelination profiles.