Neural population dynamics of direct electrical stimulation of neocortex.

Intracranial electrical stimulation is foundational in neuroscience and clinical neuromodulation, yet it remains unclear as to how applied electrical fields engage neural tissue and influence perception. Using three orthogonal Neuropixels probes in mouse visual areas, we record extracellular voltages and spikes with sub-millisecond resolution in three dimensions around a stimulation source. The evoked potential extends asymmetrically and increases sub-linearly with amplitude, influenced by anatomical heterogeneity. Increasing amplitude increases the density, but not spatial extent, of directly responsive neurons; however, fewer than 5% of neurons are activated. Fast-spiking interneurons are recruited nearer the source, whereas pyramidal neurons show anisotropic activation. Direct responses are polarity and amplitude selective. Sparse direct spiking drive large, asymmetric cortical responses and modulates >50% of neurons at higher amplitudes. Perceptually, mice weakly detect single pulses, and performance does not improve with amplitude. Thus, anatomy and spatiotemporal patterning-not spike counts-govern physiological and perceptual impact, informing biomimetic, multi-contact prostheses.