Neural population dynamics of direct electrical stimulation of neocortex

Abstract

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