Stoney vs. Histed: Quantifying the Spatial Effects of Intracortical Microstimulation

Abstract

BackgroundIntracortical microstimulation (ICMS) is used to map neural circuits and restore lost sensory modalities such as vision, hearing, and somatosensation. The spatial effects of ICMS remain controversial: Stoney and colleagues proposed that the volume of somatic activation increased with stimulation intensity, while Histed et al. suggested activation density, but not somatic activation volume, increases with stimulation intensity. ObjectiveWe used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney. MethodsWe implemented a biophysically-based computational model of a cortical column comprising neurons with realistic morphology and representative synapses. We quantified the spatial effects of single pulse ICMS, including the radial distance to activated neurons and the density of activated neurons as a function of stimulation intensity. ResultsAt all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via trans-synaptic activation. There were no occurrences of direct activation of somata or dendrites. The volume over which antidromic action potentials were initiated grew with stimulation amplitude, while the volume of somatic activations did not. However, the density of somatic activation within the activated volume increased with stimulation amplitude. ConclusionsThe results resolve the apparent paradox between Stoney and Histeds results by demonstrating that the volume over which action potentials are initiated grows with ICMS amplitude, consistent with Stoney. However, the volume occupied by the activated somata remains approximately constant, while the density of activated neurons within that volume increase, consistent with Histed. HIGHLIGHTSO_LIImplemented a biophysically-based computational model of cortical column comprising cortical neurons with realistic morphology and representative synapses. C_LIO_LIQuantified the spatial patterns of neural activation by intracortical microstimulation to resolve the paradoxical findings of Stoney et al., 1968 and Histed et al., 2009. C_LIO_LIThe dominant mode of neural activation near the electrode was direct (i.e., via antidromic propagation from direct activation of the axon) and not trans-synaptic. C_LIO_LIThe dominant effect of increased ICMS intensity was to increase the density of activated neurons but not the volume of activation. C_LI