Stoney vs. Histed: Quantifying the spatial effects of intracortical microstimulation

Background: Intracortical 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. Objective: We used computational modeling to quantify the spatial effects of ICMS intensity and unify the apparently paradoxical findings of Histed and Stoney. Methods: We 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 pulses and short trains of ICMS, including the volume of activated neurons and the density of activated neurons as a function of stimulation intensity. Results: At all amplitudes, the dominant mode of somatic activation was by antidromic propagation to the soma following axonal activation, rather than via transsynaptic 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 activation increased marginally. However, the density of somatic activation within the activated volume increased with stimulation amplitude. Conclusions: The results resolve the apparent paradox between Stoney and Histed's 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.