Axonal spike-count regimes link spinal cord stimulation periodicity to artificial sensory detection and discrimination in rodents

Abstract

Electrical stimulation is widely used to evoke artificial sensation, yet how temporal stimulation patterns are transformed into neural activity and perception remains poorly understood. Recent behavioral studies have shown that increasing the aperiodicity of spinal cord stimulation pulse trains alters both detection thresholds and discrimination performance despite constant pulse counts, suggesting a role for temporal structure beyond rate alone. However, the neural mechanisms underlying these effects remain unresolved. We developed a biophysically grounded computational framework linking a finite-element model of the rodent spinal cord, conductance-based axon simulations, and observer decision models to investigate how stimulation periodicity shapes neural responses and resulting behavior. By systematically varying stimulation amplitude, frequency, and inter-pulse interval variability, we identified distinct spike-count regimes arising from interactions between stimulation timing and axonal membrane dynamics. These regimes ranged from single spikes and small volleys to sustained spike trains, and they exhibited diverse frequency- and variability-dependent trends. No single regime was able to sufficiently explain experimentally observed detection threshold trends; instead, mixtures of regimes accurately reproduced both frequency-dependent threshold behavior and trial-level variability. Extending this framework to periodicity discrimination, we show that features derived from regime mixtures contain sufficient information to recover behavioral psychometric curves. Furthermore, observer model results provide a mechanistic account of behavioral asymmetries depending on the periodicity of the reference stimulus: discrimination relative to periodic inputs relied on combined rate and timing evidence, whereas discrimination relative to aperiodic inputs was dominated by timing irregularity. These results establish a mechanistic link between stimulation temporal structure, axonal spike generation, and perceptual behavior. This framework suggests that spinal cord stimulation does not operate within a single fixed neural regime but instead engages a spectrum of spike-count regimes whose mixtures shape perception. These findings have important implications for the design of biomimetic stimulation strategies, highlighting temporal patterning as a key dimension for controlling sensory outcomes.