Intracortical microstimulation differentially activates cortical layers based on stimulation depth.

Background: Intracortical microstimulation is one of the most common techniques to causally interfere with neuronal processing, but neuronal recordings spanning the whole cortical depth during stimulation are exceptionally rare.

Objective/hypothesis: Here we combined layer-specific intracortical microstimulation with extracellular recordings on the same shank of a linear multi-electrode array to study the effects of electrical stimulation in different cortical depths on intracortical processing in the auditory cortex in vivo.

Methods: Population responses (local field potentials and multi-unit activity) were recorded from the auditory cortex of 8 guinea pigs under ketamine/xylazine anesthesia while single current pulses (charge-balanced, biphasic, square-wave, 0.1-45 μA, 200 μs/phase) were delivered in different cortical depths.

Results: The cortical responses differed with a change in the stimulation parameters, with significant factors being the stimulating current (p < 0.0001), stimulation depth (p = 0.03) and the recording depth (p = 0.002) considering the local field potential amplitude. A cross-correlation analysis between responses evoked by intracortical microstimulation and physiological auditory stimuli revealed the closest match when stimulating the middle granular layer (p < 0.05).

Conclusion: Intracortical response profiles to low-current intracortical microstimulation were layer specific. The most natural cortical response was achieved by stimulation in the thalamo-recipient layer. These findings contribute to a basis for designing cortical neuroprosthetics.