Responses of cortical neurons to intracortical microstimulation in awake primates

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in non-human primates to stimulation, we recorded single unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex of three macaque monkeys. Stimuli between 5-50 μA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 milliseconds. ICMS pulses also induced a period of inhibition lasting up to 150 ms that typically followed the initial excitatory response. Higher current amplitudes led to a greater probability of evoking a spike and extended the duration of inhibition. The likelihood of evoking a spike in a neuron was dependent on the spontaneous firing rate as well as the delay between its most recent spike time and stimulus onset. Repetitive stimulation often modulated both the probability of evoking spikes and the duration of inhibition, although high frequency stimulation in particular was more likely to change both responses. Comparisons between stimuli that evoked a spike and stimuli that did not revealed that the excitatory and inhibitory responses were independent of one another on a trial-by-trial basis; however, their changes over time were frequently positively or negatively correlated. Our results document the complex dynamics of cortical neural responses to electrical stimulation that need to be considered when utilizing ICMS for scientific and clinical applications. ### Competing Interest Statement The authors have declared no competing interest.