Simulation Study of Intermittent Responses of Neuronal Populations to Axonal High-Frequency Stimulation.

Deep brain stimulation (DBS) have shown a promising future for treating various brain disorders. Studies have indicated that the high frequency stimulation (HFS) used in DBS could cause a partial block in axons thereby attenuating the responses of axon fibers to the pulses of HFS. The attenuated response of axons might play a desynchronization role in modulating activity of neuronal populations. To investigate the detail behavior of individual axons under HFS, we created a computational model of neuronal populations including 1250 neurons. Each neuron consisted of a myelinated axon, an axonal initial segment, a soma and dendrites. A 10-s HFS sequence with 100 Hz pulses was applied to the axon layer by a bipolar stimulation electrode. The membrane potentials and the extracellular potassium concentration [K+ ]o at axons and at somata during the stimulation were investigated. The results showed that the simulation model with a mechanism of potassium accumulation could reproduce the attenuated responses of neuronal populations to persistent axonal HFS in rat experiments. The elevation of [K+ ]o during HFS resulted in an increase of basic membrane potentials and then generated a depolarization block in the axonal membrane thereby attenuating the responses of neuronal populations. The depolarization block in axons included both complete block (~26%) and intermittent block (~74%), which generated desynchronized firing among axons in fibers and travelled to the cell bodies to induce desynchronized firing in somata. The simulation results may provide important information for revealing the modulation mechanisms of axonal HFS in the therapy of brain stimulation.