Simulation Study of Intermittent Axonal Block and Desynchronization Effect Induced by High-Frequency Stimulation of...

Deep brain stimulation (DBS) has been successfully used in treating neural disorders in brain, such as Parkinson's disease and epilepsy. However, the precise mechanisms of DBS remain unclear. Regular DBS therapy utilizes high-frequency stimulation (HFS) of electrical pulses. Among all of neuronal elements, axons are mostly inclined to be activated by electrical pulses. Therefore, the response of axons may play an important role in DBS treatment. To study the axonal responses during HFS, we developed a computational model of myelinated axon to simulate sequences of action potentials generated in single and multiple axons (an axon bundle) by stimulations. The stimulations are applied extracellularly by a point source of current pulses with a frequency of 50-200 Hz. Additionally, our model takes into account the accumulation of potassium ions in the peri-axonal spaces. Results show that the increase of extracellular potassium generates intermittent depolarization block in the axons during HFS. Under the state of alternate block and recovery, axons fire action potentials at a rate far lower than the frequency of stimulation pulses. In addition, the degree of axonal block is highly related to the distance between the axons and the stimulation point. The differences in the degree of block for individual axons in a bundle result in desynchronized firing among the axons. Stimulations with higher frequency and/or greater intensity can induce axonal block faster and increase the desynchronization effect on axonal firing. Presumably, the desynchronized axonal activity induced by HFS could generate asynchronous activity in the population of target neurons downstream thereby suppressing over-synchronized firing of neurons in pathological conditions. The desynchronization effect generated by intermittent activation of axons may be crucial for DBS therapy. The present study provides new insights into the mechanisms of DBS, which is significant for advancing the application of DBS.