Simulation Study For The Modulations Of High Frequency Electrical Stimulation On The Axons Of Brain Neurons

Deep brain stimulation(DBS)has been used in the treatment of various neurological disorders such as Parkinson's disease and epilepsy.High frequency stimulation(HFS)is most commonly used in DBS treatment,but its mechanism of action remains unclear.Recent studies have shown that the modulation of axons by HFS may be an important mechanism for DBS treatment.As the axons of neurons in brain are relatively thin,it is difficult to study the activity of single axon directly through experiments in vivo.At present,the understanding of the modulation effect of HFS on axons mostly based on the estimation of the somata activities.Therefore,this paper established a myelinated axon model of brain neuron,and investigated the response of axons during HFS,the desynchronization effect of HFS on an axon bundle and the influence of HFS on axonal information transmission.The main results were summarized as follows:(1)High frequency electrical stimulation caused intermittent axonal blockHFS could induce intermittent block of axon,which caused the failure of axon to follow each pulse to generate an action potential.The reason for this intermittent block was:continuous HFS induced K+accumulation in the peri-axonal space,and under the effect of K removal mechanism(ion diffusion and sodium-potassium pump),extracellular K+concentration fluctuated,which resulting in the fluctuation of membrane potential and open probability of Na+ channels.In addition,the response of the axons to HFS(degree of block)also has stimulation intensity and frequency dependence.Finally,the axonal block only happened in limited area.The Node of Ranvier(Node)closest to the stimulus source blocked with highest degree,and the block degree of Nodes on both sides reduced gradually.(2)High frequency stimulation incuded the desynchronized firing of axon bundleHFS could cause the desynchronized firing of different axons in an axon bundle,which was because the different block degrees of axons with different distances to the stimulation source,that was,the intervals of intermittent action potentials were different,which caused misalignment of the action potentials firing time on different axons,thereby generating the desynchronization effect.Presumably,this desynchronized axonal activity could transmit to the downstream nucleus and cause the desynchronization of nucleus activity.(3)High-frequency electrical stimulation affected the information conduction on axonThe upstream spontaneous activity could only partially conduct through the HFS action site on the axon to downstream during HFS.Due to the extension of refractory period during HFS,the spontaneous activity could only pass through the stimulating site during limited time window.In addition,the stimulus frequency effected the conduction ratio of spontaneous activity,which with lowest conduction ratio at 100 Hz and higher ratio with either lower(20 Hz)or higher(200 Hz)stimulus frequency.In summary,this paper studied the modulation effect of HFS on axons with axon model,verified the phenomenon of axonal intermittent block which cannot be directly tested by experimental studies.Moreover,this paper also revealed the desynchronization effect on axons and the effect of information conduction due to axonal block.This paper provide a new idea for the study of DBS mechanism,and is of great significance for promoting the clinical application of DBS.