Investigation Of The Waveform Changes And The Underlying Mechanisms Of Neuronal Spikes During Deep Brain Stimulation

Deep brain stimulation(DBS)is one of the hot topic of neural engineering research.The high frequency stimulation(HFS)of DBS has achieved remarkable results on treating neurological diseases like Parkinson's disease and epilepsy.However,the mechanisms remain controversial.Investigation of the changes of neuronal activity during DBS is an important method to reveal the mechanisms of DBS.Using a microelectrode array can simultaneously record extracellular multiple neuronal action potentials(spikes),which can provide important information for researching into DBS.However,the spike waveforms will change during HFS,which on one hand makes it difficult to detect and track spikes,on the other hand may provide clues for researching into DBS.Therefore,this dissertation applied orthodromic-HFS(O-HFS)and antidromic-HFS(A-HFS)trains with a duration of 1?2 min and a frequency of 100 or 200 Hz on the input and output axonal fibers in hippocampal CA1 region of anesthetized rats,tracked single unit spikes correctly,and analyzed the changes of the spike waveforms and the underlying mechanisms of neuronal spikes.In addition,we built a neuronal computational model to reveal the mechanisms of HFS through changing the level of neuronal depolarization and the extracellular potassium concentration.The main results were summarized as follows:(1)The spike amplitudes decreased and the half-height widths increased during HFSThe features of the spike waveform,such as the amplitude of falling-phase,the amplitude of rising-phase and the half-height width,were considered as representation of spike waveform.The results showed that the spike rate increased,the spike amplitudes of interneuron and pyramidal cell decreased and the half-height widths increased significantly during O-HFS.The percent ratios of the waveform features,compared to their baseline values,showed that the amplitude of falling-phase of interneuron and pyramidal cell decreased by?20%and?30%,the amplitude of rising-phase decreased by?40%and?20%,while the half-height width increased by more than 10%and 5%,respectively.Furthermore,the rising-phase amplitude of interneuron decreased by more than 10%during A-HFS.However,the amplitude of falling-phase and the half-height width had no significant differences compared with before A-HFS.(2)Excitation effect of HFS might be the underlying mechanism of the changes of spike waveformsWe analyzed the changes of spike characteristic parameters during the different frequencies and intensities of HFS,the results showed that the changes of spike during 100 Hz O-HFS,which has greater excitation,were significantly higher than 200 Hz,while,the features of spike were almost no change during the low intensity of HFS.Furthermore,the decrease of the falling-phase amplitude(up to 40%),the ring-phase amplitude(up to 55%)and the increase of half-height width(up to 20%)were enhanced during 100 Hz O-HFS with population spikes(PS).Presumably,the more excitation effect that HFS effect on neurons,the greater changes of spike waveforms.(3)Enhancement of cell membrane depolarization and increased extracellular potassium concentration could affect the spike waveformsBy analyzing the neuron model,20 s 100 Hz HFS model results showed that the amplitude of falling-phase and ring-phase of spike decreased by more than 40%and 50%,respectively,consistenting with the in-vivo animal experiments.As the level of depolarization and extracellular potassium concentration increased the amplitude of spike waveforms was decreased,the half-height width was increased gradually.It can be presumed that HFS could drive up the level of depolarization of the neurons,enhance the excitability of neurons,and could lead to the accumulation of extracellular potassium,leading to the changes of spike waveforms(action potentials).In conclusion,this dissertation showed that HFS increased the excitability of neurons,at the same time,changed the spike waveforms through in-vivo animal experiments and simulation model.Presumably,the excitation of HFS could elevate the cell membrane depolarization of neurons and increase the extracellular potassium concentration.The study provides guidance for accurately analyzing neuronal unit spike activity during high-frequency stimulation and also support the hypothesis that DBS has excitatory modulation effect on neurons,which provides important clues for revealing the mechanisms underlying the treatment of brain diseases by DBS.