深部脑刺激对大鼠丘脑底核神经活动的影响

Effect of Deep Brain Stimulationon Neural Activity of Subthalamic Nucleus in Rats

为了探求高频电刺激对受刺激核团的影响,在高频刺激丘脑底核的同时,同步记录了大鼠丘脑底核神经元活动.针对同步记录中刺激伪迹的难题,研究并应用了高效的刺激伪迹滤出算法,恢复了被掩盖的神经响应,且失真小.研究了刺激幅度、频率与神经元神经响应类型的关系,以及在临床治疗有效刺激参数下,高频刺激对神经元平均放电率的影响.研究结果显示,放电率的变化可能与帕金森症病理状态无直接关系,爆发式放电增多更可能是帕金森发病潜在的电生理基础,而受刺激核团的自发放电的抑制、放电率的降低及爆发式放电的减少则有可能是深部脑刺激作用机制的一部分.

To date, deep brain stimulation （DBS） is the most effective clinical treatment for Parkinson＇s disease （PD）. However the mechanism of action of DBS is still under investigation which hampers the further improvement of DBS and study of the pathogenesis of PD. In past decade, kinds of experiment apparatuses and means were applied to explore the mechanism of action of high frequency stimulation （HFS） on target nucleus, such as subthalamic nucleus （STN）. Among these, the change of neural spiking activity of STN during ongoing HFS can reflect precisely the influence of HFS on nucleus, thus, is the better method to determine the mechanism. However, large stimulus artifacts （SA） have greatly restrained the application of this technique. An online filter method based on template subtraction was developed and evaluated for the removal of stimulus artifacts and their harmonics from extracellular neural recording. The data presented here illustrated that although this algorithm is simple and low computation intensive, it can well recover spikes for low SNR signal, even spikes completely submerged by SA. Utilizing this effective algorithm, the relation between the type of neural response and the frequency and amplitude of stimulation was determined; meanwhile effect of HFS with clinically effective parameters on mean firing rats was studied and analyzed. Experiment results illustrated that the percentage of STN neurons which showed inhibition to HFS rise with the increment of frequency and amplitude of stimulus. In addition, Experiment results showed that the change of mean firing rat may not be directly involved with the symptoms of Parkinson＇s disease （PD）, and the increase of burst neural activity should more likely be the neurophysiologic basis of PD. Furthermore, it was found that inhibition of spontaneous neural activity leading to reduction of mean firing rate and burst activity may be the part of mechanism of action of deep brain stimulation.