深部脑刺激中单相脉冲与双相脉冲的作用比较

doi:10.3969/j.issn.0258-8021. 2015. 05.005

摘要
图/表
参考文献
相关文章 (2)

全文: PDF (1264 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要深部脑刺激在帕金森和癫痫等脑部疾病治疗中的应用不断发展，它使用的电刺激波形通常为窄脉冲。但是，对于单相脉冲与双相脉冲的刺激作用之间的差别还缺乏全面的认识。为了研究不同波形脉冲对于深部脑组织的刺激作用，在麻醉大鼠海马CA1区的输入和输出轴突纤维上，分别施加不同极性的或者不同方式的（单个或连续）单相和双相脉冲，考察CA1区神经元单细胞和神经元群体在刺激作用下的响应，以定量分析不同刺激波形的作用效果。共计18次动物实验结果如下：1）CA1区输入通道的小强度单个刺激顺向诱发单元锋电位时，以兴奋性相位为前相的双相脉冲和兴奋性单相脉冲的诱发率（分别为69.2%±10.4% 和650%±10%）显著高于以非兴奋性相位为前相的双相脉冲和非兴奋性单相脉冲的诱发率（分别为28.8%±9.5%和34.2%±12.5%）（n=6）；而且，双相脉冲的作用效果取决于前相，与无后相的单相脉冲的作用效果没有显著差别。2）CA1区输出通道的大强度单个刺激逆向诱发群峰电位时，双相脉冲的作用仍然与单相脉冲接近（n=6），由其前相主导，后相的作用较小。3）在CA1区输出通道逆向的100 Hz持续高频串刺激期间，起始0.5 s时间内单相脉冲引起群峰电位的幅值下降（54.2%±21.3%）显著高于前相与其一致的双相脉冲所引起的幅值下降（39.0%±10.2%）（n=6），说明高频串刺激时单相脉冲的作用比双相脉冲要强，但是单相脉冲可能造成神经组织的损伤。因此，长时间的高频刺激治疗应采用双相脉冲。这些研究结果对于深入了解深部脑刺激的作用机制以及安全有效地推广其临床应用都具有重要意义。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	胡娜封洲燕^*郭哲杉王兆祥余颖

关键词 ：深部脑刺激, 脉冲相位, 高频刺激, 单元锋电位, 群峰电位

Abstract：Deep brain stimulation (DBS) has been developed for treating brain diseases such as Parkinson's disease and epilepsy. Narrow pulses are the most commonly used stimulation waveforms of DBS. However, the differences between the stimulation effects of monophasic pulses and biphasic pulses are not clear yet. To investigate the different stimulation effects on deep brain tissue by different pulse waveforms, monophasic and biphasic pulses with different polarity and different patterns (single or train) were respectively applied in the afferent fibers and the efferent fibers of the hippocampus CA1 region in anaesthetized rats. Responses of single neurons and neuronal populations in the CA1 region were examined to quantitatively analyze the effect of different stimulation waveforms. Results of total 18 animal experiments were shown as following: 1) For single pulses stimulation with low intensity on the afferent fibers to evoke unit spikes orthodromically in the CA1 region, the evoked ratios of excitatoryphasefirst biphasic and excitatoryphase monophasic were
69.2%±10.4% and 65.0%±10% (n=6), respectively. These ratios were significantly higher than the evoked ratios of nonexcitatoryphasefirst biphasic and nonexcitatoryphase monophasic: 28.8%±9.5% and 34.2%±12.5% (n=6), respectively. In addition, the stimulation effect of biphasic pulses was dominated by first phases and was not significantly different from the effect of monophasic pulses without second phases. 2) For single pulses on the efferent fibers to evoke population spikes antidromically in the CA1 region, the stimulation effect of biphasic pulses was still similar to the effect of monophasic pulses without second phases (n=6). The effect of biphasic pulses was dominated by their first phases without significant effects of the second phases. 3) During 100 Hz highfrequency antidromic stimulations on the efferent fibers of CA1 region, in the 0.5 s period at the beginning of stimulation, the amplitude suppression of population spikes induced by monophasic pulses was 54.2%±21.3% and was significantly higher than the suppression induced by biphasic pulses 39.0%±10.2% (n=6). It was indicated that the effect of monophasic pulses was much stronger than the effect of biphasic pulses during high-frequency stimulations. However, trains of high-frequency monophasic pulses tended to cause damages to neuronal tissues. Therefore, biphasic pulse is more suitable for chronic therapy with highfrequency stimulation. These results are important for the further understanding of DBS mechanisms and for the efficiency and safety of wide applications of DBS in clinic.

Key words： deep brain stimulation pulse phase high-frequency stimulation unit spike population spike

基金资助:国家重点基础研究发展计划（973计划）项目（2011CB504400）

引用本文:

胡娜封洲燕^*郭哲杉王兆祥余颖. 深部脑刺激中单相脉冲与双相脉冲的作用比较[J]. 中国生物医学工程学报, 2015, 34(5): 548-557.
Hu Na Feng Zhouyan^*Guo Zheshan Wang Zhaoxiang Yu Ying. Different Stimulation Effects between Monophasic Pulses and Biphasic Pulses in Deep Brain Stimulation. journal1, 2015, 34(5): 548-557.

链接本文:

http://cjbme.csbme.org/CN/10.3969/j.issn.0258-8021. 2015. 05.005 或 http://cjbme.csbme.org/CN/Y2015/V34/I5/548

［1］Okun MS. Deepbrain stimulation for Parkinson's disease［J］. New England Journal of Medicine, 2012, 367(16): 1529-1538.
［2］Laxpati NG, Kasoff WS, Gross RE. Deep brain stimulation for the treatment of epilepsy: circuits, targets, and trials［J］. Neurotherapeutics, 2014, 11(3): 508-526.
［3］Suthana N, Haneef Z, Stern J, et al. Memory enhancement and deepbrain stimulation of the entorhinal area［J］. New England Journal of Medicine, 2012, 366(6): 502-510.［4］Gorman PH, Mortimer JT. The effect of stimulus parameters on the recruitment characteristics of direct nerve stimulation［J］. IEEE Transactions on Biomedical Engineering, 1983,30(7): 407-414.
［5］Kuncel AM, Grill WM. Selection of stimulus parameters for deep brain stimulation［J］. Clinical Neurophysiology, 2004, 115(11): 2431-2441.
［6］Merrill DR, Bikson M, Jefferys JGR. Electrical stimulation of excitable tissue: design of efficacious and safe protocols［J］. Journal of Neuroscience Methods, 2005, 141(2): 171-198.
［7］Jensen RJ, Rizzo III JF. Activation of ganglion cells in wildtype and rd1 mouse retinas with monophasic and biphasic current pulses［J］. Journal of Neural Engineering, 2009, 6(3): 035004.
［8］John SE, Shivdasani MN, Williams CE, et al. Suprachoroidal electrical stimulation: effects of stimulus pulse parameters on visual cortical responses［J］. Journal of Neural Engineering, 2013, 10(5): 056011.
［9］Shepherd RK, Javel E. Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties［J］. Hearing Research, 1999, 130(1): 171-188.
［10］Gielen FLH, Molnar GC, Basic principles of deep brain stimulation［M］// Denys D, Feenstra M, Schuurman R. Deep Brain Stimulation. Beilin: Springer Science & Business Media, 2012:1-5.
［11］Schacter DL, Slotnick SD. The cognitive neuroscience of memory distortion［J］. Neuron, 2004, 44(1): 149-160.
［12］Buzsaki G. Rhythms of the Brain［M］. UK:Oxford University Press, 2006: 35.
［13］封洲燕, 肖乾江, 胡振华. 电刺激期间神经细胞单元锋电位的检测［J］. 中国生物医学工程学报, 2013, 32(4): 403-410.
［14］Tan Xiaodong, Wang Xiao, Yang Weiguo, et al. First spike latency and spike count as functions of tone amplitude and frequency in the inferior colliculus of mice［J］. Hearing Research, 2008, 235(1): 90-104.
［15］Floresco SB, Grace AA. Gating of hippocampalevoked activity in prefrontal cortical neurons by inputs from the mediodorsal thalamus and ventral tegmental area［J］. The Journal of Neuroscience, 2003, 23(9): 3930-3943.
［16］王静, 封洲燕. 多通道神经元锋电位检测和分类的新方法［J］. 生物化学与生物物理进展, 2009, 36(5): 641-647.
［17］曹嘉悦, 封洲燕, 郑晓静, 等. 深度麻醉至脑死亡期间大鼠海马神经元活动的突变［J］. Progress in Biochemistry and Biophysics, 2014, 41(4): 379-387.
［18］封洲燕, 余颖, 曹嘉悦, 等. 大鼠海马神经元群体对于高频电刺激的响应［J］. 中国生物医学工程学报, 2014, 33(2):186-193.
［19］Feng Zhouyan, Zheng Xiaojing, Yu Ying, et al. Functional disconnection of axonal fibers generated by high frequency stimulation in the hippocampal CA1 region invivo［J］. Brain Research, 2013, 1509: 32-42.
［20］Lauritzen M, Dreier JP, Fabricius M, et al. Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury［J］. Journal of Cerebral Blood Flow & Metabolism, 2010, 31(1): 17-35.
［21］Wyckhuys T, Raedt R, Vonck K, et al. Comparison of hippocampal Deep Brain Stimulation with high (130Hz) and low frequency (5Hz) on afterdischarges in kindled rats［J］. Epilepsy Research, 2010, 88(2): 239-246.
［22］Rajdev P, Ward M, Irazoqui P. Effect of stimulus parameters in the treatment of seizures by electrical stimulation in the kainate animal model［J］. International Journal of Neural Systems, 2011, 21(02): 151-162.
［23］Cappaert NLM, Ramekers D, Martens HCF, et al. Efficacy of a new chargebalanced biphasic electrical stimulus in the isolated sciatic nerve and the hippocampal slice［J］. International Journal of Neural Systems, 2013, 23(1):1250031.
［24］van den Honert C, Mortimer JT. The response of the myelinated nerve fiber to short duration biphasic stimulating currents［J］. Annals of Biomedical Engineering, 1979, 7(2): 117-125.
［25］Piallat B, Chabardès S, Devergnas A, et al. Monophasic but not biphasic pulses induce brain tissue damage during monopolar highfrequency deep brain stimulation［J］. Neurosurgery, 2009, 64(1): 156-163.
［26］Somjen GG. Mechanisms of spreading depression and hypoxic spreading depressionlike depolarization［J］. Physiological Reviews, 2001, 81(3): 1065-1096.