用户名: 密码: 验证码:
基于闭环控制的神经电刺激器设计
详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文
摘要
电刺激在神经系统基础研究以及癫痫等大脑疾病治疗过程中都得到越来越广泛的应用,但是,能够基于大脑的电活动状态发出刺激信号的闭环式电刺激器产品却不多。因此,本文设计的闭环式刺激器对于各种电刺激实验和临床治疗仪器的开发具有重要的意义。
     本文利用美国国家仪器公司生产的数据采集卡和普通PC机的声卡,基于LabVIEW开发环境,针对大鼠脑部海马区场电位信号的特性,设计了一种闭环控制的电刺激器,主要设计工作包括如下3个部分:(1)设计场电位信号的θ节律检测及相位预测方法,能够根据需要,使电刺激发生于θ节律的波峰或者波谷。(2)设计癫痫棘波的检测方法,能够按照预先的设置,在痫样波出现后的不同延迟时间上发出电刺激,可用于大脑深部电刺激治疗癫痫的实验研究。(3)设计基于普通PC机声卡的简易癫痫脑电信号监测器,并具有声音提示功能,有利于相关仪器功能的家用普及。
     本文的主要研究结果如下:
     (1)所设计的电刺激器能够根据需要输出脉冲波、正弦波、三角波和锯齿波等刺激波形,
     并能设置脉宽、刺激间隔、刺激个数等;最小脉宽可以达到50μs,能够满足大脑神经系统电刺激实验的要求。
     (2)大鼠海马脑区场电位信号的检测结果表明,该电刺激器预测θ节律波峰位置和波谷位置的平均误差分别为波形周期的10%和15%左右,两者的预测正确率都在92%以上。
     (3)癫痫信号识别实验的结果表明,癫痫棘波检测的正确率都能达到99%,能较好的区别正常脑电信号,并不受50 Hz工频噪声的干扰。
     (4)PC机声卡频率响应特性的测试结果表明,声卡的频响能够满足癫痫脑电的监测要求,其检测准确率可达到97%以上。
     总之,本文开发的闭环式电刺激器,能够自动预测脑电信号中的θ波等节律的相位,检测癫痫棘波;并根据用户的设置,在所需时刻发出各种波形的电刺激,为大脑神经系统工作机理和电刺激作用机制的深入研究提供了有用的工具。同时,本文利用PC机声卡实现的简易癫痫棘波监测器,检测准确率较高,可以用于家庭远程医疗等领域。
Since the electrical stimulation has been widely used both in theoretic neurophysiologic research and therapeutic research of brain diseases such as epilepsy, the development of the electrical stimulators has made great progress. But the stimulators that able to generate stimulus according to the electrical activity recorded from the target area, i.e. brain, also called closed-loop stimulator, is very limited. Therefore, it is significant to design such a closed-loop control electrical stimulator either for physiologic research in laboratory or therapeutic treatments in clinical.
     In this thesis, we designed a LabVIEW-based closed-loop electrical stimulator, which mainly aimed at the rat's hippocampal field potential signals. The key hardware of this stimulator is composed from a data acquisition card (NI, USA) and an ordinary PC sound card. The main work and analyzing methods involved in the design of this stimulator were listed as followings:
     (1) Developed an algorithm to detect and predict the 9 rhythm among the field potentials of hippocampus. With this algorithm the stimulator can deliver stimulus right at the moment of the peak or trough point of 9 wave on the demand. (2) Designed a spike detection algorithm of epilepsy. This algorithm could help the stimulator generate stimulus after the emergence of epileptic spike with a pre-set delay. This function might be used in deep brain stimulation research. (3) Developed a simple epileptic EEG monitor with sound alarm. By taking advantage of a PC sound card Such vocal EEG monitor is cheap and easy to imitate.
     The main results of this thesis were summarized as followings:
     (1)The electrical stimulator can generate diverse stimulus waves selection, e.g., pulse, sine, triangle, sawtooth. It also supports alteration of stimulation settings, such as pulse width, stimulus interval, stimulus number, etc. The minimum pulse width is 50μs, meeting the need of most neurophysiological experiments.
     (2) The test results of the algorithms showed that average error between prediction ofθwave's peak and actual peak is 10% of period, while the average error of trough is 15%. The correct rates of peak and trough both are above 92%.
     (3) The results of epileptic spikes detection experiment showed that the epileptic detection algorithm could avoid the influence of normal EEG or noise signal and the accuracy of the detection of epileptic spikes could almost reach 100%.
     (4) The frequency response test of PC sound card showed that most of the sound card can meet the need of epilepsy EEG detection and the accuracy of the detection is around 97%.
     In a word, this paper designed a neural stimulator with closed-loop control, which can automatically predict the phase of 0 wave rhythm and detect epileptic spikes. It can also provide a variety of stimulus waves by users' set. Such stimulator can be used for the study of the mechanisms of nervous system or brain stimulation. At the same time, the simple epileptic EEG monitor by sound card has a high detection accuracy rate, which can be used in the field of telemedicine.
引文
[1]Liu Y, Postupna N, Falkenberg J, et al. Anderson. High frequency deep brain stimulation: What are the therapeutic mechanisms?[J]. Neuroscience & Biobehavioral Reviews,2008, 32(3):343-351.
    [2]Halpern CH, Samadani U, Litt B, et al. Deep brain stimulation for epilepsy[J]. Neurotherapeutics,2008,5(1):59-67.
    [3]Feng ZY and Durand DM. Low-Calcium Epileptiform activity in the hippocampus in vivo[J]. Journal of Neurophysiology,2003,90 (4):2253-2260.
    [4]粱华为,沈岳良,陈志雄等.低频刺激后海马CA1区场兴奋性突触后电位与群体锋电位的变化[J].生理学报,2002,54(5):431-434.
    [5]Roger ML and Peter MF. A portable device for the electrical extraction of scorpion venom[J]. Toxicon,2011,57:244-247.
    [6]王卫,黄英,张德昌.生物电与电刺激及其在医学中的应用[J].医疗卫生装备,2003,24(4):28-29.
    [7]Jarvis JC and Salmons S. A family of neuromuscular stimulators with optical transcutaneous control[J]. Journal of Medical Engineering & Technology,1991,3,15(2):53-57.
    [8]周平,李胜利,黄耀熊.基于虚拟仪器技术的时序功能电刺激系统[J].中国医学物理学杂志,2009,5,26(3):1220-1223.
    [9]牛川森,胡春华等.可编程式经皮神经肌肉电刺激系统的设计及初步实验研究[J].航天医学与医学工程,2009,22(3):211-215.
    [10]王娅,周鹏,张爽等.基于ERD/ERS脑电信号的智能化功能电刺激系统的设计[J].生物医学工程学杂志,2007,24(5):1157-1160.
    [11]王卫东,刘洪运,吕昊.多通道可植入神经刺激器的设计和实现[J].医疗卫生装备,2008,29(7):1-3.
    [12]Record P, Williams E, Hitchcock E, et al. Computer-controlled stimulation in the assessment of electrical characteristics for cortical phosphene generation for a visual prosthesis[J]. Journal of Medical Engineering & Technology,1989,13(1):52-56.
    [13]中华人民共和国国家质量监督检验检疫总局中国国家标准化管理委员会.GB9706.24-2005医用电气设备第2部分:神经和肌肉刺激器安全专用要求[S].北京: 中国标准出版社,2007.
    [14]俞跃,郝红伟,牛川森等.植入式单穴位电刺激系统研究[J].医疗卫生装备,2009,7,30(7):7-11.
    [15]张宇翔,朱天桥,黄力宇.一种新颖的反馈电刺激装置研制与应用[J].现代电子技术,2009,21:167-170.
    [16]曹建中等.智能化神经刺激器[J].中国医疗器械杂志,1990,14(6):27-30.
    [17]Langlois PJ, Demosthenous A, Pachnis I, et al. High-Power Integrated Stimulator Output Stages With Floating Discharge Over a Wide Voltage Range for Nerve Stimulation[J]. IEEE Transactions on Biomedical Circuits and Systems,2010,4:39-48.
    [18]Ativanichayaphong T, He JW, Hagains CE, et al. A combined wireless neural stimulating and recording system for study of pain processing[J]. Journal of Neuroscience Methods, 2008,170:25-34.
    [19]于霄,张华,付峰等.基于MSP430的用于大鼠癫痫实验的电刺激器研究[J].医疗卫生装备,2008,29(6):4-5.
    [20]Buzsaki G. theta oscillations in the hippocampus[J]. Neuron,2002,33(3):325-340.
    [21]冯慧琳,洪波,高小榕.海马区神经电信号相位同步化的初步研究[J].北京生物医学工程,2007,26(6):566-569.
    [22]Hajime H, Xavier L, Andras C. Firing rates of hippocampal neurons are preserved during subsequent sleep episodes and modified by novel awake experience [J]. The National Academy of Sciences,2001,98(16):9386-9390.
    [23]James MH, Bradley PW, Vikas G, et al. Stimulation in Hippocampal Region CA1 in Behaving Rats Yields Long-Term Potentiation when Delivered to the Peak of Theta and Long-Term Depression when Delivered to the Trough[J]. Journal of Neuroscience,2003, 23(37):11725-11731.
    [24]Alessandro M, Mauro G, Paolo M, et al. A novel algorithm for precise identification of spikes in extracellularly recorded neuronal signals[J]. Journal of Neuroscience Methods, 2009,117:241-249.
    [25]Ghassan G, Spiros C, Angelika D, et al. An algorithm for real-time extraction of population EPSP and population spike amplitudes from hippocampal field potential recordings[J]. Journal of Neuroscience Methods,2004,136(2):111-121.
    [26]Greene BR, Faul S, Marnane WP, et al. A comparison of quantitative EEG features for neonatal seizure detection[J]. Clinical Neurophysiology,2008,119(6):1248-1261.
    [27]Esteller R, Echauz J, Tcheng T, et al. Line length:an efficient feature for seizure onset detection[C]. Proceedings of the 23rd annual international conference of the IEEE engineering in medicine and biology society, Engineering in Medicine and Biology Society, 2001,2:1707-1710.
    [28]D'Alessandro M, Esteller R, Vachtsevanos G, et al. Epileptic seizure prediction using hybrid feature selection over multiple intracranial EEG electrode contacts:a report of four patients[J]. IEEE Transactions on Biomedical Engineering,2003,50(5):603-615.
    [29]Korn SJ, Giacchino JL, Chamberlin NL and Dingledine R. Epileptiform burst activity induced by potassium in the hippocampus and it regulation by GABA-mediated inhibition[J]. Journal of Neurophysiology,1987,57(1):325-340.
    [30]Andrew MW, Philip AW, Damien JF, et al. Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury[J]. Journal of Neuroscience Methods,2006.152:255-266.
    [31]Shriram R, Sumeet KG, Himanshu SM, et al. A hardware-algorithm co-design approach to optimize seizure detection algorithms for implantable applications [J]. Journal of Neuroscience Methods,2010,193:106-117.
    [32]Olton DS, Becker JT, Handelmann GE. Hippocampus, space and memory[J]. Behavioral and Brain Sciences,1979,2(3):313-322.
    [33]Taejib Y, Jeffrey O,Min WJ, et al. Prefrontal cortex and hippocampus subserve different components of working memory in rats [J]. Learning Memory,2008,15(3):97-105.
    [34]Volodymyr ID and Kevin JS. Transition from interictal to ictal activity in limbic networks in vitro[J]. The Journal of Neuroscience,2003,23(21):7873-7880.
    [35]李刚,张旭.生物医学电子学[M].北京:电子工业出版社,2008:1-3.
    [36]封洲燕,王静.微电极阵列大脑电信号检测技术的进展[J].电子学报,2009,1:153-159.
    [37]郑效来,邱天爽,赵庚申等.一种基于EEG特征提取的癫痫棘波综合检测判决方法[J].中国生物医学工程学报,2005,10,24(6):696-699.
    [38]Felice TS, Martha JM, Robert EW, et al. Responsive Cortical Stimulation for the Treatment of Epilepsy [J]. Neurotherapeutics,2008,5(1):68-74.
    [39]Brian L, Rosana E, Javier E, et al. Epileptic Seizures May Begin Hours in Advance of Clinical Onset:A Report of Five Patients[J]. Neuron,2001,30:51-64.
    [40]Hjorth B. EEG analysis based on time domain properties[J]. Electroencephalography and Clinical Neurophysiology,1970,29:306-310.
    [41]Niina P, Seppo L, Asla P, et al. Epileptic seizure detection:a nonlinear viewpoint[J]. Computer Methods and Programs in Biomedicine,2005,79(2):151-159.
    [42]Pfurtschellera G, Lopes FH. Event-related EEG/MEG synchronization and desynchronization:basic principles [J]. Clinical Neurophysiology,1999, 110(11):1842-1857.
    [43]章江,李满成.医用电刺激器的研制[J].电工电能新技术,1995,4:55-57.
    [44]Feng ZY, Durand DM. Propagation of low calcium non-synaptic induced epileptiform activity to the contralateral hippocampus in vivo[J]. Brain Research,2005,1055(1-2): 25-35.
    [45]Mikkonen JE, Gronfors T, Chrobak JJ, et al. Hippocampus retains the periodicity of gamma stimulation in vivo[J]. Journal of Neurophysiology,2002,88:2349-2354.
    [46]Patricio TH and John EL. Low-Frequency Stimulation at the Troughs of θ-Oscillation Induces Long-Term Depression of Previously Potentiated CA1 Synapses[J]. Journal of Neurophysiology,1996,75(2):877-884.
    [47]梁华为,沈岳良,吴迅冬等.低频刺激诱发海马突触传递去长时程增强的特性研究[J].中国应用生理学杂志,2002,18(3):218-221.
    [48]田远虎,刘绍明,司军强.大脑皮质电刺激术治疗难治性痫病[J].临床神经电生理学杂志,2008,17(2):121-123.
    [49]刘楠,屠洁,张奕等.深部脑刺激对神经精神疾病的治疗与未来展望[J].中国生物医学工程学报,2009,10,28(5):771-777.
    [50]郑宇,王庆松,向阳.反复海马CA1区惊厥阈下电刺激致实验大鼠持续性临床下痫样放电研究[J].西南国防医药,2008,18(6):790-793.
    [51]吴俊芳,王文挺,魏晓菲等.电刺激诱导大鼠海马癫痫电网络神经信息分析[J].生物物理学报,2006,22(4):259-267.
    [52]王文挺,韩丹,邹祖玉等.电刺激大鼠右后背海马诱导前背海马神经网络癫痫样电活动[J].生理学报,2003,6,55(3):339-348.
    [53]Yamamoto J, Ikeda A, Kinoshita M, et al. Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy[J]. Seizure,2006,15(7):520-527.
    [54]Kinoshita M, Ikeda A, Matsumoto R, et al. Electric Stimulation on Human Cortex Suppresses Fast Cortical Activity and Epileptic Spikes[J]. Epilepsia,2004,45(7):787-791.
    [55]诸葛正兵.低频率电刺激对杏仁核电点燃癫痫的作用研究[D].浙江:浙江大学,2007.
    [56]Handforth A, DeSalles AA, Krahl SE. Deep brain stimulation of the subthalamic nucleus as adjunct treatment for refractory epilepsy[J]. Epilepsia,2006,47(7):1239-1241.
    [57]Ghorbani P, Mohammad ZM, Mirnajafi-Zadeh J, et al. Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures [J]. Neuroscience Letters, 2007,425:162-166.
    [58]Jeffrey T and Jim K. Labview for everyone graphical programming made easy and fun[M]. Prentice Hall PTR,2006.
    [59]Jong MC, Haet BL, Cheol SP, et al. PC-Based Tele-Audiometry[J]. Telemedicine and e-Health,2007,13(5):501-508.

© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号

地址:北京市海淀区学院路29号 邮编:100083

电话:办公室:(+86 10)66554848;文献借阅、咨询服务、科技查新:66554700