摘要
基于电生理信号的靶点定位是立体定向脑神经外科手术的关键技术,本文根据临床需要,以手术中微电极记录的帕金森病人神经细胞放电为对象,以获取放电信号特征为主线,以提取核团位置关联因子为目标,实现对微电极在神经核团中的位置实时定位,达到精确引导手术的目的,解决临床术中定位难题。本文的主要研究内容是信号预处理;放电脉冲增强、检测;脉冲提取、分类;特征因子求取;微电极术中定位。经过深入系统的研究,给出了详细的处理方法和步骤,对一些关键性技术取得了如下创新性成果。
1、提出了小波变换去噪预处理方法,找出了适合于人脑神经放电的小波基和最小分解层数。剔除了神经放电信号的基线漂移和高频噪声干扰,避免了信号处理引起的放电波形失真。
2、提出了小波系数和非线性能量算子两种放电增强算法,提出了神经放电脉冲检测和脉冲提取分步独立实现的方法。对于信号弱、信噪比低的神经放电信号,经处理提高了信噪比,克服了放电检测准确性和放电波形失真的矛盾。
3、提出了自适应阈值新的检测算法,给出了两种检测阈值算法、四种放电检测方法。提取出了不同核团的脑神经放电脉冲,并对神经放电脉冲进行了分类,找出了人的神经放电持续时间及其规律。利用模拟神经放电验证了检测方法的准确性,采用临床神经放电信号验证了其可靠性。
4、找出了与位置关联的盒子维、检测阈值、能量调制、峰峰间隔四个位置特征因子,并给出了具体算法。提出了利用四种因子实现定位的方法,在脑神经外科立体定向手术中首次提出了合理的定位依据和客观的定位技术,同时还给出了神经放电信号的可视化定位方法。
5、提出了关联维无标度区中心自动选取的方法,实现了关联维的自动计算,解决了无标度区中心选取需要人工干预的难题。
6、设计并构建了动物实验系统,采集了大鼠的脑神经放电信号,验证了放电脉冲提取和四种特征因子定位方法的可靠性。
Electrophysiological target localization is the key technology in microelectrode guided stereotactic neurosurgery for Parkinson’s disease, MER-based functional targeting locate the nominal anatomical target location based on MRI more precisely. The research is based on clinic microelelctrode data of Parkinson’s disease. The goal of the study is to identify neuronal structures of microelectrode depth intraoperatively by extracting the characteristics of neuronal discharge signals; to realize objective and automated precise real time localization and to achieve microelectrode guided surgery by analyzing characteristics of the MER data. An in-depth study is given systemically of signal pretreatment, spike enhancement, spike detection, spike extraction, spike sort techniques and characteristic parameters, key technologies of locating microelectrode position, methods of signal processing is given step by step. The main achievements and innovative results are described in the following parts:
1、A wavelet transform based method is introduced for removing the baseline draft and high frequency noises in neuronal signals at the same time. The wavelet type for human neuronal spike and optimal decomposition scale levels are selected for avoiding discharge wave distortion during denosing process.
2、Two enhancement algorithms of wavelet coefficients and nonlinear energy operator are applied to improving signal to noise ratio. The process of spike detection and extraction are proposed separately to solve the contradiction between detecting accurately and wave distortion of neuronal spikes.
3、An exact detection is foundation of spike characteristic analysis. The detection precision is influenced by detection threshold . Two algorithms of threshold and four detection methods are introduced to extract neuronal spikes of different nucleus. A novel algorithm of adaptive threshold detection is presented , the threshold is adjusted automatically for various amplitude and signal to noise ratio. These algorithms are verified by simulative signal and clinical MER signal. The methods of spike detection and classification are correct. Neuronal spikes are extracted of different nucleus, the latency of human neuronal discharge is obtained. Spikes are classificated using PCA.
4、Four feature parameters of box dimension, detection threshold, energy modulation, interspike interval are extracted from microelectrode recordings for objective and quantitative target localization, four targeting techniques are presented. The subjective localization of microelectrode position intraoperatively is overcomed. Four targeting techniques can improve localization accuracy, and can be used in clinic neurosurgery. Visual targeting method is given in addition.
5、A novel method of identification the fractal scaleless center in correlative dimension is proposed. The choice of fractal scaleless is unsupervised based on the formula presented, correlative dimension can be calculated automatically.
6、The animal experimental system is set up. The neuronal spike data are sampled by microelectrode, and processed by spike extraction.four targeting parameters is ued for microelectrode localization. Methods of spike extraction and four targeting techniques are validated by animal experiment.
引文
[1] 刘承勇, 漆松涛, 王克万,等. 帕金森病外科治疗学[M]. 北京: 人民卫生出版社, 2004
[2] Guridi J, Lozano A M. A briefhistory of pallidotomy[J]. Neurosurgery,1997, 41:1169~l183
[3] Lozano A M, Lang A E,Hutchison W D, et al. New developments in understanding the etiology of Parkinson’s disease and in its treatment[J].Current Opinion in Neurobiology,1998,8:783~790
[4] Christopher H, Gross R E and Lozano A M. New developments in the surgery for Parkinson’s disease [J]. Can. J. Neurol. Sci.,1999, 26: Suppl.2,S45~S52
[5] Koller W C,Pahaw R,Lyons K E,et al. Surgical treatment of Parkinson’s disease[J]. J Neurol Sci.,1999,167(1):1~12
[6] Eskandar E N, Flaherty A, Cosgrove G R, et al. Surgery for parkinson disease in the United States, 1996 to 2000: practice patterns, short-term outcomes, and hospital charges in a nationwide sample[J].J Neurosurg,2003,99:863~871
[7] Kenneth A, Follett. The Surgical Treatment of Parkinson’s disease[J]. Annu. Rev. Med.,2000,51:135~147
[8] Lozanoa A M, Mahanta N. Deep brain stimulation surgery for Parkinson’s disease: mechanisms and consequences[J]. Parkinsonism and Related Disorders,2004, 10:S49~S57
[9] 李勇杰. 帕金森氏病若干概念的探讨[J]. 生理科学进展,1998,29(1):42~44
[10] 李勇杰. 从帕金森病谈起[J].中国微侵袭神经外科杂志,2003,8(1):481~483
[11] 张旺明,徐如祥等. 帕金森病外科治疗的发展及其启示[J]. 医学与哲学,1998,19(11):613~614
[12] 王忠诚,张建国.帕金森病的外科治疗现状和未来[J].中华神经外科杂志,2002,18(1):1~3
[13] 李勇杰. 帕金森病的手术治疗[J].现代康复,2000,4(3):332~335
[14] 张世忠,徐如祥. 帕金森病外科手术治疗[J]. 中华神经外科杂志,2003,2(5):383~389
[15] 周 青,张世忠,徐如祥. 帕金森病的治疗现状和展望[J].中国临床康复,2004,8(16):3102~3103
[16] Fillon M, Trembiay L, Bedard P J. Abnormal influences of passive limb movement on the activity of globus pallidus neurons in monkeys with MPTP induced parkinsonism[J]. Brain Res.,1988,444(1):165~176
[17] Fillon M, Trembiay L. Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP induced parkinsonism[J].Brain Res.,1991,547(1):142~151
[18] Fillon M, Trembiay L and Bedard P J. Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP induced parkinsonism[J]. Brain Res.,1991,547(1):152~161
[19] Raz A, Vaadia E and Bergman H. Firing patterns and correlations of spontaneous discharge of pallidal neurons in the normal and the tremulous 1-methyl-4-phenyl-1,2,3, 6- tetrahydropyridine vervet model of parkinsonism[J]. The Journal of Neuroscience, November 15,2000,20(22):8559~8571
[20] Bergman H, Wichmann T, Karmon B, et al. The Primate subthalamic nucleus.Ⅱ.Neuronal activity in MPTP model of parkinsonism[J]. J Neurophysiol,1994, 72(2):507~520
[21] Taha J M, Favre J and Baumann T K, et al. Functional Anatomy of the Pallidal Base in Parkinson's Disease[J]. Neurosurgery 1996,39(6):1164~1168
[22] Hardman C D, Halliday G M. The internal globus pallidus is affected in progressive supranuclear palsy and parkinson’s disease[J]. Experimental Neurology,1999,158:135~142
[23] Ping Zhuang, Yongjie Li, Hallett M. Neuronal activity in the basal ganglia and thalamus in patients with dystonia[J]. Clinical Neurophysiology, 2004, 115:2542~2557
[24] Laitinen LV. Pallidotonry for Parkinson's disease[J]. Neurosurg Clin North Am.,1995,6:105~112
[25] Tasker R R, Lang A E and Lozano A M. Pallidal and thalamic surgery for Parkinson’s disease[J]. Experimental Neurology,1997,144:35~40
[26] Matsumura M, Tremblay L and Richard H. Activity of pallidal neurons in the monkey during dyskinesia induced by injection of bicuculline in the externalpallidum[J]. Neuroscience,1995,65(1):59~70
[27] 丁宛海. 帕金森病的外科治疗[J]. 立体定向和功能性神经外科杂志,2000,13(2):113~114
[28] 陈礼刚,曾凡俊. 脑立体定向治疗帕金森病进展[J].国外医学神经病学神经外科学分册,2002,27(2):99~101
[29] Vitek J K, Babay R A, Delong M R,et al. Microelectrode guided pallidotomy for medically intractable Parkinson’s desease[J]. Adv. Neurol.,1997,74,183~190
[30] Vitek J K, Babay R A, Hashimoto T, et al. Microelectrode guided pallidotomy: technical approach and its application in medically intractable Parkinson’s disease[J]. J Neurosurgery,1998,88(6):1027~1043
[31] Latinen L V, Bergenheim A T, Hariz M I, et al. Leksell’s posteroventral pallidotomy in treatment of Parkinson’s disease[J]. J Neurosurgery, 1992, 76(1):53~61
[32] Lozano A M, Hutchison W D, Kiss Z, et al. Methods for microeletrode guided posteroventral pallidotomy[J]. J Neurosurgery,1996,84(2):194~202
[33] 伦学庆. 苍白球立体定向术研究进展[J]. 功能性和立体定向神经外科杂志,1996,9(4):55~57
[34] 王忠诚.神经导航系统的应用现状与发展前景[J].中华神经外科杂志,1998, 14(4):197~197
[35] Hallett M and Litvan I. Evaluation of surgery for Parkinson’s disease [J]. Neurology,1999,53:1910~1921
[36] Guridi J, Gorospe A, Ramos E, et al. Stereotactic targeting of the globus pallidus internus in Parkinson’s disease: imaging versus electrophysiological mapping[J]. J Neurosurgery,1999,45:278~289
[37] 张宇清,李勇杰. 神经核团毁损术治疗帕金森病[J].立体定向和功能性神经外科杂志,2004,17(3):178~182
[38] 尚爱加,潘隆盛. 微电极导向立体定向技术治疗帕金森病进展[J].中国微创外科杂志2002, 2(6):436~437
[39] 周晓平,胡小吾,王来兴,等.微电极记录技术在帕金森病手术治疗价值[J].立体定向和功能性神经外科杂志,2002,15(2):84~86
[40] Hariz M I, Bergenheim A T. A 10-year follow-up review of patients who underwentLeksell’s posteroventral pallidotomy for Parkinson disease[J]. J Neurosurgery, 2001,94:552~558
[41] 马 凯, 李勇杰. 青少年型帕金森病手术疗效分析[J], 首都医科大学学报 2002, 23(2):122~124
[42] 何江弘. 对微电极记录的评价[J]. 立体定向和功能性神经外科杂志, 2003, 16(1):54~57
[43] Iacono R P, Carlson J D, Kuniyoshi S M, et al. Electrophysiological target localization in posteroventral pallidotomy[J]. Acta. Neurochirurgiea,1997, 139:433~441
[44] Lozano A M, Lang A E, Hutchison W D, et al. Microelectrode recording guided posteroventral pallidotomy in patients with Parkinson’s disease[J]. Adv. Neurol.,1997,74:67~174
[45] Alterman R L, Sterio D, Beric A, et al. Microelectrode recording during posteroventral pallidotomy: impact on target selection and complication[J]. J Neurosurgery,1999,44(2):315~323
[46] Carlson J D, Iacono R P. Electrophysiological versus image-based targeting in the posteroventral pallidotomy[J]. Computer Aided Surgery,1999,4:93~100
[47] 李勇杰, Iacono R P. 微电极导向的苍白球腹后部切开术治疗帕金森病 100 例临床分析[J],中华外科杂志,1998,36(10):603~605
[48] 胡军民,束枫,马廉亭,等.立体定向微电极导向苍白球毁损术治疗帕金森病的实验研究[J].中国微侵袭神经外科杂志,2002,7(1):35~37
[49] 杨天明,华涛,许竹君,等.微电极引导立体定向治疗 60 例帕金森病的疗效观察[J].中国临床神经外科杂志,2001,6(3):137~139
[50] Magnin M, Morel A and Jeanmonod D. Singnal-unit analysis of the pallidum, thalamus and subthalamic nucleus in Parkinson patients[J]. Neuroscience, 2000,96(3):549~564
[51] 喻 廉,凌至培,汪业汉,等. 帕金森病人 GPi、Vim 及 STN 的电生理特性研究[J]. 立体定向和功能性神经外科杂志,2002,15(2):81~83
[52] Gross R E, Lombardi W J, Lang A E, et al. Relationship of lesion location to clinical outcome following microelectrode guided pallidotomy for Parkinson’s disease[J]. Brain,1999,122:405~416
[53] Tsao k, Wilknson S, Overman J,et al. Pallidotomy lesion locations: significance of microelectrode refinement[J].J Neurosurgery,1998,43:506~513
[54] 高国栋,张华,张宝国,等.微电极引导定向手术治疗帕金森病的定位方法[J]. 中国临床神经外科杂志,1999,4(3):11~13
[55] Hutchison W D, Lozano A M, Tasker R R,et al. Identification and characterization of neurons with tremor-frequency activity in human globus pallidus[J]. Exp. Brain Res.,1997,113:557~563
[56] 吴佐泉,宰建国,徐国政,等. 微电极技术在立体定向神经外科治疗帕金森病中的应用[J]. 中国临床神经外科杂志,2001,6(3):142~144
[57] 徐强,徐如祥,张世忠,等. 电生理功能定位在帕金森病手术治疗中的应用[J].现代神经疾病杂志,2002,10(5):270~273
[58] 胡军民. 电生理技术在帕金森病立体定向手术中的应用[J] .立体定向和功能性神经外科杂志,2000,13(3):182~185
[59] 华 涛,叶 伟,许竹君,等.微电极引导立体定向治疗 43 例帕金森病的疗效观察[J].立体定向和功能性神经外科杂志,2001,14(2):104~106
[60] 许竹君,王锡海,华涛,等.微电极引导立体定向治疗 133 例帕金森病的疗效观察[J].江苏医药杂志,2003,29(5):370~371
[61] Nambu A, Llinas R. Electrophysiology of globus pallidus neurons in vitro[J]. Journal of neurophysiology,1994,72(3):1127~1139.
[62] 蒋正方.微电极导向技术(细胞刀)在神经外科的应用[J].国外医学神经病学神经外科学分册,2000,27(4):197~200
[63] 梁培基,陈爱华. 神经元活动的多电极同步纪录及神经信息处理[M]. 北京: 北京工业大学出版社, 2003
[64] 郭光文,王 序. 人体解剖彩色图谱[M]. 北京:人民卫生出版社, 2003:138~165
[65] Fee M S, Mitre P P and Kleinfeld D. Variability of extracellular spike waveforms of cortical neurons[J]. Neurophysiology,1996,76(6):3823~3833
[66] Fee M S, Mitre P P. On the variability of extracellular spike waveforms of cortical neurons[J]. Journal of Neurophysiology,1996,76(3):3823~3833
[67] Favre J, Taha J M, Baumann T, et al. Computer analysis of the tonic,phasic and kinesthetic activity of pallidal discharges in Parkinson patients[J]. Surg. Neurol.,1999,51:665~673
[68] Dewey Jra R B, Gillerb C A,Brolinea S K, et al. Clinical outcome of unilateral stereotactic pallidotomy without microelectrode recording for intractable Parkinson’s disease[J]. Parkinsonism and Related Disorders ,2000,6:7~16
[69] 张世忠,郭燕舞,张旺明,等. 帕金森病外科治疗中苍白球内侧部神经元电生理记录的有效针道方法[J]. 中华神经外科杂志,2003,2(3):180~182
[70] 聂能,尧德中,谢正祥.生物医学信号数字处理技术及应用[M]. 北京:科学出版社,2005:24~220
[71] 杨福生,高上凯. 生物医学信号处理[M]. 北京:高等教育出版社, 1989:533~561
[72] 吴怀宇. 时间序列分析与综合[M]. 武汉:武汉大学出版社,2004:137~171
[73] 丁北生,刘 慧,万柏坤,等. 局限性癫痫脑电时间序列的分形维数计算比较[J]. 北京生物医学工程,1998,17(3):136~139。
[74] 王东生,曹磊. 混沌、分形及其应用[M]. 合肥:中国科学技术大学出版社,1995
[75] 陈丰苏. 混沌学及其应用[M]. 北京:中国电力出版社,1998
[76] 孙博玲. 分形维数(Fractal dimension) 及其测量方法[J]. 东北林业大学学报,2004,32(3):116~119
[77] 王炳雪,史忠科,吴方向. 时间序列曲线盒维数的一种快速算法[J].系统工程,2000,18(4):68~72
[78] 党建武,黄建国. 一种计算时间序列关联维的逐步递归法[J]. 电子与信息学报,2005,27(6):879~883
[79] 朱志茹,隋建峰,高洁. 大鼠海马锥体细胞放电识别算法及程序设计[J].北京生物医学工程,2003,22(2):124~126
[80] 李建平. 小波分析与信号处理[M]. 重庆:重庆出版社,1997
[81] 杨福生. 小波变换的工程分析与应用[M]. 北京:科学出版社,1999
[82] 飞思科技产品研发中心. MATLIB6.5辅助小波分析与应用[M]. 北京:电子工业出版社,2003
[83] Lewicki M S. A review of methods for spike sorting: the detection and classification of neural action potentials[J]. Network,1998,9(4):R53~78
[84] Bolton R J, Hand D J and Webb A R. Projection techniques for nonlinear principal component analysis[J]. Statistics and Computing,2003,13:267~276
[85] Horn C C, Friedman M I. Detection of single unit activity from the rat vagus using cluster analysis of principal components[J]. Neuroscience methods,2003,122:141~147
[86] 董时富,方亚,程锦泉,等. 生物统计学[M]. 北京:科学出版社, 2002:172~182
[87] 陈亚勇. MATLAB 信号处理详解[M]. 北京:人民邮电出版社,2001:131~168
[88] Diedrich A, Charoensuk W, Brychta R J, et al. Analysis of raw microneurographic recordings based on wavelet de-noising technique and classification algorithym: wavelet analysis in microneurographiy[J]. IEEE Trans on biomedical engineering,2003,50(1):41~50
[89] Aminghafari M, Cheze N and Poggi J M. Multivariate denosing using wavelets and principal component analysis[J]. Computational Statistics &Data Analysis,2006,50(9):2381~2398
[90] Nakatani H, Watanabe T and Hoshimiya N. Detection of nerve action potentials under low signal-to-noise ratio condition[J]. IEEE Trans on biomedical engineering,2001,48(8):845~849
[91] Kyung H K, Sung J K. A wavelet-based method for action potential detection from extracellular neural signal recording with low signal-to-noise ratio[J]. IEEE Trans on biomedical engineering,2003,50(8):999~1011
[92] Snider P K, Bonds A B. Classification of non-stationary neural signals[J]. Journal of Neuroscience Methods,1998,84:155~166
[93] Fee M S, Mitra P P and Kleinfeld D. Automatic sorting of multiple unit neuronal signals in the presence of anisotropic and non-gaussian variability[J]. Journal of Neuroscience Methods,1996,69:175~188
[94] Guang-Li Wang, Pei-Ji Liang. Method for robust spike sorting with overlap decomposition[J]. Proceedings of the 2005 IEEE Engineering in Medicine and Biology 27th Annual Conference Shanghai China,2005,9:1~4
[95] Aboy M, Marquez O W, McNames J, et al. Adaptive modeling and spectral estimation of nonstationary biomedical signals based on kalman filtering[J]. IEEE Transactions on biomedical engineering,2005,52(8):1485~1489
[96] Yansun Xu, Weaver J B, Dennis M H, et al. Wavelet transform domain filters: A spatially selective noise filtration technique[J]. IEEE Transactions on image processing,1994,3(6):747~758
[97] Donoho D L. De-Noising by soft-thresholding[J]. IEEE Transactions oninformation theory,1995,1(3):613~627
[98] Mark L. Wavelet-based processing of neuronal spike trains piror to discriminant analysis[J]. Journal of Neuroscience Methods,2004,134:159~168
[99] Nenadic Z, Burdick J W. Spike detection using the continuous wavelet transform[J]. IEEE Trans on biomedical engineering,2005,52(1):74~87
[100] Letelier J C, Weber P P. Spike sorting based on discrete wavelet transform coefficients[J]. Journal of Neuroscience Methods,2000,101:93~106
[101] Eyal H, Ronen S and Eshel B J. A method for sorting and detection based on wavelet packets and Shannon’s mutual information[J]. Journal of Neuroscience Methods,2002,117:1~12
[102] Eyal H, Ronen S, Yoash S, et al. Detection and Sorting of Neuro Spikes using wavelet packets[J]. Physical review letters,2000,85(21):4637~4640
[103] McNames J. Pulse frequency demodulation without spike detection[J]. Proceedings of the 2nd International IEEE EMBS Conference on Neural Engineering Arlington,Virginia USA,2005,3:5~8
[104] Kim S, McNames J and Burchiel K. Detecting tremors in microelectrode recordings without using a spike detector[J]. Proceedings of the 26th Annual International Conference of the IEEE EMBS San Francisco CA USA, 2004, 9: 357~360
[105] Xiaowei Yang, Shamma S A. A totally automated system for the detection and classification of neural spikes[J]. IEEE Transactions on biomedical engineering,1988,35(10):806~816
[106] Montgomery Jr E B, Gale J T and He H. Methods for isolating extracellular action potentials and removing stimulus artifacts from microelectrode recordings of neurons requiring minimal operator intervention[J]. J Neuroscience Methods,2004,10:1~19
[107] Kim S, McNames J, and Burchiel K. Action Potential Detection with Automatic Template Matching. Proceedings of the 26th Annual International Conference of the IEEE EMBS San Francisco CA USA,2004,9:1~5
[108] Zouridakis G, Tam D C. Identification of reliable spike templates in multi-unit extracellular recordings using fuzzy clustering[J]. ComputerMethods and Program in Biomedicine,2000,61(2):91~98
[109] Pu-Ming Zhang, Jin-Yong Wu, Yi Zhou, et al. Spike sorting based on automatic template reconstruction with a partial solution to the overlapping problem[J]. Neuroscience Methods,2004,135:55~65
[110] Bankman I N, Johson K O and Schncider W. Optimal detection, classification and superposition resolution in neural waveform recordings[J]. IEEE Trans on biomedical engineering,1993,40(8):836~841
[111] Chandra R and Optican L M. Detection, classification and superposition resolution of action potentials in multiunit single channel recordings by an on-line real-time neural network.[J]. IEEE Trans. Biomed. Eng.,1997,44(5): 403~412
[112] Garc?a P, Suarez C P, Rodrguez J, et al. Unsupervised classification of neural spikes with a hybrid multilayerartificial neural network[J]. Journal of Neuroscience Methods,1998,82:59~73
[113] Kyung H K, Sung J K. Method for unsupervised classification of multiunit neural signal recording under low singnal-to-noise ratio[J]. IEEE Trans. Biomed. Eng., 2003,50(4):421~431
[114] Kyung H K, Sung J K. Neural spike sorting under nearly 0-db signal-to-noise ratio using nonlinear energy operator and artificial Neural-Network Classifier [J]. IEEE Trans. Biomed. Eng.,2000,47(10):1406~1411
[115] Aksenova T I, Chibirova O K, Dryga O A, et al. An unsupervised automatic method for sorting neuronal spike waveforms in awake and freely moving animals[J]. Methods,2003,30:178~187
[116] Maragos P, Kaiser J F and Quatieri T F. On amplitude and frequency demodulation using energy operators[J]. IEEE Transactions on signal processing, 1993, 41(4): 1532~1550
[117] Mukhopadhyay S and Ray G C, A new Interpretation of nonlinear energy operator and its efficacy in spike detection[J]. IEEE Transactions on Biomedical Engneering,1998,45(2):180~187
[118] Sekerli M, Del Negro C A, Lee R H, et al. Estimating action potential thresholds from neuronal time-series: new metrics and evalution of methodologies[J]. IEEETrans on biomedical engineering,2004,51(9):1665~1671
[119] Mcgill K C, Dorfman L J. High-resolution alignment of sampled waveforms[J]. IEEE Transactions on biomedical engineering,1984,31(6):462~468
[120] Wheeler B C, Heetderks W J. A comparison of techniques for classification of multiple neural signals[J]. IEEE Transactions on biomedical engineering, 1982,29(12):752~759
[121] Stitt J P, Gaumond R P, Frazier J L, et al. Action potential classifiers: a functional comparison of template matching, principal components analysis and an artificial neural network[J]. Chem. Senses,1998,23:531~539
[122] Vogelstein, R J, Murari K, Thakur P H, et al. Spike sorting with support vector machines[J]. Proceedings of the 26th Annual International Conference of the IEEE EMBS San Francisco,CA,USA,2004,1(1):546~549
[123] Kyung H K,Sung S K and Sung J K. Improvement of spike train decoder under spike detection and classification errors using support vector machine[J]. Med.Biol. Eng. Comput.,2006,44(1):124~130
[124] 高国栋,张华,张保国,等. 微电极记录技术在手术治疗帕金森病中的作用[J]. 中华神经外科杂志,1998,14(4):202~205
[125] Santiagoa R A, McNames J and Burchielc K. Developments in understanding neuronal spike trains and functional specializations in brain regions[J]. Neural Networks,2003,16:601~607
[126] Schiff S J, Dunagan B K and Worth R M. Failure of single-unit neuronal activity to differentiate globus pallidus internus and externus in Parkinson disease[J]. J Neurosurgery,2002,97:119~128
[127] 王举磊,高国栋,菅 忠,等. 帕金森病苍白球神经元放电的非线性特征[J]. 中国临床康复,2005,9(17):16~18
[128] 彭召意, 蒋伟进. 非线性复杂系统特征抽取算法的研究[J]. 微机发展,2004,14(5): 69~71
[129] Kennel M B, Brown R and Henry D I. Abarbanel.Determining embedding dimension for phase-space reconstruction using a geometrical construction[J]. Physical Review A,1992,45(6):3403~3411
[130] 党建武,黄建国. 基于 G.P 算法的关联维计算中参数取值的研究[J]. 计算机应用研究,2004,1:48~51
[131] 王安良,杨春信. 评价奇怪吸引子分形特征的 Grassberger Procaccia 算法[J]. 物理学报,2002,51(12):2719~2729
[132] 党建武,王瑞玲,黄建国. 基于G.P算法的关联维计算中无标度区的识别[J]. 弹箭与制导学报,2003,23(1):35~38
[133] 党建武,施 怡,黄建国. 分形研究中无标度区的计算机识别[J]. 计算机工程与应用,2003,12:25~27
[134] 王克斌, 彭真明, 杨旭明,等.地震数据关联维的快速计算方法[J].物探化探计算技术, 2000,122(3):225~228
[135] 包新民,舒斯云. 大鼠脑立体定位图谱[M]. 北京:人民卫生出版社,1991