本論文描述一套多通道、低雜訊的小型16通道神經生理訊號放大電路，及自行發展的一套具有時間、空間與頻率分析的多元性軟體，使得我們能夠分析誘發電位波形之主要峰值的延遲時間與其在不同大腦皮層間的電位分佈，並且分析不同大腦皮層區域腦波在時間軸與頻率軸上的特殊關係。另外，使用上述多通道放大器電路為基礎，加以修改完成另一套能夠同時間記錄單一神經細胞活性與場電位的放大器電路的設計，並且證實我們有能力在清醒且自由活動大鼠大腦皮層中穩定地記錄其神經細胞活性。在多通道腦波訊號分析方面，我們發現零參考點方式將有助於降低遠場電位的影響，以凸顯近場電位腦波之功能特性。
利用此套訊號放大與分析系統，我們可記錄與分析對於傷害性刺激與非傷害性刺激所引起大鼠大腦皮層電位反應，並比較清醒與麻醉下傷害性刺激與非傷害性刺激大腦皮層誘發電位的特性。在清醒狀態下非傷害性刺激大腦皮層誘發電位波形為一個正向為主的波峰緊跟著一個大振幅的負向波；傷害性刺激大腦皮層誘發電位波形為一個延遲時間較短且略帶雙相位的負向波，再跟著一個較遲較大的負向波。經由傳導速度的計算，非傷害性刺激大腦皮層誘發電位的第一個正向波為Ab神經纖維所傳導，非傷害性刺激誘發電位的第二個負向波與傷害性刺激誘發電位的第一個負向波為Ad神經纖維所傳導，傷害性刺激誘發電位的第二個負向波為C神經纖維所傳導。觸覺初級大腦皮層對於傷害性刺激與非傷害性刺激的反應都與刺激強度成正相關。非傷害性刺激產生的誘發反應主要集中於初級觸覺大腦皮層位置，而傷害性刺激誘發反應則分佈於較大的區域包括了感覺與運動皮層的位置。另外，戊巴比妥鈉麻醉不影響Ab神經纖維所傳導的誘發波形的極性，然而對於Ad與C神經纖維所傳導的誘發波形則有明顯的抑制影響。

A system has been developed to record and analyze the cortical field potentials from multiple recording sites in the brain of freely moving rats. The hardware of this system includes a 16-channel amplifier system with high input impedance, low noise, small size, light weight and shielded multistrand connecting cable to allow high quality multichannel recording of field potentials. The software developed for this system consists of data acquisition, spectrotemporal data analysis and topographical mapping of cortical evoked potentials as well as electroencephalograms. Moreover, the 16-channel amplifier was improved to chronically record the field potentials and neuronal activities in freely moving rats. The reference-free derivation would enhance the near field potential of the cerebral cortex. Mechanical, electrical and laser stimuli were applied to the tail of the chronically implanted rats. In conscious state, the mechanical evoked potentials (MEPs) consists of a positive peak (MEP1) followed by a larger negative peak (MEP2). The portrait of electrical evoked potentials is similar to that of MEP. On the other hand, the laser evoked potentials (LEPs) consists of two distinct negative peaks (LEP1 & LEP2). Deducted from conduction velocity estimation, the MEP1 is conducted by Ab afferent fiber, the MEP2 and LEP1 is conducted by Ad afferent fiber, and the LEP2 is conducted by C afferent fiber. All these evoked components in the primary somatosensory cortex (SI) are capable of sensory/discriminatory function because they showed intensity-dependant changes in magnitude. The major cortical responsive area to innocuous stimulation is concentrated at SI, whereas the cortical responsive area to noxious stimulation distributed in the sensorymotor cortical area. Dynamic changes of these evoked components were tested before, during and after pentobarbital anesthesia. The Ab-fiber mediated component maintained its positive polarity during pentobarbital anesthesia. The Ad-fiber and C-fiber mediated components showed dynamic changes in response to sodium pentobarbital administration. There were totally abolished during pentobarbital anesthesia, and did not fully recover until several hours after the rat regained consciousness. We concluded that the MEP1 showed robust characteristics in both conscious and anesthetized conditions, the MEP2 is a state-dependant component; whereas the LEP1 is mediated by Ad fiber and the LEP2 is mediated by C fiber. The LEP1 and LEP2 are sensory-motor interacted responses and strongly influent by anesthesia.

封面
中文摘要
英文摘要
誌謝
目錄
圖目錄
表目錄
1. 簡介
2. 多通道記錄與分析系統
2.1 多通道腦波號記錄器
2.2 多通道腦波與誘發電位分析軟體
2.3 多通道神經元活性與電場記錄放大器
3. 動物實驗準備過程與實驗步驟
3.1 預埋表面電極
3.2 預埋腦內微電極與手術後處理
3.3 刺激尾巴的設備
3.4 訊號記錄與資料分析
4. 實驗結果
4.1 清醒狀態下誘發電位實驗結果
4.2 清醒與麻醉狀態下誘發電位的比較
5. 討論
5.1 多通道記錄與分析系統
5.2 大腦皮層誘發電位之結果
6. 結論及未來展望
6.1 結論
6.2 未來展望
參考文獻
著作目錄

[1] M. Abeles, "Corticonics. Neural circuits of the cerebral cortex," Cambridge, Cambridge University, 1991, pp. 59.
[2] J. C. Arezzo, H. G. Vaughan Jr. and A. D. Legatt, "Topography and intracortical sources of somatosensory evoked potentials in the monkey. II. Cortical components," Electroenceph. clin. Neurophysiol., vol. 28, pp. 1-18, 1981.
[3] E. Basar, "Chaos in brain function," New York, Spring-Verlag Berlin Heidelberg, 1990.
[4] B. Bromm, H. Neitzel, A Tecklenburg and R.-D. Treede, "Evoked cerebral potential correlates of C-fiber activity in man," Neurosci. Lett., vol. 43, pp. 109-114, 1983.
[5] B. Bromm and J. E. Desmedt, Pain and the brain, from nociception to cognition. Adances in pain research and therapy, vol. 22, New York, Raven, 1995.
[6] B. Bromm, M. T. Jahnke and R.-D. Treede, "Responses of human cutaneous afferents to CO2-laser stimuli causing pain," Exp. Brain Res., vol. 55, pp. 158-166, 1984.
[7] B. Bromm and R. D. Treede, "Human cerebral potentials evoked by CO2 laser stimuli causing pain," Exp. Brain Res., vol. 67, pp. 153-162, 1987.
[8] J. N. Campbell, S. N. Raja and R. A. Meyer, "Halothane sensitized cutaneous nociceptors in monkeys," J. Neurophysiol., vol. 52, pp. 762-770, 1984.
[9] A. Carmon, Y. Dotan and Y. Sarne, "Correlation of subjective pain experience with cerebral evoked responses to noxious thermal stimulation," Exp. Brain Res., vol. 33, pp. 445-453, 1978.
[10] K. L. Casey and T.J. Morrow, "Ventral posterior thalamic neurons differentially responsive to noxious stimulation of the awake monkey," Science, vol. 221, pp. 675-677, 1983.
[11] L. J. Cauller, "Layer I of primary sensory neocortex: where top-down converges upon bottom-up," Behav. Brain Res., vol. 71, pp. 163-170, 1995.
[12] L. J. Cauller and A. T. Kulics, "A comparison of awake and sleeping cortical states by analysis of the somatosensory-evoked responses of postcentral area 1 in rhesus monkey," Exp. Brain Res., vol. 72, pp. 584-592, 1988.
[13] L. J. Cauller and A. T. Kulics, "The neural basis of the behaviorally relevant N1 component of the somatosensory-evoked potential in SI cortex of awake monkeys: evidence that backward cortical projections signal conscious touch sensation," Exp. Brain Res., vol. 84, pp. 607-619, 1991.
[14] J. K. Chapin and C. S. Lin, "The somatic sensory cortex of the rat," in The cerebral cortex of the rat, B. Kolb and R. C. Tees, ed., Cambridge, MIT, pp. 341-380, 1990.
[15] J. K. Chapin, B. D. Waterhouse and D. J. Woodward, "Differences in cutaneous sensory response properties of single somatosensory cortical neurons in awake and halothane anesthetized rats," Brain Res. Bull., vol. 6, pp. 63-70, 1981.
[16] P. S. Churchland and T. J. Sejnowski, "Perspectives on cognitive neuroscience," Science, vol. 242, pp. 741-745, 1988.
[17] D. L. Clark and B. S. Rosner, "Neurophysiological effects of general anesthetics: I. The electroencephalogram and sensory evoked responses in man," Anesthesiology, vol. 38, pp. 564-582, 1973.
[18] D. Contreras, A. Destexhe, T. J. Sejnowski and M. Steriade, "Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic feedback," Science, vol. 274, pp. 771-774, 1996.
[19] A. D. Craig, M. C. Bushnell, E.-T. Zhang and A. Blomqvist, "A thalamic nucleus specific for pain and temperature sensation," Nature, vol. 372, pp. 770-773, 1994.
[20] A. D. Craig, E. M. Reiman, A. Evans and M. C. Bushnell, "Functional imaging of an illusion of pain," Nature, vol. 384, pp. 258-260, 1996.
[21] N. Dafny, "Neurophysiological approach as a tool to study the effects of drugs on the central nervous system: dose effect of pentobarbital," Exp. Neurol., vol. 59, pp. 263-274, 1978.
[22] M. Devor, A. Carmon and R. Frostig, "Primary afferent and spinal sensory neurons that respond to brief pulses of intense infared laser radiation: a preliminary survey in rats," Exp. Neurol., vol. 76, pp. 483-494, 1982.
[23] W. K. Dong, L. D. Salonen, Y. Kawakami, T. Shiwaku, M. Kaukoranta and R. F. Martin, "Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkey," Brain Res., vol. 484, pp. 314-324, 1989.
[24] T. Elbert, W. J. Ray, Z. J. Kowalik, J. E. Skinner, K. E. Graf and N. Birbumer, "Chaos and physiology: deterministic choas in excitable cell assemblies," Physiol. Rev., vol. 74, 1-47, 1994.
[25] G. Fein, J. Raz, F. F. Brown and E. L. Merrin, "Common reference coherence data are confounded by power and phase effects," Electroenceph. clin. Neurophysiol., vol. 69, pp. 581-584, 1988.
[26] C. C. French and J. G. Beaumont, "A critical review of EEG coherence studies of hemisphere function," Int. J. Psychophysiol., vol. 1 pp. 241-254, 1984.
[27] H. Head and G. Holmes, "Sensory disturbances from cerebral lesions," Brain, vol. 34, pp. 102-254, 1911.
[28] R. F. Hellon and N. K. Misra, "Neurons in the ventrobasal complex of the rat thalamus respoding to scrotal skin temperature changes," J. Physiol., vol. 232, pp. 389-399, 1973.
[29] R. F. Hellon, N. K. Misra and K. A. Proven, "Neurons in the somatosensory cortex of the rat responding to scrotal skin temperature changes," J. Physiol., vol. 232, pp. 401-411, 1973.
[30] M. Herkenham, "Laminar organization of thalamic projections to the rat neocortex," Science, vol. 207, pp. 532-535, 1980.
[31] B. Hjorth, "Source derivation simplifies topographical EEG interpolation," Am. J. EEG Tech., vol. 20, pp. 121-132, 1980.
[32] A. K. Jones, W. D. Brown, K. J. Friston, L. Y. Qi and R. S. Frackowiak, "Cortical and subcortical localization of response to pain in man using positron emmision tomography," Proc. R Sco. London B, vol. 244, pp. 39-44, 1991.
[33] J. Kalliomaki, H. R. Weng, H. J. Nilsson and J. Schouenborg, " Nociceptive C fiber input to the primary somatosensory cortex (SI). A field potential study in the rat," Brain Res., vol. 622, pp. 262-270, 1993.
[34] A. N. Kaspar and H. G. Schuster, "Easily calculable measure for the complexity of spatiotemporal pattern," Phys. Rev. A, vol. 36, pp. 842-848, 1987.
[35] D. R. Kenshalo, E. H. Chudler, F. Anton and R. Dubner, "SI nociceptive neurons participate in the encoding process by which monkey perceive the intensity of noxious thermal stimulation," Brain Res., vol. 454, pp. 378-382, 1988.
[36] D. R. Kenshalo and O. Isensee, "Responses of primates SI cortical neurons to noxious stimuli," J. Neurophysiol., vol. 50, pp. 1479-1496, 1983.
[37] D. R. Kenshalo and W. D. Willis, "The role of the cerebral cortex in pain system," in Cerebral Cortex: Normal and Altered States of Function, A. Peter and E. G. Jones, ed., New York & London, Plenum, vol. 9, pp. 153-212, 1991.
[38] D. R. Kenshalo Jr., R. B. Leonard, J. M. Chung and W. D. Willis, "Responses of primate spinothalamic neurons to graded and to repeated noxious heat stimuli," J. Neurophysiol., vol 42, pp. 1370-1389, 1979.
[39] Y. Kitamura, R. Kakigi, M. Hoshiyama, S. Koyama, M. Shimojo and S. Watanabe, "Pain-related somatosensory evoked magnetic fields," Electroenceph. clin. Neurophysiol., vol. 95, pp. 463-474, 1995.
[40] E. Kochs and R.-D. Treede, J. Schulte am Esch and B. Broom, "Modulation of pain-related somatosensory evoked potentials by general anesthesia, Anesth. Analg., vol. 71, pp. 225-230, 1990.
[41] A. N. Kolmogorov, "Three approaches to the definition of the concept of quantity of information," IEEE Trans. Inform. Theory, vol. 14, pp. 662-669, 1965.
[42] V. Kunde and R.-D. Treede, "Topography of middle-latency somatosensory evoked potentials following painful laser stimuli and non-painful electrical stimuli," Electroenceph. clin. Neurophysiol., vol. 88, pp. 280-289, 1993.
[43] Y. Lamour, G. Guilbaud and J. C. Willer, "Rat somatosensory (SmI) cortext: II. Laminar and columnar organization of noxious and non-noxious inputs," Exp. Brain Res., vol. 49, pp. 46-54, 1983.
[44] Y. Lamour, J. C. Willer and G. Guilbaud, "Rat somatosensory (SmI) cortex: I. Characteristics of neuronal responses to noxious stimulation and comparison with responses to non-noxious stimulation," Exp. Brain Res., vol. 49, pp. 35-45, 1983.
[45] M. S. Lemos and B. J. Fisch, "The weighted average reference montage," Electroenceph. clin. Neurophysiol., vol. 79, pp. 361-370, 1991.
[46] A. Lempel and J. Ziv, "On the complexity of finite sequences," IEEE Trans. Inform. Theory, vol. 22, pp. 75-81, 1976.
[47] H. Luders, R. P. Lesser, D. S. Dinner and H. H. Morris, "Optimizing stimulating and recordingparameters in somatosensory evoked potential studies," J. Clin. Neurophysiol., vol. 2, pp. 383-396, 1985.
[48] N. Matsumoto, T. Sato and T. A. Suzuki, "Characteristics of the tooth pulp-driven neurons in a functional column of the cat''s somatosensory cortex (SI)," Exp. Brain Res., vol. 74, pp. 263-271, 1988.
[49] R. A. Meyer and J. N. Campbell, "Myelinated nociceptive afferents account for the hyperalgesia that follows a burn to the hand," Science, vol. 213, pp. 1527-1529, 1981.
[50] J. Montagne-Clavel, J.-L. Oliveras and G. Martin, "Single-unit recordings at dorsal raphe nucleus in the awake-anesthetized rat: spontaneuous activity and response to cutaneuous innocuous and noxious stimulations," Pain, vol. 60, pp. 303-310, 1995.
[51] R. Morrison, "Grounding and shielding techniques in instrumentation," New York, Wiley-Interscience, 1986.
[52] A. V. Oppenheim and R. W. Schafer, "Discrete-time signal processing," New Jersey, Prentice-Hall, 1989.
[53] J. W. Osselton, "Acquisition of EEG data by bipolar, unipolar and average reference methods: a theoretical comparison," Electroenceph. clin. Neurophysiol., vol. 19, pp. 527-528, 1965.
[54] H. W. Ott, "Noise reduction techniques in electronic systems," New York, Wiley-Interscience, 1976.
[55] M. Peschanski, G. Guilbaud, M. Gautron and J.-M. Besson, "Encoding of noxious heat messages in neurons of the ventrobasal thalamic complex of the rat," Brain Res., vol. 197, pp. 401-413, 1980.
[56] P. Rainville, G. H. Duncan, D. D. Price, B. Carrier and M.C. Bushnell, "Pain affect encoded in human anterior cigulate but not somatosensory cortex," Science, vol. 277, pp. 968-971, 1997.
[57] J. Schouenborg, J. Kalliomaki, P. Gustavsson and I. Rosen, "Field potentials evoked in the rat somatosensory cortex (SI) by impulses in cutaneous Ab- and C-fibers," Brain Res., vol. 397, pp. 86-92, 1986.
[58] F.-Z. Shaw, R.-F. Chen, H.-W. Tsao and C.-T. Yen, " A multichannel system for recording and analysis of cortical field potentials in freely moving rats," J. Neurosci. Methods, in press, 1999.
[59] F.-Z. Shaw, R.-F. Chen, H.-W. Tsao and C.-T. Yen, "Comparison of touch- and laser heat-evoked cortical field potentials in conscious rats," Brain Res., in press, 1999.
[60] F.-Z. Shaw, R.-F. Chen, H.-W. Tsao and C.-T. Yen, " Dynamic changes of touch- and laser heat-evoked cortical field potentials in awake and pentobarbital-treated rats," in preparation.
[61] G. M. Shepherd, "Neurobiology," New York, Oxford University, 1994, pp. 300.
[62] Y. Shigenaga and R. Inoki, "Effects of morphine and barbiturate on the SI and SII potentials evoked by tooth pulp stimulation of rats," Eur. J. Pharmacol., vol. 36, pp. 347-353, 1976.
[63] B. C. Shyu, B. Olausson and B. Rydenhag, " Field potential analysis of the cortical projection of the central lateral nucleus in the cat," Acta Physiol. Scand, vol. 137, pp. 503-512, 1989.
[64] M. Steriade, E. G. Jones and R. R. Llinas, "Thalamic oscillations and signaling," New York, Wiley, 1990.
[65] M. Steriade., D. A. McCormick and T. J. Sejnowski, "Thalamocortical oscillations in the sleeping and aroused brain," Science, vol. 262, pp. 679-685, 1993.
[66] J. D. Talbot, S. Marrett, A. C. Evans, E. Meyer, M. C. Bushnell and G. H. Duncan, "Multiple representations of pain in human cerebral cortex," Science, vol. 251, pp. 1355-1358, 1991.
[67] B. A. Vogt, "The role of layer I in cortical function," in Cerebral Cortex: Normal and Altered States of Function, A. Peter and E. G. Jones, ed., vol. 9, New York & London, Plenum, pp. 49-80, 1991.
[68] P. D. Wall and R. Melzack, "Textbook of Pain," New York, Churchill Livingstone, 1994.
[69] W. D. Willis, "The pain system," Basal, Karger, 1985.
[70] W. D. Willis and R. E. Coggeshall, "Sensory mechanisms of the spinal cord," New York, Plenum, 1991.
[71] C.-T. Yen, T.-C. Fu and R.-C. Chen, "Distribution of thalamic nociceptive neurons activated from the tail of the rat," Brain Res.,vol. 498, pp. 118-122, 1989.
[72] C.-T. Yen, C. H. Huang and S. E. Fu, " Surface temperature change, cortical evoked potential and pain behavior elicited by CO2 lasers," Chinese J. Physiol., vol. 37, pp. 193-199, 1994.