连续经颅磁刺激系统的研制及其对睡眠作用机理的研究
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摘要
睡眠是人类最为重要的生理现象之一,是人类认知、代谢、免疫等功能正常运转所不可或缺的重要生理过程,睡眠质量的好坏直接影响到人类的身心健康。然而,随着社会现代化发展,生活节奏不断加快,各种压力不断增多,致使失眠症像流行病一样蔓延。失眠可以导致各种心脑血管疾病,还可能引发抑郁症,焦虑症等多种精神疾病,给患者带来极大的痛苦。因此,探索行之有效的治疗失眠的方法已是目前国内外关注的热点课题。
本文在以往研究的基础上,自行研制了连续经颅磁刺激系统,并进行了大鼠和人体睡眠实验,研究了连续经颅磁刺激对睡眠相关神经递质的影响,探讨了磁刺激诱导睡眠的作用机理。主要工作如下:
(1)研制了连续经颅磁刺激系统。硬件部分采用C8051F020单片机作为主控单元,采用TDA7294芯片进行功率放大,可实现0.001Hz~20KHz的交变磁场。设计制作了动物用和人用刺激线圈,并对线圈所产生磁场进分析和仿真。软件部分采用C#语言基于.net框架,可实现三种形式信号输出,包括:正常人入睡脑电信号、催眠音乐和典型波形刺激,其中典型波包括正弦,锯齿波,脉冲波等。每种刺激模式下可对信号频率,刺激时间,刺激间隙等参数进行自定义设置。PC机软件通过串口与单片机通信,保证数据传输的实时性。
(2)进行了磁诱导睡眠的动物实验和人体实验。大鼠实验结果显示当给予1Hz和10Hz低频磁刺激后,促进睡眠的抑制性递质呈现较大的增长趋势,而抑制慢波睡眠的兴奋性递质的释放则受到了较大的抑制;但100Hz的刺激结果相反。人体实验结果显示入睡脑电的磁刺激对慢波睡眠递质5-HT和Glu有有效的增强作用,对主要的抑制慢波睡眠的递质Ach释放有明显的抑制作用。
本文研制的连续磁刺激系统性能稳定可靠,操作方便,适宜医院使用,经过初步的实验验证对促进慢波睡眠,延长睡眠时间,增加快波睡眠有较好的效果。使用者可以针对睡眠疾病采用不同的刺激模式以达到不同的治疗目的。本系统也为进一步研究磁诱导睡眠的神经机制建立了很好的实验平台。
Human sleep is one of the most important physiological phenomenons. It, as an important physiological process, is essential for the work of human cognition, metabolism, immune. The quality of sleep has a direct influence to human physical and mental health. However, with the development of social modernization, the accelerating pace of life, increasing pressures, it has resulted in the spread of insomnia like epidemics. Insomnia can lead to a variety of cardiovascular and cerebrovascular diseases, but also may lead to sorts of mental illness such as depression, anxiety , which makes the patients suffer from great pain. Therefore, it has been brought into focus to explore an effective method of treatment of insomnia at home and abroad.
Based on previous studies, this paper develops independently a continuous transcranial magnetic stimulation system, conducts experiments in rat and human sleep, researches the influence of continuous transcranial magnetic stimulation to the sleep-related neurotransmitters, and then discusses the mechanism of magnetic stimulation-induced sleep. Major ones are as follows:
Firstly, develop a continuous transcranial magnetic stimulation system. In hardware part,it takes C8051F020 single chip as the main control unit, the TDA7294 as power amplifier chip to achieve the 0.001Hz ~ 20KHz alternating magnetic field. What’s more, the paper designs and produces stimulating coil for animal and human , analyzes and simulates the magnetic field generated by the coil. In Software part, it uses of C# language based on .Net framework, to achieve three forms output including: normal sleep EEG, hypnotic music and the typical waveform stimulation which includes a typical sine wave, sawtooth, pulse and so on. In each stimulation mode, signal frequency, stimulation time, space and other parameters of stimulation are all custom settings. PC software communicates with the single-chip by the serial port, to ensure real-time data transmission.
Secondly, take the magnetic induced sleep experiments in the animal and human trials. The results in rats experiment show that when given 1Hz and 10Hz low-frequency magnetic stimulation, the inhibitory neurotransmitter which can promote the sleep has a larger trend of growth, while excitatory transmitter which can inhibit the slow-wave sleep is inhibited by the larger; but In contrast the results of 100Hz stimulation. Experimental results in human experiment show that human sleep EEG magnetic stimulation can enhanced the release of the neurotransmitter 5-HT and Glu effectively ,and has significant inhibition effect to enhanced the role of the main transmitters like Ach which could suppress the slow wave sleep.
In this paper, the magnetic stimulation system developed has a character of stable and reliable performance, convenient operation, suitable for hospital use. Additionally, the system has been demonstrated preliminary to have well effect in promoting slow-wave sleep, extending the sleep time and increasing the fast wave sleep. Disorders user can select different stimulate patterns to reach different treatment, The system also offers a great experimental platform for further study on the neural mechanisms of the magnetic induced sleep.
本文在以往研究的基础上,自行研制了连续经颅磁刺激系统,并进行了大鼠和人体睡眠实验,研究了连续经颅磁刺激对睡眠相关神经递质的影响,探讨了磁刺激诱导睡眠的作用机理。主要工作如下:
(1)研制了连续经颅磁刺激系统。硬件部分采用C8051F020单片机作为主控单元,采用TDA7294芯片进行功率放大,可实现0.001Hz~20KHz的交变磁场。设计制作了动物用和人用刺激线圈,并对线圈所产生磁场进分析和仿真。软件部分采用C#语言基于.net框架,可实现三种形式信号输出,包括:正常人入睡脑电信号、催眠音乐和典型波形刺激,其中典型波包括正弦,锯齿波,脉冲波等。每种刺激模式下可对信号频率,刺激时间,刺激间隙等参数进行自定义设置。PC机软件通过串口与单片机通信,保证数据传输的实时性。
(2)进行了磁诱导睡眠的动物实验和人体实验。大鼠实验结果显示当给予1Hz和10Hz低频磁刺激后,促进睡眠的抑制性递质呈现较大的增长趋势,而抑制慢波睡眠的兴奋性递质的释放则受到了较大的抑制;但100Hz的刺激结果相反。人体实验结果显示入睡脑电的磁刺激对慢波睡眠递质5-HT和Glu有有效的增强作用,对主要的抑制慢波睡眠的递质Ach释放有明显的抑制作用。
本文研制的连续磁刺激系统性能稳定可靠,操作方便,适宜医院使用,经过初步的实验验证对促进慢波睡眠,延长睡眠时间,增加快波睡眠有较好的效果。使用者可以针对睡眠疾病采用不同的刺激模式以达到不同的治疗目的。本系统也为进一步研究磁诱导睡眠的神经机制建立了很好的实验平台。
Human sleep is one of the most important physiological phenomenons. It, as an important physiological process, is essential for the work of human cognition, metabolism, immune. The quality of sleep has a direct influence to human physical and mental health. However, with the development of social modernization, the accelerating pace of life, increasing pressures, it has resulted in the spread of insomnia like epidemics. Insomnia can lead to a variety of cardiovascular and cerebrovascular diseases, but also may lead to sorts of mental illness such as depression, anxiety , which makes the patients suffer from great pain. Therefore, it has been brought into focus to explore an effective method of treatment of insomnia at home and abroad.
Based on previous studies, this paper develops independently a continuous transcranial magnetic stimulation system, conducts experiments in rat and human sleep, researches the influence of continuous transcranial magnetic stimulation to the sleep-related neurotransmitters, and then discusses the mechanism of magnetic stimulation-induced sleep. Major ones are as follows:
Firstly, develop a continuous transcranial magnetic stimulation system. In hardware part,it takes C8051F020 single chip as the main control unit, the TDA7294 as power amplifier chip to achieve the 0.001Hz ~ 20KHz alternating magnetic field. What’s more, the paper designs and produces stimulating coil for animal and human , analyzes and simulates the magnetic field generated by the coil. In Software part, it uses of C# language based on .Net framework, to achieve three forms output including: normal sleep EEG, hypnotic music and the typical waveform stimulation which includes a typical sine wave, sawtooth, pulse and so on. In each stimulation mode, signal frequency, stimulation time, space and other parameters of stimulation are all custom settings. PC software communicates with the single-chip by the serial port, to ensure real-time data transmission.
Secondly, take the magnetic induced sleep experiments in the animal and human trials. The results in rats experiment show that when given 1Hz and 10Hz low-frequency magnetic stimulation, the inhibitory neurotransmitter which can promote the sleep has a larger trend of growth, while excitatory transmitter which can inhibit the slow-wave sleep is inhibited by the larger; but In contrast the results of 100Hz stimulation. Experimental results in human experiment show that human sleep EEG magnetic stimulation can enhanced the release of the neurotransmitter 5-HT and Glu effectively ,and has significant inhibition effect to enhanced the role of the main transmitters like Ach which could suppress the slow wave sleep.
In this paper, the magnetic stimulation system developed has a character of stable and reliable performance, convenient operation, suitable for hospital use. Additionally, the system has been demonstrated preliminary to have well effect in promoting slow-wave sleep, extending the sleep time and increasing the fast wave sleep. Disorders user can select different stimulate patterns to reach different treatment, The system also offers a great experimental platform for further study on the neural mechanisms of the magnetic induced sleep.
引文
[1]姜佐宁,李文标,黄淑贞,等.咪达唑仑与艾司唑仑治疗失眠症的多中心双盲对照研究.中华精神科杂志,2000 ,33(4) :229 ~ 232
[2]Seifritz E, Gillin JC ,Rapaport MH ,et al. Sleep electroen cephalographic response to muscarinic with major depression and in normal controls. Biol Psychiatry ,1998 ,44 :21 ~ 23
[3]张跃琴,朱雪琴.丁螺环酮与苯二氮类药物合用治疗失眠症.天津药学,1999 ,11 (3) :42
[4]Mattila MJ ,Vanakoski J, Kalska H ,et al. Pharm Biochem Behav,1998 ,59 (4) :917
[5]赵艳红,单义辉,马连华等.催眠疗法对广泛性焦虑的临床疗效对照.中国心理卫生杂志, 2005,19(8):543~544
[6]徐俊冕,季建林.认知心理治疗.贵阳:贵州教育出版社,1999,8
[7]赵瑞祥,周向东.低能量氦氖激光血管内照射治疗脑卒中失眠的疗效观察,中国疗养医学,1998 ,31 (7) :11～12.
[8]王明时,冯远明,郭青,利用低频脉冲磁场诱导入眠的实验研究,中国生物医学工程学报,1997,16(2):P20~P27.
[9]失眠专家组,失眠定义、诊断及药物治疗专家共识.中华神经科杂志,2006,39(2): 141~143.
[10]吴天诚.药物治疗无效神经症患者的门诊森田疗法.中国心理卫生杂志,1999,13(6):333~334
[11] Jack DE ,Melanie KM.Cognitive-behavioral therapy for primary Psychology Review,2005,25 :53 9~5
[12] Lai HL. Music sleep quality in older adults of Advanced Nursing. Journal of 2005,49
[13]胡立荣,叶敏捷.失眠症患者孤独感、人格特征和家庭环境的关系.浙江临床医学,2004,6(4):280~81
[14]周卫东等,声、光、磁物理磁机对人体脑电影响的计算机分析和实验结果.中国生物医学工程学杂志,1991,8(2):155~160
[15]周卫东等.脑电反馈的研究及其临床应用,中国生物医学工程学报,1995,14(2):182~186
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[17]慈书平等.睡眠与睡眠疾病.军事医学科学出版社,2005,27~34.
[18]Jung R, Kuhlo W.Neurophysiological studies of abnormal night sleep and the pickwickian syndrome.Pros Brain Rse,1965,18:140~159
[19]Dement WC.A personal history of sleep disorders medicine. JClin,Neurophysiol,1990,7:17~47
[20]Guilleminauh C,Dement WC.235 cases of excessive daytime sleepiness:diagnose and tentative classification. Neurol Sci, 1977,31:13~27
[21]Aserinsky E, Kleitman N.Two types of ocular motility occurring in sleep, ApplPhysiol,1955,8:1~10
[22]DementW,Kleitman N.Cyclic variations in EEG during sleep and their relation to eye movements, body motility,and dreaming. Electroencephalogy ClinNeurophysiology , 1957,9:673~690
[23]Barker AT, Freeston IL, Jalinous R, etc. Magnetic stimulation of the human brainand peripheral nervous system: an introduction and the results of an initialclinical evaluation. Neurosurgery, 1987,20(1):100~109
[24]Walsh V, Rushworth M,A primer of magnetic stimulation as a tool for neuropsychology.Neuropsychologia, 1999,37:125~135
[25]BoroojerdiB.Pharmacologic influences on TMS effects. J Clin Neurophysiol,2002,19:255~271.
[26]Ueno S. Functional mapping of the human motor cortex obtained by focal andvectorial magnetic stimulation of the brain. IEEE Transactions on Magnetics,1990,26:15~39
[27]Reiter RJ. Static and extremely low frequency electro-magnetic field expo sure: reported effects on the ircadian product ion of melatonin . J Cell Biochem, 1993,51: 3~4.
[28]郭明霞,王学民,王明时.磁刺激应用及机理研究进展.国外医学生物医学工程分册. 2001; 24 (1)∶23
[29]AnandanS,HotsonJ.Transcranial magnetic stimulation: neurophysiologicalapplications and safety. Brain Cogn, 2002,50:366~386
[30]吴涛,Martin Sommer,李蕴琛等.经颅重复磁刺激对人脑皮层兴奋性的影响.中华神经科杂志2001,34(1):40
[31]Bickford RG Fremming BD.Neural stimulation by pulsed magnetic fields in animals and man.Digest of the 6th International Conference on Medical Electronics and Biological Engineering Tokyo.1965.7:6
[32]Polson MJ,Barker AT,Freeston IL.Stimulaion of nerve trunks with time-varying magnetic fields.Med & Biol Eng &Comput.1982,20(2):243~244
[33]Pascual-Leone A,Ruio B,Pallardo F et al.Beneficial effect of rapid-rate transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in drug-resistant depression.Lancet ,1996 ,347 :233~237.
[34]王明时,冯远明等.磁刺激促进睡眠方法研究.天津大学学报.1993,1(21):146~150
[35]Wassermann EM ,Lisanby SH. Therapeutic application of repetitive transcranial magnetic stimulation .Clin Neurophysiol ,2001 ,112 :1367~1377.
[36]许绍芬主编.神经生物学.上海医科大学出版社,1992
[37]M.J.Owens,C.B.Nemeroff,Role of Serotionin in the Pathophysiology of Depression:Focus on the Serotonin Transporter, Clin.Chem,1994,40(2):288~295
[38]钟明奎,赵乐章,张瑾等.海马微量注射乙酞胆碱对大鼠睡眠一觉醒的影响.中国中医基础医学杂志,2002;8(l):9~10
[39]MarrosuF,Portas C,Mascia MS. Mierodialysis measurement of cortical and hippocampal acetyleholine release during sleep-wake cycle in freely moving cats. Brain Res,1996:671(2):329~332
[40]刘少雄.大鼠脑干5-羟色胺神经元的分布-免疫细胞化学研究和定量分析.解剖学杂志, 1987, 3 (2) : 169~176
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[47]张瑾等.海马CA1区微量注射去甲肾上腺素对慢波睡眠的影响.安徽医科大学学报.2006,41(1):7~9
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[49]Manfridi A,Brambilla D,Mancia M.Sleep is differently modulated by basal forebrain GABA(A) and GABA(B)receptors. Physiol Regul Integr Comp Physiol,2001,281(1):R170~5
[2]Seifritz E, Gillin JC ,Rapaport MH ,et al. Sleep electroen cephalographic response to muscarinic with major depression and in normal controls. Biol Psychiatry ,1998 ,44 :21 ~ 23
[3]张跃琴,朱雪琴.丁螺环酮与苯二氮类药物合用治疗失眠症.天津药学,1999 ,11 (3) :42
[4]Mattila MJ ,Vanakoski J, Kalska H ,et al. Pharm Biochem Behav,1998 ,59 (4) :917
[5]赵艳红,单义辉,马连华等.催眠疗法对广泛性焦虑的临床疗效对照.中国心理卫生杂志, 2005,19(8):543~544
[6]徐俊冕,季建林.认知心理治疗.贵阳:贵州教育出版社,1999,8
[7]赵瑞祥,周向东.低能量氦氖激光血管内照射治疗脑卒中失眠的疗效观察,中国疗养医学,1998 ,31 (7) :11～12.
[8]王明时,冯远明,郭青,利用低频脉冲磁场诱导入眠的实验研究,中国生物医学工程学报,1997,16(2):P20~P27.
[9]失眠专家组,失眠定义、诊断及药物治疗专家共识.中华神经科杂志,2006,39(2): 141~143.
[10]吴天诚.药物治疗无效神经症患者的门诊森田疗法.中国心理卫生杂志,1999,13(6):333~334
[11] Jack DE ,Melanie KM.Cognitive-behavioral therapy for primary Psychology Review,2005,25 :53 9~5
[12] Lai HL. Music sleep quality in older adults of Advanced Nursing. Journal of 2005,49
[13]胡立荣,叶敏捷.失眠症患者孤独感、人格特征和家庭环境的关系.浙江临床医学,2004,6(4):280~81
[14]周卫东等,声、光、磁物理磁机对人体脑电影响的计算机分析和实验结果.中国生物医学工程学杂志,1991,8(2):155~160
[15]周卫东等.脑电反馈的研究及其临床应用,中国生物医学工程学报,1995,14(2):182~186
[16]汤晓芙.神经系统临床电生理学,人民军医出版社,2002,3,1~97.
[17]慈书平等.睡眠与睡眠疾病.军事医学科学出版社,2005,27~34.
[18]Jung R, Kuhlo W.Neurophysiological studies of abnormal night sleep and the pickwickian syndrome.Pros Brain Rse,1965,18:140~159
[19]Dement WC.A personal history of sleep disorders medicine. JClin,Neurophysiol,1990,7:17~47
[20]Guilleminauh C,Dement WC.235 cases of excessive daytime sleepiness:diagnose and tentative classification. Neurol Sci, 1977,31:13~27
[21]Aserinsky E, Kleitman N.Two types of ocular motility occurring in sleep, ApplPhysiol,1955,8:1~10
[22]DementW,Kleitman N.Cyclic variations in EEG during sleep and their relation to eye movements, body motility,and dreaming. Electroencephalogy ClinNeurophysiology , 1957,9:673~690
[23]Barker AT, Freeston IL, Jalinous R, etc. Magnetic stimulation of the human brainand peripheral nervous system: an introduction and the results of an initialclinical evaluation. Neurosurgery, 1987,20(1):100~109
[24]Walsh V, Rushworth M,A primer of magnetic stimulation as a tool for neuropsychology.Neuropsychologia, 1999,37:125~135
[25]BoroojerdiB.Pharmacologic influences on TMS effects. J Clin Neurophysiol,2002,19:255~271.
[26]Ueno S. Functional mapping of the human motor cortex obtained by focal andvectorial magnetic stimulation of the brain. IEEE Transactions on Magnetics,1990,26:15~39
[27]Reiter RJ. Static and extremely low frequency electro-magnetic field expo sure: reported effects on the ircadian product ion of melatonin . J Cell Biochem, 1993,51: 3~4.
[28]郭明霞,王学民,王明时.磁刺激应用及机理研究进展.国外医学生物医学工程分册. 2001; 24 (1)∶23
[29]AnandanS,HotsonJ.Transcranial magnetic stimulation: neurophysiologicalapplications and safety. Brain Cogn, 2002,50:366~386
[30]吴涛,Martin Sommer,李蕴琛等.经颅重复磁刺激对人脑皮层兴奋性的影响.中华神经科杂志2001,34(1):40
[31]Bickford RG Fremming BD.Neural stimulation by pulsed magnetic fields in animals and man.Digest of the 6th International Conference on Medical Electronics and Biological Engineering Tokyo.1965.7:6
[32]Polson MJ,Barker AT,Freeston IL.Stimulaion of nerve trunks with time-varying magnetic fields.Med & Biol Eng &Comput.1982,20(2):243~244
[33]Pascual-Leone A,Ruio B,Pallardo F et al.Beneficial effect of rapid-rate transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in drug-resistant depression.Lancet ,1996 ,347 :233~237.
[34]王明时,冯远明等.磁刺激促进睡眠方法研究.天津大学学报.1993,1(21):146~150
[35]Wassermann EM ,Lisanby SH. Therapeutic application of repetitive transcranial magnetic stimulation .Clin Neurophysiol ,2001 ,112 :1367~1377.
[36]许绍芬主编.神经生物学.上海医科大学出版社,1992
[37]M.J.Owens,C.B.Nemeroff,Role of Serotionin in the Pathophysiology of Depression:Focus on the Serotonin Transporter, Clin.Chem,1994,40(2):288~295
[38]钟明奎,赵乐章,张瑾等.海马微量注射乙酞胆碱对大鼠睡眠一觉醒的影响.中国中医基础医学杂志,2002;8(l):9~10
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