WO2006133636A1 - Magnetic stimulating circuit for nervous centralis system, apparatus , purpose, and method thereof - Google Patents

Magnetic stimulating circuit for nervous centralis system, apparatus , purpose, and method thereof Download PDF

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Publication number
WO2006133636A1
WO2006133636A1 PCT/CN2006/001289 CN2006001289W WO2006133636A1 WO 2006133636 A1 WO2006133636 A1 WO 2006133636A1 CN 2006001289 W CN2006001289 W CN 2006001289W WO 2006133636 A1 WO2006133636 A1 WO 2006133636A1
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WIPO (PCT)
Prior art keywords
circuit
magnetic stimulation
nervous system
central nervous
coil
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PCT/CN2006/001289
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English (en)
French (fr)
Inventor
Yunfeng Zheng
Jiang Wang
Lin Xu
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Individual
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Priority to CN2006800232712A priority Critical patent/CN101208132B/zh
Priority to JP2008516110A priority patent/JP4746675B2/ja
Priority to EP06761298.6A priority patent/EP1894600B1/en
Priority to US11/917,732 priority patent/US8172742B2/en
Publication of WO2006133636A1 publication Critical patent/WO2006133636A1/zh
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • A61N2/004—Magnetotherapy specially adapted for a specific therapy
    • A61N2/006—Magnetotherapy specially adapted for a specific therapy for magnetic stimulation of nerve tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N2/00—Magnetotherapy
    • A61N2/02—Magnetotherapy using magnetic fields produced by coils, including single turn loops or electromagnets

Definitions

  • the present invention relates to a central nervous system magnetic stimulation device and its circuitry, and to the use and use of the device.
  • magnetic stimulation technology is mainly developed in TMS (transcranial magnetic stimulation) or rTMS (repetitive transcranial magnetic stimulation), and it is painless and non-invasive due to magnetic stimulation, such as pain, convulsions, memory loss and other side effects.
  • TMS transcranial magnetic stimulation
  • rTMS repetitive transcranial magnetic stimulation
  • magnetic stimulation technology is mainly developed in TMS (transcranial magnetic stimulation) or rTMS (repetitive transcranial magnetic stimulation)
  • it is painless and non-invasive due to magnetic stimulation, such as pain, convulsions, memory loss and other side effects.
  • the non-contact characteristics and efficacy in clinical treatment are constantly being discovered, and the field of application is expanding.
  • existing instruments are difficult to effectively stimulate the deep brain, or the brain surface is subjected to super-stimulation for deep stimulation; although, patents: (96180330.4) and other technologies are expected to meet
  • the need to focus magnetic stimulation in the deep however, it is difficult to achieve high frequencies simultaneously with high-energy magnetic fields.
  • the problem to be solved by the present invention is to overcome the deficiencies of focused magnetic stimulation, to provide a central nervous system magnetic stimulation device that magnetically stimulates the entire brain, and to use and use the neuropsychiatric treatment and brain function improvement.
  • a central nervous system magnetic stimulation circuit comprising a sequentially connected control circuit, a driving power supply circuit and a coil, the driving power supply circuit including a driving circuit,
  • the detecting circuit, the main circuit, the driving circuit and the detecting circuit are respectively connected to the control circuit and the main circuit, and the coil is connected to the main circuit.
  • the main circuit may include a conversion circuit for controlling the direction of current flow of the pair of coils to be in the same direction or in the opposite direction.
  • the main circuit may include at least one insulated gate bipolar transistor, and the PWM signal generated by the control circuit drives the insulated gate bipolar transistor in the main circuit to output a time-varying current to the coil through a driving circuit, thereby generating a required Time-varying magnetic field.
  • the insulated gate bipolar transistor is replaced by other fully controlled power semiconductor devices, and the drive circuit is modified accordingly according to the technical characteristics of the substitute device.
  • the control circuit may include a DSP chip serving as a master chip, the drive circuit including an optical coupler for transmitting a control signal sent from the control circuit to the main circuit, the control circuit controlling the drive circuit and the main circuit
  • the coil produces a desired magnetic field
  • the conversion circuit includes at least one relay.
  • the invention also provides a central nervous system magnetic stimulation device, comprising a magnetic stimulation circuit; the magnetic stimulation circuit comprises a control circuit, a driving power supply circuit and a coil connected in sequence; the driving power supply circuit comprises a driving circuit, a detecting circuit, and a main The driving circuit and the detecting circuit are respectively connected to the control circuit and the main circuit.
  • the coil is connected to the main circuit.
  • the coil is at least one pair of coaxial, parallel, symmetrically placed identical coils, each pair of coils being synchronized with the same intensity, and the main circuit includes a conversion circuit for controlling the current direction of the pair of coils In the same direction or in the opposite direction.
  • the main circuit may include at least one insulated gate bipolar transistor, and the control circuit is The raw PWM signal is driven by the driving circuit to drive the insulated gate bipolar transistor in the main circuit to output a time varying current to the coil to generate a desired time varying magnetic field.
  • the insulated gate bipolar transistor may be replaced by other fully controlled power semiconductor devices, and the drive circuit is modified accordingly according to the technical characteristics of the substitute device.
  • the control circuit may include a DSP chip serving as a master chip, the drive circuit including an optical coupler for transmitting a control signal sent from the control circuit to the main circuit, the control circuit controlling the drive circuit and the main circuit
  • the coil produces a desired magnetic field and the conversion circuit includes a relay.
  • the present invention also provides a use of a central nervous system magnetic stimulation device for stimulating a whole body of an animal or a human brain by selecting a time-varying magnetic field of an appropriate parameter, treating a central nervous system disease or a mental disease, or improving brain function.
  • the appropriate parameters include at least a current waveform, a frequency, a peak intensity associated with the coils in the device, a parameter corresponding to the waveform, frequency, and peak intensity of the induced magnetic field.
  • the appropriate parameters also include intra-string frequency and inter-string frequency when the pulse train is magnetically stimulated.
  • the steps include: applying magnetic stimulation of appropriate parameters to the entire brain for a suitable period of time; or performing a behavioral guidance or thinking guidance or psychological guidance to a person who is receiving or has received magnetic stimulation during or after the magnetic stimulation.
  • magnetic stimulation before magnetic stimulation, conduct behavioral guidance or mind guidance or psychological guidance for those who are to receive magnetic stimulation; magnetic stimulation that applies appropriate parameters to the entire brain, for an appropriate period of time; after magnetic stimulation, conduct behavioral guidance for those who receive magnetic stimulation Or thinking or psychological guidance.
  • the diseases include depression, anxiety, insomnia, chronic pain, post-traumatic stress syndrome, drug or alcohol-dependent addictive disease, psychological dependence on bad behavior, attention deficit disorder in children, mood disorder, schizophrenia , Parkinson's syndrome, neurodegenerative diseases or Alzheimer's disease, nerve damage, etc.
  • the brain functions include learning and memory ability, cognitive ability, and anti-psychological stress ability.
  • the present invention also provides a method of controlling a central nervous system magnetic stimulation device for treating a central nervous system disease or a mental illness, or improving brain function.
  • the controller controls the magnetic stimulation circuit to energize the coil pair, and applies a time-varying magnetic field to the target region, the magnetic induction intensity gradient of the magnetic field is less than 100 Gs/cm, and the range of the target region is adapted to the size of the animal or human head.
  • the magnetic field magnetic induction peak value may be less than 0.1T.
  • the magnetic field is a waveform or a combination of at least two waveforms, and the time-varying magnetic field frequency ranges from 0.5 Hz to 2000 ⁇ .
  • the present invention designs and outputs a waveform signal to a driving power source to cause a driving power source to output a current of a corresponding waveform to a coil, and is designed in a certain area in the middle of the coil by a coil shape, a number of turns, a size, and a pitch design.
  • the time-varying magnetic field required to act on the animal or human brain allowing the central nervous system to receive precise waveforms, high frequency or multiple frequency combinations, wide-area synergistic magnetic stimulation, combined with behavioral guidance or thought-directed or psychological guidance, Achieve the treatment of neuropsychiatric diseases or improve brain function.
  • FIG. 1 is a circuit block diagram of a device according to Embodiment 1 of the present invention.
  • FIG. 2 is a schematic structural view of a coil of Embodiment 1 of the present invention.
  • FIG. 3 is a schematic diagram of a main circuit of Embodiment 1 of the present invention.
  • Figure 4 is a waveform diagram used in Embodiment 1 of the present invention.
  • Fig. 5 is a view showing the distribution of magnetic lines of force of a magnetic field generated by a reverse current in the coil of the first embodiment
  • Figure 6 is a view showing the distribution of magnetic lines of force generated by the coils in the same direction in the first embodiment
  • Figure 7 is a waveform diagram used in Embodiment 2 of the present invention.
  • Wide-area synergistic magnetic stimulation including high frequency
  • multiple waveform/frequency combinations may have new meanings: Ability to adjust neurotransmitter and/or neuromodulation release, adjust receptor number and activity, and activate silent synapses It can facilitate long-term potentiation of synaptic transmission, enhance synaptic plasticity, and regulate neuroendocrine. And, combined with behavioral guidance or thinking after magnetic stimulation Guidance or psychological guidance, through the synergistic or causal connection of the above effects, the cognitive ability and the improvement of learning and memory ability, the improvement of mental state, the treatment of neuropsychiatric diseases and the like. The reasons are as follows:
  • the NMDA receptor is a voltage-dependent excitatory amino acid transmitter-gated calcium channel receptor blocked by magnesium ions, which is partially depolarized in the membrane of nerve cells by the interaction of glutamate and glycine (usually as an inhibitory neurotransmitter). Activation in the state, influx of calcium ions, complete the whole process of depolarization of nerve cells and the subsequent cascade reaction.
  • NMDA receptors occupy a very important position in the study of cellular and molecular mechanisms of learning and memory. In particular, LTP and LTD are considered to be intrinsic mechanisms of synaptic modification, and the involvement of MDA receptors is a prerequisite.
  • the hippocampus and the amygdala are out of sync or unbalanced, the hippocampus replacement is replaced by the amygdala, which will make the negative feedback suppression system unbalanced. God disease.
  • NR2B can be called a smart gene.
  • rats overexpressing NR2B not only had stronger learning and memory abilities, but also were able to adapt to changes more quickly and have a faster regression of nociceptive memory (called re-learning ability).
  • re-learning ability Recently, Giovanni Marsicano et al.
  • Calcium complexing agent MD6Q0 blocks magnetic stimulation of nerve regeneration (Rusovan A, Kanje M 1992); Electrical stimulation of nerve-derived release of brain-derived neurotrophic factor BDNF with stimulation frequency/waveform combination and NMDA receptor association, high-frequency multi-column small interval pulse waveform (0.5ms platform square wave, 100HZ, 4 waves) A string, interval 200ms, a total of 75 strings of 300 pulses) instead of continuous low frequency (1HZ, 480 pulses) or high frequency less series long interval (100HZ, 100 waves, 10S interval, 3 or 6 strings in total) BDNP is promoted but inhibited by the NMDA anti-caries D-AP-5 (Isolpel J. Lever et al., 2001). These are constantly suggesting that there is a correlation between calcium ions, NGF, BDNF, LTP ( LTD ), NMDA receptors, electrical and magnetic field frequencies.
  • Magnetic wave stimulation with precise waveform high frequency or multiple frequency combinations may be a safe NMDA receptor agonistic means.
  • High frequency magnetic stimulation may be brought by NMDA related LTP pathway.
  • the profound changes in many aspects of the central nervous system affect the process of obtaining, extracting, modifying, and consolidating memory, and thus improve the ability of re-learning, thereby treating some neuropsychiatric diseases under certain conditions (such as behavioral guidance after magnetic stimulation);
  • One point is that we have developed a wide-area synergistic magnetic stimulator that is suitable for clinical applications and can generate high-frequency or multiple frequency/waveform combinations with precise waveforms. It overcomes the shortcomings of rTMS and the lack of electrical stimulation, and is a neuropsychiatric disease.
  • Treatment or even prevention offers new options.
  • the device in the present invention includes a control circuit, a driving power supply circuit, and a coil.
  • the driving power supply circuit includes a driving circuit, a detecting circuit, and a main circuit
  • the control circuit includes a host computer and a lower computer, and the upper device
  • the machine is a general-purpose PC or industrial computer, which is convenient for operation in actual application, and connects and communicates with the lower-position machine through RS232 interface, and sends commands and parameters.
  • the lower-position machine adopts DSP chip as the main control chip, and receives from the upper position.
  • a corresponding PWM signal is generated and transmitted to the driving circuit, and the driving circuit and the detecting circuit are respectively connected to the lower computer and the main circuit, and the coil and the main circuit Connected, the control circuit generates a PWM signal, and the driving circuit drives the main circuit to operate, and the insulated gate bipolar transistor (IGBT) in the main circuit outputs a time-varying current to excite the pair of coils, and excites to generate a time-varying magnetic field.
  • the detecting circuit samples the voltage and current values in the main circuit, monitors the working state of the main circuit in real time, and adjusts the output PWM signal as needed, or cuts the coil circuit in time when the overcurrent is generated to prevent the coil from being damaged.
  • the driving circuit includes an optical coupler connected between the lower computer and the main circuit, and its main function is to isolate the interference signal and drive the main circuit (this part of the circuit is not shown in the figure).
  • the main circuit includes a rectifier bridge BR1 and five IGBTs Q1 to Q5, two electrolytic capacitors C2 and C3, and the electrolytic capacitors C2 and C3 are connected in parallel to the output end of the rectifier bridge BR1.
  • the IGBT Q1 is connected in series between the negative terminal of the electrolytic capacitor C2 and the rectifier bridge BR1, and the trigger terminal is connected to a pulse width modulation terminal PWM1 end of the driving circuit, and the IGBTs Q4 and Q5 are connected in series to the electrolytic capacitor C3.
  • the two trigger terminals are also connected to the other two PWM1 terminals of the driving circuit (the three PWM1 terminals are independent of each other), and the capacitors C2 and C3 are also connected to the other two.
  • the IGBTs Q2 and Q3 are connected in parallel at both ends, and the trigger terminals of the two IGBTs Q2>Q3 are respectively connected to the other two PWM terminals PWM2 and PWM3 of the driving circuit.
  • the coil L2 is connected between the emitter of the IGBT Q2 and the collector of the IGBT Q3.
  • the conversion circuit is composed of a double-pole Han-throw relay K1.
  • the two common ends of the relay K1 are connected in parallel with the two ends of the coil L2, one normally-open end is connected to the other normally-closed end, and the other is normally closed.
  • the normally open ends of the previous circuit are connected, and the coil L3 is respectively connected to the two connecting ends, and the coil of the relay K1 is connected to the two control ends of the lower computer.
  • the IGBT can be a discrete IGBT component or an integrated IGBT module, and the function of the optocoupler in the driving circuit can also be realized by an IGBT module integrated with a driving function.
  • the detection circuit uses a LEM voltage sensor and a current sensor to detect the voltage across the capacitors C2 and C3 in the circuit and the current flowing through the two coils L2 and L3, and filter, amplify, AD convert and transmit the detection signal to the lower computer. in.
  • the number of turns of the coil is 40, and the peak current of the single turn is 5 A, and a magnetic field gradient of 0.5 Gs/cm in the central region can be obtained.
  • the number of turns is 40, the single-turn current can reach 40A, and the magnetic field gradient can reach 4Gs/cm, which will have a better therapeutic effect.
  • the connection direction of the coil L3 is converted to the opposite direction to the original direction, thereby realizing the action of changing the direction of the coil current, and the direction of the switching coil current is the same current, which will be at the center.
  • the region produces a larger magnetic field strength, while the magnetic field uniformity is increased and the gradient is lowered, which can achieve different effects from the reverse current in practical applications.
  • the user sets the parameters of the system operation through the host computer and transmits it to the lower computer through the serial port.
  • the lower computer sends the PWM signal to control the main circuits Q1 and Q4 to make the capacitor C2 and
  • the voltage on C3 reaches the calculated demand value, and the voltages on capacitors C2 and C3 are obtained by the AD conversion portion of the lower computer through the detection circuit.
  • the lower computer controls the on/off by sending different PWM signals to Q2 and Q3 to generate various current waveforms on L2 and L3, thereby generating corresponding various time-varying magnetic fields.
  • the control of the main circuit can be divided into three phases, namely, a rising phase of the current, a holding phase, and a falling phase.
  • the first is the rising phase of the current, Q2, Q3 are always on, L2, L3 plus a fixed voltage (which is equal to the voltage on C2), its current shows a linear rise, change the voltage on C2 Change the rising slope of the current, change the time of the phase to change the maximum value of the coil current; then the holding phase, Q3 remains on, Q2 is intermittently turned on and off, so that the current of L2 and L3 is basically maintained.
  • the final stage is the falling phase
  • Q2, Q3 are kept off
  • the current of the inductor L2, L3 can only charge the capacitor C3 through D2 and D3, the two ends of the inductor L2, L3 are equivalent to plus one equal to the capacitor
  • the reverse voltage of the C3 voltage, the current of the inductors L2 and L3 decreases linearly until its value is equal to zero. Changing the voltage on C3 changes the slope of the current drop. After the falling phase, a new rising phase is started again after a zero current interval, and thus a time-varying current of a fixed period accurate waveform is generated, thereby generating a time-varying magnetic field of a precise waveform of one cycle.
  • an isosceles trapezoidal wave as shown in FIG. 4 is generated and applied to the pair of coils to generate a corresponding time-varying magnetic field, which is raised by the isosceles trapezoidal wave.
  • a positive and negative square wave pulse electric field is induced in the target area to meet the needs of treatment. For example, the rising edge of 128 microseconds is connected to the 768 microsecond platform and then the falling edge of 128 microseconds and the zero current platform of 768 microseconds.
  • the period is 1792 microseconds (high frequency), the current direction of the coil pair is opposite, and the single peak current is 20 Ampere (corresponding to the magnetic field gradient value of 2Gs/cm), it is also possible to realize a combination of various waveforms and frequencies.
  • the magnetic stimulation series is composed, including the intra-string frequency and the inter-string The parameters of the frequency.
  • the above waveform output 10 cycles stop 27 cycles to form a string period
  • the induced electric field pulse train frequency is about 558Hz (regardless of the electric field direction is about 1116Hz)
  • the inter-string frequency is about 15Hz ((3 rhythm); or, the same
  • the waveform stops for 90 cycles after 20 cycles of continuous stimulation, and the frequency between strings is about 5 ⁇ ( ⁇ rhythm).
  • Users can set different magnetic stimulation parameters according to the needs of treatment through the upper computer.
  • the above-mentioned magnetic stimulation is applied to the brain of the needy (such as depressed patients) for a suitable period of time.
  • each uninterrupted stimulation does not last too long, so as to avoid excessive activation of NMDA receptors.
  • the magnetic stimulation in tandem can last longer, such as 20 minutes; the magnetic stimulation in tandem can also be intermittent, such as outputting 2 seconds in 10 seconds, stopping 8 seconds in series , looping.
  • the so-called problem can be specifically standardized question bank, the type of problem It can be a question of natural science or social science or common sense of life.
  • FIG. 5 is a magnetic line distribution diagram of a magnetic field generated when a coil pair is connected with a reverse current according to the present invention, (only half of the figure is shown), wherein it can be seen that the magnetic field lines are distributed in a linear gradient in the target region, wherein 501 is a coil. 502 is the magnetic field line, and the area within 503 is the target area, that is, the area in which the human brain is placed during the treatment.
  • Fig. 6 is a diagram showing the distribution of magnetic lines of force when a coil pair is passed in the same direction, wherein it can be seen that the magnetic field lines are approximately uniform in the target region.
  • 601 is a coil
  • 602 is a magnetic field line
  • 603 is the target area, that is, an area in which a human brain is placed during treatment.
  • Another embodiment 2 of the present invention has the same construction as that of the embodiment 1.
  • a combination of the other two waveforms is generated, so that the coil pair generates a corresponding magnetic field, as shown in FIG. 7, wherein the A waveform is a continuous sawtooth wave with a frequency of 1000 Hz for 3 minutes.
  • the B waveform is an intermittent triangular wave with a frequency of 2 Hz and a duration of 3 minutes.
  • the two waveforms are alternately performed for 3 cycles for 18 minutes to form a magnetic stimulation process. After the magnetic stimulation process is completed, the aforementioned behavioral guidance or thought guidance or psychological guidance is performed to complete the treatment of neuropsychiatric diseases or the improvement of brain function.
  • the method of use may further comprise performing behavioral guidance or thinking guidance or psychological guidance before magnetic stimulation, and the guidance before the magnetic stimulation may be different from the guidance after the magnetic stimulation, the purpose is to pass Guide, extract negative memory from the brain and express it; and the purpose of magnetic stimulation is to modify negative memory by stressing the "resistance to stress", remodel the negative feedback pathway of HPA axis or improve anti-stress ability.
  • the coil described in the present invention may also adopt an elliptical shape, a rectangular shape or other reasonably shaped coil including a three-dimensional shape, and change parameters such as coil pitch and number of turns, and use two pairs or more.
  • the combination of multiple pairs of coils can also be a larger size coil or a solenoid; it can also achieve more combinations of waveforms, frequencies and intensities through the control of the control circuit and the drive circuit to complete a magnetic stimulus.
  • Processes such as more current waveforms including the isosceles trapezoidal waveform, including the isosceles trapezoid, isosceles triangle, isosceles triangle, etc.; the output current frequency is generally less than 1000Hz, can be various Waveform and multiple frequency combinations complete a magnetic stimulation process, and can also make high frequency match reverse current, low
  • the frequency matching contract current can also replace the IGBT in the main circuit with other fully-controlled power semiconductor devices, such as GRT or power MOSFET or GTO.
  • the drive circuit is also modified according to the technical characteristics of the device to realize the main circuit function.
  • the main circuit can also add two IGBTs or other power semiconductor devices and corresponding drive and control circuits to allow the coil current to flow in both directions.

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Description

中枢神经系统磁刺激电路、 装置、 用途及其使用方法
技术领域
本发明涉及一种中枢神经系统磁刺激装置及其电路， 以及所述装置 的用途和使用方法。
背景技术
中枢神经系统疾病或精神疾病， 被认为是二十一世纪的第一杀手： 随着生活节奏和压力的增大， 越来越多的人患上抑郁症等精神疾病； 流 行病学调查发现， 精神分裂症和抑郁症有着很高的患病率， 特别是终身 患病率极高， 而且严重者的自杀现象时有发生。 90年代以后， 一些特殊 群体抑郁障碍的调查结果显示患病率多在千分之 10-20, 而国际卫生组织 公布的数据表明 （WHO, 2001 )， 我国精神疾病导致的负担占伤残 +疾病 总负担的 20%, 排名全球第一， 还在不断上升， 导致了沉重的社会和经 济负担。可以称为头号致残疾病（病人终身丧失劳动力和生活自理能力 )。 精神疾病是一大类慢性脑疾病， 包括了精神分裂症、 抑郁症、 强迫症、 幼儿注意缺失多动症、 创伤后应激综合症等。 最近科学家们把毒品、 网 络和赌博成瘾等也看作是精神疾病。 其中危害最大、 导致的社会和经济 负担最重的是抑郁症，发病率占全国人口的 7-8%, 而 60岁以上的老人发 病率可高达 20-50%。 目前， 除了药物和心理治疗以外， 在物理因子治疗 方面， 主要由电刺激或磁刺激来实现。 其中， 磁刺激技术以 TMS (经颅 磁刺激）或 rTMS (重复经颅磁刺激）为主要发展领域， 相对于电刺激的 疼痛、 抽搐、 记忆减退等副作用， 由于磁刺激的无痛、 无创伤、 非接触 的特性以及在临床治疗中的疗效被不断发现， 应用领域正在扩大。 但是， 因为磁感应强度是随距离的指数量级衰减， 现有仪器难以有效刺激大脑 深部， 或是使大脑表层接受超强刺激换得深部的有效刺激； 虽然， 专利： ( 96180330.4 )等技术有望满足在深部聚焦磁刺激的需要， 但是， 产生高 能磁场又难以同时实现高频率，目前， rTMS的工作频率一般最高在 25Hz。 另外， 在目前常用于生物医学应用领域的磁刺激装置， 通常采用一个或 多个平面布置的圆形线圈， 使用时是在需要刺激的部位上面单侧使用 , 因此研究方向都仅局限于磁刺激的聚焦和由此带来的神经电生理意义。 发明内容
本发明要解决的问题是克服聚焦磁刺激的不足， 提供一种对大脑全 域进行磁刺激的中枢神经系统磁刺激装置以及作为神经精神疾病治疗和 脑功能改善的用途和使用方法。
为解决上述技术问题， 本发明的目的是通过以下技术方案实现的： 一种中枢神经系统磁刺激电路， 包括顺次连接的控制电路、 驱动电源电 路和线圈， 所述驱动电源电路包括驱动电路、 检测电路、 主电路， 所述 驱动电路和检测电路， 都分别与所述控制电路和主电路相连， 所述线圈 与主电路相连。
所述主电路可包括一个转换电路， 用于控制所述线圈对的电流方向 为同向或反向。
所述主电路可包括至少一个绝缘栅双极型晶体管， 所述控制电路产 生的 PWM信号，通过驱动电路驱动主电路中的绝缘栅双极型晶体管输出 时变电流给所述线圈， 产生所需的时变磁场。
所述绝缘栅双极型晶体管由其他全控型电力半导体器件替代， 驱动 电路根据所述替代器件的技术特性进行相应的修改。
所述控制电路可包括用作主控芯片的 DSP芯片， 所述驱动电路包括 用于将控制电路发来的控制信号传递给主电路的光耦合器， 所述控制电 路控制驱动电路和主电路使线圈产生所需的磁场， 所述转换电路包括至 少一个继电器。
本发明还提供一种中枢神经系统磁刺激装置， 包括磁刺激电路； 所 述磁刺激电路包括顺次连接的控制电路、 驱动电源电路和线圈； 所述驱 动电源电路包括驱动电路、 检测电路、 主电路； 所述驱动电路和所述检 测电路， 都分别与所述控制电路和主电路相连。 所述线圈与所述主电路 相连。
所述线圏为至少一对同轴、 平行、 对称放置的相同线圈对， 所述每 对线圈电流同步同强度， 所述主电路包括一个转换电路， 用于控制所述 线圈对的电流方向为同向或反向。
所述主电路可包括至少一个绝缘栅双极型晶体管， 所述控制电路产 生的 PWM信号，通过驱动电路驱动主电路中的绝缘栅双极型晶体管输出 时变电流给所述线圈， 产生所需的时变磁场。
所述绝缘栅双极型晶体管可以由其他全控型电力半导体器件替代， 驱动电路根据所述替代器件的技术特性进行相应的修改。
所述控制电路可包括用作主控芯片的 DSP芯片， 所述驱动电路包括 用于将控制电路发来的控制信号传递给主电路的光耦合器， 所述控制电 路控制驱动电路和主电路使线圈产生所需的磁场， 所述转换电路包括一 个继电器。
本发明还提供一种中枢神经系统磁刺激装置的用途， 通过选择适当 参数的时变磁场刺激动物或人的大脑全域， 治疗中枢神经系统疾病或精 神疾病， 或改善大脑功能。
所述适当参数至少包括与装置中线圈关联的电流波形、 频率、 峰值 强度， 对应感生磁场的波形、 频率和峰值强度的参数。
所述适当参数还包括脉冲串列磁刺激时的串内频率和串间频率。 在磁刺激前或磁刺激中或磁刺激后， 结合行为引导或思维引导或心 理引导， 提高治疗中枢神经系统疾病或精神疾病的疗效。 具体包括步骤： 对大脑全域施加适当参数的磁刺激， 持续适当时间； 磁刺激过程中或磁 刺激结束后 , 对正在接受或已经接受了磁刺激者进行行为引导或思维引 导或心理引导。
或者， 磁刺激前， 对于将要接受磁刺激者进行行为引导或思维引导 或心理引导； 对大脑全域施加适当参数的磁刺激， 持续适当时间； 磁刺 激结束后， 对接受了磁刺激者进行行为引导或思维引导或心理引导。
所述疾病包括抑郁症、 焦虑症、 失眠症、 慢性疼痛、 创伤后应激综 合症、 药物或酒精依赖成瘾疾病、 对不良行为的心理依赖、 儿童注意缺 陷障碍、 心境情感障碍、 精神分裂症、 帕金森综合症、 神经退行性疾病 或老年痴呆症、 神经损伤等。
所述大脑功能包括学习记忆能力、 认知能力、 抗心理应激能力等。 本发明还提供一种中枢神经系统磁刺激装置的控制方法， 所述装置 用于治疗中枢神经系统疾病或精神疾病， 或改善大脑功能。 所述控制方 法通过控制磁刺激电路， 给线圈对通电， 在目标区域施加时变磁场， 所 述磁场的磁感应强度的梯度小于 100Gs/cm, 所述目标区域的范围与动物 或人头部的尺寸相适应。
所述磁场磁感应强度峰值可小于 0.1T。
所述磁刺激过程中， 磁场为一种波形或至少两种波形的组合， 所述 时变磁场频率范围为 0.5Hz ~ 2000Ηζ。
以上技术方案可以看出， 本发明通过控制电路设计并输出波形信号 到驱动电源使驱动电源输出相应波形的电流到线圈， 通过线圈形状、 匝 数、 尺寸、 间距的设计， 在线圈中间一定区域产生所需的时变磁场， 作 用于动物或人的大脑， 使中枢神经系统接受精确波形的、 高频率或多种 频率组合的、 广域的协同磁刺激， 结合行为引导或思维引导或心理引导， 实现神经精神疾病的治疗或脑功能改善。
附图说明
图 1为本发明中实施例 1的装置电路框图；
图 2为本发明中实施例 1的线圈结构示意图；
图 3为本发明中实施例 1的主电路原理图；
图 4为本发明中实施例 1所采用的波形图；
图 5为实施例 1 中， 线圈通以反向电流所产生磁场的磁力线分布示 意图；
图 6为实施例 1 中， 线圈通以同向电流所产生磁场的磁力线分布示 意图；
图 7为本发明中实施例 2所采用的波形图。
具体实施方式
为更好地理解本发明中的技术内容， 现对相关技术做简要的介绍： 从分子生物学、 神经生物学和精神医学角度， 精确波形的、 可调频
(含高频）和多种波形 /频率组合的广域协同磁刺激可能具有新的意义： 能够调整神经递质和 /或神经调质释放， 能够调整受体数量和活性， 能够 激活静寂突触， 能够易化神经突触传递的长时程增强， 能够增强突触可 塑性， 能够调整神经内分泌。 并且， 结合磁刺激后的行为引导或思维引 导或心理引导， 通过上述作用的协同或因果联系而带来认知能力和学习 记忆能力的提高、 精神状态的改善、 神经精神疾病的治疗等效果。 原因 如下：
由于可引起分裂样症状的物质 PCP被发现是兴奋性氨基酸 NMDA受 体阻滞剂，精神分裂症与该受体的联系正受到越来越多的关注。 Kim(1980) 首先提出精神分裂症 DA释放增加并非原发，而是可能继发于谷氨酸机能 低下所致。 最近 10年， NMDA受体和递质功能与精神分裂症发病机制的 研究， 特别是与阴性症状、 认知症状等缺陷性症状的相关性研究取得了 明显进展， 形成了精神分裂症的 NMDA机能低下假说。
NMDA受体是镁离子阻断的电压依赖型兴奋性氨基酸递质门控钙离 子通道受体， 通过谷氨酸和甘氨酸（通常作为抑制性神经递质）共同作 用， 在神经细胞膜部分去极化状态下激活， 使钙离子内流， 完成神经细 胞去极化全过程并弓 I起后续級连反应。 在学习记忆的细胞和分子机制相 关研究中， NMDA受体占有非常重要的位置。 特别地， LTP和 LTD被认 为是突触修饰的内在机制， MDA受体的参与是其前提条件。
徐林等（ 1997 )研究发现应激易化海马 LTD, 而 Michael T. Rogan等 ( 1997 ) 的研究表明应激带来杏仁核的 LTP易化。 在控制情绪表现的主 要通路 HPA轴中， 海马与杏仁核互为负反馈。 李拴德等（ 2004 )研究表 明， 杏仁核摘除后， 神经递质的改变方向与精神病性改变是反向的， 提 示我们，杏仁核的 LTP和 /或海马的 LTD是否带来神经递质鋒放的精神病 性改变？
许多精神疾病多多少少与应激等生活事件相关， 特别是童年或早期 的伤害性经历， 因而就有素质一一应激支说。 那么， 为什么是早期或童 年的伤害性经历？ 在此提出一种设想： 早期的伤害性经历形成了联合型 记忆（条件化）， 与环境形成了广泛的联系， 疾病发生既是对伤害性记忆 的再提取和强化。 青春期开始， NR2A逐步取代 与精神疾病一般 的首发年龄相关， 这不是偶然的： 较 NR2A产生更强的 LTP, 被替 代就弱化了海马 LTP。 如果，替代的过程， 在海马与杏仁核中不同步或不 平衡， 海马替代先于杏仁核替代， 就会使负反馈抑制系统失衡， 发生精 神疾病。
钱卓等（ 1999 )的研究表明， NR2B可以称为聪明基因。 在他们的研 究中， NR2B过表达的大鼠不仅具有更强的学习记忆能力， 也能够更快地 适应变化，对伤害性记忆的消退更快（称为再学习能力）。 最近， Giovanni Marsicano等（ 2002 )发现， 内源性大麻素系统在伤害性记忆的消退中起 着关键性作用，加速伤害性记忆的消退； 其受体 CB不足的基因突变型小 鼠的伤害性记忆消退比 CB过表达的小鼠慢许多， 而 CB不足的基因突变 型和加 CB抗颉剂小鼠的杏仁核 LTP易化， LTD弱化或不产生。 CB1受 体是脑中 G蛋白耦联受体中最多的一类， 其天然配体尚不确定。
神经肽， 特别是内源性阿片肽与情绪之间有着极大的相关性。 韩济 生等研究了不同频率电刺激与神经肽释放的相关性（2004 )， 发现： 电针 刺提高内源性阿片肽的释放， 不同频率引起不同种类阿片肽释放增加， 既； 阿片肽释放具有频率依赖性。 还发现（2004 ): NMDAR抗颉剂克他 命在伏隔核注射改善吗啡戒断症状。 韩济生在 2002年， 关于不同频率电 刺激对神经肽释放的影响作过系统的论述。
在更早的研究中 , 许多人针对磁刺激影响神经再生所作的研究表明： 磁刺激促神经再生的作用是频率依赖性的 （RUSOVAN,等， 1992 ), 而即 便是较强的静磁场也不起作用 （Cordeiro PG等， 1989 ); 电磁场刺激神经 对提高神经生长因子 NGF的活性和水平有益（Longo FM等， 1999 ), 钙 络合剂 MD6Q0阻断磁刺激神经再生作用 （ Rusovan A, Kanje M. 1992 ); 电刺激神经促释放脑源性神经营养因子 BDNF与刺激频率 /波形组合以及 NMDA 受体关联， 高频多串列小间隔脉冲波形 （0.5ms 平台的方波， 100HZ, 4个波一串， 间隔 200ms, 共 75 串 300个脉冲） 而不是持续低 频（1HZ, 480个脉冲）或高频少串列长间隔 （100HZ, 100个波一串， 10S间隔， 共 3或 6串）促释放 BDNP,但被 NMDA抗颉剂 D-AP-5抑制 ( Isolpel J. Lever等, 2001 )。这些，都在不断提示：钙离子、 NGF、 BDNF, LTP ( LTD )、 NMDA受体、 电、 磁场的频率等因素之间存在某种关联。
在精神疾病临床研究中， Rohan M ( 2004 )等偶然发现 MRSI的某一 序列改善躁郁症患者的情绪， 且有非常显箸的统计学意义， 并且， 在此 基础上的动物实验验证了这种磁刺激所具有的 "抗抑郁药样" 作用 ( 2005 )。
我们发现， 在强迫游泳（一种习得性无助的动物模型， 一般可以用 来筛选或验证抗抑郁药物效果） 实验中， 磁刺激后结合行为引导 （开放 场 15 分钟）， 极其显著地改善了模型动物的抑郁样行为， 而单纯的行为 引导或是单纯的磁刺激没有显著的效果。
我们还发现， 在条件性恐惧记忆消退的实验中 （声光提示的足部电 击后， 记录实验动物对单纯声光刺激的条件反射）， 不同参数的磁刺激带 来不同的结果， 增强或减弱已经建立的恐惧条件反射， 提示： 适当的单纯 磁刺激可能有利于负性事件记忆的干预。
以上的综合与分析， 得出两点提示， 其一： 精确波形高频或多种频 率组合的磁刺激也许可以成为安全的 NMDA受体激动手段， 高频磁刺激 可能通过 NMDA相关 LTP途径带来中枢神经系统多方面的深刻改变，影 响记忆的获得、 提取、 修饰、 巩固等过程并因此而提高再学习能力， 从 而在一定条件下 (比如磁刺激后的行为引导） 治疗一些神经精神疾病; 这一点， 促使我们开发一种适合于临床应用的， 可以产生精确波形的高 频率或多种频率 /波形组合的广域协同磁刺激仪， 克服 rTMS存在的不足 和电刺激的不足， 为神经精神疾病的治疗乃至预防提供新的选择。 其二： 综合研究高频磁刺激和多种波形 /频率組合在 LTP, 学习记忆， 神经递质， 记忆消退， 神经肽释放， 突触可塑性等多方面的影响， 也许会对人类提 高智力， 预防精神系统疾病， 乃至戒毒等等产生深远的影响。
现以具体实施例对本发明内容进行详细的描述。
如图 1所示， 本发明中的装置包括控制电路、 驱动电源电路、 线圈， 所述驱动电源电路包括驱动电路、 检测电路、 主电路， 所述控制电路包 括上位机和下位机， 所述上位机为通用 PC机或工控机， 便于实际应用中 的操作， 并通过 RS232接口与所述下位机进行连接和通讯， 发送命令和 参数， 所述下位机采用 DSP芯片作为主控芯片， 接收来自上位机的命令 和参数后， 产生相应的 PWM信号， 再传送给所述驱动电路， 所述驱动电 路和检测电路， 都分别与所述下位机和主电路相连， 所述线圈与主电路 相连， 所述控制电路产生 PWM信号， 通过驱动电路驱动主电路工作， 由 主电路中的绝缘栅双极型晶体管 (IGBT)输出时变电流激励所述线圈对， 并激励产生时变磁场。 同时， 所述检测电路采样主电路中的电压与电流 值， 实时监控主电路的工作状态， 并根据需要调节输出的 PWM信号， 或 在过电流产生时及时切断线圏电路， 防止线圈损坏。
■ 所述驱动电路包括一个光耦合器， 连接在所述下位机与主电路之间， 其主要作用是隔离干扰信号和驱动主电路的工作 （此部分电路未在图中 表示）。
所述主电路如图 3所示，包括一个整流桥 BR1和五个 IGBT Ql ~ Q5、 两个电解电容 C2、 C3 ,所述电解电容 C2、 C3并联连接到所述整流桥 BR1 的输出端， 所述 IGBT Ql串接在电解电容 C2的负极端和整流桥 BR1之 间，触发端与所述驱动电路的一个脉宽调制端 PWM1端相连，所述 IGBT Q4和 Q5串接在电解电容 C3的负极端和整流桥 BR1之间， 两个触发端 也与所述驱动电路的另两个 PWM1端相连（以上所述三个 PWM1端是各 自独立的）， 所述电容 C2、 C3还与另两个 IGBT Q2、 Q3两端并联， 两 IGBT Q2> Q3的触发端分别与所述驱动电路的另两个脉宽调制端 PWM2 和 PWM3端相连。所述线圈 L2连接在所述 IGBT Q2的发射极和 IGBT Q3 的集电极之间。 所述转换电路由一个双刀汉掷继电器 K1构成， 所述继电 器 K1的两公共端与所述线圈 L2的两端并联连接， 一路常开端与另一路 常闭端相连， 另一路常闭端与前一路的常开端相连， 所述线圈 L3分别连 接在所述两连接端上所述继电器 K1 的线圈与所述下位机的两个控制端 相连。所述 IGBT可以是分立的 IGBT元件，也可以是集成的 IGBT模块， 所述驱动电路中光耦合器的功能也可以通过集成有驱动功能的的 IGBT 模块来实现。
所述检测电路采用 LEM电压传感器和电流传感器， 检测出电路中电 容 C2、 C3两端的电压和流过两线圈 L2、 L3的电流， 并将检测信号进行 滤波、 放大、 AD转换后传送到下位机中。 （此部分电路， 图中未作标示） 所述线圈为一对同轴对称平行放置的相同圆形线圈对， 所述其结构 如图 2所示， 取半径为 R、 间距 2a=^R, 即构成麦克斯维线圈对， 并通 以反向电流， 使所述两线圈之间的目标区域内产生线性梯度的磁场， 在 通以同向电流时在目标区域产生近似均匀的磁场， 所述目标区域的大小 与人头部的尺寸相适应。 所述线圈通以反向电流时， 在原点为 0, 半径 为 Q.5a的球形区域产生线性梯度的磁场，尽量使人脑处于该球形区域内， 而线圈半径和匝数尽量小以使电感小， 从而对驱动电源的硬件难度要求 和功率降低、 容易实现， 使线圈发热也降低， 从而适应高频电流产生高 频磁场。取 R=180mm时， 牺牲一点磁场梯度的线性度要求但可以基本得 到近似均匀的磁场区域并满足人体工学的要求， 因此， 这一尺寸作为一 种优选实施例。 这时， 线圈匝数取 40, 单匝峰值电流取 5A， 就可以得到 中心区域内 0.5Gs/cm的磁场梯度。 实际应用时， 线圏匝数取 40， 单匝电 流可以达到 40A, 磁场梯度就可以达到 4Gs/cm， 会有较好的治疗效果。 同时， 通过下位机的控制所述继电器 K1 , 将所述线圈 L3的连接方向转 换为与原方向相反方向， 从而实现改变线圈电流方向的作用， 切换线圈 电流的方向为同向电流， 会在中心区域产生更大的磁场强度， 而磁场均 匀性提高， 梯度降低， 能够在实际应用中取得不同于反向电流的效果。
工作过程中， 使用者通过上位机设定系统运行的各项参数， 并通过 串行口传送到下位机， 下位机接收到运行命令后， 首先发送 PWM信号控 制主电路 Q1和 Q4使电容 C2和 C3上的电压达到计算出的需求值，电容 C2和 C3上的电压通过检测电路由下位机的 AD转换部分得到。 当电容 C2和 C3上的电压达到要求后， 下位机通过给 Q2、 Q3发送不同的 PWM 信号控制其通断以在 L2、 L3上产生各种电流波形， 从而生成相应的各种 时变磁场。 主电路的控制可分为三个阶段， 即电流的上升阶段、 保持阶 段和下降阶段。 首先是电流的上升阶段， Q2、 Q3 均一直导通， L2、 L3 上加上固定不变的电压 （其等于 C2上的电压）， 其电流呈现线性上升的 趋势， 改变 C2上的电压即可改变电流的上升斜率， 改变阶段的时间即可 改变线圈电流的最大值； 接着是保持阶段， Q3 仍然保持一直导通， Q2 则断续的导通和截止， 从而使 L2、 L3的电流基本保持稳定； 最后阶段为 下降阶段， Q2、 Q3均保持截止， 电感线圈 L2、 L3 的电流只能通过 D2 和 D3给电容 C3充电， 电感线圈 L2、 L3两端相当于加上一个等于电容 C3电压的反向电压， 电感线圈 L2、 L3的电流线性下降直到其值等于零， 改变 C3上的电压即可改变电流的下降斜率。下降阶段后经过一个零电流 间隔又从新开始一个新的上升阶段， 如此周而复始产生一个固定周期精 确波形的时变电流， 从而产生了一个周期的精确波形的时变磁场。
在使用过程中， 通过对控制电路的设定和控制， 产生如图 4所示的 等腰梯形波， 并施加在所述线圈对上， 产生相应的时变磁场， 通过等腰 梯形波的上升沿和下降沿， 在目标区域感生出正负方波脉冲电场， 从而 满足治疗的需要。 例如 128微秒的上升沿接 768微秒平台再接 128微秒 的下降沿和 768微秒的零电流平台， 周期 1792微秒（高频）， 线圈对的 电流方向相反， 单匝峰值电流 20安培（对应 2Gs/cm的磁场梯度值）， 还 可以实现多种波形和频率的组合,通过设计一种波形的输出和停止的周期 个数， 构成磁刺激串列， 包含串内频率和串间频率的参数。 例如： 上述 波形输出 10个周期停止 27个周期組成一个串周期， 感生电场脉冲串内 频率约 558Hz (不考虑电场方向约为 1116Hz ), 串间频率约 15Hz ( (3节 律）； 或者， 同样波形每连续刺激 20个周期后停止 90个周期， 串间频率 约 5Ηζ ( Θ节律）。 使用者可以通过上位机， 根据治疗的需要设定不同的 磁刺激参数。作为神经精神疾病治疗或脑功能改善的用途，对需要者（比 如抑郁症患者） 大脑全域施加上述磁刺激， 持续适当时间。 对于连续的 磁刺激， 每一次不间断的刺激不可持续太长时间， 以免带来 NMDA受体 过度激活可能引起的副作用， 而串列形式的磁刺激却能够持续更长的时 间， 比如 20分钟； 串列形式的磁刺激也可以间断进行， 比如每 10秒中 输出 2秒串列停止 8秒串列， 循环进行。 对于正在接受或已经接受了磁 刺激者， 进行行为引导或思维引导或心理引导， 完成疾病治疗或脑功能 改善的全过程。 例如： 使接受了磁刺激者经过或处于新奇的环境； 或者 通过智力游戏或问题解答引导其进行思考， 所谓问题可以具体为标准化 的题库， 问题的类型可以是自然科学或社会科学或生活常识的问题， 根 据病人的受教育程度和智力水平选取其中的一些组合， 由接受了磁刺激 者进行解答。 或者还可以通过具体音乐或影像使其感受良性刺激； 或者 通过心理辅导使大脑良性兴奋。 这些行为引导或思维引导或心理引导， 重要的特征是应该既使患者感觉有难度又能使其成功地结束。
图 5为本发明在线圈对通以反向电流时， 产生磁场的磁力线分布图， (图中仅为半侧）其中可以看出， 在目标区域内磁力线分布为线性梯度， 其中 501为线圈， 502为磁力线， 503内的区域为所述目标区域， 也就是 在治疗过程中， 将人脑置于其中的区域。
图 6为本发明在线圈对通以同向电流时， 产生磁场的磁力线分布图， 其中， 可以看出在目标区域内， 磁力线分布为近似均匀。 其中 601 为线 圈， 602为磁力线， 603为所述目标区域， 也就是在治疗过程中， 将人脑 置于其中的区域。
本发明的另一种实施例 2, 其结构与实施例 1完全相同。 通过对控制 电路的设定和控制， 产生另两种波形的组合， 使所述线圈对产生相应的 磁场， 如图 7所示， 其中 A波形为连续的锯齿波， 频率为 1000Hz, 持续 3分钟， B波形为间歇的三角波， 频率为 2Hz, 持续时间为 3分钟， 这两 种波形交替进行 3个循环， 共进行 18分钟， 构成一次磁刺激过程。 磁刺 激过程结束后， 进行前述的行为引导或思维引导或心理引导， 完成神经 精神疾病的治疗或脑功能的改善。
作为神经精神疾病治疗或脑功能改善的用途， 使用方法还可以包括 在磁刺激之前进行行为引导或思维引导或心理引导， 这种磁刺激前的引 导可以不同于磁刺激之后的引导， 目的是通过引导， 提取大脑中存留的 负性记忆并使其表达； 而磁刺激后引导的目的是通过对应激的 "抗拒成 功" 来修饰负性记忆， 重塑 HPA轴的负反馈通路或提高抗应激能力。
除此两种优选实施例外， 本发明中所述的线圈还可以采用椭圆形、 矩形或包括立体形状在内的其他合理形状的线圈， 改变线圈间距、 匝数 等参数， 釆用两对或更多对线圈的组合，也可以是一个较大尺寸的线圈， 也可以是螺线管； 还可以通过控制电路和驱动电路的控制， 实现更多种 波形、 频率、 强度的组合， 完成一个磁刺激过程， 例如包括等腰梯形在 内的更多的电流波形感生的磁场波形， 包括不等腰梯形， 等腰三角形， 不等腰三角形等等； 输出电流的频率一般在 1000Hz以内， 可以多种波形 和多种频率組合完成一个磁刺激过程， 也可以使高频配合反向电流， 低 频配合同向电流， 还可以用其他全控型电力半导体器件、 比如 GRT或功 率 MOSFET或 GTO等替代主电路中的 IGBT, 驱动电路也根据器件的技 术特性进行相应的修改， 实现主电路功能。 主电路还可以增加两个 IGBT 或其他电力半导体器件以及相应的驱动电路和控制电路， 使线圈电流能 够双向流动。
以上对本发明所提供的中枢神经系统磁刺激方法及其装置进行了详 以上实施例的说明只是用于帮助理解本发明的方法及其核心思想； 同时， 对于本领域的一般技术人员， 依据本发明的思想， 在具体实施方式及应 用范围上均会有改变之处， 综上所述， 本说明书内容不应理解为对本发 明的限制。

Claims

权 利 要 求
1、 一种中枢神经系统磁刺激电路， 包括顺次连接的控制电路、 驱动 电源电路和线圈； 其特征在于， 所述驱动电源电路包括驱动电路、 检测 电路、 主电路， 所述驱动电路和检测电路， 都分别与所述控制电路和主 电路相连， 所述线圈与主电路相连。
2、 根据权利要求 1所述的中枢神经系统磁刺激电路， 其特征在于， 所述主电路包括一个转换电路， 用于控制所述线圈对的电流方向为同向 或反向。
3、 根据权利要求 1或 2所述的中枢神经系统磁刺激电路， 其特征在 于， 所述主电路包括至少一个绝缘栅欢极型晶体管， 所述控制电路产生 的 PWM信号，通过驱动电路驱动主电路中的绝缘栅双极型晶体管输出时 变电流给所述线圈， 产生所需的时变磁场。
4、 根据权利要求 3所述的中枢神经系统磁刺激电路， 其特征在于， 所述绝缘栅汉极型晶体管由其他全控型电力半导体器件替代， 驱动电路 根据所述替代器件的技术特性进行相应的修改。
5、 根据权利要求 1或 2所述的中枢神经系统磁刺激电路， 其特征在 于， 所述控制电路包括用作主控芯片的 DSP芯片， 所述驱动电路包括用 于将控制电路发来的控制信号传递给主电路的光耦合器， 所述控制电路 控制驱动电路和主电路使线圈产生所需的磁场， 所述转换电路包括至少 一个继电器。
6、 一种中枢神经系统磁刺激装置， 包括磁刺激电路； 所述磁刺激电 路包括， 顺次连接的控制电路、 驱动电源电路和线圈； 其特征在于， 所 述驱动电源电路包括驱动电路、 检测电路、 主电路； 所述驱动电路和所 述检测电路， 分别与所述控制电路和所述主电路相连； 所述线圈与所述 主电路相连。
7、 根据权利要求 6所述的中枢神经系统磁刺激装置， 其特征在于， 所述线圈为至少一对同轴、 平行、 对称放置的相同线圈对， 所述每对线 圈电流同步同强度， 所述主电路包括一个转换电路， 用于控制所述线圈 对的电流方向为同向或反向。
8、 根据权利要求 6或 7所述的中枢神经系统磁刺激装置， 其特征在 于， 所述主电路包括至少一个绝缘栅双极型晶体管， 所述控制电路产生 的 PWM信号，通过驱动电路驱动主电路中的绝缘栅双极型晶体管输出时 变电流给所述线圈， 产生所需的时变磁场。
9、 根据权利要求 8所述的中枢神经系统磁刺激装置， 其特征在于， 所述绝缘栅双极型晶体管由其他全控型电力半导体器件替代， 驱动电路 根据所述替代器件的技术特性进行相应的修改。
10、 根据权利要求 6或 7所述的中枢神经系统磁刺激装置， 其特征 在于， 所述控制电路包括用作主控芯片的 DSP芯片， 所述驱动电路包括 用于将控制电路发来的控制信号传递给主电路的光耦合器， 所述控制电 路控制驱动电路和主电路使线圈产生所需的磁场， 所述转换电路包括一 个继电器。
11、 一种中枢神经系统磁刺激装置的用途， 其特征在于， 通过选择 适当参数的时变磁场刺激动物或人的大脑全域， 治疗中枢神经系统疾病 或精神疾病， 或改善大脑功能。
12、 根据权利要求 11所述的中枢神经系统磁刺激装置的用途， 其特 征在于， 所述适当参数至少包括与装置中线圈关联的电流波形、 频率、 峰值强度， 对应感生磁场的波形、 频率和峰值强度的参数。
13、 根据权利要求 11所述的中枢神经系统磁刺激装置的用途， 其特 征在于， 所述适当参数还包括脉冲串列磁刺激时的串内频率和串间频率。
14、 根据权利要求 11所述的中枢神经系统磁刺激装置的用途， 其特 征在于， 在磁刺激前或磁刺激中或磁刺激后， 结合行为引导或思维引导 或心理引导， 提高治疗中枢神经系统疾病或精神疾病的疗效。
15、 根据权利要求 11或 14所述的中枢神经系统磁刺激装置的用途， 其特征在于， 对大脑全域施加适当参数的磁刺激， 持续适当时间； 磁刺 激过程中或磁刺激结束后， 对正在接受或已经接受了磁刺激者进行行为 引导或思维引导或心理引导。
16、 根据权利要求 11或 14所述的中枢神经系统磁刺激装置的用途， 其特征在于： 磁刺激前， 对于将要接受磁刺激者进行行为引导或思维引 导或心理引导； 对大脑全域施加适当参数的磁刺激， 持续适当时间； 磁 刺激结束后， 对接受了磁刺激者进行行为引导或思维引导或心理引导。
17、 根据权利要求 11或 14所述的中枢神经系统磁刺激装置的用途， 其特征在于： 所述疾病是抑郁症、 或焦虑症、 或失眠症、 或慢性疼痛、 或创伤后应激综合症、 或药物或酒精依赖成瘾疾病、 或对不良行为的心 理依赖、 或儿童注意缺陷障碍、 或心境情感障碍、 或精神分裂症、 或帕 金森综合症、 或神经退行性疾病或老年痴呆症、 或神经损伤。
18、 根据权利要求 11所述的中枢神经系统磁刺激装置的用途， 其特 征在于： 所述大脑功能是学习记忆能力、 或认知能力、 或抗心理应激能 力。
19、 一种中枢神经系统磁刺激装置的控制方法， 所述装置用于治疗 中枢神经系统疾病或精神疾病， 或改善大脑功能， 其特征在于， 通过控 制磁刺激电路， 给线圈通电， 在目标区域施加时变磁场， 所述磁场的磁 感应强度的梯度小于 100Gs/cm, 所述目标区域的范围与动物或人头部的 尺寸相适应。
20、 根据权利要求 19所述的中枢神经系统磁刺激装置的控制方法， 其特征在于： 所述磁场磁感应强度峰值小于 0.1T。
21、 根据权利要求 19或 20所述的中枢神经系统磁刺激装置的控制 方法， 其特征在于， 所述磁刺激过程中， 磁场为一种波形或至少两种波 形的组合， 所述时变磁场频率范围为 0.5Hz至 2000Ηζ。
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CN101208132B (zh) 2011-12-28
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EP1894600B1 (en) 2019-04-03
EP1894600A4 (en) 2011-06-22
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