TMS stimulation device

Abstract

The invention provides a TMS stimulation device which comprises a transcranial magnetic stimulation circuit and a control unit, the control unit is used for controlling the transcranial magnetic stimulation circuit to generate continuous and repeated magnetic field stimulation signals, and a small, light and high-safety household machine type can be designed to adapt to the characteristic that cranial nerve diseases need to be treated periodically and repeatedly. The action range of the stimulation probe can be effectively narrowed, a brain target stimulation area can be accurately positioned, and the problems that due to the fact that the stimulation range of the probe of an existing transcranial magnetic therapeutic instrument is too large, irrelevant brain areas except a therapeutic target area are stimulated, the therapeutic effect is not ideal, and various side effects are possibly caused are solved.

Description

Technical Field

[0001] This application belongs to the field of electromagnetic technology, and particularly relates to a TMS stimulation device. Background Art

[0002] Currently, there are hundreds of millions of patients with craniocerebral nerve diseases in the world, and there are also tens of millions in China, and the number is still increasing. These diseases seriously affect people's quality of life.

[0003] Due to the existence of the blood-brain barrier, ordinary drugs are difficult to enter the brain tissue, the existing drug treatment has poor effects, and the toxic and side effects are relatively large.

[0004] For example: Parkinson's disease (PD) is the second most common chronic neurodegenerative disease, accompanied by a significant death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Parkinson's disease is mainly characterized by motor symptoms, such as dyskinesia, tremors, muscle stiffness, and bradykinesia, which seriously affect the quality of life of Parkinson's disease patients (Kalia and Lang, The Lancet, 2015; Morris et al., The Lancet, 2024).

[0005] Transcranial Magnetic Stimulation (TMS) technology is a technology that uses pulsed magnetic fields to act on the central nervous system.

[0006] TMS has been used to treat brain nerve-related diseases such as depression, Parkinson's disease, epilepsy, and movement disorders for decades. The application of this treatment technology has experienced an explosive growth in recent years. However, what is out of step with this is that the current transcranial magnetic stimulation instrument technology has not advanced accordingly.

[0007] The above statements are only used to provide background technical information related to this application. Unless otherwise indicated, the content described in this part is not prior art for other parts of this application. Summary of the Invention

[0008] The TMS stimulation device proposed by the present invention, through the provided transcranial magnetic stimulation coil probe and various drive circuits, can effectively reduce the action range of the stimulation probe, accurately locate the target stimulation area in the brain, and solve the problem that the existing transcranial magnetic therapy instrument has an overly large stimulation range of the probe, stimulates irrelevant brain areas outside the treatment target area, resulting in unsatisfactory treatment effects and possibly causing various side effects. TMS stimulation device TMS stimulation method

[0009] According to the second aspect of the embodiments of the present application, a TMS stimulation device is provided, including a transcranial magnetic stimulation circuit and a control unit, and the control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal;

[0010] The magnetic field stimulation signal acts on at least one target point, where the target point includes the cerebellar cortex. The magnetic field stimulation signal inhibits the activities of cerebellar cortical neurons and activates cerebellar nuclear neurons, thereby enhancing the functional connection with the substantia nigra pars compacta.

[0011] In some embodiments of the present application, the transcranial magnetic stimulation circuit includes a coil driving circuit, and the coil driving circuit includes a controller, a charging switch unit, a capacitive energy storage unit, and an electromagnetic induction unit;

[0012] The controller controls the charging switch unit to store energy for the capacitive energy storage unit and drives the electromagnetic induction unit to generate a magnetic induction electric field to form a coil driving loop;

[0013] The controller increases the change rate of the stimulating coil current, thereby increasing the magnetic induction electric field intensity of the magnetic induction electric field;

[0014] And / or the controller extends the dynamic range of the electromagnetic field of the stimulating coil, thereby increasing the action time of the magnetic induction electric field.

[0015] In some embodiments of the present application, in the transcranial magnetic stimulation circuit, the charging switch unit includes a first electronic switch S1; the capacitive energy storage unit includes a first capacitor C1; the electromagnetic induction unit includes a first inductance coil L1;

[0016] The transcranial magnetic stimulation circuit includes a second capacitor C2 and a damping resistor; the first inductance coil L1 is a stimulating coil;

[0017] Specifically, the driving power input terminal is connected to one end of the first capacitor C1 and one end of the first inductance coil L1, and the other end of the first capacitor C1 is grounded; the other end of the first inductance coil L1 is grounded after being connected in series with the first electronic switch S1, and the other end of the first inductance coil L1 is also connected in series with the damping resistor and the second capacitor C2 in sequence and then grounded.

[0018] In some embodiments of the present application, in the transcranial magnetic stimulation circuit, the charging switch unit includes a second electronic switch S2, a third electronic switch S3, a fourth electronic switch S4, and a fifth electronic switch S5; the capacitive energy storage unit includes a third capacitor C3; the electromagnetic induction unit includes a third inductance coil L3, and the third inductance coil L3 is a stimulating coil;

[0019] The transcranial magnetic stimulation circuit further includes a second inductance coil L2, and the second inductance coil L2 is a constant current inductance;

[0020] Specifically, one end of a third capacitor C3 is connected to the driving power input terminal, and the other end of the third capacitor C3 is grounded; the driving power input terminal is grounded after being connected in series with a fifth electronic switch S5 and a second electronic switch S2 in sequence; the driving power input terminal is grounded after being connected in series with a second inductor coil L2, a third electronic switch S3, and a fourth electronic switch S4 in sequence; one end of the third electronic switch S3 is connected to the second inductor coil L2, and the other end is connected to one end of a third inductor coil L3. The other end of the third inductor coil L3 is connected to the common terminal of the fifth electronic switch S5 and the second electronic switch S2.

[0021] In some embodiments of the present application, in the transcranial magnetic stimulation circuit, the charging switch unit includes a sixth electronic switch S6 and a seventh electronic switch S7; the capacitive energy storage unit includes a fourth capacitor C4 and a fifth capacitor C5; the electromagnetic induction unit includes a fourth inductor coil L4, and the fourth inductor coil L4 is a stimulation coil.

[0022] The transcranial magnetic stimulation circuit further includes a fifth inductor coil L5, a first zener diode DW1, a second zener diode DW2, and a voltage stabilizing resistor; the fifth inductor coil L5 is a constant current inductor; the first zener diode DW1, the second zener diode DW2, and the voltage stabilizing resistor form a voltage balancing circuit.

[0023] Specifically, the driving power input terminal V+ is grounded after being connected in series with the fourth capacitor C4 and the fifth capacitor C5 in sequence; the driving power input terminal V+ is grounded after being connected in series with the fifth inductor coil L5, the sixth electronic switch S6, and the seventh electronic switch S7 in sequence; the common terminal of the sixth electronic switch S6 and the seventh electronic switch S7 is connected to one end of the fourth inductor coil L4, and the other end of the fourth inductor coil L4 is connected to one end of the fourth inductor coil L4. The other end of the first inductor coil L1 is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5.

[0024] The driving power input terminal is grounded after being connected in series with the first zener diode DW1 and the second zener diode DW2 in sequence; the common connection point of the first zener diode DW1 and the second zener diode DW2 is connected to one end of the voltage stabilizing resistor, and the other end of the voltage stabilizing resistor is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5.

[0025] In some embodiments of the present application, the transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, and the auxiliary coil reverse pre-magnetization circuit includes a sixth inductor coil L6, a seventh inductor coil L7, an eighth electronic switch S8, and a sixth capacitor C6.

[0026] Specifically, the driving power input terminal is grounded after being connected to the sixth capacitor C6, and is grounded after being sequentially connected to the eighth electronic switch S8, the sixth inductor coil L6, and the seventh inductor coil L7; the seventh inductor coil L7 is a pre-magnetized bias magnetic winding, and the seventh inductor coil L7 is coupled in the same direction as the stimulation winding in the coil driving circuit; the sixth inductor coil L6 is a constant current coil.

[0027] In some embodiments of the present application, in the transcranial magnetic stimulation circuit, the charging switch unit includes a tenth electronic switch S10; the capacitor energy storage unit includes a seventh capacitor C7; the electromagnetic induction unit includes an inductive stimulation coil L 刺激 ;

[0028] The transcranial magnetic stimulation circuit further includes an eighth capacitor C8 and a damping resistor;

[0029] The transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, and the auxiliary coil reverse pre-magnetization circuit includes an eighth inductor coil L8, a ninth inductor coil L9, a ninth electronic switch S9, a voltage stabilizing resistor, and a voltage stabilizing diode;

[0030] Specifically, the driving power input terminal is grounded after being connected to the seventh capacitor C7; the driving power input terminal is grounded after being sequentially connected to the inductive stimulation coil L 刺激 , the damping resistor, and the eighth capacitor C8; the tenth electronic switch S10 is connected in parallel with the branch formed by the voltage stabilizing resistor and the voltage stabilizing diode;

[0031] The driving power input terminal is grounded after being sequentially connected to the eighth inductor coil L8, the ninth inductor coil L9, and the ninth electronic switch S9; the driving power input terminal is grounded after being sequentially connected to the voltage stabilizing resistor, the voltage stabilizing diode, and the ninth electronic switch S9.

[0032] In some embodiments of the present application, a soft magnetic core is arranged in the stimulation coil or a permanent magnet for reverse bias magnetization is added on the basis of the original magnetic core to improve the magnetic permeability of the magnetic circuit of the stimulation coil.

[0033] According to the third aspect of the embodiments of the present application, a method for using a TMS stimulation device is provided, including:

[0034] The stimulation frequency of the TMS treatment device is 1-5 Hz; the depth of the action range is 0-7 mm, and the radius is 0-8 mm; the magnetic field strength can reach 1.6 T; after repeatedly stimulating the target in the classical repetitive transcranial magnetic stimulation mode, by analyzing the improvement of the brain defects of the target after stimulation at different frequencies, the transcranial magnetic stimulation parameters suitable for the current individual are determined.

[0035] According to the fourth aspect of the embodiments of the present application, a TMS stimulation method is provided, including:

[0036] Using any of the above TMS stimulation devices, a continuous and repetitive magnetic field stimulation signal is generated through the magnetic induction electric field of the transcranial magnetic stimulation circuit;

[0037] The magnetic field stimulation signal acts on at least one target point, and the target point includes the cerebellar cortex area; the magnetic field stimulation signal enhances the functional connection between the cerebellar nucleus neurons and the substantia nigra pars compacta by activating them, thereby improving the PD motor deficit.

[0038] Adopting a TMS stimulation device of the present application, including a transcranial magnetic stimulation circuit and a control unit, the control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal. Through the TMS treatment device targeting the cerebellar cortex of the user, it can significantly improve brain nerve defects including PD motor deficits and significantly delay the death of dopamine neurons in the SNc. With the provided transcranial magnetic stimulation circuit, the present application realizes the design of a small, light and safer household model to adapt to the characteristics of the need for periodic and repeated treatment of cranial nerve diseases. It can effectively reduce the action range of the stimulation probe, accurately locate the target stimulation area of the brain, and solve the problems of the existing transcranial magnetic therapy instrument, such as the over-large stimulation range of the probe, which stimulates irrelevant brain areas outside the treatment target area, resulting in unsatisfactory treatment effects and possible multiple side effects. Description of the Drawings

[0039] The drawings described herein are used to provide a further understanding of the present application, form a part of the present application, and the schematic embodiments and descriptions thereof are used to explain the present application without unduly limiting the present application. In the drawings:

[0040] Figure 1 Shows the forward converter stimulation coil drive circuit diagram adopted by existing transcranial magnetic stimulator products;

[0041] Figure 2 Shows Figure 1 Schematic diagram of the change process of the magnetic induction electric field intensity of the stimulation coil of the existing product shown;

[0042] Figure 3 Shows the circuit structure diagram of the transcranial magnetic stimulation circuit according to the embodiment of the present application;

[0043] Figure 4 Shows the schematic diagram of the model of neurons under the action of the electric field according to the embodiment of the present application;

[0044] Figure 5 Shows the schematic diagram of obtaining the required stimulation range by changing the shape of the coil magnetic core according to the embodiment of the present application;

[0045] Figure 6 Shows the schematic diagram of reverse pre-magnetization of the permanent magnet of the coil magnetic core according to the embodiment of the present application;

[0046] Figure 7 The coil driving circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application is shown; Figure 1 (Flyback driving circuit);

[0047] Figure 8 The one according to an embodiment of the present application is shown; Figure 7 Schematic diagram of the magnetic induction electric field intensity of the driving circuit;

[0048] Figure 9 The coil driving circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application is shown Figure 2 (Asymmetric full-bridge driving circuit);

[0049] Figure 10 The one according to an embodiment of the present application is shown Figure 9 Diagram showing the bias magnetization of the coil core and the change of the magnetic induction electric field intensity shown;

[0050] Figure 11 The coil driving circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application is shown Figure 3 (Asymmetric half-bridge driving circuit);

[0051] Figure 12 The auxiliary coil reverse pre-magnetization circuit diagram of the transcranial magnetic stimulation circuit according to an embodiment of the present application is shown;

[0052] Figure 13 Shows Figure 12 Diagram showing the change of the extended magnetic field dynamic range of the reverse pre-magnetization of the auxiliary coil shown;

[0053] Figure 14 The schematic diagram of the stimulation probe structure for obtaining the required magnetic stimulation range by changing the shape of the magnetic core according to an embodiment of the present application is shown;

[0054] Figure 15 The schematic diagram of the in-situ heat dissipation structure of the probe semiconductor according to an embodiment of the present application is shown;

[0055] Figure 16 The circuit diagram of the comprehensive application of two techniques, namely, reverse pre-magnetization of the stimulation coil magnetic core and increase of the stimulation coil current change rate, according to an embodiment of the present application is shown;

[0056] Figure 17 For the one according to an embodiment of the present application Figure 16 Single-pulse signal timing diagram of the transcranial magnetic stimulation coil;

[0057] Figure 18 The step schematic diagram of the TMS stimulation method according to an embodiment of the present application is shown; Figure 19 The structural schematic diagram of the TMS stimulation device according to an embodiment of the present application is shown;

[0058] Figure 20 The schematic diagram of the principle of the TMS stimulation device according to an embodiment of the present application is shown;

[0059] Figure 21 The schematic structural diagram of the transcranial magnetic stimulation system according to an embodiment of the present application is shown. Detailed implementation manners

[0060] Regarding the present application, there are hundreds of millions of patients with cranial nerve diseases in the world currently, and tens of millions in China, and the number is still increasing. It can be seen from the following Table 1 of the statistics of cranial nerve diseases that the number of these diseases is large and seriously affects people's quality of life.

[0061]

[0062] Table 1 Statistics of cranial nerve diseases

[0063] Considering the following two aspects of the current situation: on the one hand, for neurological diseases, for example, Parkinson's disease (PD) is the second largest chronic neurodegenerative disease. In medical treatment, a transient high-intensity current is passed through an insulated coil to generate a changing magnetic field, which can thus change the membrane potential of cortical neurons and make them generate an induced current that affects nerve electricity and metabolic activities. The primary motor cortex and the dorsolateral prefrontal cortex are usually the target areas for the use of transcranial magnetic stimulation technology TMS (Transcranial Magnetic Stimulation) in the adjuvant treatment of PD. However, the effect is not satisfactory and its mechanism is not clearly understood at present. Currently, the parameters for treating Parkinson's disease using repetitive transcranial magnetic stimulation technology TMS in clinical practice are diverse and the treatment effects are uneven.

[0064] We hope to combine the changes at the molecular, cellular, and circuit levels to evaluate the optimal stimulation parameters and stably and effectively improve the motor ability of Parkinson's model animals.

[0065] Therefore, it is urgent to study how TMS specifically improves Parkinson's motor disorder and how to treat and improve the motor defects of PD and to form a practical treatment plan.

[0066] However, in contrast, the current progress of the transcranial magnetic stimulation instrument technology itself is slow. For example, the stimulation inductance coils of the current transcranial magnetic stimulation technology (TMS) generally have too large a range, and it is difficult to accurately locate the target stimulation area in the brain during application, resulting in the stimulation coil probe stimulating brain areas outside the target treatment area, causing various side effects in clinical practice, such as discomfort or headache in the stimulated area and its vicinity; the treated person fainting or becoming manic, and in severe cases, epilepsy may be triggered.

[0067] At present, transcranial magnetic stimulation (TMS) technology has a high research popularity in the academic community. However, due to the overly large action area of the stimulation coil probe, the stimulation target area cannot be accurately positioned, making it difficult to deepen the theoretical research work.

[0068] Existing transcranial magnetic stimulation devices are large in volume and have certain risks during treatment, requiring doctors to guard beside patients, seriously occupying resources such as doctors and medical space. Periodic treatment at the hospital also brings many inconveniences to patients.

[0069] In response to this, the inventors of this application conducted extensive experimental research and found that the functional connection between the cerebellar nuclei (CN) and the substantia nigra pars compacta (SNc) in PD patients is reduced. Specifically, CN mainly sends projections to TH-positive neurons in SNc, and most of the dopaminergic neurons receiving CN projections are ANXA1-positive. At the same time, fiber photometry measurements showed that 1Hz TMS targeted at the cerebellum activates the CN-SNc circuit and increases dopamine release; activating the CN-SNc circuit can greatly improve the motor deficits of PD rats; and through persistent research, it was found that TMS treatment can enhance the synaptic plasticity between the CN-SNc loops and slow down the death of dopaminergic neurons, producing a lasting effect; after one week of 1Hz TMS treatment, the activation of CN neurons and dopaminergic nerves in SNc of PD experimental rats increased.

[0070] Based on this, the present invention provides a TMS stimulation method targeting the cerebellum, and the frequency of the magnetic field stimulation signal is 1Hz, which can significantly improve PD motor deficits.

[0071] In addition, considering that TMS has been used to treat brain nerve-related diseases such as depression, Parkinson's disease, epilepsy, and movement disorders for decades, the application of this treatment technology has experienced an explosive growth in recent years. However, in contrast, the current transcranial magnetic stimulation instrument technology has not advanced accordingly. As a result, the TMS stimulation inductance coils of the current transcranial magnetic stimulation technology generally have an overly large range, and it is difficult to accurately locate the brain target stimulation area during application, resulting in serious waste of the power of the stimulation device or poor stimulation effects and other problems.

[0072] The current transcranial magnetic stimulation instrument technology has not advanced accordingly, and most of the core technologies still adopt the circuit structure of discharging a high-voltage capacitor energy storage to a hollow coil.

[0073] Transcranial magnetic stimulation (TMS) technology is a magnetic stimulation technology that uses pulsed magnetic fields to act on the central nervous system (mainly the brain), changes the membrane potential of cortical nerve cells, causes induced current to be generated, affects cerebral metabolism and nerve electrical activities, and thus causes a series of physiological and biochemical reactions.

[0074] At present, the application of transcranial magnetic stimulation technology (TMS) is very extensive, but the mechanism of its treatment for PD is unclear. Clinically, the parameters of repetitive transcranial magnetic stimulation technology (TMS) used to treat Parkinson's disease are diverse, resulting in uneven treatment effects.

[0075] Therefore, it is urgent to study how TMS specifically improves Parkinson's motor disorders and how to treat and improve brain nerve defects including PD motor defects, and to form a practical treatment plan.

[0076] Figure 1 The forward excitation type stimulation coil drive circuit diagram adopted by existing transcranial magnetic stimulator products is shown.

[0077] Figure 2 Shown in Figure 1 The schematic diagram of the change process of the magnetic induction electric field intensity of the stimulation coil of the existing product shown.

[0078] As Figure 1 and Figure 2 Shown, the working process is to first charge the capacitor C through the switch S11, then disconnect S11 and close S12 to discharge the coil, thereby obtaining a stimulating magnetic pulse. R12 is a damping resistor to prevent the RC circuit from oscillating.

[0079] To obtain sufficient stimulation intensity, the voltage V+ is usually several thousand volts, the capacitance C is several hundred uF, and the coil inductance is about 20 uH. At present, companies such as Magstim in the UK and Nexstim in Finland have mature products for sale, and there are also many domestic companies providing similar instruments.

[0080] Therefore, the instruments designed based on the above circuit in the current market all have the following disadvantages:

[0081] Disadvantage 1: The range of the stimulating inductance coil is too large, making it difficult to accurately locate the target stimulation area in the brain. To obtain sufficient inductance of the stimulation coil (the stimulation loop efficiency is determined by the ratio of the coil inductive reactance to the loop impedance), the current coil sizes are relatively large, mostly with diameters between 40 - 70 mm, and the position with the maximum magnetic field intensity is the annular area near the coil winding, and the magnetic field intensity at the coil center is much weaker. It is difficult to achieve precise positioning of the stimulated brain area. With the development of the research on the biological mechanism of transcranial magnetic stimulation, the precise positioning of the stimulation area has been put on the agenda. The existing equipment cannot achieve stimulation positioning due to the overly large stimulation coverage area. For research work using small experimental animals (such as rats), these devices cannot be used at all. In addition, the controllable stimulation parameters are limited.

[0082] Disadvantage 2: The device is large and expensive to manufacture, making it unsuitable for home use. While transcranial magnetic stimulation can quickly and significantly alleviate symptoms of neurological disorders, most conditions return after a period of time, requiring periodic transcranial magnetic therapy. The best treatment option is for patients to administer the therapy themselves at home.

[0083] Disadvantage 3: Safety Issues. Existing stimulation coil discharge circuits typically operate at voltages of several thousand volts, with discharge currents ranging from several thousand to tens of thousands of amperes. The stimulation coils require water cooling, which places high demands on production processes while also compromising safety.

[0084] Based on the above considerations, the present invention also provides a transcranial magnetic stimulation circuit for the specific implementation of TMS treatment, which can effectively narrow the range of the stimulation probe and accurately locate the target stimulation area of the brain. It can to a certain extent solve the problems that current equipment is difficult to accurately locate the target stimulation area of the brain, resulting in serious power waste of the stimulation equipment or poor stimulation effect.

[0085] The technical solution for the TMS treatment device provided in this application includes a transcranial magnetic stimulation coil probe and multiple drive circuits. These technologies can effectively reduce the probe's range of action and accurately locate the target brain stimulation area. This addresses the problem with existing transcranial magnetic therapy devices, where the probe's wide stimulation range can stimulate irrelevant brain areas outside the target area, resulting in suboptimal treatment effects and potentially causing multiple side effects.

[0086] The operating voltage and current used in the technology of this application are significantly lower than those of traditional circuits, so that a compact, lightweight and safer home model can be designed to adapt to the characteristics of brain and nerve diseases that require periodic and repeated treatment.

[0087] First, the present application provides a set of device functional components for improving the performance of a transcranial magnetic stimulation (TMS) therapeutic device, wherein the functional components include a magnetic field stimulation coil probe and a probe driving circuit.

[0088] Functional components achieve performance improvements by working in the following ways:

[0089] (1) By reducing the time course of the stimulation coil current change, the rate of change of the stimulation coil current is increased, thereby increasing the pulse intensity of the magnetic induction electric field. (2) By adding a reverse magnetizing permanent magnet to the stimulation coil core, or by reverse pre-magnetizing the stimulation coil by loading current on the reverse pre-magnetization coil, the dynamic range of the magnetic field of the stimulation coil core is expanded, thereby increasing the action time of the magnetic induction electric field, that is, the pulse width of the magnetic induction electric field. (3) The in-situ heat dissipation technology combined with the above two points can greatly reduce the power consumption of the stimulation coil, and can achieve miniaturization of the stimulation area, providing the premise for precise positioning of transcranial magnetic therapy. (4) The above three types of technical solutions can be used independently or in combination.

[0090] The circuit for implementing the performance improvement method (1) is as Figure 7 shown: L1 is the stimulating inductance coil, S1 is the coil current control switch, C1 is the energy storage capacitor of the drive circuit, C2 is the stimulating waveform correction capacitor, and R is the stimulating waveform correction resistor. The specific device connection method is as follows: The energy storage capacitor C1 is connected between the power supply and the ground. The stimulating coil L1 and the coil current control switch S1 are connected in series between the power supply and the ground. The stimulating waveform correction capacitor C2 and the stimulating waveform correction resistor R are connected in series and then connected in parallel across the coil current control switch S1.

[0091] There are 4 schemes for implementing the performance improvement method (2): (1) Install a permanent magnet on the coil core to perform reverse pre-magnetization on the coil core. The device is as Figure 6 shown; (2) The current reverse pre-magnetization circuit is as Figure 12 shown; (3) The asymmetric full-bridge drive circuit is as Figure 9 shown; (4) The asymmetric full-bridge drive circuit is as Figure 11 shown.

[0092] As Figure 6 shown, install a permanent magnet on the coil core to perform reverse pre-magnetization on the coil core. The specific method is as follows: Install a permanent magnet on the magnetic stimulation coil core to form a pre-magnetization magnetic field on the stimulating coil core. The direction of this magnetic field is opposite to the driving current of the magnetic stimulation coil, so that the magnetic stimulation coil can pass a larger current without saturation, thereby increasing the dynamic range of the core magnetic field.

[0093] The current reverse pre-magnetization circuit is as Figure 12 shown. Among them, L 刺激 is the magnetic stimulation coil, L2 is the reverse pre-magnetization coil of the stimulating coil core, C6 is the energy storage capacitor of the pre-magnetization circuit, S8 is the switch of the pre-magnetization circuit, and L6 is the pre-magnetization constant current inductor.

[0094] The specific device connection method is as follows: The energy storage capacitor C6 is connected between the power supply and the ground. The pre-magnetization circuit switch S8, the pre-magnetization constant current inductor L6, and the reverse pre-magnetization coil L2 of the core are connected in series between the power supply and the ground. The reverse pre-magnetization coil L2 of the core and the magnetic stimulation coil L 刺激 are coupled through the core.

[0095] The asymmetric full-bridge drive circuit is as Figure 9 shown: Among them, L3 is the magnetic stimulation coil, L2 is the reverse pre-magnetization constant current inductor, S2, S3, S4, and S5 form two switch arms of the bridge to control the on-off and direction of the current of the stimulating coil L3, and C3 is the energy storage capacitor of the drive circuit.

[0096] The specific device connection method is as follows: The energy storage capacitor C3 is connected between the power supply and the ground. The power switches S5 and S2 are connected in series to form a symmetric bridge arm of the full bridge and are connected between the power supply and the ground. The power switches S3, S4, and the constant current inductor L2 are connected in series to form an asymmetric bridge arm of the full bridge and are connected between the power supply and the ground. The magnetic stimulation coil L3 is connected across the middle of the two bridge arms.

[0097] The asymmetric half-bridge drive circuit is as Figure 11 shown: where L4 is the magnetic stimulation coil, L5 is the reverse pre-magnetization constant current inductor, the energy storage capacitors C4 and C5 form a bridge arm of the bridge, and the power switches S6, S7 and the constant current inductor L5 are connected in series to form the switching bridge arm of the bridge, controlling the on / off and direction of the current in the stimulation coil L3. The voltage regulator devices DW1, DW2 and the resistor R form the voltage equalization circuit of C4 and C5.

[0098] The specific device connection method is as follows: The energy storage capacitors C3 and C4 are connected in series to form a symmetric bridge arm of the full bridge and are connected between the power supply and the ground. The power switches S6, S7, and the constant current inductor L2 are connected in series to form an asymmetric bridge arm of the full bridge and are connected between the power supply and the ground. The magnetic stimulation coil L4 is connected across the middle of the two bridge arms. The voltage regulator devices DW1 and DW2 are connected in series between the power supply and the ground. The series midpoint of the voltage regulator devices DW1 and DW2 and the series midpoint of the energy storage capacitors C3 and C4 are connected through R.

[0099] The in-situ heat dissipation technology is as Figure 15 shown: The heat generated by the magnetic stimulation coil is forced to conduct to the heat sink through the semiconductor refrigeration device, keeping the temperature of the magnetic core at room temperature, and the heat transferred to the heat sink is dissipated in-situ by active or passive means.

[0100] An example of the combined use of multiple technologies is as Figure 16 shown: This application scheme is an example of the combined use of two technologies, namely the flyback magnetic stimulation coil drive circuit and the current reverse pre-magnetization circuit. Among them, the energy storage capacitor C7, the stimulation coil L 刺激 , the power switch S10, the stimulation waveform correction capacitor C8 and the stimulation waveform correction resistor R form the flyback coil drive circuit as Figure 8 shown.

[0101] The energy storage capacitor C7, the reverse pre-magnetization coil L9, and the reverse pre-magnetization power switch S9 form Figure 12The current reverse pre-magnetization circuit shown; R and D form an absorption circuit to absorb the energy released in L8 and L9 when the power switch S9 of the current reverse pre-magnetization circuit is turned off. To make the technical solutions and advantages in the embodiments of the present application clearer and more understandable, the exemplary embodiments of the present application will be further described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than an exhaustive list of all embodiments. It should be noted that, without conflict, the embodiments in the present application and the features in the embodiments can be combined with each other.

[0102] Embodiment 1

[0103] Figure 19 The structural schematic diagram of the TMS stimulation device according to the embodiment of the present application is shown.

[0104] As Figure 19 shown, the TMS stimulation device includes a transcranial magnetic stimulation circuit and a control unit. The control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal.

[0105] Among them, the transcranial magnetic stimulation circuit includes a coil driving circuit, and the coil driving circuit includes a charging switch unit, a capacitor energy storage unit, and an electromagnetic induction unit.

[0106] Specifically, the coil driving circuit stores energy for the capacitor energy storage unit by controlling the charging switch unit and drives the electromagnetic induction unit to generate a magnetic induction electric field to form a coil driving loop.

[0107] The coil driving circuit increases the change rate of the stimulation coil current, thereby increasing the magnetic induction electric field intensity; and / or the coil driving circuit expands the dynamic range of the electromagnetic field of the stimulation coil through reverse pre-magnetization of the magnetic core of the stimulation coil, thereby increasing the action time of the magnetic induction electric field.

[0108] Figure 20 The principle schematic diagram of the TMS stimulation device according to the embodiment of the present application is shown.

[0109] As Figure 20 shown, the TMS stimulation device includes modules such as a touch screen, a single-chip microcomputer, a signal buffer driver, a switch component, a stimulation coil, and a coil driving power supply. Among them, the single-chip microcomputer integrates the transcranial magnetic stimulation circuit of the present application. For details, please refer to Figure 16 , which will be further described in detail later.

[0110] Furthermore, the present application can develop a very small desktop transcranial magnetic stimulator (for experimental animals) compared with market machines and achieve good results in experiments.

[0111] In a specific example, the cross-section of the instrument stimulation coil core of the stimulation device of the present application is 10 mm × 10 mm, and the specification of the stimulation end is 4 mm × 4 mm. When the machine stimulation probe operates at a magnetic field strength of 1.5 T, it can generate a magnetic induction electric field strength greater than that of the existing conventional transcranial magnetic stimulation probe at a magnetic field strength of 7 T.

[0112] The driving voltage of the probe stimulation coil in the embodiment of the present application is only 200 V, the current is less than 150 A, and the heat generation of the probe coil is only 1% of that of the conventional instrument. When the stimulation intensity is set to the maximum and the stimulation frequency is 5 Hz, the heat generation problem can be ignored.

[0113] The average power consumption of the coil driving circuit in the embodiment of the present application is 0.5 W, and the overall power consumption of the instrument is 4.5 W. After optimizing the circuit, the power consumption can be further reduced, and based on this, a "pocket machine" that can be applied to human treatment and powered by a battery is developed.

[0114] Figure 3 The circuit structure diagram of the transcranial magnetic stimulation circuit according to the embodiment of the present application is shown.

[0115] As Figure 3 shown, the transcranial magnetic stimulation circuit includes a coil driving circuit, a charging switch unit 10, a capacitor energy storage unit 20, and an electromagnetic induction unit 30.

[0116] The charging switch unit 10 stores energy for the capacitor energy storage unit 20 and drives the electromagnetic induction unit 30 to generate a magnetic induction electric field to form a coil driving loop.

[0117] The coil driving circuit increases the magnetic induction electric field strength by increasing the change rate of the stimulation coil current; and / or the coil driving circuit increases the action time of the magnetic induction electric field by expanding the dynamic range of the stimulation coil electromagnetic field.

[0118] Preferably, the controller increases the magnetic induction electric field strength by increasing the change rate of the stimulation coil current; the controller expands the dynamic range of the stimulation coil electromagnetic field by reverse pre-magnetizing the core of the stimulation coil, thereby increasing the action time of the magnetic induction electric field.

[0119] First, the inventors of the present application obtained the model of neurons under the action of an electric field based on the principle of transcranial magnetic stimulation and the biological model.

[0120] Figure 4 The schematic diagram of the model of neurons under the action of an electric field according to the embodiment of the present application is shown.

[0121] As Figure 4As shown in the figure, in the model diagram of a neuron under the action of an electric field, C11 and C12 respectively represent the membrane capacitances of the two hemispherical surfaces of the neuron perpendicular to the electric field direction, with a capacitance of several to dozens of PF. R14 is the equivalent resistance of the intracellular fluid, R13 and R15 are the equivalent resistances of the extracellular fluid, and R11 and R12 are the transmembrane resistances of the two hemispherical surfaces of the cell membrane. In the resting state of the cell, the resistance values of R11 and R12 are very large, while the resistance values of R13, R14, and R15 are very small (in the order of kiloohms). It can be calculated that the time constant of the neuron model is less than the microsecond order. Also, since the opening of the cell voltage-gated channel has no requirement for the depolarization time of the transmembrane voltage, as long as the stimulation intensity is satisfied, a stimulation of the uS order is sufficient to cause facilitation or firing of the neuron. In fact, the magnetic stimulation pulses used by researchers have been reduced from the initial about 2000 uS to about 100 uS.

[0122] Considering the reasons for the existing equipment problems, according to Faraday's law of electromagnetic induction: e = -n(dΦ) / (dt), the stimulation intensity e is proportional to the change rate of the magnetic field intensity. Therefore, it can be considered from two aspects: increasing dΦ and decreasing dt. Currently, air-core coils (which do not undergo magnetic saturation) are used in the market, and the coil diameter is very large, mainly to obtain as large a magnetic flux as possible: Φ = BS. However, due to the very low magnetic permeability of the air-core coil, a very large coil excitation current (thousands to tens of thousands of amperes) is required, resulting in serious heating and the need for water cooling. This leads to inaccurate stimulation sites in current transcranial magnetic stimulation equipment, restricting the application scenarios. The strict production technology and high cost also make it unfavorable for promotion.

[0123] Based on this, the embodiments of this application mainly propose various improvement methods for the transcranial magnetic stimulation circuit through the following improvement ideas and corresponding circuit diagrams. The embodiments of this application are described through six improvement ideas: Improvement idea one, by adding a soft magnetic core in the coil, increasing the magnetic permeability of the magnetic circuit, and achieving a larger magnetic field intensity with a smaller current; Improvement idea two, improving the working mode of the coil drive to increase the change rate of the coil current; Improvement idea three, using the bidirectional magnetic field of the coil to expand the dynamic range of the stimulation magnetic field; Improvement idea four, applying a current to the bias magnetic winding to form a bias magnetic opposite to the working excitation direction of the stimulation winding. On this basis, the magnetic stimulation winding effectively uses the bidirectional magnetization space of the magnetic core to obtain a double magnetic field dynamic range; Improvement idea five, by changing the shape of the soft magnetic core, the required magnetic field stimulation range can be obtained; Improvement idea six, adopting the probe semiconductor cooling technology. The technologies of the above improvement ideas can be freely combined according to actual needs.

[0124] Regarding improvement idea one, by adding a soft magnetic core in the coil, increasing the magnetic permeability of the magnetic circuit, and achieving a larger magnetic field intensity with a smaller current. It effectively reduces the volume and heat generation of the coil.

[0125] Figure 5A schematic diagram showing the acquisition of a required stimulation range by changing the shape of a coil core according to an embodiment of the present application is shown.

[0126] As Figure 5 shown, it is more beneficial to increase the magnetic permeability by increasing the core structure.

[0127] Figure 6 A schematic diagram of reverse pre-magnetization of a permanent magnet of a coil core according to an embodiment of the present application is shown.

[0128] As Figure 6 shown, a permanent magnet is added to the core of the stimulation winding to keep the core with a reverse bias magnetic field, which increases the dynamic range of the magnetic field of the stimulation coil to a certain extent.

[0129] The specific method is: a permanent magnet is installed on the core of the magnetic stimulation coil to form a pre-magnetized magnetic field on the core of the stimulation coil, and the direction of this magnetic field is opposite to the driving current of the magnetic stimulation coil, so that the magnetic stimulation coil can pass a larger current without saturation, thereby increasing the dynamic range of the magnetic field of the core.

[0130] In the embodiment of the present application, by setting a soft magnetic core in the stimulation coil or adding a permanent magnet with a reverse bias magnetic field on the original core, it is used to increase the magnetic permeability of the magnetic circuit of the stimulation coil.

[0131] Regarding the second improvement idea, the working mode of the coil drive is improved to increase the change rate of the coil current.

[0132] Figure 7 The coil drive circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application is shown Figure 1 . That is, a flyback drive circuit.

[0133] As Figure 7 shown, the charging switch unit is the first electronic switch S1; the capacitor energy storage unit includes the first capacitor C1; the electromagnetic induction unit includes the first inductance coil L1; the first inductance coil L1 is the stimulation coil. The transcranial magnetic stimulation circuit further includes a second capacitor C2 and a stimulation waveform correction resistor R.

[0134] Specifically, the input terminal V+ of the drive power supply is connected to one end of the first capacitor C1 and one end of the first inductance coil L1, and the other end of the first capacitor C1 is grounded; the other end of the first inductance coil L1 is connected to the ground in series with the first electronic switch S1, and the other end of the first inductance coil L1 is also connected to the ground in series with the stimulation waveform correction resistor R and the second capacitor C2 in sequence.

[0135] Figure 7The flyback stimulation coil drive circuit to be adopted, C1 is an energy storage capacitor that instantaneously provides high-power energy output for the magnetic stimulation circuit, L1 is the stimulation coil, S1 is an electronic switch device, and the electronic switch device can be a power electronic switch device such as a bipolar junction transistor (BJT), a field effect transistor (FET), an insulated gate bipolar transistor (IGBT), or a gate turn-off thyristor (GTO) (the same applies to other circuits below as S1). C2 is a damping capacitor, and R is a stimulation waveform correction resistor. The two are connected in series to adjust the rate of change of the current in the stimulation coil L1 and prevent the switch device S1 from being broken down by the high voltage generated by L1.

[0136] Figure 8 shows the Figure 7 schematic diagram of the magnetic induction electric field intensity of the drive circuit according to an embodiment of the present application.

[0137] As Figure 8 shown, at the beginning of operation, S1 is closed under the drive of the control signal, and the drive current in the stimulation coil L1 increases linearly. When a certain current value (less than the magnetic core saturation current value) is reached, S1 is turned off, and the inductor current flows to C2 and decreases rapidly. After C2 is charged to the maximum value, it discharges through L1. The pulse width of the magnetic induction electric field is determined by L1 and C1, and the amplitude is determined by the current in the stimulation coil at the moment when S1 is turned off. The stimulation waveform correction resistor R prevents the magnetic induction electric field from oscillating and reduces the loss caused by the energy stored in C2 before S1 is turned on on S1.

[0138] Different from the traditional coil drive circuit, in the embodiment of the present application, since R is not connected in series in the drive loop and no additional loss is generated, the drive efficiency of this circuit is very high (two orders of magnitude higher), and a very low drive voltage (several hundred volts) and drive current (several hundred amperes) can be used. At the same time, the drive time is reduced, which is beneficial to increasing the rate of change of the coil current.

[0139] Regarding the third improvement idea, the bidirectional magnetic field of the coil is used to expand the dynamic range of the stimulation magnetic field.

[0140] Figure 9 shows the coil drive circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application Figure 2 . That is, an asymmetric full-bridge drive circuit.

[0141] Figure 10 shows the Figure 9 shown coil magnetic core bias magnetization and magnetic induction electric field intensity change diagram according to an embodiment of the present application.

[0142] As Figure 9As shown, the charging switch unit includes a second electronic switch S2, a third electronic switch S3, a fourth electronic switch S4, and a fifth electronic switch S5; the capacitive energy storage unit includes a third capacitor C3; the electromagnetic induction unit includes a third inductance coil L3; the third inductance coil L3 is a stimulation coil. The transcranial magnetic stimulation circuit further includes a second inductance coil L2, and the second inductance coil L2 is a constant current inductor.

[0143] Specifically, the driving power input terminal V+ is connected to one end of the third capacitor C3, and the other end of the third capacitor C3 is grounded; the driving power input terminal V+ is connected to the ground after sequentially connecting the fifth electronic switch S5 and the second electronic switch S2 in series; the driving power input terminal V+ is connected to the ground after sequentially connecting the second inductance coil L2, the third electronic switch S3, and the fourth electronic switch S4 in series; one end of the third electronic switch S3 is connected to the second inductance coil L2, and the other end is connected to one end of the third inductance coil L3. The other end of the third inductance coil L3 is connected to the common terminal of the fifth electronic switch S5 and the second electronic switch S2.

[0144] Figure 9 It is an asymmetric full-bridge coil driving circuit. C is the energy storage capacitor that instantaneously provides high-power energy output for the magnetic stimulation circuit. L3 is the stimulation coil, and L2 is the constant current inductor, which is connected in series in the circuit to reduce the current rising rate of L3. S2, S3, L3, and L2 form a slow bridge arm, and S5, S4, and L3 form a fast bridge arm. The magnetic induction electric field generated when the slow bridge arm conducts is very small (determined by L3 / L2).

[0145] As Figure 10 shown, the magnetic induction electric field caused by the conduction of the fast bridge arm is the transcranial magnetic stimulation electric field. When the two bridge arms work alternately, both magnetization directions of the magnetic core are utilized, increasing the magnetic field range between point B and point C, which is beneficial to improving the coil stimulation intensity.

[0146] In this embodiment, the inductive energy storage will finally return to the power supply, and there is no additional energy loss in the circuit. The reduction of energy consumption is beneficial to the miniaturized design of the device. All parameters of the magnetic induction electric field intensity generated by this driving circuit are very easy to control, which is suitable for designing experimental instruments.

[0147] Figure 11 shows the coil driving circuit structure of the transcranial magnetic stimulation circuit according to an embodiment of the present application Figure 3 . That is, an asymmetric half-bridge driving circuit, and its coil core bias magnetization and magnetic induction electric field intensity change as Figure 10 shown.

[0148] As Figure 11 shown, it is an asymmetric half-bridge coil driving circuit, and its working principle is similar to that of the Figure 9 full-bridge circuit. The variation law of the stimulation coil bias magnetization and magnetic induction electric field is as Figure 10 shown.

[0149] In the transcranial magnetic stimulation circuit, the charging switch unit includes a sixth electronic switch S6 and a seventh electronic switch S7; the capacitive energy storage unit includes a fourth capacitor C4 and a fifth capacitor C5; the electromagnetic induction unit includes a fourth inductance coil L4, and the fourth inductance coil L4 is a stimulation coil.

[0150] The transcranial magnetic stimulation circuit further includes a fifth inductance coil L5, a first zener diode DW1, a second zener diode DW2, and a voltage stabilizing resistor; the fifth inductance coil L5 is a constant current inductor; the first zener diode DW1, the second zener diode DW2, and the voltage stabilizing resistor form a voltage balancing circuit.

[0151] Figure 11 Among them, C4 and C5 are energy storage capacitors, which respectively provide instantaneous high-power energy output for reverse bias magnetization of the stimulation coil and stimulation pulse output. The zener diodes DW1, DW2, and R form a voltage balancing circuit for C4 and C5 to limit the voltage variation range of C4 and C5. L4 is the stimulation coil, and L5 is a constant current inductor to limit the current rising rate in L4. During operation, S6 is first turned on to magnetize the stimulation coil with a low-variation-rate current. When the set current value is reached, S6 is turned off, and S7 is turned on simultaneously to generate a magnetic stimulation pulse.

[0152] Specifically, the driving power input terminal V+ is grounded after being sequentially connected in series with the fourth capacitor C4 and the fifth capacitor C5; the driving power input terminal V+ is grounded after being sequentially connected in series with the fifth inductance coil L5, the sixth electronic switch S6, and the seventh electronic switch S7; the common terminal of the sixth electronic switch S6 and the seventh electronic switch S7 is connected to one end of the fourth inductance coil L4, and the other end of the fourth inductance coil L4 is connected to one end of the fourth inductance coil L4, and the other end of the first inductance coil L1 is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5.

[0153] The driving power input terminal is grounded after being sequentially connected in series with the first zener diode DW1 and the second zener diode DW2; the common connection point of the first zener diode DW1 and the second zener diode DW2 is connected to one end of the voltage stabilizing resistor, and the other end of the voltage stabilizing resistor is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5.

[0154] Regarding the fourth improvement idea, a current is applied to the bias winding to form a bias magnetic field opposite to the working excitation direction of the stimulation winding. On this basis, the magnetic stimulation winding effectively uses the double-direction magnetization space of the magnetic core to obtain a double magnetic field dynamic range.

[0155] Figure 12 It shows the auxiliary coil reverse pre-magnetization circuit diagram of the transcranial magnetic stimulation circuit according to the embodiment of the present application. Figure 13 It shows Figure 12 The shown auxiliary coil reverse pre-magnetization extended magnetic field dynamic range change diagram.

[0156] As Figure 12 shown, the transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, which includes a sixth inductor coil L6, a seventh inductor coil L7, an eighth electronic switch S8, and a sixth capacitor C6.

[0157] Specifically, the drive power input terminal is connected to the sixth capacitor C6 and then grounded. The drive power input terminal is sequentially connected to the eighth electronic switch S8, the sixth inductor coil L6, and the seventh inductor coil L7 and then grounded. The seventh inductor coil L7 is a pre-magnetization bias winding, and the seventh inductor coil L7 is coupled in the same direction as the stimulation winding in the coil drive circuit. The sixth inductor coil L6 is a constant current coil.

[0158] Figure 12 is the auxiliary coil reverse pre-magnetization circuit. L6 and L7 are magnetic core stimulation coil windings. Among them, the right-side L7 is the stimulation winding, and the left-side L6 is the pre-magnetization bias winding. During operation, a current is first applied to the bias winding to form a bias magnetic field opposite to the working excitation direction of the stimulation winding. On this basis, the magnetic stimulation winding effectively uses the bidirectional magnetization space of the magnetic core to obtain a double magnetic field dynamic range. See Figure 13 , the magnetic field dynamic range is extended from ΔB1 to ΔB2. L6 is a constant current coil to ensure that the current in the reverse pre-magnetization coil remains basically unchanged during the excitation process of the stimulation winding.

[0159] Regarding improvement idea five, by changing the shape of the soft magnetic core, the required magnetic field stimulation range can be obtained.

[0160] Figure 14 shows a schematic structural diagram of a stimulation probe for obtaining a required magnetic stimulation range by changing the shape of the magnetic core according to an embodiment of the present application.

[0161] As Figure 14 shown, according to the different spatial ranges required for treatment or experiments, the magnetic core can be processed into stimulation end faces with different shapes and sizes to effectively ensure the accuracy of the magnetic stimulation range.

[0162] Regarding improvement idea six, the probe semiconductor cooling technology is adopted.

[0163] Figure 15 shows a schematic structural diagram of in-situ heat dissipation of a probe semiconductor according to an embodiment of the present application.

[0164] The heat generated by the magnetic stimulation coil is forcibly conducted to the heat sink through the magnetic core by a semiconductor refrigeration device to keep the temperature of the magnetic core at room temperature, and the heat transferred to the heat sink is dissipated in-situ by an active or passive method.

[0165] As Figure 15As shown, it is a structure that effectively reduces the heat of the stimulating core using a semiconductor refrigerator. The radiator is made of an insulating material with a relatively high thermal conductivity to avoid affecting the operation of the stimulating coil.

[0166] In summary, the above improvement ideas and technologies can be freely combined according to actual needs.

[0167] One combination idea is the comprehensive application of a flyback coil drive circuit and an auxiliary coil reverse pre-magnetization circuit.

[0168] Figure 16 The figure shows a circuit diagram of the comprehensive application of two technologies, namely, reverse pre-magnetization of the stimulating coil core and increasing the rate of change of the stimulating coil current, according to an embodiment of the present application. Figure 17 For the embodiment according to the present application Figure 16 Single-pulse signal timing diagram of a transcranial magnetic stimulation coil.

[0169] As Figure 16 shown, in the transcranial magnetic stimulation circuit, the charging switch unit includes the tenth electronic switch S10; the capacitor energy storage unit includes the seventh capacitor C7; the electromagnetic induction unit includes the inductive stimulating coil L 刺激 ; the transcranial magnetic stimulation circuit further includes the eighth capacitor C8 and a damping resistor.

[0170] The transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, which includes the eighth inductive coil L8, the ninth inductive coil L9, the ninth electronic switch S9, a voltage stabilizing resistor, and a voltage stabilizing diode. The ninth inductive coil L9 and the inductive stimulating coil L 刺激 are coupled in the same direction.

[0171] Specifically, the driving power input terminal V+ is connected to the seventh capacitor C7 and then grounded; the driving power input terminal is sequentially connected to the inductive stimulating coil L 刺激 , the damping resistor, and the eighth capacitor C8 and then grounded; the tenth electronic switch S10 forms a branch in parallel with the voltage stabilizing resistor and the voltage stabilizing diode; the driving power input terminal V+ is sequentially connected to the eighth inductive coil L8, the ninth inductive coil L9, and the ninth electronic switch S9 and then grounded; the driving power input terminal is sequentially connected to the voltage stabilizing resistor, the voltage stabilizing diode, and the ninth electronic switch S9 and then grounded.

[0172] As Figure 16 shown, it is a comprehensive application of a flyback coil drive circuit and an auxiliary coil reverse pre-magnetization circuit. In the figure, C7 is an energy storage capacitor, S10, the stimulation waveform correction resistor R, C2, and the inductive stimulating coil L 刺激A flyback stimulation coil drive circuit is formed. S9 and the ninth inductor coil L9 are the reverse drive windings of the L9 coil core, and L8 is a constant current inductor that limits the rate of change of the current in L9. The pre-magnetization circuit flyback absorption resistor R0 and the zener diode D form a damping circuit to release the energy stored in L8 and L9 after S9 is turned off.

[0173] Figure 17 This is the timing relationship of various signals in the stimulation coil. During operation, S9 is turned on first, and the reverse magnetization current in L9 rises slowly due to the limitation of L8. The rate of increase of the magnetization current in the inductive stimulation coil L 刺激 is much greater than that in L9. When the forward magnetization intensity of the core reaches Bm, S10 is turned off. The rate of change of the current in the inductive stimulation coil L 刺激 is jointly determined by L 刺激 , the stimulation waveform correction resistor R, and C2, that is, it determines the magnetically induced electric field intensity caused by the stimulation coil, that is, the magnetic stimulation intensity. Then S9 is disconnected, and the energy stored in L8 and L9 is released through the circuit formed by the pre-magnetization circuit flyback absorption resistor R0 and the diode D.

[0174] The embodiments of the present application achieve the following technical effects through the above improved circuit:

[0175] 1) By improving the flyback coil in Idea 2, the drive circuit effectively realizes the rapid switching of the coil current, so as to achieve the magnetically induced electric field intensity (stimulation intensity) of the traditional drive circuit (kilovolt level, kiloampere to megaampere level) under low drive voltage (hundred-volt level) and small current (hundred-ampere level), effectively reducing the power consumption of the coil and the instrument (below 1%). Under low-frequency stimulation (several Hz), the stimulation coil does not require active cooling at all. It is very beneficial to the miniaturization of the device, and a portable machine or pocket machine can be made.

[0176] 2) The application of the bidirectional magnetic flux of the core enables the stimulation coil of the same size to generate a greater magnetically induced electric field intensity (stimulation intensity), which is beneficial to the improvement of the stimulation efficiency (intensity and depth) and the miniaturization of the stimulation coil.

[0177] 2) Through the asymmetric full-bridge and half-bridge coil drive circuits, the energy stored in the stimulation coil can be fed back to the power supply, so as to obtain a regular magnetically induced electric field, which is very convenient for the quantization and control of stimulation parameters.

[0178] 3) By changing the shape of the core, different action ranges of the stimulation magnetic field can be obtained to facilitate the precise positioning of the stimulation site. For experimental animals such as mice and rats, the action range of the magnetic field must be small enough to implement the experimental project.

[0179] In this application, considering that for most neurons, after being stimulated by a magnetic field pulse, they return to the pre-stimulus state after several milliseconds, it can be expected that in future research or treatment, stimulation frequencies reaching dozens to hundreds of Hz may be used. At this time, the stimulation coil and the magnetic core will generate severe heat. For a small-sized magnetic core coil, a semiconductor refrigerator will be an effective heat dissipation method.

[0180] In summary, by adopting a TMS stimulation device of this application, which includes a transcranial magnetic stimulation circuit and a control unit, the control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal. Through the TMS treatment device targeting the cerebellar cortex of the user, brain nerve defects including PD motor defects can be significantly improved. The transcranial magnetic stimulation circuit provided by the embodiments of this application can, to a certain extent, solve the problems that the current equipment is difficult to accurately locate the brain target stimulation area, resulting in serious waste of the power of the stimulation device or poor stimulation effect.

[0181] Through the provided transcranial magnetic stimulation coil probe and various drive circuits of this application, a small, portable and safer home model can be designed to adapt to the characteristics of the need for periodic and repeated treatment of cranial nerve diseases. It can effectively reduce the action range of the stimulation probe and accurately locate the brain target stimulation area, solving the problems that the existing transcranial magnetic therapy instrument has an overly large stimulation range of the probe, stimulating irrelevant brain areas outside the treatment target area, resulting in an unsatisfactory treatment effect and possibly causing various side effects.

[0182] Embodiment 2

[0183] Figure 18 The schematic diagram of the steps of the TMS stimulation method according to the TMS stimulation device of this application is shown.

[0184] As Figure 18 shown, the TMS stimulation method includes the following steps:

[0185] S1: Generate a continuous and repetitive magnetic field stimulation signal through the magnetic induction electric field of the transcranial magnetic stimulation circuit;

[0186] S2: The magnetic field stimulation signal acts on at least one target point, and the target point includes the cerebellar cortex area of the patient; the magnetic field stimulation signal enhances the functional connection with the substantia nigra pars compacta by activating cerebellar nuclear neurons, thereby improving brain nerve defects. Preferably, the frequency of the magnetic field stimulation signal is 1 Hz.

[0187] Specifically in implementation, it includes: the magnetic field stimulation signal acts on the cerebellar cortex area, stimulating or strengthening the loop connection between the patient's cerebellar nucleus CN and the substantia nigra pars compacta SNc; increasing the expression of the signaling molecule PKCι in the substantia nigra pars compacta SNc, thereby playing a role in improving motor symptoms.

[0188] It is found through research in this application that the functional connection between the cerebellar nuclei (CN) and the substantia nigra pars compacta (SNc) in PD patients is weakened. Based on this finding, a TMS stimulation method targeting the cerebellum is studied and provided. The frequency of the magnetic field stimulation signal is 1 Hz, which can significantly improve PD motor defects.

[0189] Example 3

[0190] This example provides a TMS stimulation device for improving PD motor defects. For details not disclosed in the TMS stimulation device of this example, please refer to the specific implementation content of the TMS stimulation method in other examples.

[0191] Figure 19 The structural schematic diagram of the TMS stimulation device according to the embodiment of the present application is shown.

[0192] As Figure 19 shown, the TMS stimulation device for improving PD motor defects includes a transcranial magnetic stimulation circuit and a control unit. The control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal.

[0193] Among them, the magnetic field stimulation signal acts on at least one target point, and the target point includes the cerebellar cortex area of the patient; the frequency of the magnetic field stimulation signal is 1 Hz.

[0194] Figure 20 The principle schematic diagram of the TMS stimulation device according to the embodiment of the present application is shown.

[0195] As Figure 20 shown, the TMS stimulation device includes modules such as a touch screen, a single-chip microcomputer, a signal buffer driver, a switch component, a stimulation coil, and a coil drive power supply. Among them, the single-chip microcomputer integrates the transcranial magnetic stimulation circuit of the present application. For details, please refer to Figure 16 .

[0196] Furthermore, the present application has developed a very small desktop transcranial magnetic stimulator (for experimental animals) compared with market machines, and good results have been obtained in experiments.

[0197] The cross-section of the magnetic core of the stimulation coil of this instrument is 10 mm × 10 mm, and the specification of the stimulation end is 4 mm × 4 mm. When the stimulation probe of this machine works at a magnetic field strength of 1.5 T, it can generate a magnetic induction electric field strength greater than that of the probe of the existing conventional transcranial magnetic stimulator at a magnetic field strength of 7 T.

[0198] The driving voltage of the probe stimulation coil is only 200 V, the current is less than 150 A, and the heat generated by the probe coil is only 1% of that of the conventional instrument. When the stimulation intensity is set to the maximum and the stimulation frequency is 5 Hz, the heat generation problem can be ignored.

[0199] The average power consumption of the coil drive circuit is 0.5 W, and the overall power consumption of the instrument is 4.5 W. After optimizing the circuit, the power consumption can be further reduced. Based on this, a "pocket machine" that can be applied to human treatment and powered by batteries is developed.

[0200] Correspondingly, the embodiment of the present application further provides a method for using a TMS stimulation device, including: the stimulation frequency of the TMS treatment device is 1-5 Hz; the depth of the action range is 0-7 mm, and the radius is 0-8 mm; the magnetic field intensity can reach 1.6 T; after repeatedly stimulating the target by using the classical repetitive transcranial magnetic stimulation method for multiple times, by analyzing the improvement of the brain defects of the target after stimulation at different frequencies, the transcranial magnetic stimulation parameters suitable for the current individual are determined.

[0201] Embodiment 4

[0202] This embodiment provides a transcranial magnetic stimulation system. For the details not disclosed in the transcranial magnetic stimulation system of this embodiment, please refer to the specific implementation content of the TMS stimulation method or device in other embodiments.

[0203] Figure 21 The structural schematic diagram of the transcranial magnetic stimulation system 400 according to the embodiment of the present application is shown.

[0204] As Figure 21 shown, the transcranial magnetic stimulation system 400 includes: a storage unit 402: used to store executable instructions; and a processing unit 401: used to connect to the storage unit 402 to execute the executable instructions to complete the TMS stimulation method.

[0205] Those skilled in the art can understand that the schematic Figure 21 is only an example of the transcranial magnetic stimulation system 400, and does not constitute a limitation on the transcranial magnetic stimulation system 400. It may include more or fewer components than shown in the figure, or combine some components, or different components. For example, the transcranial magnetic stimulation system 400 may further include input / output devices, network access devices, buses, etc.

[0206] The so-called processing unit 401 (Central Processing Unit, CPU) can also be other general-purpose processors, digital signal processors (Digital Signal Processor, DSP), application-specific integrated circuits (ApplicationSpecific Integrated Circuit, ASIC), field-programmable gate arrays (Field-Programmable Gate Array, FPGA), or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor can be a microprocessor or the processing unit 401 can also be any conventional processor, etc. The processing unit 401 is the control center of the transcranial magnetic stimulation system 400, and connects all parts of the entire transcranial magnetic stimulation system 400 through various interfaces and lines.

[0207] The storage unit 402 can be used to store computer-readable instructions. The processing unit 401 realizes various functions of the transcranial magnetic stimulation system 400 by running or executing the computer-readable instructions or modules stored in the storage unit 402, and by calling the data stored in the storage unit 402. The storage unit 402 mainly includes a storage program area and a storage data area. Among them, the storage program area can store an operating system, application programs required for at least one function (such as a sound playback function, an image playback function, etc.); the storage data area can store data created according to the use of the transcranial magnetic stimulation system 400. In addition, the storage unit 402 can include a hard disk, memory, plug-in hard disk, smart media card (Smart Media Card, SMC), secure digital (Secure Digital, SD) card, flash card (Flash Card), at least one magnetic disk storage device, flash device, read-only memory (Read-Only Memory, ROM), random access memory (Random Access Memory, RAM), or other non-volatile / volatile storage devices.

[0208] If the modules integrated in the transcranial magnetic stimulation system 400 are implemented in the form of software function modules and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on such an understanding, to implement all or part of the processes in the above-mentioned embodiment methods of the present invention, it can also be completed by computer-readable instructions to instruct relevant hardware. The computer-readable instructions can be stored in a computer-readable storage medium. When the computer-readable instructions are executed by a processor, the steps of the above-mentioned various method embodiments can be implemented.

[0209] Embodiment 5

[0210] This embodiment provides a computer-readable storage medium, on which a computer program is stored; the computer program is executed by a processor to implement the TMS stimulation method in other embodiments.

[0211] In summary, by using the transcranial magnetic stimulation system and storage medium of the present application, through the TMS treatment device targeting the cerebellum, the frequency of the magnetic field stimulation signal is 1 Hz, which can significantly improve the PD motor defect. The provided transcranial magnetic stimulation circuit can, to a certain extent, solve the problems that the current equipment is difficult to accurately locate the brain target stimulation area, resulting in serious waste of the power of the stimulation device or poor stimulation effect.

[0212] Those skilled in the art should understand that the terms used in the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The singular forms "a", "the" and "said" used in the present invention and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term "and / or" used herein refers to and includes any and all possible combinations of one or more of the associated listed items.

[0213] It should be understood that although the terms first, second, third, etc. may be used in the present invention to describe various information, these information should not be limited to these terms. These terms are only used to distinguish the same type of information from each other. For example, without departing from the scope of the present invention, the first information may also be referred to as the second information, and similarly, the second information may also be referred to as the first information. Depending on the context, the word "if" as used herein may be interpreted as "when" or "while" or "in response to a determination".

[0214] Although the preferred embodiments of the present application have been described, those skilled in the art can make additional changes and modifications once they learn the basic creative concept. Therefore, the appended claims are intended to be construed to include the preferred embodiments and all changes and modifications falling within the scope of the present application.

[0215] Obviously, those skilled in the art can make various changes and modifications to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalent technologies, the present application is also intended to include these changes and modifications.

Claims

1. A TMS stimulation device, characterized in that, It includes a transcranial magnetic stimulation circuit and a control unit, and the control unit is used to control the transcranial magnetic stimulation circuit to generate a continuous and repetitive magnetic field stimulation signal; The transcranial magnetic stimulation circuit includes a coil driving circuit, and the coil driving circuit includes a charging switch unit, a capacitor energy storage unit, and an electromagnetic induction unit; By controlling the charging switch unit to store energy for the capacitor energy storage unit and driving the electromagnetic induction unit to generate a magnetic induction electric field to form a coil driving loop; The coil driving circuit increases the change rate of the stimulating coil current, thereby increasing the magnetic induction electric field intensity; And / or the coil driving circuit extends the dynamic range of the stimulating coil electromagnetic field through reverse pre-magnetization of the stimulating coil magnetic core, thereby increasing the action time of the magnetic induction electric field.

2. The TMS stimulation device according to claim 1, wherein In the transcranial magnetic stimulation circuit, the charging switch unit includes a first electronic switch S1; the capacitor energy storage unit includes a first capacitor C1; the electromagnetic induction unit includes a first inductance coil L1; The transcranial magnetic stimulation circuit further includes a second capacitor C2 and a damping resistor; the first inductance coil L1 is a stimulating coil; Specifically, the driving power input terminal is connected to one end of the first capacitor C1 and one end of the first inductance coil L1, and the other end of the first capacitor C1 is grounded; the other end of the first inductance coil L1 is connected to the ground after being connected in series with the first electronic switch S1, and the other end of the first inductance coil L1 is also connected to the ground after being connected in series with the damping resistor and the second capacitor C2 in sequence.

3. The TMS stimulation device according to claim 1, characterized in that, In the transcranial magnetic stimulation circuit, the charging switch unit includes a second electronic switch S2, a third electronic switch S3, a fourth electronic switch S4, and a fifth electronic switch S5; the capacitor energy storage unit includes a third capacitor C3; the electromagnetic induction unit includes a third inductance coil L3, and the third inductance coil L3 is a stimulating coil; The transcranial magnetic stimulation circuit further includes a second inductance coil L2, and the second inductance coil L2 is a constant current inductor.

4. The TMS stimulation device according to claim 3, characterized in that, The driving power input terminal is connected to one end of the third capacitor C3, and the other end of the third capacitor C3 is grounded; the driving power input terminal is connected to the ground after being connected in series with the fifth electronic switch S5 and the second electronic switch S2 in sequence; The driving power input terminal is connected to the ground after being connected in series with the second inductance coil L2, the third electronic switch S3, and the fourth electronic switch S4 in sequence; one end of the third electronic switch S3 is connected to the second inductance coil L2, and the other end is connected to one end of the third inductance coil L3, and the other end of the third inductance coil L3 is connected to the common terminal of the fifth electronic switch S5 and the second electronic switch S2.

5. The TMS stimulation device according to claim 1, characterized in that, In the transcranial magnetic stimulation circuit, the charging switch unit includes a sixth electronic switch S6 and a seventh electronic switch S7; the capacitor energy storage unit includes a fourth capacitor C4 and a fifth capacitor C5; the electromagnetic induction unit includes a fourth inductance coil L4, and the fourth inductance coil L4 is a stimulating coil; The transcranial magnetic stimulation circuit further includes a fifth inductance coil L5, a first zener diode DW1, a second zener diode DW2, and a voltage stabilizing resistor; the fifth inductance coil L5 is a constant current inductor; the first zener diode DW1, the second zener diode DW2, and the voltage stabilizing resistor form a voltage balancing circuit.

6. The TMS stimulation device according to claim 5, characterized in that, The drive power input terminal is grounded after being sequentially connected in series with the fourth capacitor C4 and the fifth capacitor C5; the drive power input terminal is grounded after being sequentially connected in series with the fifth inductance coil L5, the sixth electronic switch S6, and the seventh electronic switch S7; the common terminal of the sixth electronic switch S6 and the seventh electronic switch S7 is connected to one end of the fourth inductance coil L4, the other end of the fourth inductance coil L4 is connected to one end of the fourth inductance coil L4, and the other end of the first inductance coil L1 is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5; The drive power input terminal is grounded after being sequentially connected in series with the first zener diode DW1 and the second zener diode DW2; the common connection point of the first zener diode DW1 and the second zener diode DW2 is connected to one end of the voltage stabilizing resistor, and the other end of the voltage stabilizing resistor is connected to the common terminal of the fourth capacitor C4 and the fifth capacitor C5.

7. The TMS stimulation device according to claim 1, wherein, The transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, and the auxiliary coil reverse pre-magnetization circuit includes a sixth inductance coil L6, a seventh inductance coil L7, an eighth electronic switch S8, and a sixth capacitor C6.

8. The TMS stimulation device according to claim 7, characterized in that, The drive power input terminal is grounded after being connected to the sixth capacitor C6, and the drive power input terminal is grounded after being sequentially connected to the eighth electronic switch S8, the sixth inductance coil L6, and the seventh inductance coil L7; the seventh inductance coil L7 is a pre-magnetization bias winding, and the seventh inductance coil L7 is coupled in the same direction as the stimulation winding in the coil drive circuit; the sixth inductance coil L6 is a constant current coil.

9. The TMS stimulation device according to claim 1, characterized in that, In the transcranial magnetic stimulation circuit, the charging switch unit includes a tenth electronic switch S10; the capacitor energy storage unit includes a seventh capacitor C7; the electromagnetic induction unit includes an inductive stimulation coil L 刺激 ; The transcranial magnetic stimulation circuit further includes an eighth capacitor C8 and a damping resistor; The transcranial magnetic stimulation circuit further includes an auxiliary coil reverse pre-magnetization circuit, and the auxiliary coil reverse pre-magnetization circuit includes an eighth inductance coil L8, a ninth inductance coil L9, a ninth electronic switch S9, a voltage stabilizing resistor, and a voltage stabilizing diode; the ninth inductance coil L9 and the inductance stimulation coil L 刺激 are coupled in the same direction.

10. The TMS stimulation device according to claim 9, wherein, The drive power input terminal is grounded after being connected to the seventh capacitor C7; the drive power input terminal is sequentially connected to the inductive stimulation coil L 刺激 , a damping resistor, and an eighth capacitor C8 and then grounded; the tenth electronic switch S10 is connected in parallel with a branch formed by the voltage stabilizing resistor and the voltage stabilizing diode; The drive power input terminal is grounded after being sequentially connected to the eighth inductance coil L8, the ninth inductance coil L9, and the ninth electronic switch S9; the drive power input terminal is grounded after being sequentially connected to the voltage stabilizing resistor, the zener diode, and the ninth electronic switch S9.

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