Device for improving cognitive competence of brain based on pulsed electric field, application and wearable equipment

Abstract

The invention belongs to the technical field of medical equipment, and particularly discloses a device for improving the cognitive competence of the brain based on a pulsed electric field, application and wearable device.The device comprises a pulse generator and a treatment electrode array, and the pulse generator is connected with the treatment electrode array through a wire; and the pulse generator is used for outputting a pulsed electric field and acting on the hippocampal region and / or the cortical region of the brain through the treatment electrode array to induce a degradation effect and remove A beta protein. The pulse electric field is adopted for non-invasive intervention, that is, a non-invasive electrode is used for electric field stimulation, treatment safety is guaranteed, meanwhile, Abeta protein distributed in brain tissue is effectively degraded, and therefore the cognitive ability of the brain of a patient is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of medical equipment, and in particular to a device and application and wearable device for improving brain cognitive ability based on pulsed electric fields. Background Art

[0002] Alzheimer's disease (AD) is a neurodegenerative disease that occurs in the elderly and pre-elderly with progressive memory loss, intellectual disability and personality changes. It is commonly known as senile dementia. AD is clinically manifested as memory impairment, language impairment, cognitive impairment and movement disorders, which seriously affect the patient's daily activities. In the late stage of AD, patients are often bedridden and need full-time care, which greatly increases the care and economic costs of the patient's family. The International Alzheimer's Disease Organization pointed out that in 2018, 50 million people in the world suffered from dementia, and the number will reach 152 million by 2050. With the aging of my country's population, the number of AD patients in my country will continue to increase in the next 30 years. By 2050, the number of AD patients will exceed 30 million, reaching twice that of 2020. The proportion of patients over 80 years old is close to 50%, which may become the main population of AD patients in my country. Alzheimer's disease not only seriously threatens the life and health of the elderly in my country. At the same time, it also increases the burden on my country's families and even the health care system. Therefore, in May 2024, the newly released "China Alzheimer's Disease Blue Book" clearly pointed out that the treatment of Alzheimer's disease is urgent. my country will increase support for innovation in Alzheimer's disease diagnosis and treatment technologies and promote the application of advanced auxiliary diagnostic technologies and intervention methods.

[0003] Clinically, Alzheimer's disease is a chronic degenerative disease of the central nervous system with a long course and gradually worsening symptoms. At present, the pathogenesis of AD is still unclear. The medical community has a variety of possible mechanisms for the onset of AD, among which amyloid β deposition and neurofibrillary tangles caused by abnormal phosphorylation of Tau protein are the main pathogenic factors. Aβ deposition can cause changes in neural function, and Tau protein overphosphorylation can pair with other proteins and disintegrate the neuronal transport system, leading to cognitive decline and memory dysfunction; other factors such as cholinergic deficiency, abnormal intracellular oxidative stress, abnormal metabolism of neurotransmitters, mitochondrial dysfunction, and autophagy dysfunction also play an important role in the progression of the disease.

[0004] Existing treatments include drug therapy, cognitive rehabilitation, etc., but these therapies can only slow down the aggravation of symptoms, but cannot fundamentally stop or reverse the course of the disease. Among them, drug therapy is the most important means of treating AD, mainly including acetylcholinesterase inhibitors (such as donepezil, rivastigmine, etc.), NMDA receptor antagonists (such as memantine), brain metabolism nootropics (such as piracetam, oxiracetam), etc. These drugs can increase acetylcholine concentrations, enhance central choline activity, and improve the transmission function of neurotransmitters to a certain extent, thereby improving the symptoms of AD. However, due to the extremely complex pathogenesis and influencing factors of AD, there is still no recognized definite conclusion in the existing scientific community. At the same time, existing drugs are only symptomatic and not fundamental, which leads to poor patient effects and repeated illnesses. In addition, the condition and pathological characteristics of patients in different regions and genders are significantly different, and the disease response to drug treatment is also different. The types and dosages of existing drugs cannot achieve personalized treatment for patients. Therefore, drug treatment cannot meet the increasingly severe incidence of AD, and more patients are in a dilemma of no drug available. The treatment of AD still faces major challenges. Therefore, exploring and developing a cutting-edge medical technology that can deeply act on the patient's fundamental lesion target area and achieve individualized precision treatment will have important scientific significance and clinical prospects. Summary of the invention

[0005] In view of the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide a device and application and wearable device for improving brain cognitive ability based on pulsed electric fields, so as to solve the problem that the degradation effect of Aβ protein is not significant.

[0006] One of the purposes of the present invention is to provide a device for improving brain cognitive ability based on pulsed electric fields, which performs non-invasive intervention through pulsed electric fields, that is, uses non-invasive electrodes for electric field stimulation, thereby improving the safety of treatment and enhancing the degradation effect of Aβ protein.

[0007] In order to achieve the above object, the present invention adopts the following technical scheme:

[0008] A device for improving brain cognitive ability based on pulsed electric fields, comprising a pulse generator and a therapeutic electrode array, wherein the pulse generator is connected to the therapeutic electrode array via a wire, and the pulse generator is used to output a pulsed electric field and act on the hippocampus and / or cortex of the brain through the therapeutic electrode array to induce neuronal cells to degrade Aβ protein and Tau protein and promote the proliferation of neuronal cells.

[0009] In a possible design, the pulse generator is used to output a unipolar or bipolar pulse electric field with a pulse width of 1 ns to 100 us, a frequency of 0.1 Hz to 1 MHz, and an amplitude of 1 kV to 20 kV.

[0010] In a possible design, the pulse generator is used to output a unipolar or bipolar pulse electric field with a pulse width of 10 ns to 20 μs, a frequency of 0.1 Hz to 100 kHz, and an amplitude of 1 to 10 kV.

[0011] In a possible design, the therapeutic electrode array includes at least two electrodes, each of which is connected to a metal hydrogel layer so that the electrodes can be non-invasively attached to the hippocampus and / or cortex of the brain through the metal hydrogel layer.

[0012] In a possible design, it also includes a signal feedback module and a controller. The signal feedback module is used to obtain EEG detection results. The signal feedback module is connected to the controller to feed the EEG detection results to the controller. The controller is connected to the pulse generator to control the pulse generator to output pulses with set parameters based on the EEG detection results.

[0013] In a possible design, a connector is provided on the electrode, the connector is connected to one end of the wire, and the other end of the wire is connected to the pulse generator.

[0014] In one possible design, the pulse generator includes a control unit, an interaction unit and a pulse generating circuit; wherein the interaction unit is signal-connected to the control unit to transmit control parameters to the control unit, and the control unit is signal-connected to the pulse generating circuit to control the pulse output circuit to output a pulse electric field with set parameters based on the control parameters, and the set parameters include a set pulse width, a set frequency, a set amplitude and a set polarity.

[0015] In one possible design, the pulse generator also includes a data acquisition unit, which is arranged at the output end of the pulse generating circuit and is used to collect parameters of the pulse electric field output by the pulse generating circuit. The control unit is signal-connected to the data acquisition unit to control the on and off of the pulse generating circuit according to the parameters of the pulse electric field output by the pulse generating circuit.

[0016] In one possible design, the control unit is a FPGA controller.

[0017] In a possible design, the interaction unit is a human-computer screen interaction unit.

[0018] In a possible design, the data acquisition unit is a current sensor and / or a voltage sensor.

[0019] A second object of the present invention is to provide an application of the above-mentioned pulse electric field or pulse electric field generating device.

[0020] To achieve the above object, the technical solution of the present invention is:

[0021] The use of the device as described above in preparing a device for degrading Aβ protein and / or Tau protein, and / or a device for promoting neuronal cells; or the use of a pulsed electric field in preparing a field for degrading Aβ protein and / or Tau protein, and / or a field for promoting neuronal cells; the Aβ protein and Tau protein are located in the hippocampus and / or cortex of the brain.

[0022] Use of the device as described above in preparing an induction device for autophagy in human neuroblastoma cells; or use of a pulsed electric field in preparing an induction field for autophagy in human neuroblastoma cells.

[0023] In one possible design, the autophagic effect can further degrade Aβ protein in nerve cells.

[0024] Use of the device as described above in preparing a device for treating Alzheimer's disease; or use of a pulsed electric field in preparing a field for treating Alzheimer's disease.

[0025] A third object of the present invention is to provide a wearable device to improve the convenience of AD treatment.

[0026] To achieve the above object, the technical solution of the present invention is:

[0027] A wearable device includes a wearable component, on which a therapeutic electrode array is fixed. The therapeutic electrode array is fixed to the hippocampus and / or cortex of the brain through the wearable component. The therapeutic electrode array is used to apply a pulsed electric field to the hippocampus and / or cortex of the brain.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] According to the device for improving brain cognitive ability based on pulsed electric fields of the present invention, the pulsed electric field output by the pulse generator is non-invasively applied to the hippocampus and / or cortex area of ​​the brain through the therapeutic electrode array, which can avoid damage to normal brain tissue and effectively degrade Aβ protein under the action of the pulsed electric field, while promoting the proliferation of neuronal cells, improving brain cognitive ability, and thus improving AD symptoms (short-term memory ability and spatial recognition ability) of AD individuals. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0031] Figure 1 It is a structural diagram of a device for improving brain cognitive ability based on pulsed electric fields according to an embodiment of the invention.

[0032] Figure 2 Schematic diagrams of unipolar and bipolar pulse waveforms with different pulse widths, frequencies and amplitudes according to an embodiment of the present invention, wherein: (a) 10ns-1000ns waveform; (b) 20μs-100μs waveform; (c) bipolar adjustable pulse width waveform; (d) bipolar 10kHz waveform; (e) bipolar 1MHz waveform.

[0033] Figure 3 Schematic diagram of the structure of electrodes in a treatment electrode array according to an embodiment of the present invention.

[0034] Figure 4 is a structural diagram of a pulse generator according to an embodiment of the present invention.

[0035] Figure 5 FIG. 4 is another structural diagram of a pulse generator according to an embodiment of the present invention.

[0036] Figure 6 It is another structural diagram of a device for improving brain cognitive ability based on pulsed electric fields according to an embodiment of the invention.

[0037] Figure 7 Figure 1 is a diagram of a mouse model according to an embodiment of the present invention, wherein: (a) a mouse model; (b) a mouse hippocampus diagram; and (c) a physical model of a mouse skull.

[0038] Figure 8 2 is a diagram of a mouse brain model according to an embodiment of the present invention.

[0039] Fig. 9 : The diagrams show the distribution of the electric field model of the rat brain and the electric field model waveform of the hippocampus according to an embodiment of the present invention, wherein: (a) is the distribution of the electric field model of the rat brain; (b) is the electric field model waveform of the hippocampus.

[0040] Fig.10 Schematic diagram of a mouse experimental platform according to an embodiment of the present invention.

[0041] Fig.11 1 is a mouse trajectory diagram in a water maze according to an embodiment of the present invention.

[0042] Fig.12 The figure is a statistical result of the number of crossings of the water maze experimental platform according to an embodiment of the present invention.

[0043] Fig.13 Schematic diagram of mouse brain slice parts according to an embodiment of the present invention.

[0044] Fig.14 This is a graph showing the immunohistochemistry results of mouse brain slices according to an embodiment of the present invention.

[0045] Fig.15 1 is a graph showing the statistical results of Aβ plaques according to an embodiment of the present invention; wherein, (1) the therapeutic effect of 150ns-500ns; and (2) the therapeutic effect of 10ns-100μs.

[0046] Fig.16 4 is a diagram of a human brain model according to an embodiment of the present invention.

[0047] Fig.17 1 is a distribution diagram of an electric field model in a human brain model according to an embodiment of the present invention, wherein: (a) is a rear view of the human brain model; (b) is a side view of the human brain model; and (c) is a front view of the human brain model.

[0048] Fig.18 3 is a distribution diagram of the electric field model in the brain according to an embodiment of the present invention.

[0049] Fig.19 1 is a waveform diagram of the electric field model in the hippocampus region of the brain according to an embodiment of the present invention.

[0050] In the figure, 100 is a pulse generator, 101 is a control unit, 102 is an interaction unit, 103 is a pulse generating circuit, 104 is a data acquisition unit, 200 is a treatment electrode array, 201 is an electrode, 202 is a metal hydrogel layer, 203 is a connector, 300 is a wire, 400 is a signal feedback module, and 500 is a controller. DETAILED DESCRIPTION

[0051] The following describes the embodiments of the present invention by specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention. It should be noted that the following embodiments and features in the embodiments can be combined with each other without conflict.

[0052] In the description of the present invention, unless otherwise specified, "plurality" means two or more than two; the orientations or positional relationships indicated by the terms "upper", "lower", "left", "right", "inner", "outer", "front end", "rear end", "head", "tail", etc. are based on the orientations or positional relationships shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, be constructed and operate in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", "third", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance.

[0053] In the description of the present invention, it should be noted that, unless otherwise clearly specified and limited, the terms "connected" and "connection" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0054] The present invention will now be further described with reference to the accompanying drawings.

[0055] Currently, existing technologies can effectively degrade Aβ protein in the hippocampus of experimental mice and improve their cognitive memory function by implanting electrodes in the brains of experimental mice and applying AC or DC stimulation. However, the dosage of AC or DC applied without damaging normal brain tissue is limited, making the degradation effect of Aβ protein insignificant.

[0056] Based on this, an embodiment of the present invention provides a device for improving brain cognitive ability based on pulsed electric fields, so as to enhance the degradation effect of Aβ protein through pulsed electric fields. Pulsed electric fields have the advantage of window effect compared to AC or DC electric fields. By simulating the distribution of pulsed electric fields in the brain, it is easy to obtain that the pulsed electric field can effectively act on the hippocampus of the brain, making the pulsed electric field have a targeted characteristic. In addition, the instantaneous high-power output of the pulsed electric field can achieve a higher electric field dose while ensuring that normal brain tissue is not damaged, thereby providing a theoretical basis for the non-invasive application of pulsed electric fields and the degradation of Aβ protein and Tau protein in the brain. On the other hand, pulsed electric fields can effectively induce autophagy of human neuroblastoma cells SH-SY5Y, and the Aβ protein in nerve cells can be further degraded through the autophagy effect, providing feasibility for the treatment of AD with pulsed electric fields.

[0057] like Figure 1As shown, the device for improving brain cognitive ability based on pulsed electric fields includes a pulse generator 100 and a treatment electrode array 200. The pulse generator 100 is connected to the treatment electrode array 200 through a wire 300. The pulse generator 100 is used to output a pulsed electric field and act on the hippocampus and / or cortex of the brain through the treatment electrode array 200 to induce neuronal cells to degrade Aβ protein and Tau protein and promote the proliferation of neuronal cells. The treatment electrode array 200 is a non-invasive electrode. Compared with the existing AC and DC stimulation methods, this embodiment uses a pulsed electric field for non-invasive intervention, that is, non-invasive electrodes are used for electric field stimulation to improve the safety of treatment.

[0058] In some embodiments, the pulse generator is used to output a unipolar or bipolar pulse electric field with a pulse width of 1 ns to 100 us, a frequency of 0.1 Hz to 1 MHz, and an amplitude of 10 kV.

[0059] As a preferred embodiment, the pulse generator is used to output a unipolar or bipolar pulse electric field with a pulse width of 10ns to 20μs, a frequency of 0.1Hz to 100kHz, and an amplitude of 1 to 10kV.

[0060] For example, this embodiment provides some unipolar and bipolar pulse waveforms with different pulse widths, frequencies, and amplitudes, such as Figure 2 As shown, (a) to (e) in the figure respectively show a 10ns-1000ns waveform, a 20μs-100μs waveform, a bipolar adjustable pulse width waveform, a bipolar 10kHz waveform, and a bipolar 1MHz waveform.

[0061] In some embodiments, Figure 3 As shown, the treatment electrode array 200 includes at least two electrodes 201, each electrode 201 is connected to a metal hydrogel layer 202, so that the electrode can be non-invasively attached to the hippocampus and / or cortex of the brain through the metal hydrogel layer 202, so that the pulsed electric field can be non-invasively intervened through the treatment electrode array, thereby having higher treatment safety. The specific attachment method of the treatment electrode array 200 can be referred to Figure 6 and Fig.14 shown.

[0062] In some embodiments, Figure 3 As shown, a connector 203 is provided on the electrode 201 , and the connector 203 is connected to one end of the wire 300 , and the other end of the wire 300 is connected to the pulse generator 100 .

[0063] In some embodiments, Figure 4As shown, the pulse generator 100 includes a control unit 101, an interaction unit 102 and a pulse generating circuit 103; wherein the interaction unit 102 is signal-connected to the control unit 101 to transmit control parameters to the control unit 101, and the control unit 101 is signal-connected to the pulse generating circuit 103 to control the pulse output circuit 103 to output a pulse electric field of set parameters based on the control parameters, and the set parameters include set pulse width, set frequency, set amplitude and set polarity.

[0064] Exemplarily, the interaction unit 102 can be selected as a human-machine screen interaction unit, such as a touch screen, which is used to feed control parameters to the control unit 101 by typing or importing, wherein the control parameters can be specific set pulse width, frequency, amplitude and polarity, wherein the set pulse width, frequency, amplitude and polarity can be a specific signal value selected in the range of 1ns~100us, 0.1Hz~1MHz, 1~20kV, unipolar or bipolar, such as the setting of polarity can be set by the values ​​0 and 1, 0 represents unipolarity, 1 represents bipolarity. The control unit 101 can be selected as an FPGA controller, and after receiving the control parameters, the pulse output circuit 103 is controlled to output the pulse electric field of the set parameters, and the set parameters are the specific values ​​indicated by the control parameters. It should be noted that in actual implementation, different values ​​will be selected according to the different symptoms of the treatment object, and the specific value selection in the control parameters is not limited in this embodiment.

[0065] In some embodiments, Figure 5 As shown, the pulse generator 100 also includes a data acquisition unit 104, which is arranged at the output end of the pulse generating circuit 103 and is used to collect parameters of the pulse electric field output by the pulse generating circuit 103. The control unit 101 is signal-connected with the data acquisition unit 104 to control the on and off of the pulse generating circuit 103 according to the parameters of the pulse electric field output by the pulse generating circuit 103.

[0066] The data acquisition unit 104 is provided to cooperate with the control unit 101 to improve the safety of treatment. For example, the data acquisition unit 104 can be a sensor array capable of collecting the current or voltage of the pulse electric field output by the pulse generating circuit 103. Taking the current as an example, a safe current threshold is pre-set, and the safe current threshold is determined according to the control parameters. For example, when a pulse electric field with a certain pulse width, a certain frequency, a certain amplitude and a certain polarity is output, the current value of the pulse electric field can be determined, and the error value added to the current value is the safe current threshold. Within the safe current threshold range, it can be basically considered that the pulse generating circuit 103 outputs a pulse electric field with set parameters. If the current collected by the data acquisition unit 104 is not within the safe current threshold range, it means that the pulse generating circuit 103 may output a pulse electric field outside the treatment range, which may have an adverse effect on the treatment. The pulse generating circuit 103 should be immediately cut off by the control unit 101, the treatment should be suspended, and the pulse generator 100 should be checked to find out the cause of the pulse electric field output failure.

[0067] In some embodiments, Figure 6 As shown, the device for improving brain cognitive ability based on pulsed electric fields also includes a signal feedback module 400 and a controller 500. The signal feedback module 400 is used to obtain EEG detection results. The signal feedback module 400 is connected to the controller 500 to feed the EEG detection results to the controller 500. The controller 500 is connected to the pulse generator 100 to control the pulse generator 100 to output pulses with set parameters based on the EEG detection results.

[0068] In this embodiment, the signal feedback module included in the device can be an ECG electroencephalogram detection element, so as to evaluate AD symptoms and form an integrated diagnosis and treatment electroencephalogram interface device. In the integrated diagnosis and treatment device, the ECG electroencephalogram detection element serves as a signal feedback path to transmit the electroencephalogram detection results to the controller, which evaluates the AD symptoms based on the electroencephalogram results, determines the output pulse of the set parameters and the corresponding treatment plan, and finally controls the pulse output for treatment.

[0069] The following embodiments of the present invention will combine specific examples to further illustrate the feasibility and advancement of the present invention.

[0070] Example 1:

[0071] like Figure 7 and Figure 8 As shown in the figure, this example uses COMSOL finite element simulation software to build a mouse brain model, and the distribution of the electric field in various tissues of the mouse brain under the action of pulsed electric fields with different parameters is shown in the figure. Figure 7 shown.

[0072] from Fig. 9 It can be seen that under the action of a pulse electric field with a pulse width of 100 ns and an amplitude of 3 kV, the electric field modulus in the hippocampus of the mouse brain can reach 1.8×10 5 V / m. This proves that pulsed electric fields can effectively act on the hippocampus of rats.

[0073] Example 2:

[0074] In order to verify the effectiveness and safety of pulsed electric field therapy for AD, mouse experiments were conducted. The experiments included: the construction of the experimental platform, mouse behavioral experiments, and mouse brain slice results.

[0075] 1) Construction of experimental platform

[0076] according to Fig.10 The experimental platform is built, which includes a pulse power supply, non-invasive electrodes, a mouse fixing platform, and electrode connecting wires. The pulse electric field is generated by the pulse source and transmitted to the electrode sheet through the electrode wire. The electrode sheet is attached to the mouse head through hydrogel, thereby applying a pulse electric field to the mouse brain.

[0077] 2) Mouse behavioral experiments

[0078] In order to evaluate the spatial memory and cognitive ability of mice, the Morris water maze experiment was used. Four groups were set up in the experiment: control group (normal mice: C57 mice), AD group (AD model mice: 5xFAD mice), C57+PEF group (normal mice were given pulse intervention), and 5xFAD+PEF group (AD model mice were given pulse intervention). Pulse intervention was performed once every 2 days, 1 hour each time, with parameters of 500ns and 3kV.

[0079] The experimental results are as follows Fig.11 As shown in Figure 1, the spatial memory cognitive ability of mice can be evaluated based on the trajectory of mice in the water maze. The more concentrated the trajectory is in the platform area, the stronger the spatial memory cognitive ability of the mouse is. Fig.11 It can be seen that the tracks of AD mice treated with PEF are more concentrated in the platform area than those of AD mice not treated with pulses, which proves that pulsed electric fields can effectively improve the spatial memory cognitive ability of AD mice and that pulsed electric fields are effective in treating AD. At the same time, the tracks of normal mice after pulsed electric field intervention are still concentrated in the platform area, which proves that pulsed electric fields have no effect on the spatial memory cognitive ability of normal mice and are safe.

[0080] The number of times the four groups of mice crossed the platform is counted as follows Fig.12As shown in the figure, the number of times that AD mice that have undergone pulse electric field intervention (PEF Sim) cross the platform is higher than that of AD mice that have not undergone pulse electric field intervention, proving that pulse intervention can enhance the spatial memory ability of AD mice. At the same time, for normal mice, the number of platform crossings increased after pulse intervention, proving that pulse intervention not only does not damage the spatial cognitive ability of normal mice, but will promote the spatial memory and cognitive ability of normal mice.

[0081] 3) Mouse brain slice results

[0082] Brain sections of AD mice were sliced ​​and Aβ plaques were immunohistochemically stained. The results were as follows: Fig.13 and Fig.14 As shown in Figure 2, the results of Aβ immunohistochemical staining showed that the number and density of Aβ plaques in the brains of AD mice after PEF intervention were significantly reduced compared with those of AD mice not treated with PEF. The number of Aβ plaques in the whole hemisphere, cerebral cortex, and hippocampus of mice was counted, as shown in Figure 2. Fig.15 Among them, from the statistical results of the whole hemisphere, the pulse intervention with high amplitude and wide pulse width has the most significant effect. Comparing the cortical area and the hippocampus area, the Aβ clearance effect in the cortical area is better than that in the hippocampus area.

[0083] Example 3:

[0084] The COMSOL finite element simulation software was used to construct the Fig.16 The human brain model shown in the figure is mainly divided into electrodes, skin, cerebrospinal fluid, skull, white matter, gray matter, and brainstem, of which the hippocampus is included in the gray matter. The electrode patch is connected to the skin through hydrogel.

[0085] Fig.17 and Fig.18 The distribution of the electric field norm in the whole brain and gray matter at the time of the maximum electric field norm, combined with Fig.19 It can be seen that under the action of a 3kV pulsed electric field, the electric field modulus in the hippocampus is in the range of 1 to 3e4V / m, proving that the pulsed electric field can effectively act on the target area.

[0086] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions described in the above embodiments may still be modified, or some or all of the technical features may be replaced by equivalents. Such modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present invention, and should all be included in the scope of the claims and specification of the present invention.

Claims

1. A device for improving brain cognitive ability based on pulsed electric fields, characterized in that: It includes a pulse generator and a non-invasive treatment electrode array. The pulse generator is connected to the treatment electrode array through a wire. The pulse generator is used to output a pulse electric field and act on the hippocampus and / or cortex area of ​​the brain through the treatment electrode array to induce a degradation effect and clear Aβ protein.

2. The device for improving brain cognitive ability based on pulsed electric fields according to claim 1, characterized in that: The pulse generator is used to output a unipolar or bipolar pulse electric field with a pulse width of 1ns to 100μs, a frequency of 0.1Hz to 1MHz, and an amplitude of 1kV to 20kV.

3. The device for improving brain cognitive ability based on pulsed electric fields according to claim 1, characterized in that: The pulse generator is used for outputting a unipolar or bipolar pulse electric field with a pulse width of 10ns to 20μs, a frequency of 0.1Hz to 100kHz, and an amplitude of 1 to 10kV.

4. The device for improving brain cognitive ability based on pulsed electric fields according to claim 1, characterized in that: The therapeutic electrode array includes at least two electrodes, each of which is made of a metal sheet. The electrodes are then non-invasively attached to the hippocampus and / or cortex of the brain through the hydrogel layer.

5. The device for improving brain cognitive ability based on pulsed electric fields according to claim 1, characterized in that: It also includes a signal feedback module and a controller. The signal feedback module is used to obtain EEG detection results. The signal feedback module is connected to the controller to feed the EEG detection results to the controller. The controller is connected to the pulse generator to control the pulse generator to output pulses with set parameters based on the EEG detection results.

6. The device for improving brain cognitive ability based on pulsed electric fields according to claim 4, characterized in that: The electrode is provided with a connector, the connector is connected to one end of the wire, and the other end of the wire is connected to the pulse generator.

7. The device for improving brain cognitive ability based on pulsed electric fields according to claim 1, characterized in that: The pulse generator includes a control unit, an interaction unit and a pulse generating circuit; wherein the interaction unit is connected to the control unit signal to transmit control parameters to the control unit, and the control unit is connected to the pulse generating circuit signal to control the pulse output circuit to output a pulse electric field with set parameters based on the control parameters, and the set parameters include a set pulse width, a set frequency, a set amplitude and a set polarity.

8. The device for improving brain cognitive ability based on pulsed electric fields according to claim 7, characterized in that: The pulse generator also includes a data acquisition unit, which is arranged at the output end of the pulse generating circuit and is used to collect parameters of the pulse electric field output by the pulse generating circuit. The control unit is signal-connected to the data acquisition unit to control the on and off of the pulse generating circuit according to the parameters of the pulse electric field output by the pulse generating circuit.

9. The device for improving brain cognitive ability based on pulsed electric fields according to claim 7, characterized in that: The control unit is a FPGA controller.

10. The device for improving brain cognitive ability based on pulsed electric fields according to claim 7, characterized in that: The interaction unit is a human-computer screen interaction unit.

11. The device for improving brain cognitive ability based on pulsed electric fields according to claim 7, characterized in that: The data acquisition unit is a current sensor and / or a voltage sensor.

12. Use of the device according to any one of claims 1 to 11 in preparing a device for degrading Aβ protein and / or Tau protein, and / or a device for promoting neuronal cells; or the use of pulsed electric fields in preparing degradation fields for Aβ protein and / or Tau protein, and / or promotion fields for neuronal cells; It is characterized in that The Aβ protein and Tau protein are located in the hippocampus and / or cortex of the brain.

13. Use of the device according to any one of claims 1 to 11 in preparing a device for inducing autophagy of human neuroblastoma cells; Or the application of pulsed electric field in preparing the inducing field of autophagy in human neuroblastoma cells.

14. The use according to claim 13, characterized in that The autophagic effect can further degrade Aβ protein in nerve cells.

15. Use of the device according to any one of claims 1 to 11 in preparing a device for treating Alzheimer's disease; or use of a pulsed electric field in preparing a field for treating Alzheimer's disease.

16. A wearable device, characterized in that: It includes a wearable component, on which a therapeutic electrode array is fixed. The therapeutic electrode array is fixed to the hippocampus and / or cortex of the brain through the wearable component, and the therapeutic electrode array is used to apply a pulsed electric field to the hippocampus and / or cortex of the brain.

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