Polarity-adjustable non-invasive deep brain stimulation system

Abstract

Disclosed is a polar-adjustable non-invasive deep brain electrical stimulation system, comprising a waveform generation module, a first signal generator for generating a first frequency waveform and a second signal generator for generating a second frequency waveform; a waveform rectification module, a first rectification component and a second rectification component for full-wave rectification of the first frequency waveform and the second frequency waveform to obtain a first rectified waveform and a second rectified waveform; a current stabilization module, the first rectified waveform and the second rectified waveform passing through a first current stabilization component and a second current stabilization component to obtain a first stimulation waveform and a second stimulation waveform; and a stimulation electrode for outputting the stimulation waveform to a stimulation target to generate a low-frequency envelope stimulation waveform in the deep brain. The application obtains a polar-adjustable time interference waveform through stimulation current rectification, so as to selectively apply appropriate electrical stimulation to different abnormal brain activity characteristics by using low-frequency envelope current with different polarities, thereby improving the targeting and effectiveness of electrical stimulation.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical devices, and in particular, relates to a polarity-adjustable non-invasive deep brain electrical stimulation system. BACKGROUND

[0002] Deep brain electrical stimulation technology adjusts the nerve signal transduction in the central nervous system and peripheral nervous system through a non-invasive mode of action, thereby controlling the electrical activity of the brain neural network and improving neural function. Non-invasive deep brain electrical stimulation refers to fixing electrodes on the scalp surface of a specific area, and using a pulse generator connected to the electrodes to generate electrical pulses to interfere with and regulate abnormal brain signals related to nervous system diseases, so as to alleviate the symptoms of patients and improve their quality of life.

[0003] The paper "Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields" and the patent US10173061B2 disclose a non-invasive deep brain electrical stimulation technology based on temporal interference. This technology is to apply two high-frequency sinusoidal wave stimulation currents (for example, the frequencies can be f1 and f2, respectively) to the brain through scalp electrodes. The two high-frequency currents themselves cannot effectively activate neurons due to the excessively high frequency, but the two currents can overlap in the deep brain and form interference, thereby generating a low-frequency envelope (Δf = |f1-f2|), amplitude-modulated current, which can effectively activate neurons located in the deep brain.

[0004] This temporal interference-based electrical stimulation method can non-invasively and selectively stimulate the deep brain without affecting the brain surface, realizing non-invasive deep brain electrical stimulation and providing a safer and more effective method for deep regulation of brain diseases. Based on this technology, the patents CN108744273B and US11071862B2 further propose a non-invasive deep brain dual-focus stimulation method, which generates two stimulation foci in the deep brain through transcranial current interference, and simultaneously targets the stimulation of two deep brain areas in specific neural circuits to assist the brain to achieve certain functional effects.

[0005] In particular, the brain abnormal activity related to brain diseases has characteristics, which can be divided into abnormal enhanced brain activity and abnormal weakened brain activity, such as abnormal inhibition of brain related to depression. Therefore, deep brain electrical stimulation for different diseases can achieve more precise symptomatic stimulation on the basis of existing non-invasive deep brain electrical stimulation based on time interference, so as to more effectively regulate the corresponding brain diseases according to the characteristics of brain abnormal activity (excitation or inhibition) of specific brain diseases. However, the aforementioned non-invasive deep brain electrical stimulation based on sinusoidal time interference contains both positive waveform part and negative waveform part in the stimulation waveform, that is, the stimulation of specific brain regions of the brain does not contain the selection of specific polarity, so it cannot provide specific polarity stimulation to specific brain function areas.

[0006] Therefore, if the polarity-adjustable electrical stimulation model can be constructed based on the non-invasive deep brain electrical stimulation technology disclosed in the aforementioned patents (US10173061B2, CN108744273B, and US11071862B2), for example, if enhanced stimulation or inhibitory stimulation can be set and used for electrical stimulation treatment of target patients, brain activity can be more accurately regulated, thereby achieving more precise intervention for brain-related brain diseases. However, due to the relative difficulty of generating and maintaining unipolar stimulation waveform and the limitations of researchers in the field at this stage in the application and improvement of time interference electrical stimulation method due to technical maturity, safety, no one has proposed such a polarity-adjustable non-invasive deep brain electrical stimulation technology, and no corresponding stimulation regulation device has been developed or produced. SUMMARY

[0007] In order to solve the problems existing in the prior art, the purpose of the present application is to provide a polarity-adjustable non-invasive deep brain electrical stimulation system, which obtains full positive waveform or full negative waveform by rectifying the stimulation current before generating time interference waveform of double-channel stimulation waveform, so as to selectively stimulate target patients with different brain abnormal activity characteristics by using two low-frequency envelope amplitude-modulated currents.

[0008] Specifically, the present application relates to the following aspects:

[0009] 1. A non-invasive deep brain stimulation system with adjustable polarity, comprising: a waveform generating module, which generates a first frequency waveform by a first signal generator and a second frequency waveform by a second signal generator; a waveform rectifying module, which is connected to the output of the waveform generating module, rectifies the first frequency waveform by a first rectifying component to obtain a first rectified waveform, and rectifies the second frequency waveform by a second rectifying component to obtain a second rectified waveform; a current stabilizing module, which is connected to the output of the waveform rectifying module, stabilizes the first rectified waveform by a first current stabilizing component to obtain a first stimulation waveform with high frequency and no distortion, and stabilizes the second rectified waveform by a second current stabilizing component to obtain a second stimulation waveform with high frequency and no distortion; and a stimulation output module, which is connected to the output of the current stabilizing module, and outputs the first stimulation waveform and the second stimulation waveform to a scalp stimulation target of a target by a stimulation electrode to generate a low frequency envelope stimulation waveform in a deep brain.

[0010] 2. The stimulation system according to item 1, wherein the first rectifying component and the second rectifying component comprise a voltage input unit, a unidirectional conductive unit and a load, wherein the voltage input unit adjusts the voltage amplitude of the first frequency waveform or the second frequency waveform to a preset voltage amplitude; the unidirectional conductive unit adjusts the current direction flowing through the load in the positive half cycle and the negative half cycle of the first frequency waveform or the second frequency waveform respectively, so that the current direction flowing through the load is consistent in a whole cycle of the first frequency waveform or the second frequency waveform, and the first rectified waveform or the second rectified waveform with constant current direction is generated.

[0011] 3. The stimulation system according to item 2, wherein the unidirectional conductive unit comprises a first rectifying diode and a second rectifying diode, wherein the first rectifying diode and the second rectifying diode have a first end and a second end respectively; in the positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is turned on and the second rectifying diode is reverse cut-off, and the current flows from the first end of the first rectifying diode to the second end of the first rectifying diode; in the negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is reverse cut-off and the second rectifying diode is turned on, and the current flows from the first end of the second rectifying diode to the second end of the second rectifying diode.

[0012] 4. The stimulation system according to item 2, wherein the unidirectional conductive unit comprises a first rectifying diode and a second rectifying diode, wherein the first rectifying diode and the second rectifying diode have a first end and a second end respectively; in the positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is turned on and the second rectifying diode is reverse cut-off, and the current flows from the second end of the first rectifying diode to the first end of the first rectifying diode; in the negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is reverse cut-off and the second rectifying diode is turned on, and the current flows from the second end of the second rectifying diode to the first end of the second rectifying diode.

[0013] 5. The stimulation system according to item 1, wherein the first current stabilizing component and the second current stabilizing component respectively comprise a first constant current unit and a second constant current unit, wherein the first constant current unit adjusts the current of the first rectified waveform or the second rectified waveform to be constant, and the second constant current unit adjusts the high frequency component of the current of the first rectified waveform or the second rectified waveform passed through the first constant current unit to be constant.

[0014] 6. The stimulation system according to item 1, further comprising a stimulation polarity detection module for collecting resting state functional magnetic resonance data of the target, extracting the blood oxygen level dependent signal of the brain function network and / or the brain region of the target in the resting state functional magnetic resonance data through the data preprocessing unit and the data post-processing unit, and determining the scalp stimulation target of the target, the current direction of the first rectified waveform obtained by the first rectifying component, and the current direction of the second rectified waveform obtained by the second rectifying component according to the abnormal state of the blood oxygen level dependent signal of the target.

[0015] 7. The stimulation system according to item 6, wherein the extraction of the blood oxygen level dependent signal of the brain function network and / or the brain region of the target in the resting state functional magnetic resonance data through the data preprocessing unit and the data post-processing unit comprises: quality inspection, time point removal, layer scanning time correction, head motion correction, image registration, standardization processing, smoothing processing and / or low frequency band pass filtering of the resting state functional magnetic resonance data by the data preprocessing unit; and the functional magnetic resonance data post-processing unit comprises time series extraction, functional connection matrix calculation and / or statistical analysis of the resting state functional magnetic resonance data processed by the data preprocessing unit.

[0016] 8. The stimulation system according to item 1, further comprising a stimulation evaluation module for detecting the electrical stimulation parameters and effects on the target by the non-invasive deep brain electrical stimulation evaluation unit, and adjusting the frequency, amplitude, wave rise, wave fall or on-off ratio of the first stimulation waveform and / or the second stimulation waveform according to the electrical stimulation effect to improve the electrical stimulation effect.

[0017] Advantages

[0018] 1. The polarity adjustable non-invasive deep brain electrical stimulation system proposed in the present application, compared with the existing sinusoidal wave time interference electrical stimulation system, can adjust the polarity of the electrode stimulation signal on demand by using the waveform rectifying module, so that the stimulation polarity of the time interference deep brain electrical stimulation wave can be adjusted, the individualized stimulation of the target brain region can be realized, and the effectiveness and accuracy of the individual neural regulation can be improved, thereby providing a more effective application system for regulating the brain and intervening the brain disease process through the non-invasive deep brain electrical stimulation technology of time interference.

[0019] 2. The polarity-adjustable non-invasive deep brain electrical stimulation system proposed in the present application uses its current stabilizing module to stabilize the intensity of the stimulation signal output to the electrode and control the distortion attenuation of the high-frequency part of the stimulation signal that is prone to occur, thereby ensuring that high-quality stable stimulation signals are delivered to the target deep brain to form more accurate low-frequency envelope stimulation currents; based on this stable stimulation signal current stabilization function, the accuracy of parameter adjustment of the stimulation signal based on the treatment effect of the target patient can also be facilitated, providing more effective electrical stimulation scheme optimization for the target patient and further avoiding discomfort or accidents for the target patient.

[0020] 3. The present application can also evaluate the effect of the target receiving electrical stimulation, and then adjust the frequency, amplitude, and other stimulation parameters of the stimulation signal according to the electrical stimulation effect, in order to improve the treatment effect, patient comfort, and change the treatment process of the stimulation, and other clinical indicators. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1A Fig. 1 shows a schematic diagram of a stimulation electrode connection according to an embodiment of the present application;

[0022] Figure 1B Fig. 2 shows a structural schematic diagram of a polarity-adjustable non-invasive deep brain electrical stimulation system according to an embodiment of the present application;

[0023] Figure 2A Fig. 3 shows a time-domain waveform diagram of a first stimulation waveform, a second stimulation waveform, and a corresponding time-interference stimulation waveform with full positive amplitude according to an embodiment of the present application;

[0024] Figure 2B Fig. 4 shows a frequency spectrum diagram of a first stimulation waveform, a second stimulation waveform, and a corresponding time-interference stimulation waveform with full positive amplitude according to an embodiment of the present application;

[0025] Figure 3A Fig. 5 shows a time-domain waveform diagram of a first stimulation waveform, a second stimulation waveform, and a corresponding time-interference stimulation waveform with full negative amplitude according to an embodiment of the present application;

[0026] Figure 3B Fig. 6 shows a frequency spectrum diagram of a first stimulation waveform, a second stimulation waveform, and a corresponding time-interference stimulation waveform with full negative amplitude according to an embodiment of the present application;

[0027] Figure 4A Fig. 7 shows a structural schematic diagram of a first rectifier assembly and a second rectifier assembly according to an embodiment of the present application;

[0028] Figure 4B Fig. 8 shows another structural schematic diagram of a first rectifier assembly and a second rectifier assembly according to an embodiment of the present application;

[0029] Figure 5FIG. 1 illustrates a flow chart of a method of using a polarity-adjustable noninvasive deep brain electrical stimulation system according to embodiments of the present application. DETAILED DESCRIPTION

[0030] The present application is further illustrated by the following examples, which are not intended to limit the present application in any way.

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, illustrative materials and methods are described below. However, if there is a conflict between the definitions in the specification and the definitions in the patent, the patent takes precedence. Although embodiments of the application are not limited in this regard, the materials and methods are described in sufficient detail to enable others skilled in the art to practice the application. The examples provided herein are to explain the application and are not intended to limit the scope of the application.

[0032] As described above, the sinusoidal waveform-based time-interleaved noninvasive deep brain electrical stimulation technology has been widely verified, while the polarity-adjustable time-interleaved noninvasive deep brain electrical stimulation technology has not been proposed, which includes the following factors:

[0033] (1) The stimulation waveform of the polarity-adjustable time-interleaved noninvasive deep brain electrical stimulation technology is more complex, has more high-frequency components, and has higher requirements for the performance of the constant current source circuit; (2) There is currently a lack of clinical research on the polarity-adjustable time-interleaved noninvasive deep brain electrical stimulation technology to verify its stability and feasibility relative to the polarity-fixed time-interleaved noninvasive deep brain electrical stimulation technology when treating specific diseases.

[0034] Nonetheless, this polarity-adjustable time-interleaved noninvasive deep brain electrical stimulation technology has its unique advantages for the regulation of specific diseases. The conventional sinusoidal waveform-based time-interleaved noninvasive deep brain electrical stimulation technology can regulate brain activity, but cannot produce special polarity stimulation, such as enhancement or inhibition. Brain abnormalities associated with brain diseases have special characteristics, which can be divided into abnormal enhancement of brain activity, such as abnormal excitation of the brain of people with Alzheimer's disease, and abnormal reduction of brain activity, such as the related abnormal inhibition of the brain of people with depression. In these cases, using a polarity-adjustable noninvasive deep brain electrical stimulation device to produce unipolar time-interleaved electrical stimulation to regulate the abnormal excitation or abnormal inhibition of the brain of the above-mentioned example diseases can more accurately regulate brain activity, thereby achieving the purpose of specific disease intervention.

[0035] Based on this consideration, the application provides a polar adjustable non-invasive deep brain electrical stimulation system, which can include a waveform generating module, a waveform rectifying module, a current stabilizing module and a stimulation output module. The waveform generating module can generate and output two high-frequency stimulation waveforms with different frequencies. The waveform rectifying module rectifies the two stimulation waveforms and forms stimulation waveforms with the same specified polarity. The current stabilizing module regulates the current of the stimulation waveforms, and the two stimulation waveforms are delivered to the scalp of the target subject at the specified stimulation target point through two pairs of stimulation electrodes of the stimulation output module, so as to form a low-frequency envelope amplitude modulation stimulation current with a specific polarity in the brain region of the target subject, as shown in Figure 1A

[0036] In some embodiments, the waveform generating module can include two signal generators, for example, a first signal generator and a second signal generator, to generate two high-frequency sinusoidal waveforms with different frequencies, for example, a first frequency waveform and a second frequency waveform. The first frequency waveform and the second frequency waveform can overlap and interfere in the deep brain, thereby generating a low-frequency envelope amplitude modulation current with a frequency difference between the frequencies of the interference waveforms, which can effectively activate the neurons of the functional area of the deep brain and precisely control the brain activity.

[0037] However, the low-frequency envelope stimulation current generated by the interference of the two high-frequency sinusoidal waveforms has both positive and negative waveform parts in the stimulation waveform, which does not contain a specified polarity for the stimulation of a specific brain region of the brain, and cannot regulate the polarity, so it cannot generate a stimulation current with a specific polarity for a certain brain.

[0038] To overcome this defect, the application proposes to use a waveform rectifying module to regulate the polarity of the stimulation waveform to generate a stimulation current with a specified polarity. Specifically, as shown in Figure 1B The waveform rectifying module can include two waveform rectifying components, for example, a first rectifying component and a second rectifying component, to rectify the two high-frequency sinusoidal waves output by the waveform generating module. For each waveform rectifying component, it can include a voltage input unit for receiving the high-frequency sinusoidal waveforms output by the signal generator and adjusting the amplitude to a preset size required by the functional electrical stimulation; and a unidirectional conductive unit for rectifying the high-frequency sinusoidal waveforms to obtain a direct current waveform with a specified polarity; and a load for loading the obtained direct current waveform.

[0039] In one embodiment, the voltage input unit can be exemplified as a power transformer, preferably, the voltage input unit is a power transformer SMW3225S102HTE, which has high insulation resistance and stable electrical performance, can ensure that the current and voltage fluctuate within a safe range, and reduce the risk of potential harm to the target subject.

[0040] ​In some embodiments, the unidirectional conduction unit can output a full positive direct current waveform through the load by adjusting the direction of the current flowing through the load within the alternating negative half cycle of the high-frequency sinusoidal waveform, such as the first frequency waveform or the second frequency waveform, so that the direction of the current flowing through the load does not change within the alternating full cycle of the first frequency waveform or the second frequency waveform.

[0041] To this end, the unidirectional conduction unit needs to provide a high-frequency stable stimulation waveform without polarity change through rectification. A rectifier bridge, a rectifier diode, a filter circuit, etc. can all use the voltage signal of a signal generator or a transformer to rectify and generate a unipolar stimulation waveform. Although the rectifier bridge can achieve rectification function, its structure is relatively complex, consisting of multiple diodes. In the case of complex system logic link and more electronic components, the high-frequency direct current waveform obtained by the rectifier bridge may be distorted to varying degrees. The filter circuit can further smooth the rectified direct current waveform, but it does not have an independent rectification function. Therefore, in an advantageous embodiment, the unidirectional conduction unit is designed with a rectification circuit composed of multiple rectifier diodes, as shown in Figure 4A . Among them, the first rectifier diode (D1) and the second rectifier diode (D2) have a first end 1 and a second end 2 respectively. The first end of D1 and the first end of D2 are connected to the two ends of the secondary coil of the power transformer SMW3225S102HTE respectively, and the second end of D1 and the second end of D2 are connected to one end of the load R1 respectively. The connection end of the load R1 and D1, D2 is also connected to the middle tap of the secondary coil of the power transformer SMW3225S102HTE. D1, D2 can be turned on from the first end 1 to the second end 2. After the first frequency waveform converted by the power transformer SMW3225S102HTE is input into the rectification circuit, D1 is turned on and D2 is reverse cut-off in the positive half cycle of the first frequency waveform. The current flows from the first end 1 to the second end 2 of D1 and forms a left positive right negative direct current waveform across the load R1. In the negative half cycle of the first frequency waveform, D1 is reverse cut-off and D2 is turned on. The current flows from the first end 1 to the second end 2 of D2 and forms a left positive right negative direct current waveform across the load R1. In this way, the direction of the direct current waveform formed across the load R1 does not change within one full cycle of the first frequency waveform, and has a fixed polarity. This direct current waveform with a forward voltage drop across the load R1 can be defined as a forward direct current waveform, as shown in Figures 2A-2B .

[0042] Thus, in the reverse cut-off state, the relationship of the PN junction inside the rectifier diode makes the reverse leakage current effectively prevented and very small, and the input voltage usually required by the deep brain electrical stimulation is within the maximum reverse working voltage range of the rectifier diode, which does not cause the polarity of the rectified waveform to be reversed due to the adjustment of the voltage size or the current intensity. Compared with the rectifier bridge, this design of the double rectifier diode is more suitable for the non-invasive deep brain electrical stimulation system and is easy to repair and replace. In addition, the rectifier diode has a very low on-resistance when forward biased, which can efficiently conduct current, so that the rectifier diode can reduce energy loss when rectifying the alternating waveform into a direct current waveform, and the power consumption is lower than that of the rectifier bridge or the filter circuit.

[0043] Further, the unidirectional conduction units of the two rectifier assemblies can be used to generate direct current waveforms of different frequencies and the same polarity, for example, a first rectified waveform and a second rectified waveform, and the two direct current waveforms with only amplitude changes in the forward direction are used to generate a stimulation current with a low-frequency envelope with only amplitude changes in the forward direction in the deep brain.

[0044] In another embodiment, the unidirectional conduction unit includes a rectifier circuit composed of a plurality of rectifier diodes, as shown in Figure 4B The first rectifier diode (D1) and the second rectifier diode (D2) have a first end 1 and a second end 2, respectively, and the first end of D1 and the first end of D2 are connected to the two ends of the secondary coil of the power transformer SMW3225S102HTE, respectively, and the second end of D1 and the second end of D2 are connected to one end of the load R1, respectively, and the connection ends of the load R1 and D1, D2 are also connected to the intermediate tap of the secondary coil of the power transformer SMW3225S102HTE. D1 and D2 can be turned on from the second end 2 to the first end 1, and after the first frequency waveform input into the rectifier circuit through the power transformer SMW3225S102HTE, D1 is turned on and D2 is reverse cut-off in the positive half cycle of the first frequency waveform, and the current flows from the second end 2 to the first end 1 of D1 and forms a left negative and right positive direct current waveform across the load R1; in the negative half cycle of the first frequency waveform, D1 is reverse cut-off and D2 is turned on, and the current flows from the second end 2 to the first end 1 of D2 and forms a left negative and right positive direct current waveform across the load R1. In this way, the direction of the direct current waveform formed across the load R1 does not change in one cycle of the first frequency waveform, and has a fixed polarity. This direct current waveform with a negative voltage drop across the load R1 can be defined as a negative direct current waveform, as shown in Figures 3A-3B .

[0045] Further, the unidirectional conduction units of the two rectification assemblies can be utilized to generate DC waveforms with different frequencies and same polarity, such as a first rectification waveform and a second rectification waveform, and the two DC waveforms with amplitude change only in the negative direction can be utilized to generate a stimulation current with low frequency envelope and amplitude change only in the negative direction in deep brain intervention.

[0046] It is particularly noted that the DC waveforms, such as the first rectification waveform and the second rectification waveform, proposed in the present application have the characteristic that the direction of the DC signal does not change over time, but they can still have an alternating period with amplitude changing over time, i.e., the phase of the first rectification waveform and the second rectification waveform changes periodically in the same direction over time, thus still having the characteristics of alternating signals, which can interfere with other alternating signals.

[0047] In this way, by full-wave rectifying the high-frequency sinusoidal waveforms in the non-invasive deep brain electrical stimulation system proposed in the present application, two positive DC waveforms or negative DC waveforms with different frequencies can be obtained. The interference of the two positive DC waveforms in deep brain can obtain a positive stimulation waveform with low frequency envelope, such as an enhanced stimulation waveform, which can provide effective unipolar electrical stimulation to target subjects with abnormal inhibition in the target deep brain functional network region; and the interference of the two negative DC waveforms in deep brain can obtain a negative stimulation waveform with low frequency envelope, such as a suppression stimulation waveform, which can provide effective unipolar electrical stimulation to target subjects with abnormal excitation in the target deep brain functional network region.

[0048] In some embodiments, the current stabilizing module can include two current stabilizing assemblies, such as a first current stabilizing assembly and a second current stabilizing assembly, which respectively regulate and stabilize the current of the positive DC waveform or the negative DC waveform output by the waveform rectification module to control the current of the positive DC waveform or the negative DC waveform. Specifically, the current stabilizing assembly can include adjusting the current intensity of the positive DC waveform or the negative DC waveform, adjusting the current change rate of the positive DC waveform or the negative DC waveform, and stabilizing the high-frequency component of the current of the positive DC waveform or the negative DC waveform.

[0049] To achieve the current regulation and stabilization function, the current stabilizing assembly can include two series-connected constant current units, such as a first constant current unit and a second constant current unit. The first constant current unit is used to adjust the current of the positive DC waveform or the negative DC waveform, such as the current intensity, the current change rate, etc. Since the positive DC waveform or the negative DC waveform output by the current stabilizing assembly does not have direction variability, the first constant current unit can be configured as a current constant current source based on an operational amplifier.

[0050] The secondary constant current unit is configured to maintain the high frequency component of the positive or negative direct current waveform. It is known that the high frequency component of the high frequency direct current waveform obtained after the full-wave rectification of the high frequency sinusoidal waveform by the waveform rectification module is prone to distortion due to the nonlinear characteristics and frequency response characteristics of the elements. When further considering the influence of system noise, how to avoid high frequency distortion is a problem that needs attention. Therefore, the secondary constant current unit can be configured as a transistor-based current constant current source to protect the high frequency component of the direct current waveform and ensure the frequency accuracy of the stimulation waveform.

[0051] That is, the secondary constant current unit can include a constant current circuit composed of a transistor-based constant current source circuit, which makes the secondary constant current unit have a higher frequency response to ensure that the output amplitude of the high frequency component in the first or second rectified waveform after passing through the first constant current unit can maintain high stability. This is also an important prerequisite for the first or second rectified waveform to be used for target stimulation, thereby avoiding distortion of the high frequency component in the rectified waveform, i.e., ensuring that the output amplitude of the high frequency component in the rectified waveform is stable and does not decay in amplitude, so as to avoid reducing the stimulation treatment effect.

[0052] In some embodiments, the non-invasive deep brain electrical stimulation system of the present application can further include a stimulation polarity detection module including a polarity selection switch, which can be used to collect resting-state functional magnetic resonance data of a target subject, extract blood oxygen level dependent (BOLD) signals of the brain function network and / or brain region of the target subject in the resting-state functional magnetic resonance data through a data preprocessing unit and a data post-processing unit, and determine the preset stimulation mode information of the target subject according to the abnormal state of the target BOLD signal, including the scalp stimulation target point, the current direction of the first rectified waveform obtained by the first rectification component, and the current direction of the second rectified waveform obtained by the second rectification component, and the polarity of the first or second rectified waveform can be controlled by the polarity selection switch.

[0053] In particular, the resting-state functional magnetic resonance data is selected to extract the BOLD signal in order to evaluate the abnormal excitation or abnormal inhibition of a specific brain region and determine the stimulation polarity and stimulation target point. Functional magnetic resonance can non-invasively detect deep brain signals and has high spatial resolution, i.e., high spatial accuracy in submitting the stimulation target point; in addition, the BOLD signal of resting-state functional magnetic resonance is a marker for effectively detecting the activity of a specific target brain region, i.e., detecting whether the target brain region is abnormally excited or abnormally inhibited.

[0054] That is, the non-invasive deep brain electrical stimulation system according to the embodiments of the present application can determine the stimulation mode required by the target subject through the stimulation polarity detection module before applying any type of monopolar time interference electrical stimulation to the target subject, and give targeted enhanced stimulation or inhibitory stimulation. The purpose of doing so is to determine or adjust the stimulation scheme according to the real-time state of the target subject before treatment, for example, for a target subject who has been receiving enhanced stimulation for a long time, the current stimulation scheme may have interfered with the normal functioning of the brain, such as interfering with the transmission of neural signals, affecting the brain's processing and integration of information, and other issues that need to be paid special attention to during long-term treatment of monopolar time interference electrical stimulation.

[0055] Therefore, the non-invasive deep brain electrical stimulation system of the present application can determine the stimulation scheme according to the resting-state functional magnetic resonance of the target subject before each treatment based on the stimulation polarity detection module, for example, adjust the scalp stimulation target to ensure that the monopolar electrical stimulation reaches the target brain area, to reduce adverse interference on other non-target brain areas; or adjust the direction of the rectified waveform according to the degree of improvement of the condition to avoid potential safety problems such as brain electrolyte disorder caused by long-term strong stimulation.

[0056] In some embodiments, extracting the blood oxygen level dependent signal of the target brain function network and / or brain area in the resting-state functional magnetic resonance data through the data preprocessing unit and the data post-processing unit can include:

[0057] The data preprocessing unit is used to perform quality inspection, time point removal, layer scanning time correction, head motion correction, image registration, standardization processing, smoothing processing, and / or low-frequency band pass filtering preprocessing operations on the resting-state functional magnetic resonance data to obtain standard data for functional network state analysis;

[0058] Further, the functional magnetic resonance data post-processing unit can be used to complete functional network state analysis including time series extraction, functional connection matrix calculation, and / or statistical analysis of the resting-state functional magnetic resonance data processed by the data preprocessing unit.

[0059] By obtaining the analysis results, for example, if a certain specific functional network or brain area of the target subject is in abnormal inhibition, the stimulation polarity detection module can obtain a treatment scheme of giving the target subject enhanced stimulation, which can be achieved by providing the target subject with an enhanced stimulation waveform; otherwise, a treatment scheme of giving the target subject negative waveform inhibitory stimulation can be obtained. In this way, the non-invasive deep brain electrical stimulation system of the present application can obtain the guidance results of the selection of the stimulation polarity based on the magnetic resonance BOLD signal, thereby enhancing the accuracy of the time interference electrical stimulation for target subjects in different physical states.

[0060] According to some embodiments, the non-invasive deep brain electrical stimulation system of the present application can further comprise a stimulation evaluation module for detecting the electrical stimulation parameters and effects on the target, the electrical stimulation parameters including the frequency, amplitude, rise, fall or on-off ratio of the first stimulation waveform and / or the second stimulation waveform, and the electrical stimulation effects can include the therapeutic effects on the target subject and the effects of each system output of the stimulation components of the frequency, amplitude, rise and / or fall or on-off ratio of the first stimulation waveform and / or the second stimulation waveform, and in addition, the stimulation evaluation module can also continuously monitor the current amplitude and frequency of the stimulation waveform output by the stimulation output module to monitor the electrical stimulation of the target subject in real time.

[0061] Specifically, detecting the electrical stimulation parameters and effects on the target by the stimulation evaluation module can include evaluating the electrical stimulation effects on the target by the stimulation evaluation unit using the results of the neuroelectrophysiological electroencephalogram, local field potential, functional magnetic resonance, functional ultrasound and behavior of the target subject, and on this basis, by analyzing the correlation between the electrical stimulation effects and the stimulation parameters, the recommended adjustment parameters of the first stimulation waveform and / or the second stimulation waveform can be obtained. In this way, through long-term targeted stimulation and real-time regulation, functional intervention on the brain of the target subject can be achieved, and further effective treatment of brain diseases of the target subject can be achieved.

[0062] Another advantage of configuring the stimulation evaluation module is that it can be a supplement or alternative to the stimulation polarity detection module, and by evaluating the electrical stimulation effects after each stimulation, the feasibility of the entire system for the target subject can be evaluated and the treatment plan can be adjusted or strengthened accordingly, such as changing the stimulation waveform polarity. That is, the applicability of the stimulation plan provided by the entire system to the target subject is further enhanced by the cooperation of the stimulation polarity detection module and the stimulation evaluation module; when it is difficult to pre-prepare the stimulation plan of the target subject by multiple acquisition of resting-state functional magnetic resonance data of the target subject, the existing stimulation plan can also be adjusted in time based on the evaluation of the effects after treatment, so as to reduce the use cost of the non-invasive deep brain electrical stimulation system according to the embodiments of the present application.

[0063] The non-invasive deep brain electrical stimulation system of the present application can further comprise a power module and a microprocessor, wherein the power module can be connected to and powered by the waveform generation module, the waveform rectification module, the current stabilization module, the stimulation output module and the microprocessor; the microprocessor can be electrically connected to the waveform generation module, the waveform rectification module, the current stabilization module, the stimulation output module, the polarity detection module and the stimulation evaluation module to realize the functional control of each module. In particular, the current stabilization module can also independently implement the current stabilization function of the rectified waveform after presetting the current stabilization parameters, such as the current intensity of the rectified waveform.

[0064] Specifically, the power module can include a first power output, a second power output, a third power output, a fourth power output and a fifth power output, which respectively supply power to the waveform generating module, the waveform rectifying module, the constant current module, the stimulation output module and the microprocessor, wherein the constant current module receives high-voltage power supplied by the second power output, and the other power outputs supply low-voltage power to the corresponding modules.

[0065] According to some embodiments, the non-invasive deep brain electrical stimulation system of the present application performs a targeted procedure of regulated polarity non-invasive electrical stimulation on a target subject as shown in Figure 5 as follows:

[0066] The polarity detection module performs data preprocessing and post-processing based on the collected functional magnetic resonance data of the target subject to obtain preset stimulation mode information;

[0067] The microprocessor receives the preset stimulation mode information of the stimulation polarity detection module and determines the required stimulation polarity of the target subject to obtain a first control instruction;

[0068] The microprocessor sends the first control instruction to the stimulation output module to control the stimulation output module to determine the stimulation target point position, stimulation duration, current amplitude and frequency of the stimulation waveform of the stimulation electrode;

[0069] The stimulation output module is controlled to start outputting the stimulation waveform to the designated area of the scalp of the target subject through the two pairs of stimulation electrodes, and the stimulation evaluation module continuously monitors the stimulation current within the preset stimulation duration to ensure that the target subject receives accurate and safe electrical stimulation;

[0070] After the preset stimulation duration, the stimulation output module stops outputting the stimulation waveform, and the stimulation evaluation module collects the neuroelectrophysiological electroencephalogram, local field potential, functional magnetic resonance, functional ultrasound and behavioral test results of the target subject at this time to obtain the electrical stimulation effect;

[0071] The microprocessor receives the electrical stimulation effect of the stimulation evaluation module and determines the required adjustment scheme of the stimulation waveform of the target subject to obtain a second control instruction; the microprocessor sends the second control instruction to the waveform generating module for adjusting the frequency of the stimulation waveform output next time; sends the second control instruction to the waveform rectifying module for adjusting the voltage amplitude, polarity and on-off ratio of the stimulation waveform output next time; sends the second control instruction to the constant current module for adjusting the current intensity and change rate of the stimulation waveform output next time; and sends the second control instruction to the stimulation output module for adjusting the stimulation target point position of the stimulation waveform output next time.

[0072] The basic principles of the application are described above in connection with specific embodiments, but it should be noted that the advantages, benefits, effects and the like mentioned in the present application are only examples and are not intended to be limiting, and it should not be considered that these advantages, benefits, effects and the like are necessarily possessed by each embodiment of the present application. In addition, the above specific details of the disclosure are only for the purpose of example and understanding, and are not limiting, and the above details do not limit the present application to be necessarily implemented with the above specific details.

[0073] The words "comprise", "comprising", "include", "including", "have", "has", "contain", "containing", or similar words are open-ended words, i.e., they are not limited to the elements that follow them. The words "comprise", "comprising", "include", "including", "have", "has", "contain", "containing", or similar words are interchangeable with each other. The words "or" and "and" as used herein mean "and / or", and are interchangeable with each other, unless the context clearly indicates otherwise. The words "such as" as used herein mean "such as but not limited to", and are interchangeable with each other.

[0074] It should also be noted that in the methods, systems and devices of the present application, each step or module can be decomposed and / or recombined. These decompositions and / or recombinations should be considered as equivalents of the present application.

[0075] The above description has been given for the purpose of illustration and description. Furthermore, this description is not intended to limit the embodiments of the present application to the forms disclosed herein. Although a number of example aspects and embodiments have been discussed above, those skilled in the art will recognize certain modifications, permutations, additions, sub-combinations, substitutions, and the like, of the above-described aspects and embodiments.

Claims

1. A polar-adjustable non-invasive deep brain electrical stimulation system, comprising: a waveform generating module configured to generate a first frequency waveform using a first signal generator and a second frequency waveform using a second signal generator; a waveform rectifying module connected to an output end of the waveform generating module, configured to perform full-wave rectification on the first frequency waveform using a first rectifying component to obtain a first rectified waveform, and perform full-wave rectification on the second frequency waveform using a second rectifying component to obtain a second rectified waveform; a current stabilizing module connected to an output end of the waveform rectifying module, the first rectified waveform passing through a first current stabilizing component to obtain a high-frequency distortionless first stimulation waveform, and the second rectified waveform passing through a second current stabilizing component to obtain a high-frequency distortionless second stimulation waveform; a stimulation output module connected to an output end of the current stabilizing module, configured to output the first stimulation waveform and the second stimulation waveform to a scalp stimulation target of a target using a stimulation electrode to generate a low-frequency envelope stimulation waveform in a deep brain; a stimulation polarity detection module configured to collect resting-state functional magnetic resonance data of the target, extract a blood oxygen level dependent signal of a brain function network and / or a brain region of the target in the resting-state functional magnetic resonance data through a data preprocessing unit and a data postprocessing unit, and evaluate the brain region according to an abnormal state of the blood oxygen level dependent signal: in response to abnormal excitation of the brain region, determine a scalp stimulation target of the brain region, and make the current directions of the first rectified waveform and the second rectified waveform output by the waveform rectifying module both negative; in response to abnormal inhibition of the brain region, determine a scalp stimulation target of the brain region, and make the current directions of the first rectified waveform and the second rectified waveform output by the waveform rectifying module both positive.

2. The system of claim 1, wherein the first rectifying component and the second rectifying component comprise a voltage input unit, a unidirectional conduction unit, and a load, wherein the voltage input unit adjusts a voltage amplitude of the first frequency waveform or the second frequency waveform to a preset voltage amplitude; the unidirectional conduction unit adjusts a current direction flowing through the load in a positive half cycle and a negative half cycle of the first frequency waveform or the second frequency waveform, respectively, so that the current direction flowing through the load is consistent in a whole cycle of the first frequency waveform or the second frequency waveform, thereby generating the first rectified waveform or the second rectified waveform with a constant current direction.

3. The system of claim 2, wherein the unidirectional conduction unit comprises a first rectifying diode and a second rectifying diode, wherein the first rectifying diode and the second rectifying diode each have a first end and a second end; in the positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is turned on and the second rectifying diode is reverse cut-off, and the current flows from the first end of the first rectifying diode to the second end of the first rectifying diode; in the negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is reverse cut-off and the second rectifying diode is turned on, and the current flows from the first end of the second rectifying diode to the second end of the second rectifying diode.

4. The system of claim 2, wherein, the unidirectional conductive unit comprises a first rectifier diode and a second rectifier diode, wherein, the first rectifier diode and the second rectifier diode have a first end and a second end, respectively; in a positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is turned on and the second rectifier diode is turned off, and the current flows through the second end of the first rectifier diode to the first end of the first rectifier diode; in a negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is turned off and the second rectifier diode is turned on, and the current flows through the second end of the second rectifier diode to the first end of the second rectifier diode.

5. The system of claim 1, wherein, the first current stabilizing component and the second current stabilizing component comprise a first constant current unit and a second constant current unit, respectively, wherein, the first constant current unit adjusts the current of the first rectified waveform or the second rectified waveform to be constant, and the second constant current unit comprises a transistor-based constant current source circuit with a higher frequency response to ensure the output amplitude of high-frequency components in the first rectified waveform or the second rectified waveform is stable.

6. The system of claim 1, wherein, the extracting of the blood oxygen level dependent signal of the brain function network and / or the brain region of the target in the resting state functional magnetic resonance data by the data preprocessing unit and the data post-processing unit comprises: the data preprocessing unit performs quality inspection, time point removal, layer scanning time correction, head motion correction, image registration, standardization processing, smoothing processing, and / or low-frequency band filtering on the resting state functional magnetic resonance data; the data post-processing unit comprises time series extraction, functional connectivity matrix calculation, and / or statistical analysis on the resting state functional magnetic resonance data processed by the data preprocessing unit.

7. The system of claim 1, further comprising: a stimulation evaluation module for detecting the electrical stimulation parameters and effects on the target.

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