A non-invasive deep coupling electrical stimulation method, device, apparatus and storage medium

Abstract

The application discloses a non-invasive deep coupling electrical stimulation method, device, equipment and storage medium, the non-invasive deep coupling electrical stimulation method combines cross-frequency coupling electrical stimulation and temporally interfering electrical stimulation (TIS) technology, proposes TIS-CFC-tACS, the technology utilizes the high spatial specificity and deep selectivity of TIS to carry out accurate regulation to deep brain area, simultaneously generates another tACS stimulation and TIS stimulation to form cross-frequency coupling, and is expected to overcome the deficiency of conventional CFC-tACS in stimulation depth and spatial specificity, improves the efficiency and precision of cross-frequency coupling electrical stimulation.The application relates to neural regulation technology.

Description

TECHNICAL FIELD

[0001] The present application relates to neuromodulation technology, and in particular to a non-invasive deep coupling electrical stimulation system. BACKGROUND

[0002] Existing treatments for cognitive impairment, including medication, surgical intervention and behavioral intervention, face many challenges due to inconsistent treatment effects, slow symptom improvement and related risks and side effects. Therefore, there is an urgent need for innovative and personalized treatment options to achieve rapid and lasting cognitive improvement and minimize side effects. Non-invasive neuromodulation technology, particularly transcranial electrical stimulation (tES), as an emerging tool, has shown valuable potential and is expected to make breakthroughs in the treatment of neurocognitive disorders.

[0003] Many cognitive disorders are accompanied by abnormalities in neural oscillation patterns, which manifest as abnormal or disrupted functional connectivity within and between brain regions. To improve this abnormal functional connectivity, a cross-frequency coupling transcranial electrical stimulation scheme (CFC-tACS) has been proposed. Several studies have shown that CFC-tACS can induce changes in brain network coupling characteristics and has shown strong application prospects in cognitive function regulation. However, due to the diffusion of electrical current in biological tissue, conventional electrical stimulation techniques have low spatial specificity, making it difficult to accurately regulate deep brain regions such as the hippocampus, thalamus and nucleus accumbens, which play a key role in cognitive processes.

[0004] Therefore, there is a need for a new transcranial electrical stimulation scheme that can overcome the shortcomings of conventional CFC-tACS in terms of stimulation depth and spatial specificity, and improve the efficiency and accuracy of cross-frequency coupling electrical stimulation. SUMMARY

[0005] To at least partially solve one of the technical problems existing in the prior art, the purpose of the present application is to provide a non-invasive deep coupling electrical stimulation method, device, equipment and storage medium, which can overcome the shortcomings of conventional CFC-tACS in terms of stimulation depth and spatial specificity, and improve the efficiency and accuracy of cross-frequency coupling electrical stimulation.

[0006] The first technical solution adopted by the present application is:

[0007] A non-invasive deep coupling electrical stimulation method, comprising the following steps:

[0008] The controller outputs a first waveform signal, a second waveform signal and a third waveform signal, wherein the first waveform signal and the second waveform signal use high-frequency sinusoidal currents with different frequencies to superimpose a low-frequency envelope waveform signal, and the third waveform signal forms a cross-frequency coupling with the low-frequency envelope waveform signal;

[0009] The first waveform signal, the second waveform signal and the third waveform signal are respectively input to digital-to-analog converters for digital-to-analog conversion, the digital-to-analog converters corresponding to each waveform signal are controlled by the same clock signal, and are controlled by the controller;

[0010] The first waveform signal, the second waveform signal and the third waveform signal are respectively input to a voltage-to-current conversion module to be converted into current signals;

[0011] The current signals corresponding to the first waveform signal, the second waveform signal and the third waveform signal are output to electrodes, and the electrodes guide the current to the head of the subject.

[0012] According to some embodiments of the present application, the positions of the electrodes and the current intensity need to be optimized and analyzed first, and the steps of the optimization and analysis include:

[0013] Obtaining a nuclear magnetic structure image of the subject;

[0014] Determining an image region containing a stimulation target through brain mapping registration;

[0015] Segmenting the nuclear magnetic structure image to separate various types of tissues with different electrical conductivities;

[0016] Constructing a finite element model based on the segmented brain image;

[0017] Registering scalp electrode sites to place the electrodes;

[0018] Calculating the electric field distribution in each voxel of the finite element model when injecting 1 mA current into each electrode with Cz as a reference to calculate the pilot field matrix;

[0019] Constructing constraint conditions such as total injected current constraint, single electrode injected current constraint, electrode channel non-repetition constraint, and avoidance of activated brain area constraint, and combining with the stimulation target coordinates to form a non-convex multi-objective optimization problem;

[0020] Solving by using a genetic algorithm to output the optimal solution of the electrode positions and current intensity that satisfy the constraint conditions.

[0021] According to some embodiments of the present application, the cross-frequency coupling between the third waveform signal and the low-frequency envelope waveform signal is a phase synchronization coupling mode, the beat frequency of the low-frequency envelope waveform signal is the same as the frequency of the third waveform signal, and the constant phase difference between brain areas is realized by adjusting the phase of the third waveform signal.

[0022] According to some embodiments of the present application, the cross-frequency coupling between the third waveform signal and the low-frequency envelope waveform signal is a phase-amplitude coupling mode, and the low-frequency envelope waveform signal adopts a Theta rhythm, and a constant phase difference between brain regions is achieved by adjusting the phase of the third waveform signal.

[0023] According to some embodiments of the present application, after the first waveform signal, the second waveform signal and the third waveform signal are converted into digital signals, the first waveform signal, the second waveform signal and the third waveform signal are subjected to signal conditioning to adapt to a suitable voltage and frequency range.

[0024] According to some embodiments of the present application, after the first waveform signal, the second waveform signal and the third waveform signal are converted into current signals, the first waveform signal, the second waveform signal and the third waveform signal are subjected to voltage isolation by an isolation module.

[0025] The second technical solution adopted by the present application is:

[0026] A non-invasive deep coupling electrical stimulation device for performing the non-invasive deep coupling electrical stimulation method described above, comprising:

[0027] a controller for outputting the first waveform signal, the second waveform signal and the third waveform signal;

[0028] a digital-to-analog converter for converting the first waveform signal, the second waveform signal and the third waveform signal into digital signals;

[0029] a signal conditioning module for conditioning the first waveform signal, the second waveform signal and the third waveform signal;

[0030] a voltage-to-current converter for converting the first waveform signal, the second waveform signal and the third waveform signal into current signals;

[0031] an isolation module for voltage isolation of the current signals converted by the first waveform signal, the second waveform signal and the third waveform signal;

[0032] an electrode for outputting the current signals converted by the first waveform signal, the second waveform signal and the third waveform signal to the head of a subject.

[0033] According to some embodiments of the present application, the electrodes corresponding to the first waveform signal and the second waveform signal adopt a dual-electrode configuration scheme, and the electrode corresponding to the third waveform signal adopts a 4x1 electrode configuration scheme.

[0034] The third technical solution adopted by the present application is:

[0035] An electronic device, comprising a processor and a memory, the memory having stored therein at least one instruction, at least one program, a code set or an instruction set, the at least one instruction, the at least one program, the code set or the instruction set being loaded and executed by the processor to implement the non-invasive deep coupling electrical stimulation method as described above.

[0036] The fourth technical solution adopted by the present application is:

[0037] A computer-readable storage medium, the storage medium having stored therein at least one instruction, at least one program, a code set or an instruction set, the at least one instruction, the at least one program, the code set or the instruction set being loaded and executed by a processor to implement the non-invasive deep coupling electrical stimulation method as described above.

[0038] The present application has the beneficial effects that: the present application combines cross-frequency coupling electrical stimulation and temporally interfering electrical stimulation (TIS) technology, proposes temporally interfering cross-frequency coupling transcranial alternating current stimulation (TIS-CFC-tACS), which uses the high spatial specificity and deep selectivity of TIS to precisely regulate deep brain regions, and at the same time generates another tACS stimulation to form cross-frequency coupling with the TIS stimulation, which is expected to overcome the shortcomings of conventional CFC-tACS in stimulation depth and spatial specificity, and improve the efficiency and precision of cross-frequency coupling electrical stimulation. BRIEF DESCRIPTION OF DRAWINGS

[0039] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the following introduces the drawings of the related technical solutions in the embodiments of the present application or the prior art. It should be understood that the drawings in the following introduction are only for the convenience of clearly describing part of the embodiments in the technical solutions of the present application, and for those skilled in the art, other drawings can also be obtained from these drawings without creative labor.

[0040] Figure 1 is the optimization flowchart of electrode position and current intensity in the non-invasive deep coupling electrical stimulation method of the embodiments of the present application;

[0041] Figure 2 is the working flowchart of the non-invasive deep coupling electrical stimulation device of the embodiments of the present application;

[0042] Figure 3 is the connection schematic diagram of the multiple non-invasive deep coupling electrical stimulation devices and the control center in the embodiments of the present application.

[0043] Reference signs: 001-controller, 101-first digital-to-analog converter, 102-first signal conditioning module, 103-first voltage current converter, 104-first isolation module, 105-first electrode, 201-second digital-to-analog converter, 202-second signal conditioning module, 203-second voltage current converter, 204-second isolation module, 205-second electrode, 301-third digital-to-analog converter, 302-third signal conditioning module, 303-third voltage current converter, 304-third isolation module, 305-third electrode. DETAILED DESCRIPTION

[0044] Embodiments of the present application are described below in detail, examples of which are shown in the drawings, wherein the same or similar reference signs represent the same or similar elements or elements having the same or similar functions throughout. The embodiments described below by referring to the drawings are exemplary and are only used to explain the present application, and cannot be understood as a limitation of the present application. For the step numbers in the following embodiments, they are only set for the convenience of explaining the description, and the order between the steps is not limited in any way, and the execution order of each step in the embodiments can be adaptively adjusted according to the understanding of those skilled in the art.

[0045] In the description of the present application, it should be understood that the orientation description, such as the orientation or position relationship indicated by up, down, front, back, left, right, etc. is based on the orientation or position relationship shown in the drawings, and is only for the convenience of describing the present application and simplifying the description, and does not indicate or imply that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation of the present application.

[0046] In the description of the present application, several meanings are one or more, and the meaning of multiple is two or more, greater than, less than, more than, etc. are understood as not including the number, above, below, etc. are understood as including the number. If it is described as first, second, it is only used for the purpose of distinguishing technical features, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features or implicitly indicating the order of indicated technical features.

[0047] In the description of the present application, unless otherwise explicitly limited, the words such as setting, installing, connecting, etc. should be broadly understood, and those skilled in the art can reasonably determine the specific meaning of the above words in the present application in combination with the specific content of the technical solution.

[0048] Existing treatments for cognitive impairment, including medication, surgical intervention, and behavioral intervention, face many challenges due to inconsistent treatment effects, slow symptom improvement, and associated risks and side effects. Therefore, there is an urgent need for innovative and personalized treatment options to achieve rapid and lasting cognitive improvement and minimize side effects. Non-invasive neuromodulation techniques, particularly transcranial electrical stimulation (tES), show valuable potential and are expected to make breakthroughs in the treatment of neurocognitive disorders.

[0049] Many cognitive disorders are accompanied by abnormalities in neural oscillation patterns, manifested as abnormal or interrupted functional connectivity within and between brain regions. To improve this abnormal functional connectivity, a cross-frequency coupling transcranial alternating current stimulation (CFC-tACS) scheme is proposed. Studies have shown that CFC-tACS can induce changes in brain network coupling characteristics and has strong application prospects in cognitive function regulation. However, due to the diffusion of electrical current in biological tissue, conventional electrical stimulation techniques have low spatial specificity, making it difficult to accurately regulate deep brain regions such as the hippocampus, thalamus, and nucleus accumbens, which play a key role in cognitive processes.

[0050] To this end, the present application proposes a non-invasive deep coupling electrical stimulation method, device, equipment and storage medium. The present application combines cross-frequency coupling electrical stimulation and temporally interfering electrical stimulation (TIS) technology to propose temporally interfering cross-frequency coupling transcranial alternating current stimulation (TIS-CFC-tACS). This technology uses the high spatial specificity and deep selectivity of TIS to accurately regulate deep brain regions, while generating another tACS stimulation to form cross-frequency coupling with the TIS stimulation, which is expected to overcome the shortcomings of conventional CFC-tACS in stimulation depth and spatial specificity, and improve the efficiency and accuracy of cross-frequency coupling electrical stimulation.

[0051] Embodiment 1

[0052] The present embodiment provides a non-invasive deep coupling electrical stimulation method, comprising the following steps:

[0053] S100. Outputting, by the controller 001, a first waveform signal, a second waveform signal, and a third waveform signal, wherein the first waveform signal and the second waveform signal superimpose high-frequency sinusoidal currents with different frequencies to generate a low-frequency envelope waveform signal, and the third waveform signal forms cross-frequency coupling with the low-frequency envelope waveform signal;

[0054] S200. The first waveform signal, the second waveform signal, and the third waveform signal are respectively input to digital-to-analog converters for digital-to-analog conversion, the digital-to-analog converters corresponding to the respective waveform signals are controlled by the same clock signal, and the digital-to-analog converters are controlled by the controller, to ensure synchronization of the signals of the respective channels;

[0055] S300. The first waveform signal, the second waveform signal, and the third waveform signal are respectively input to a voltage-to-current conversion module to be converted into current signals;

[0056] S400. The current signals corresponding to the first waveform signal, the second waveform signal, and the third waveform signal are output to the electrode, and the electrode guides the current to the head of the subject.

[0057] In the cross-frequency coupling mode of the third waveform signal and the low-frequency envelope waveform signal, first, two high-frequency sinusoidal currents (TIS1 and TIS2) with slightly different frequencies are used to superimpose to generate a low-frequency envelope waveform. Due to the low-pass effect of neurons to some extent, high-frequency stimulation close to the surface cannot directly cause neuron firing, but the envelope frequency formed by superimposition in the deep brain can be within the dynamic range of neuron firing. This low-frequency envelope waveform can penetrate brain tissue and achieve stimulation effect. The third waveform signal and the low-frequency envelope waveform signal of the deep brain region form a specific cross-frequency coupling (CFC).

[0058] Further, for the form of cross-frequency coupling, in some embodiments, the cross-frequency coupling of the third waveform signal and the low-frequency envelope waveform signal is a phase synchronous coupling mode, the beat frequency of the low-frequency envelope waveform signal is the same as the frequency of the third waveform signal, and a constant phase difference between brain regions is achieved by adjusting the phase of the third waveform signal.

[0059] In other embodiments, the cross-frequency coupling of the third waveform signal and the low-frequency envelope waveform signal is a phase-amplitude coupling mode, the frequencies of the first waveform signal and the second waveform signal are in the Gamma band, and the low-frequency envelope waveform signal adopts a Theta rhythm. For example, the frequency of the first waveform signal is 37 Hz, the frequency of the second waveform signal is 43 Hz, and the beat frequency of the low-frequency envelope is 6 Hz. In this way, Theta-gamma phase-amplitude coupling in the deep brain region can be achieved, and a constant phase difference between brain regions is achieved by adjusting the phase of the third waveform signal. This stimulation mode can simultaneously regulate the Theta-gamma phase-amplitude coupling of the local brain region and the phase synchronization between brain regions.

[0060] Further, the position of the electrode and the current intensity need to be optimized and analyzed in advance, with reference to Figure 1 The steps of the optimization and analysis include:

[0061] S010. Obtain a nuclear magnetic structure image of the subject;

[0062] S020. Determine the image region containing the stimulation target by brain atlas registration;

[0063] S030. Segment the magnetic structure image to separate different types of tissues with different conductivities;

[0064] S040. Construct a finite element model based on the segmented brain image;

[0065] S050. Register the scalp electrode sites and place the electrodes according to the international 10 / 10 electrode system;

[0066] S060. Calculate the electric field distribution in each voxel of the finite element model when a 1mA current is injected at each electrode with Cz as the reference, and calculate the pilot field matrix;

[0067] S070. Construct constraint conditions such as total injected current constraint, single electrode injected current constraint, electrode channel non-repetition constraint, and avoidance of activated brain area constraint, and combine with the stimulation target coordinates to form a non-convex multi-objective optimization problem;

[0068] S080. Solve using genetic algorithm, output the optimal solution of electrode position and current intensity that satisfies the constraint conditions.

[0069] Further, the first waveform signal, the second waveform signal and the third waveform signal are converted into digital signals, and then are signal-conditioned to suitable voltage and frequency ranges.

[0070] Further, the first waveform signal, the second waveform signal and the third waveform signal are converted into current signals, and then are voltage-isolated by an isolation module.

[0071] Compared with the traditional transcranial electrical stimulation method, the present method uses a multi-channel signal source driven by a synchronous clock combined with an isolation module to construct a synchronous and isolated electrical stimulation channel, meeting the requirements of TIS-CFC-tACS for the number of channels, synchronization and isolation. Moreover, by combining the cross-frequency coupling electrical stimulation and the temporally interfering electrical stimulation (TIS) technology, the present method proposes a temporally interfering cross-frequency coupling transcranial alternating current stimulation (TIS-CFC-tACS), which uses the high spatial specificity and deep selectivity of TIS to precisely regulate deep brain regions, and at the same time generates another tACS stimulation to form cross-frequency coupling with the TIS stimulation, which is expected to overcome the shortcomings of conventional CFC-tACS in stimulation depth and spatial specificity, and improve the efficiency and precision of cross-frequency coupling electrical stimulation.

[0072] In addition, in order to ensure effective stimulation of the target area while avoiding unnecessary effects on surrounding tissues, individual parameter optimization of the stimulation electrode position and stimulation current size is performed through finite element simulation technology to ensure the safety of the stimulation process.

[0073] Embodiment 2

[0074] With reference to Figure 2 The embodiment provides a non-invasive deep coupling electrical stimulation device for performing the non-invasive deep coupling electrical stimulation method, which comprises:

[0075] a controller 001 for outputting a first waveform signal, a second waveform signal and a third waveform signal.

[0076] a digital-to-analog converter for digital-to-analog conversion of the first waveform signal, the second waveform signal and the third waveform signal. Specifically, the digital-to-analog converter comprises a first digital-to-analog converter 101 for digital-to-analog conversion of the first waveform signal, a second digital-to-analog converter 201 for digital-to-analog conversion of the second waveform signal, and a third digital-to-analog converter 301 for digital-to-analog conversion of the third waveform signal. The first digital-to-analog converter 101, the second digital-to-analog converter 201 and the third digital-to-analog converter 301 are all controlled by the same clock signal and are all controlled by the controller 001, ensuring the synchronization of the signals of the channels.

[0077] a signal conditioning module for signal conditioning of the first waveform signal, the second waveform signal and the third waveform signal. Specifically, the signal conditioning module comprises a first signal conditioning module 102 for signal conditioning of the first waveform signal, a second signal conditioning module 202 for signal conditioning of the second waveform signal, and a third signal conditioning module 302 for signal conditioning of the third waveform signal.

[0078] a voltage-to-current converter for converting the first waveform signal, the second waveform signal and the third waveform signal into current signals. Specifically, the voltage-to-current converter comprises a first voltage-to-current converter 103 for signal conversion of the first waveform signal, a second voltage-to-current converter 203 for signal conversion of the second waveform signal, and a third voltage-to-current converter 303 for signal conversion of the third waveform signal.

[0079] an isolation module for voltage isolation of the current signals converted by the first waveform signal, the second waveform signal and the third waveform signal. Specifically, the isolation module comprises a first isolation module 104 for voltage isolation of the first waveform current signal, a second isolation module 204 for voltage isolation of the second waveform current signal, and a third isolation module 304 for voltage isolation of the third waveform current signal.

[0080] An electrode for outputting the current signals converted from the first, second and third waveform signals to the head of the subject. Specifically, the electrode includes a first electrode 105 for outputting the first waveform current signal, a second electrode 205 for outputting the second waveform current signal, and a third electrode 305 for outputting the third waveform current signal.

[0081] For each waveform signal, there is a corresponding digital-to-analog converter, signal conditioning module, voltage-to-current converter, isolation module and electrode for signal processing and conversion, ensuring that each waveform signal does not affect each other, maintaining the accuracy of the signal.

[0082] Further, the electrodes corresponding to the first and second waveform signals adopt a double electrode configuration scheme for time domain interference electric stimulation. The electrode corresponding to the third waveform signal adopts a 4x1 electrode configuration scheme to improve the focusing of the stimulation. It is easy to understand that each electrode can also adopt other configuration schemes, which will not be described here.

[0083] Further, the number of the non-invasive deep coupling electric stimulation devices can also be set to multiple and controlled by a unified control center. Referring to Figure 3 , the control center includes a main processor and a clock module for providing a unified reference time base. The control center is provided with several transceivers and is connected to each interface through an isolation module. Each interface is connected to the controller 001 of each non-invasive deep coupling electric stimulation device through a cable.

[0084] Each non-invasive deep coupling electric stimulation device includes an interface port for connecting with the control center interface, which is connected to the transceiver to receive the synchronization clock signal and control data from the host. The transceiver transmits the received signal to the transceiver module 400 or communicates with it bidirectionally, and sends it to the controller 001 inside the non-invasive deep coupling electric stimulation device. In the controller 001, the clock module can be directly adopted as its own working clock, or the external clock module can be used to regularly calibrate its local clock, so as to realize the synchronization of the clock domain between different sub-devices.

[0085] The non-invasive deep coupling electric stimulation device converts the generated waveform data into analog signals through the digital-to-analog converter under the control of the main processor, and adjusts the amplitude, frequency or waveform shape of the waveform through the signal conditioning module. Subsequently, the voltage signal is converted into a corresponding current signal through the voltage-to-current converter, and finally output to the electrode, providing a variety of programmable stimulation waveforms for the subject's organization or part.

[0086] Through the above design scheme, the control center distributes the unified clock to each sub-device, so that any number of non-invasive deep coupling electric stimulation devices can work synchronously through the master clock or the locally calibrated clock. At the same time, each non-invasive deep coupling electric stimulation device has relatively independent processing and driving functions at the hardware level, which is convenient for flexible expansion and meets the multi-channel or large-scale stimulation demand. The discrete implementation mode improves the flexibility and expansibility of the system, and also guarantees the time synchronization accuracy of the stimulation signal.

[0087] Embodiment 3

[0088] The embodiment of the present application also provides an electronic device, which comprises a processor and a memory, and the memory stores at least one instruction, at least one program, a code set or an instruction set, which are loaded and executed by the processor to realize the non-invasive deep coupling electric stimulation method described above.

[0089] It can be understood that the memory can include a random access memory (RAM) and a read-only memory (ROM). Optionally, the memory includes a non-transitory computer-readable storage medium. The memory can be used to store instructions, programs, codes, code sets or instruction sets. The memory can include a program storage area and a data storage area, wherein the program storage area can store instructions for implementing an operating system, instructions for at least one function, instructions for implementing various method embodiments described above, etc.; and the data storage area can store data created according to the use of the server, etc.

[0090] The processor can include one or more processing cores. The processor connects various parts within the entire server by various interfaces and lines, executes various functions of the server and processes data by running or executing instructions, programs, code sets or instruction sets stored in the memory, and calling data stored in the memory. Optionally, the processor can be implemented in at least one of a hardware form of a digital signal processing (DSP), a field-programmable gate array (FPGA), and a programmable logic array (PLA). The processor can be integrated with one or several combinations of a central processing unit (CPU) and a modem. Among them, the CPU mainly processes operating systems and application programs; the modem is used to process wireless communication. It can be understood that the above-mentioned modem can also not be integrated into the processor, but be implemented by a separate chip.

[0091] Since the electronic device is an electronic device corresponding to the closed-loop transcranial electrical stimulation method of the embodiments of the present application, and the principle of solving problems of the electronic device is similar to that of the method, the implementation of the electronic device can be referred to the implementation process of the above-mentioned method embodiments, and the repeated parts will not be described again.

[0092] Embodiment 4

[0093] The embodiments of the present application also provide a computer readable storage medium, wherein at least one instruction, at least one program, a code set or an instruction set are stored in the storage medium, and the at least one instruction, the at least one program, the code set or the instruction set are loaded and executed by the processor to realize the non-invasive deep coupling electrical stimulation method described above.

[0094] Those skilled in the art can understand that all or part of the steps of various methods in the above embodiments can be completed by instructing the relevant hardware through a program, and the program can be stored in a computer readable storage medium, including Read-Only Memory (ROM), Random Access Memory (RAM), Programmable Read-only Memory (PROM), Erasable Programmable Read Only Memory (EPROM), One-time Programmable Read-Only Memory (OTPROM), Electrically-Erasable Programmable Read-Only Memory (EEPROM), Compact Disc Read-Only Memory (CD-ROM) or other optical disk storage, magnetic disk storage, magnetic tape storage, or any other medium that can be used to carry or store data which can be read by a computer.

[0095] Since the storage medium is a storage medium corresponding to the closed-loop transcranial electrical stimulation method of the embodiments of the present application, and the problem solving principle of the storage medium is similar to that of the method, the implementation of the storage medium can refer to the implementation process of the above-mentioned method embodiments, and the repeated parts will not be described again.

[0096] Embodiment 5

[0097] In some possible implementations, various aspects of the method of the embodiments of the present application can also be implemented in the form of a program product, which includes program codes for causing a computer device to execute the steps of the non-invasive deep coupling electrical stimulation method according to various exemplary embodiments of the present application described above in the specification when the program product is run on the computer device. Among them, the executable computer program code or "code" for executing various embodiments can be written in a high-level programming language such as C, C++, C#, Smalltalk, Java, JavaScript, Visual Basic, Structured Query Language (for example, Transact-SQL), Perl, or in various other programming languages.

[0098] It should be understood that various aspects of the application can be implemented in hardware, software, firmware or a combination of them. In the above embodiments, various steps or methods can be implemented in software or firmware which is stored in memory and executed by a suitable instruction execution system. For example, if implemented in hardware, and in another embodiment, any of the following technologies, known in the art, or their combination, can be used: discrete logic circuitry having logic gates for implementing logic functions upon an application of data signals, application-specific integrated circuits having appropriate combinational logic gates, programmable gate arrays (PGA), field-programmable gate arrays (FPGA), and so forth.

[0099] In the description of the specification, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Also, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, the person skilled in the art can combine and combine the different embodiments or examples described in the specification and the features of the different embodiments or examples, without contradiction.

[0100] The above embodiments are only for the purpose of illustrating the technical concept and characteristics of the present application, and the purpose is to enable those skilled in the art to understand the content of the present application and to implement it, and cannot limit the protection scope of the present application. Any equivalent changes or modifications made according to the essence of the present application should be covered within the protection scope of the present application.

Claims

1. A non-invasive deep coupling electro-stimulation device, characterized in that, The method comprises the following steps: a controller is used to output a first waveform signal, a second waveform signal and a third waveform signal; a digital-to-analog converter is used to convert the first waveform signal, the second waveform signal and the third waveform signal into analog signals; a signal conditioning module is used to condition the first waveform signal, the second waveform signal and the third waveform signal; a voltage-to-current converter is used to convert the first waveform signal, the second waveform signal and the third waveform signal into current signals; an isolation module is used to isolate the current signals converted from the first waveform signal, the second waveform signal and the third waveform signal; an electrode is used to output the current signals converted from the first waveform signal, the second waveform signal and the third waveform signal to the head of a subject. The method for practicing the non-invasive deep coupling electrical stimulation method performed by the non-invasive deep coupling electrical stimulation device comprises the following steps: the controller outputs the first waveform signal, the second waveform signal and the third waveform signal, wherein the first waveform signal and the second waveform signal superimpose high-frequency sinusoidal currents with different frequencies to generate a low-frequency envelope waveform signal, and the third waveform signal forms a cross-frequency coupling with the low-frequency envelope waveform signal; the first waveform signal, the second waveform signal and the third waveform signal are input into the digital-to-analog converter for digital-to-analog conversion, the digital-to-analog converters corresponding to the waveform signals are controlled by the same clock signal, and the digital-to-analog converters are controlled by the controller; the first waveform signal, the second waveform signal and the third waveform signal are input into the voltage-to-current conversion module to be converted into current signals; the current signals corresponding to the first waveform signal, the second waveform signal and the third waveform signal are output to the electrode.

2. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The position and current intensity of the electrode need to be optimized and analyzed, and the steps of the optimization and analysis comprise: obtaining a nuclear magnetic structure image of a subject; determining an image area containing a stimulation target through brain atlas registration; segmenting the nuclear magnetic structure image to separate different types of tissues with different electrical conductivities; constructing a finite element model based on the segmented brain image; registering scalp electrode sites to place the electrodes; calculating the electric field distribution in each voxel of the finite element model when 1 mA current is injected into each electrode with Cz as a reference to calculate a pilot field matrix; constructing constraint conditions of total injected current, single electrode injected current, electrode channel non-repetition, and avoidance of activated brain areas, and combining the stimulation target coordinates to form a non-convex multi-objective optimization problem; solving the problem by using a genetic algorithm to output an optimal solution of the electrode position and current intensity satisfying the constraint conditions.

3. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The cross-frequency coupling between the third waveform signal and the low-frequency envelope waveform signal is a phase synchronous coupling mode, the beat frequency of the low-frequency envelope waveform signal is the same as the frequency of the third waveform signal, and a constant phase difference between brain areas is achieved by adjusting the phase of the third waveform signal.

4. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The cross-frequency coupling between the third waveform signal and the low-frequency envelope waveform signal is a phase-amplitude coupling mode, the low-frequency envelope waveform signal adopts a Theta rhythm, and a constant phase difference between brain regions is achieved by adjusting the phase of the third waveform signal.

5. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The first waveform signal, the second waveform signal, and the third waveform signal are converted into digital signals, and then are converted into analog signals.

6. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The first waveform signal, the second waveform signal, and the third waveform signal are converted into current signals, and then are subjected to voltage isolation through an isolation module.

7. The non-invasive deep-coupled electrical stimulation device of claim 1, wherein: The electrodes corresponding to the first waveform signal and the second waveform signal adopt a double-electrode configuration scheme, and the electrodes corresponding to the third waveform signal adopt a 4x1 electrode configuration scheme.

8. An electronic device, comprising: The electronic device includes a processor and a memory, and the memory stores at least one instruction, at least one program, a code set, or an instruction set, which are loaded and executed by the processor to practice the non-invasive deep coupling electrical stimulation method performed by the non-invasive deep coupling electrical stimulation device as claimed in any one of claims 1 to 6.

9. A computer-readable storage medium, characterized in that, The storage medium stores at least one instruction, at least one program, a code set, or an instruction set, which are loaded and executed by the processor to practice the non-invasive deep coupling electrical stimulation method performed by the non-invasive deep coupling electrical stimulation device as claimed in any one of claims 1 to 6.

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