Multi-target time interference electrical stimulation method, system, device and program

Abstract

The invention discloses a multi-target time interference electrical stimulation method, system, device and program. The method comprises the following steps: connecting an electrode to a tested head; wherein the electrodes comprise two return electrodes and a plurality of input electrodes; the return electrode comprises a first return electrode and a second return electrode, and a coordinate is established by taking the central point of the head of the subject as an original point and taking a connecting line of the first return electrode and the second return electrode penetrating through the central point of the head as an X axis; adjusting the position of a stimulation target spot along the Y-axis direction by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y axis is perpendicular to the X axis; and the position of the stimulation target in the X-axis direction is adjusted by adjusting the excitation amplitude of the input electrode. Through the treatment scheme disclosed by the invention, the problems of single stimulation target spot, frequent electrode position adjustment, more electrodes and the like in the prior art can be solved.

Description

Technical Field

[0001] The present invention relates to the field of neural stimulation technology, and in particular to a multi-target time-interference electrical stimulation method, system, device and program. Background Art

[0002] Neurological and psychiatric diseases have become a major component of the global disease burden, accounting for 28%, exceeding cardiovascular disease and cancer. Therefore, the need for diagnosis and treatment of major brain diseases has become particularly urgent. In recent years, neuromodulation technology has played an important role in the rehabilitation and treatment of neurological diseases. Among them, transcranial electrical stimulation is a common non-invasive neuromodulation method.

[0003] With the development of neuromodulation technology and the increasing demand for clinical treatment of neurological diseases, traditional single-target electrical stimulation technology has been unable to meet the requirements. When stimulating the brain with traditional transcranial alternating current stimulation (tACS), the electrical properties of human tissue change with frequency. Under its commonly used low-frequency stimulation (such as around 100 Hz), the conductivity of biological tissue is low and the relative dielectric constant is large, which is not conducive to the conduction of stimulation current and the induction of electric field. As a result, the stimulation area is mostly concentrated on the surface of the cerebral cortex, and it is difficult to reach deep brain regions such as the basal forebrain, thalamus, hippocampus, amygdala and hypothalamus. In addition, there is a problem that non-target areas are damaged by the spread of current.

[0004] Time Interference Technology (TI) is a technology that generates a low-frequency envelope signal at a specific location through two or more high-frequency signals with a certain frequency difference. The frequency of the low-frequency envelope signal is equal to the frequency difference of the two high-frequency signals. In recent years, some researchers have combined time interference technology with transcranial alternating current stimulation and proposed time interference transcranial alternating current stimulation technology (TI-tACS). The schematic diagram is as follows Figure 7 As shown, this technology uses high-frequency signals to transmit multiple electric fields to deep brain areas and generate low-frequency envelope electric fields in specific areas deep in the brain, thereby regulating the depolarization or hyperpolarization of deep neurons.

[0005] However, the current TI-tACS technology still faces some challenges. For example, its stimulation strategy is mostly limited to single-target stimulation. In practical applications, since different patients or the same patient may need to stimulate targets in different locations at different stages of treatment, it is often necessary to frequently change the electrode position to adjust the stimulation target, which not only causes physical discomfort to the patient, but also increases the difficulty and workload of the operator. In addition, current technology often requires a large number of electrodes when achieving multi-target stimulation, which makes the system complex and costly. Therefore, there is an urgent need for a new electrical stimulation method and system that can achieve multi-target stimulation and dynamically adjust the target position, while reducing the number of electrodes used and the complexity of operation. Summary of the invention

[0006] In view of this, an embodiment of the present disclosure provides a multi-target time-interference electrical stimulation method, which at least partially solves the problems existing in the prior art.

[0007] In a first aspect, the present disclosure provides a multi-target time-interference electrical stimulation method, the method comprising the following steps: Connecting electrodes to the subject's head; wherein the electrodes include two return electrodes and a plurality of input electrodes; the return electrodes include a first return electrode and a second return electrode, taking the center point of the subject's head as the origin and taking the connecting line of the first return electrode and the second return electrode passing through the center point of the head as the X-axis to establish coordinates; Adjust the position of the stimulation target along the Y-axis direction by adjusting the angle between the input electrode and the nearest return electrode; The position of the stimulation target point along the X-axis direction is adjusted by adjusting the excitation amplitude of the input electrode.

[0008] According to a specific implementation manner of the embodiment of the present disclosure, the method further includes: two-dimensional plane dual-target stimulation and three-dimensional multi-target stimulation.

[0009] According to a specific implementation of the embodiment of the present disclosure, the two-dimensional plane dual-target stimulation includes the following steps: The two-dimensional plane where the electrodes are located is divided into two regions based on the X-axis, and two input electrodes are set on the circumference of the head corresponding to each region; By synchronously adjusting the angle θ between the two input electrodes and the nearest return electrode in each area, the position of the stimulation target along the Y axis is adjusted; The position of the stimulation target along the X-axis direction was adjusted by adjusting the excitation amplitude of the two input electrodes in each area.

[0010] According to a specific implementation of the embodiment of the present disclosure, adjusting the position of the stimulation target along the Y-axis direction by synchronously adjusting the angle between the two input electrodes in each area and the nearest return electrode includes: The angle θ between the two input electrodes and the nearest return electrode and the displacement of the stimulation target along the Y axis are calculated based on the following formula: y=k 1 θ+y 0 Where y is the displacement of the stimulation target along the Y axis; k 1 is the proportionality coefficient; y 0 is the initial position offset; θ is the angle between the input electrode and the nearest return electrode.

[0011] According to a specific implementation of the embodiment of the present disclosure, adjusting the position of the stimulation target along the X-axis direction by adjusting the excitation amplitude of two input electrodes in each area includes: The excitation amplitude of the two input electrodes and the displacement of the stimulation target along the X-axis are calculated based on the following formula: d=k 2 ΔI Where d is the displacement of the stimulation target along the X-axis; ΔI is the change in the current amplitude between the two input electrodes; k 2 is the proportionality coefficient.

[0012] According to a specific implementation of the embodiment of the present disclosure, the three-dimensional multi-target stimulation includes: three-dimensional dual-target stimulation and three-dimensional three-target stimulation; The three-dimensional dual-target stimulation includes: keeping the positions of the two return electrodes fixed, changing the positions of the four input electrodes along the Z-axis, and changing the positions of the stimulation targets by adjusting the excitation amplitude of the input electrodes and the angle of the plane formed by the input electrodes and the two return electrodes; wherein the Z-axis is perpendicular to both the X-axis and the Y-axis; The three-dimensional three-target stimulation includes: on the basis of the three-dimensional two-target stimulation, two input electrodes are added to the plane to be stimulated, and the position of the stimulation target is changed by adjusting the excitation amplitude of the two added input electrodes and the angle of the plane formed by the input electrode and the two return electrodes.

[0013] In a second aspect, the present disclosure provides a multi-target time-interference electrical stimulation system, the system comprising: An electrode configuration module is configured to connect electrodes to a subject's head; wherein the electrodes include two return electrodes and a plurality of input electrodes; the return electrodes include a first return electrode and a second return electrode, and coordinates are established with a center point of the subject's head as an origin and a connecting line between the first return electrode and the second return electrode passing through the center point of the head as an X-axis; The adjustment module is configured to adjust the position of the stimulation target along the Y-axis by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y-axis is perpendicular to the X-axis; and adjust the position of the stimulation target along the X-axis by adjusting the excitation amplitude of the input electrode.

[0014] According to a specific implementation of the embodiment of the present disclosure, the system further includes: The stimulation target adjustment module is configured to divide the two-dimensional plane where the electrode is located into two areas based on the X-axis, and two input electrodes are arranged on the circumference of the head corresponding to each area; Adjust the position of the stimulation target along the Y axis by synchronously adjusting the angle θ between the two input electrodes and the nearest return electrode in each area; and The position of the stimulation target along the X-axis direction was adjusted by adjusting the excitation amplitude of the two input electrodes in each area.

[0015] In a third aspect, an embodiment of the present disclosure further provides an electronic device, the electronic device comprising: at least one processor; and, a memory communicatively connected to the at least one processor; wherein, The memory stores instructions that can be executed by the at least one processor. When the instructions are executed by the at least one processor, the at least one processor implements the multi-target time-interference electrical stimulation method described in any one of the first aspect or any one of the implementations of the first aspect.

[0016] In a fourth aspect, an embodiment of the present disclosure further provides a computer program product, comprising a computer program stored on a non-transitory computer-readable storage medium, wherein the computer program comprises program instructions, and when the program instructions are executed by a computer, the computer executes the multi-target time-interference electrical stimulation method of the first aspect or any implementation of the first aspect.

[0017] The multi-target time-interference electrical stimulation method in the disclosed embodiments can realize a time-interference electrical stimulation method and system with dynamically adjustable positions of multiple targets in the whole brain, so as to solve the problems of single stimulation target, frequent adjustment of electrode positions and large number of electrodes in the prior art, realize simultaneous stimulation of multiple targets in multiple brain regions, and dynamically adjust the target positions, thereby reducing patient discomfort and operation complexity. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The above is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, the present invention is further described in detail below in conjunction with the accompanying drawings and specific implementation methods.

[0019] Figure 1 A schematic flow chart of a multi-target time-interference electrical stimulation method provided in an embodiment of the present disclosure; Figure 2 A schematic diagram of a two-dimensional plane and three-dimensional multi-objective dynamic modulation strategy provided by an embodiment of the present disclosure; Figure 3 A schematic diagram of a dynamic adjustment result of a single stimulation target point on a two-dimensional plane provided in an embodiment of the present disclosure; Figure 4 A schematic diagram of simulation results of a dual stimulation target in a three-dimensional plane provided by an embodiment of the present disclosure; Figure 5 A schematic diagram of simulation results of a three-stimulus target in a three-dimensional plane single-layer sphere model provided by an embodiment of the present disclosure; Figure 6A schematic diagram of simulation results of three stimulation targets in a three-dimensional plane real human brain model provided by an embodiment of the present disclosure; Figure 7 A schematic diagram of the basic principle of TI-tACS provided in an embodiment of the present disclosure; Figure 8 A schematic diagram showing the electrode array position of a single-layer spherical model from the front, side and top views provided in an embodiment of the present disclosure; Fig. 9 A schematic diagram of the electrode array position of a real human brain model provided in an embodiment of the present disclosure; Fig.10 A schematic diagram of an experimental verification diagram of a resistor network single stimulation target point platform provided in an embodiment of the present disclosure; Fig.11 A schematic diagram of a hardware block diagram of a multi-channel time-interference electrical stimulation device provided in an embodiment of the present disclosure; Fig.12 A schematic diagram of a single-target and multi-target dynamically adjustable experimental verification diagram of a salt water platform provided in an embodiment of the present disclosure; Fig.13 A schematic diagram of the structure of a multi-target time-interference electrical stimulation system provided in an embodiment of the present disclosure; and Fig.14 A schematic diagram of an electronic device provided in an embodiment of the present disclosure. DETAILED DESCRIPTION

[0020] The embodiments of the present disclosure are described in detail below with reference to the accompanying drawings.

[0021] The following describes the embodiments of the present disclosure through specific examples, and those skilled in the art can easily understand other advantages and effects of the present disclosure from the contents disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present disclosure, rather than all of the embodiments. The present disclosure can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present disclosure. It should be noted that the following embodiments and features in the embodiments can be combined with each other without conflict. Based on the embodiments in the present disclosure, all other embodiments obtained by ordinary technicians in the field without making creative work are within the scope of protection of the present disclosure.

[0022] It should be noted that various aspects of the embodiments within the scope of the appended claims are described below. It should be apparent that the aspects described herein may be embodied in a wide variety of forms, and any specific structure and / or function described herein is merely illustrative. Based on the present disclosure, it should be understood by those skilled in the art that an aspect described herein may be implemented independently of any other aspect, and two or more of these aspects may be combined in various ways. For example, any number of aspects described herein may be used to implement a device and / or practice a method. In addition, other structures and / or functionalities other than one or more of the aspects described herein may be used to implement this device and / or practice this method.

[0023] It should also be noted that the illustrations provided in the following embodiments are only schematic illustrations of the basic concept of the present disclosure. The drawings only show components related to the present disclosure rather than being drawn according to the number, shape and size of components in actual implementation. In actual implementation, the type, quantity and proportion of each component may be changed arbitrarily, and the component layout may also be more complicated.

[0024] Additionally, in the following description, specific details are provided to facilitate a thorough understanding of the examples. However, it will be understood by those skilled in the art that the aspects described may be practiced without these specific details.

[0025] Figure 1 A schematic diagram of the process of the multi-target time-interference electrical stimulation method provided in an embodiment of the present disclosure.

[0026] like Figure 1 As shown, at step S110, the electrodes are connected to the subject's head; wherein the electrodes include 2 return electrodes and multiple input electrodes; the return electrodes include a first return electrode and a second return electrode, and the coordinates are established with the center point of the subject's head as the origin and the connecting line between the first return electrode and the second return electrode passing through the center point of the head as the X-axis.

[0027] More specifically, the selection of the initial target position can be determined based on the actual situation of the patient. Taking a single target as an example, if the patient is diagnosed to need stimulation of the M1 brain area (C3), the two return electrodes are fixed. The two stimulation electrodes can be placed symmetrically on both sides of the head and roughly moved so that the stimulation target and the target target are roughly in the same plane. Then, fine-tuning is performed through the two methods described below to finally stimulate the target target.

[0028] like Figure 2As shown in the figure, electrodes 1 and 6 are designated as return electrodes and grounded to provide a return path for the current. Other electrodes (such as electrodes 2, 3, 4, 5, etc.) are used as input electrodes in a two-dimensional plane. For example, a current with a frequency of 2 kHz and a current amplitude of 2 mA is passed through electrodes 2 and 4, and a current with a frequency of 2.05 kHz and a current amplitude of 2 mA is passed through electrodes 3 and 5.

[0029] More specifically, the process proceeds to step S120.

[0030] In step S120, the position of the stimulation target along the Y-axis direction is adjusted by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y-axis is perpendicular to the X-axis.

[0031] In an embodiment of the present invention, the method further includes: two-dimensional plane dual-target stimulation and three-dimensional multi-target stimulation.

[0032] In an embodiment of the present invention, the two-dimensional plane dual-target stimulation includes the following steps: dividing the two-dimensional plane where the electrode is located into two areas based on the X-axis, and two input electrodes are arranged on the head circumference corresponding to each area; by synchronously adjusting the angle θ between the two input electrodes in each area and the nearest return electrode, the position of the stimulation target along the Y-axis direction is adjusted.

[0033] In an embodiment of the present invention, adjusting the position of the stimulation target along the Y-axis direction by synchronously adjusting the angle between two input electrodes and the nearest return electrode in each area includes: The angle θ between the two input electrodes and the nearest return electrode and the displacement of the stimulation target along the Y axis are calculated based on the following formula: y=k 1 θ+y 0 Where y is the displacement of the stimulation target along the Y axis; k 1 is the proportionality coefficient; y 0 is the initial position offset; θ is the angle between the input electrode and the nearest return electrode.

[0034] More specifically, by adjusting the positions of electrodes 2, 3, 4 and 5 along the circumference (i.e., changing the angle θ), the stimulation target can be moved up and down along the Y axis. Through a large number of simulations and experiments, it is found that in the model adopted by the present invention, the position y of the stimulation target on the Y axis and the angle θ roughly satisfy the relationship

[0035] y=k 1 θ+y 0 Among them, k 1 is the proportionality coefficient, y 0 is the initial position offset.

[0036] For example, in the model used in this experiment, when the angle θ changes from 0° to 90°, the position of the stimulation target on the Y axis moves from approximately -10 mm to 10 mm. At this time, k 1 =0.2,y 0 =-10 (the specific value may vary slightly due to individual differences and model parameters). y=0.2 θ-10 (unit: mm, unit: degree, this relationship is approximate and may require fine-tuning in actual applications). For example, when θ=30°, y=0.2×30-10=-4 mm, that is, the stimulation target moves downward to the -4mm position on the Y axis. The change in angle θ will change the conduction path and distribution of the current in the biological tissue, thereby affecting the superposition effect of the electric field. The simulation results are shown in Figure 3 As shown in (a), when the angle of θ gradually increases from 20° to 70° in steps of 10°, the position of the stimulation target on the Y axis is adjusted.

[0037] Next, go to step S130.

[0038] In step S130, the position of the stimulation target point along the X-axis direction is adjusted by adjusting the excitation amplitude of the input electrode.

[0039] In the embodiment of the present invention, the position of the stimulation target along the X-axis direction is adjusted by adjusting the excitation amplitudes of the two input electrodes in each area.

[0040] In the embodiment of the present invention, adjusting the position of the stimulation target along the X-axis direction by adjusting the excitation amplitude of two input electrodes in each area includes: The excitation amplitude of the two input electrodes and the displacement of the stimulation target along the X-axis are calculated based on the following formula: d=k 2 ΔI Where d is the displacement of the stimulation target along the X-axis; ΔI is the change in the current amplitude between the two input electrodes; k 2 is the proportionality coefficient.

[0041] More specifically, in terms of lateral displacement adjustment, the movement of the target along the X-axis is achieved by changing the excitation amplitude of electrodes of different frequencies. For example, the current amplitude of electrode 2 is increased (such as increasing x mA) while the current amplitude of electrode 3 is reduced (reducing x mA). Due to the conduction and attenuation characteristics of biological tissues to current, the stimulation intensity will change at different positions, so that the position that meets the stimulation conditions moves to the side with weaker current output (the side of electrode 3), thereby achieving lateral displacement of the stimulation target on the X-axis.

[0042] The experiment showed that within a certain range, the change in electrode current amplitude ΔI is roughly linearly related to the distance d of the stimulation target moving along the X-axis: d=k 2 ΔI Among them, k 2 is the proportionality coefficient (unit: mm / mA).

[0043] The experimental data were analyzed by linear regression to determine k 2 For example, under the model and parameter conditions used in this experiment, when the current amplitude changes from -1mA to 1mA, the linear relationship is good, k 2 It is about 5mm / mA (the actual data may vary due to many factors). When the current of electrode 2 increases by 0.5 mA and the current of electrode 3 decreases by 0.5 mA, ΔI=1 mA, then d=5×1=5 mm, and the stimulation target moves 5 mm in the negative direction of the X axis. Figure 3 (b) The simulation realizes the change of stimulation target position when changing the current ratio between electrode pairs 2, 3 and 4, 5, including 1:1, 2:1 and 3:1. Although the current ratio between the two stimulation electrodes is changing, the total current is fixed at 4 mA.

[0044] In an embodiment of the present invention, the three-dimensional multi-target stimulation includes: three-dimensional dual-target stimulation and three-dimensional three-target stimulation; wherein the three-dimensional dual-target stimulation includes: keeping the positions of two return electrodes fixed, changing the positions of four input electrodes along the Z-axis direction, and changing the positions of the stimulation targets by adjusting the excitation amplitude of the input electrodes and the angle of the plane formed by the input electrodes and the two return electrodes (such as Figure 2 As shown); wherein the Z axis is perpendicular to both the X axis and the Y axis; the three-dimensional three-target stimulation comprises: on the basis of the three-dimensional two-target stimulation, two input electrodes are added to the plane to be stimulated, and the position of the stimulation target is changed by adjusting the excitation amplitude of the two added input electrodes and the angle of the plane formed by the input electrode and the two return electrodes.

[0045] More specifically, if dual-target stimulation is to be achieved in three-dimensional space, such as stimulating the target in other planes (along the Z axis), the return electrode (such as electrodes 1 and 6) is kept fixed and the input electrode position is changed. For example, to achieve dual-target stimulation in the plane in the positive direction of the Z axis, the input electrodes (such as electrodes 2, 3, 4, and 5) originally in the two-dimensional plane can be translated along the positive direction of the Z axis by a certain distance (set as Z 0 ), the position of the electrode after translation is determined according to specific needs, and is generally optimized by simulating the electric field distribution through simulation software. The translated electrode and the return electrode form a new electric field distribution, thereby generating a stimulation target on a new plane.

[0046] By adjusting the translation distance Z 0and the current frequency and amplitude of the input electrode (such as the method of adjusting the angle θ and the current amplitude in the two-dimensional plane mentioned above), the dynamic adjustment of the position of the two targets in the three-dimensional plane can be achieved. For example, first determine through simulation when Z 0 =10 mm, the dual target points are initially formed on the new plane, and then the current frequency, amplitude and angle θ are fine-tuned to make the dual target points accurately reach the desired position.

[0047] On the basis of the above three-dimensional plane dual-target stimulation, if three target stimulation is to be achieved, two input electrodes (set as electrodes 7 and 8) can be added to the corresponding plane. For example, in the plane in the positive direction of the Z axis, in addition to the translated electrodes 2, 3, 4, and 5, electrodes 7 and 8 are added.

[0048] Electrodes 7 and 8 are passed with a current of a specific frequency and amplitude (e.g., 2 kHz, 1.5 mA current for electrode 7, and 2.05 kHz, 1.5 mA current for electrode 8). By adjusting the positions of electrodes 7 and 8 (similar to the method of adjusting the positions of electrodes in a two-dimensional plane, such as changing the angle relationship with other electrodes) and current parameters, combined with the existing current parameter adjustment of electrodes 1-6, the three target points can be dynamically adjusted in three-dimensional space. The specific adjustment logic is as follows: first, the approximate positions of electrodes 7 and 8 are preliminarily determined through simulation software, so that the three target points are preliminarily formed in three-dimensional space, and then, according to the electric field distribution and the requirements for the position of the stimulation target point, the current frequency, amplitude, position angle and other parameters of each electrode are finely adjusted so that the three target points are accurately located at the target position.

[0049] Theoretically, only six electrodes are needed to achieve simultaneous stimulation of two targets at any position in a two-dimensional plane. Moreover, this strategy has good scalability and can be applied to three-dimensional space: to stimulate targets in other planes (along the Z-axis direction), only the position of the input electrode needs to be changed accordingly, while the position of the return electrode remains fixed. The simulation results of dual-target stimulation in a three-dimensional plane of a single-layer sphere model are shown in Figure 4 (a) The simulation results of the real human brain model with dual-target stimulation in three-dimensional plane are shown in Figure 4 (b).

[0050] If more targets need to be stimulated simultaneously, for example, three targets, two input electrodes can be added on the corresponding plane to achieve dynamic and adjustable multi-target stimulation of the whole brain. Figure 5 (a), the target position adjustment results are shown in Figure 5 (b); the simulation results of the real human brain model are shown in Figure 6 (a), the target position adjustment results are shown in Figure 6 (b).

[0051] The present invention is verified by simulation model as follows: 1. Construction of multi-target stimulation model The commercial software COMSOL was selected as a multi-physics field coupling finite element simulation tool, and its electromagnetic module was used for numerical calculations. First, a single-layer sphere model was used to simulate the human brain. The radius of the sphere was set to 92 mm, and the interior was filled with saline. The electrode was replaced by a cylinder with a diameter of 10 mm and a height of 4 mm. The electrical property parameters of the material were: conductivity 5.998×107 S / m, relative dielectric constant 1; the electrical property parameters of the saline were: conductivity 0.333 S / m. The electrode was Figure 8 The specific array shown is placed in which electrodes 1 and 6 are placed at the center points on the left and right sides of the spherical model as return electrodes, and the surrounding circle is the input electrode.

[0052] At the same time, a four-layer real human brain model was constructed, including scalp, skull, cerebrospinal fluid and gray matter. The electrical characteristic parameters of each tissue are as follows: scalp conductivity 0.00020023 S / m, relative dielectric constant 1135.3; skull conductivity 0.081848 S / m, relative dielectric constant 6842.5; cerebrospinal fluid conductivity 2 S / m, relative dielectric constant 109; gray matter conductivity 0.10276 S / m, relative dielectric constant 93983. According to the EEG 10-10 system, the electrode array is as follows Fig. 9 Placed in the manner shown, return electrodes 1 and 6 are located at positions C6 and C5 respectively.

[0053] 2. Single Target Stimulation Verification In the single-layer spheroid model electrode array, two pairs of electrodes (e.g., electrodes 2 and 3, electrodes 4 and 5) were selected to receive stimulation current input. Sinusoidal currents of 2 mA, 2 kHz and 2 mA, 2.5 kHz were applied, respectively. The angle θ was gradually increased (from 20° to 70°, with a step of 10°). AM nx In the two-dimensional distribution of the xy plane (AMnx is the amplitude modulation intensity, which is used to represent the stimulation intensity of the TI-tACS induced electric field at any point n in space), it was found that the focal area migrated toward the positive direction of the Y axis, the stimulation depth gradually decreased, and the maximum modulation depth value increased. At the same time, keeping the total current of electrodes 2 and 3 unchanged, adjusting their current ratios to 1:1, 1:2, and 1:3, it was observed that the stimulation target moved toward the side with weaker current output on the axis, moving 15 mm when the current ratio was 1:2, and 25 mm when the current ratio was 1:3.

[0054] 3. Dual-target stimulation verification In the single-layer spherical electrode array simulation model, the input electrodes 2 and 3 were adjusted to form a 60° angle with electrodes 1 and 6, and the input electrodes 4 and 5 were adjusted to form a 60° angle with electrodes 1 and 6. The input current of electrodes 2 and 3 was set to 2 mA, 2 kHz, and the input current of electrodes 4 and 5 was set to 2 mA, 2.05kHz. Dual-target stimulation in the same plane can be achieved, and the focal area is elliptical. By changing the current amplitude of electrodes 2, 3, 4, and 5, the movement pattern of the dual-target position is similar to that of the single target, moving to the side of the electrode with smaller output current. In dual-target stimulation in different planes, setting the input current of electrodes 2 and 3 to 2 mA, 2 kHz, and the input current of electrodes 4 and 5 to 2 mA, 2.05 kHz can achieve dual-target stimulation in different planes, and changing the input electrode current ratio (such as the current ratio of electrode 2 to electrode 3 is 1:4, and the current ratio of electrode 4 to electrode 5 is 4:1) can cause the focal area to shift significantly in the transverse plane and coronal plane.

[0055] 4. Multi-target stimulation verification In the saline model, based on the above electrode deployment, electrodes 7 and 8 were added, and currents of 2 mA, 2 kHz and 2 mA, 2.05 kHz were passed through them respectively, which could generate two stimulation targets in the xy plane and one stimulation target in the xz plane, for a total of three stimulation targets. By changing the stimulation current ratio between the electrode pairs, the dynamic adjustment of the positions of multiple targets could be achieved. In the real human brain model, the electrode deployment for dynamic adjustment of three targets was also constructed (such as adding electrodes 7 and 8), and the size of the electrode pairs was changed. This could generate one stimulation target in the coronal plane of the gray matter of the brain and two stimulation targets in the transverse plane, and achieve dynamic adjustment.

[0056] 5. System Experimental Verification Using resistor networks to establish a single stimulation target platform (such as Fig.10 As shown), set the control output channels 1 and 2 to have a phase difference of 180° (as shown in the figure), amplitude 1 mA, and frequency 2 kHz; channels 5 and 6 have a phase difference of 180°, amplitude 1 mA, and frequency 2.05 kHz. Introduce the current reversal method to reduce crosstalk, select the four positions 5, 6, 7, and 9 in the resistor network for analysis, and find that the interference effect of position 5 is the best, AM nx In the saline platform experiment, 0.9% saline was filled, a circular platform with a radius of 90 mm was placed, and the output of the multi-channel time interference electrical stimulation device was set to a sinusoidal current of a specific frequency and amplitude. Fig.12 (a) AM at each point was measured nx Compared with the single-target time interference simulation results, it was found that the overall distribution trend was similar, which verified the correctness of the single-target stimulation. In the multi-target stimulation experiment, the left input electrode was set to be excited by a 1 mA, 2 kHz sinusoidal current, and the right input electrode was set to be excited by a 1 mA, 2.05 kHz current. Fig.12(b) AM of each point nx ,The experimental results are similar to the two-dimensional distribution of the simulation results, and changing the input electrode current amplitude ratio can dynamically adjust the stimulation target position, which is consistent with the simulation results (e.g. Fig.12 (c) shows that the feasibility of multi-target dynamically adjustable time-interference electrical stimulation was verified.

[0057] Through the above series of specific implementation methods, the feasibility, accuracy and effectiveness of the time-interference electrical stimulation method and system of the present invention that can realize dynamic adjustment of multiple target positions are fully verified, providing a solid experimental basis for its application in the fields of neurological disease treatment and so on.

[0058] The multi-target time-interference electrical stimulation method proposed in the present invention can achieve simultaneous stimulation of multiple targets in multiple brain regions and multiple planes, and can dynamically adjust the target position by simply changing the current excitation parameters without changing the physical position of the electrode. This feature overcomes many problems caused by frequent replacement of electrodes in traditional technologies, such as patient discomfort, cumbersome operations of operators, and the resulting unstable stimulation effect. The adjustment of target position is achieved through precise current control, which greatly improves the accuracy and stability of stimulation and provides a more flexible and effective means for neural regulation.

[0059] Compared with the traditional technology, the present invention significantly reduces the number of electrodes used. The reduction in the number of electrodes not only simplifies the structure of the system, reduces the complexity of the system, makes the installation, commissioning and maintenance of the system easier, but also greatly reduces the cost of the system. This makes the technology of the present invention more economically feasible and practical in the field of clinical application and scientific research, and is conducive to its wide promotion and application.

[0060] Moreover, based on the principle of TI-tACS technology, the present invention utilizes the changing characteristics of the conductivity and relative dielectric constant of high-frequency stimulation current in human tissue, which can effectively stimulate the deep areas of the brain, and the focus area is more concentrated and the stimulation depth is deeper. Compared with traditional tACS technology, it has obvious advantages in stimulating deep brain structures (such as the basal forebrain, thalamus, etc.), provides a more effective means for neural regulation, and helps to improve the treatment effect of neurological diseases.

[0061] Fig.13 The multi-target time-interference electrical stimulation system 1300 provided by the present invention is shown, including an electrode configuration module 1310 and an adjustment module 1320 .

[0062] The electrode configuration module 1310 is used to connect the electrodes to the subject's head; wherein the electrodes include two return electrodes and a plurality of input electrodes; the return electrodes include a first return electrode and a second return electrode, and the center point of the subject's head is taken as the origin, and the connecting line of the first return electrode and the second return electrode passing through the center point of the head is taken as the X-axis to establish the coordinates; The adjustment module 1320 is used to adjust the position of the stimulation target along the Y-axis by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y-axis is perpendicular to the X-axis; and adjust the position of the stimulation target along the X-axis by adjusting the excitation amplitude of the input electrode.

[0063] In an embodiment of the present invention, the system also includes: a stimulation target adjustment module, which is configured to divide the two-dimensional plane where the electrode is located into two areas based on the X-axis, and two input electrodes are arranged on the head circumference corresponding to each area; by synchronously adjusting the angle θ between the two input electrodes in each area and the nearest return electrode, the position of the stimulation target along the Y-axis direction is adjusted; and, by adjusting the excitation amplitude of the two input electrodes in each area, the position of the stimulation target along the X-axis direction is adjusted.

[0064] See also Fig.14 The present disclosure also provides an electronic device 140, which includes: at least one processor; and, a memory communicatively connected to the at least one processor; wherein, The memory stores instructions that can be executed by the at least one processor, and the instructions are executed by the at least one processor so that the at least one processor can execute the multi-target time-interference electrical stimulation method in the aforementioned method embodiment.

[0065] In the embodiment of the present invention, the time interference electrical stimulation system is mainly composed of the following key modules, and the device hardware block diagram is as follows: Fig.11 As shown: 1. Power module: Its main function is to provide stable and reliable power supply for the entire system to ensure the normal operation of all parts of the system.

[0066] 2. Human-machine interface module: This module serves as the interactive interface between the operator and the system. The operator can input various stimulation parameters, such as current amplitude, frequency, phase, etc., through this module to meet different stimulation requirements.

[0067] 3. Main control circuit: It is the control core of the system and is responsible for coordinating and controlling the work of other modules. The main control circuit receives the stimulation parameter setting instructions from the human-machine interface module and generates corresponding control signals according to these instructions. The control signal generation module generates appropriate signals and adjusts the voltage to control the current source to output the required current.

[0068] 4. Voltage-controlled current source: According to the control signal sent by the main control circuit, it can accurately generate a stable stimulation current. This current source has good performance and can meet the system's requirements for current amplitude, frequency and other parameters to ensure the accuracy and stability of the stimulation current.

[0069] 5. Signal generation module: Its function is to generate signals of specific frequency and phase. These signals serve as driving signals, driving the voltage to control the current source to output the stimulation current that meets the requirements, thereby achieving precise stimulation of the target.

[0070] The system has eight sinusoidal current output channels with adjustable amplitude, frequency and phase, which can provide a maximum peak-to-peak current of 2 mA, with a current accuracy of up to 0.01 mA, a frequency of up to 20 kHz, and a frequency accuracy of 1 Hz. Such performance parameters can fully meet the various requirements of multi-channel time interference electrical stimulation output, ensuring that the system can accurately control the stimulation parameters of each target during multi-target stimulation, and achieve efficient and accurate neural stimulation.

[0071] The present disclosure also provides a computer program product, which includes a computer program stored on a non-transitory computer-readable storage medium. The computer program includes program instructions, which, when executed by a computer, enable the computer to execute the multi-target time-interference electrical stimulation method in the aforementioned method embodiment.

[0072] Reference below Fig.14 , which shows a schematic diagram of the structure of an electronic device 140 suitable for implementing the embodiment of the present disclosure. The electronic device in the embodiment of the present disclosure may include, but is not limited to, mobile terminals such as mobile phones, laptop computers, digital broadcast receivers, PDAs (personal digital assistants), PADs (tablet computers), PMPs (portable multimedia players), vehicle-mounted terminals (such as vehicle-mounted navigation terminals), etc., and fixed terminals such as digital TVs, desktop computers, etc. Fig.14 The electronic device shown is only an example and should not bring any limitation to the functions and scope of use of the embodiments of the present disclosure.

[0073] like Fig.14As shown, the electronic device 140 may include a processing device (e.g., a central processing unit, a graphics processing unit, etc.) 1401, which can perform various appropriate actions and processes according to a program stored in a read-only memory (ROM) 1402 or a program loaded from a storage device 1408 to a random access memory (RAM) 1403. In the RAM 1403, various programs and data required for the operation of the electronic device 140 are also stored. The processing device 1401, the ROM 1402, and the RAM 1403 are connected to each other via a bus 1404. An input / output (I / O) interface 1405 is also connected to the bus 1404.

[0074] Typically, the following devices may be connected to the I / O interface 1405: input devices 1406 including, for example, a touch screen, a touchpad, a keyboard, a mouse, an image sensor, a microphone, an accelerometer, a gyroscope, etc.; output devices 1407 including, for example, a liquid crystal display (LCD), a speaker, a vibrator, etc.; storage devices 1408 including, for example, a magnetic tape, a hard disk, etc.; and communication devices 1409. The communication device 1409 may allow the electronic device 140 to communicate wirelessly or wired with other devices to exchange data. Although the electronic device 140 with various devices is shown in the figure, it should be understood that it is not required to implement or have all the devices shown. More or fewer devices may be implemented or have alternatively.

[0075] In particular, according to an embodiment of the present disclosure, the process described above with reference to the flowchart can be implemented as a computer software program. For example, an embodiment of the present disclosure includes a computer program product, which includes a computer program carried on a computer-readable medium, and the computer program contains program code for executing the method shown in the flowchart. In such an embodiment, the computer program can be downloaded and installed from the network through the communication device 1409, or installed from the storage device 1408, or installed from the ROM 1402. When the computer program is executed by the processing device 1401, the above-mentioned functions defined in the method of the embodiment of the present disclosure are executed.

[0076] It should be noted that the computer-readable medium mentioned above in the present disclosure may be a computer-readable signal medium or a computer-readable storage medium or any combination of the above two. The computer-readable storage medium may be, for example, but not limited to, an electrical, magnetic, optical, electromagnetic, infrared, or semiconductor system, device or device, or any combination of the above. More specific examples of computer-readable storage media may include, but are not limited to: an electrical connection with one or more wires, a portable computer disk, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or flash memory), an optical fiber, a portable compact disk read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the above. In the present disclosure, a computer-readable storage medium may be any tangible medium containing or storing a program that can be used by or in combination with an instruction execution system, device or device. In the present disclosure, a computer-readable signal medium may include a data signal propagated in a baseband or as part of a carrier wave, which carries a computer-readable program code. This propagated data signal may take a variety of forms, including but not limited to an electromagnetic signal, an optical signal, or any suitable combination of the above. Computer readable signal media may also be any computer readable medium other than computer readable storage media, which may send, propagate or transmit a program for use by or in conjunction with an instruction execution system, apparatus or device. The program code contained on the computer readable medium may be transmitted using any appropriate medium, including but not limited to: wires, optical cables, RF (radio frequency), etc., or any suitable combination of the above.

[0077] The computer-readable medium may be included in the electronic device, or may exist independently without being installed in the electronic device.

[0078] The computer-readable medium carries one or more programs. When the one or more programs are executed by the electronic device, the electronic device: obtains at least two Internet Protocol addresses; sends a node evaluation request including the at least two Internet Protocol addresses to a node evaluation device, wherein the node evaluation device selects an Internet Protocol address from the at least two Internet Protocol addresses and returns it; receives the Internet Protocol address returned by the node evaluation device; wherein the obtained Internet Protocol address indicates an edge node in a content distribution network.

[0079] Alternatively, the computer-readable medium carries one or more programs, and when the one or more programs are executed by the electronic device, the electronic device: receives a node evaluation request including at least two Internet Protocol addresses; selects an Internet Protocol address from the at least two Internet Protocol addresses; and returns the selected Internet Protocol address; wherein the received Internet Protocol address indicates an edge node in a content distribution network.

[0080] Computer program code for performing the operations of the present disclosure may be written in one or more programming languages ​​or a combination thereof, including object-oriented programming languages ​​such as Java, Smalltalk, C++, and conventional procedural programming languages ​​such as "C" or similar programming languages. The program code may be executed entirely on the user's computer, partially on the user's computer, as a separate software package, partially on the user's computer and partially on a remote computer, or entirely on a remote computer or server. In cases involving a remote computer, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or may be connected to an external computer (e.g., via the Internet using an Internet service provider).

[0081] The flow chart and block diagram in the accompanying drawings illustrate the possible architecture, function and operation of the system, method and computer program product according to various embodiments of the present disclosure. In this regard, each square box in the flow chart or block diagram can represent a module, a program segment or a part of a code, and the module, the program segment or a part of the code contains one or more executable instructions for realizing the specified logical function. It should also be noted that in some implementations as replacements, the functions marked in the square box can also occur in a sequence different from that marked in the accompanying drawings. For example, two square boxes represented in succession can actually be executed substantially in parallel, and they can sometimes be executed in the opposite order, depending on the functions involved. It should also be noted that each square box in the block diagram and / or flow chart, and the combination of the square boxes in the block diagram and / or flow chart can be implemented with a dedicated hardware-based system that performs a specified function or operation, or can be implemented with a combination of dedicated hardware and computer instructions.

[0082] The units involved in the embodiments described in the present disclosure may be implemented by software or hardware. The name of a unit does not limit the unit itself in some cases. For example, the first acquisition unit may also be described as a "unit for acquiring at least two Internet Protocol addresses".

[0083] It should be understood that various parts of the present disclosure may be implemented in hardware, software, firmware, or a combination thereof.

[0084] The above is only a specific implementation of the present disclosure, but the protection scope of the present disclosure is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present disclosure should be included in the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure should be based on the protection scope of the claims.

Claims

1. A multi-target time-interference electrical stimulation method, characterized in that: The method comprises the following steps: Connecting electrodes to the subject's head; wherein the electrodes include two return electrodes and a plurality of input electrodes; the return electrodes include a first return electrode and a second return electrode, taking the center point of the subject's head as the origin and taking the connecting line of the first return electrode and the second return electrode passing through the center point of the head as the X-axis to establish coordinates; The position of the stimulation target along the Y-axis direction is adjusted by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y-axis is perpendicular to the X-axis; The position of the stimulation target point along the X-axis direction is adjusted by adjusting the excitation amplitude of the input electrode.

2. The multi-target time-interference electrical stimulation method according to claim 1, characterized in that: The method also includes: two-dimensional plane dual-target stimulation and three-dimensional multi-target stimulation.

3. The multi-target time-interference electrical stimulation method according to claim 2, characterized in that: The two-dimensional plane dual-target stimulation comprises the following steps: The two-dimensional plane where the electrodes are located is divided into two regions based on the X-axis, and two input electrodes are set on the circumference of the head corresponding to each region; By synchronously adjusting the angle θ between the two input electrodes and the nearest return electrode in each area, the position of the stimulation target along the Y axis is adjusted; The position of the stimulation target along the X-axis direction was adjusted by adjusting the excitation amplitude of the two input electrodes in each area.

4. The multi-target time-interference electrical stimulation method according to claim 3, characterized in that: The method of adjusting the position of the stimulation target along the Y-axis direction by synchronously adjusting the angle between the two input electrodes in each area and the nearest return electrode comprises: The angle θ between the two input electrodes and the nearest return electrode and the displacement of the stimulation target along the Y axis are calculated based on the following formula: y=k1θ+y0 Where y is the displacement of the stimulation target along the Y axis; k1 is the proportional coefficient; y0 is the initial position offset; θ is the angle between the input electrode and the nearest return electrode.

5. The multi-target time-interference electrical stimulation method according to claim 3, characterized in that: The step of adjusting the position of the stimulation target along the X-axis direction by adjusting the excitation amplitude of two input electrodes in each area comprises: The excitation amplitude of the two input electrodes and the displacement of the stimulation target along the X-axis are calculated based on the following formula: d = k2ΔI Where d is the displacement of the stimulation target along the X-axis; ΔI is the change in current amplitude between the two input electrodes; and k2 is the proportional coefficient.

6. The multi-target time-interference electrical stimulation method according to claim 2, characterized in that: The three-dimensional multi-target stimulation includes: three-dimensional dual-target stimulation and three-dimensional three-target stimulation; The three-dimensional dual-target stimulation includes: keeping the positions of the two return electrodes fixed, changing the positions of the four input electrodes along the Z-axis, and changing the positions of the stimulation targets by adjusting the excitation amplitude of the input electrodes and the angle of the plane formed by the input electrodes and the two return electrodes; wherein the Z-axis is perpendicular to both the X-axis and the Y-axis; The three-dimensional three-target stimulation includes: on the basis of the three-dimensional two-target stimulation, two input electrodes are added to the plane to be stimulated, and the position of the stimulation target is changed by adjusting the excitation amplitude of the two added input electrodes and the angle of the plane formed by the input electrode and the two return electrodes.

7. A multi-target time-interference electrical stimulation system, characterized in that: The system comprises: An electrode configuration module is configured to connect electrodes to a subject's head; wherein the electrodes include two return electrodes and a plurality of input electrodes; the return electrodes include a first return electrode and a second return electrode, and coordinates are established with a center point of the subject's head as an origin and a connecting line between the first return electrode and the second return electrode passing through the center point of the head as an X-axis; The adjustment module is configured to adjust the position of the stimulation target along the Y-axis by adjusting the angle between the input electrode and the nearest return electrode; wherein the Y-axis is perpendicular to the X-axis; and adjust the position of the stimulation target along the X-axis by adjusting the excitation amplitude of the input electrode.

8. The multi-target temporal interference electrical stimulation system according to claim 7, characterized in that: The system further comprises: The stimulation target adjustment module is configured to divide the two-dimensional plane where the electrode is located into two areas based on the X-axis, and two input electrodes are arranged on the circumference of the head corresponding to each area; Adjust the position of the stimulation target along the Y axis by synchronously adjusting the angle θ between the two input electrodes and the nearest return electrode in each area; and The position of the stimulation target along the X-axis direction was adjusted by adjusting the excitation amplitude of the two input electrodes in each area.

9. An electronic device, characterized in that: The electronic device includes: at least one processor; and, a memory communicatively connected to the at least one processor; wherein, The memory stores instructions that can be executed by the at least one processor, and when the instructions are executed by the at least one processor, the at least one processor executes the multi-target time-interference electrical stimulation method as described in any one of claims 1 to 6.

10. A computer program product, characterized in that The computer program product includes a computer program stored on a non-transitory computer-readable storage medium, and the computer program includes program instructions. When the program instructions are executed by a computer, the computer executes the multi-target time-interference electrical stimulation method as described in any one of claims 1 to 6.

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