Time interference electrical stimulation system for suppressing, controlling and adjusting

Abstract

The invention discloses a time interference electrical stimulation system for suppressing, controlling and adjusting, which comprises an image acquisition module for acquiring functional magnetic resonance images to acquire functional connection data; the stimulation module is used for respectively generating time interference electrical stimulation waveforms in the plurality of stimulation areas so as to stimulate the corresponding stimulation areas and adjusting stimulation parameters; the evaluation module is electrically connected with the image acquisition module and the stimulation module, acquires cognitive emotion evaluation data, and obtains an emotion and cognitive neural circuit regulation result by combining the emotion evaluation data and the function connection data as an inhibition control capability evaluation index; and the control module is electrically connected with the stimulation module and the evaluation module, and controls the stimulation module to adjust the stimulation parameters based on the emotion and cognitive neural circuit adjustment result. According to the system, effective time interference electrical stimulation is carried out on a plurality of inhibition control intervention brain regions, stimulation parameters are improved by implementing stimulation effect evaluation, and a favorable adjustment means is provided for inhibition control of multi-region and complex network modulation.

Description

Technical Field

[0001] This application belongs to the technical field of neuromodulation, and specifically, relates to a temporal interference electrical stimulation system for inhibitory control regulation. Background Art

[0002] Inhibitory control is a cognitive process that is used to prevent automatic or preprogrammed responses so that an individual can achieve behavioral goals. It is significantly impaired in patients with major depressive disorder (MDD), manifested as decreased positive emotion inhibition and cognitive functions (such as memory and attention). Currently, multiple cortical regions in the brain are known to be key regions responsible for inhibitory control functions. However, existing research shows that inhibitory control depends on a widely distributed neural network rather than a single dedicated region such as the multi-demand frontal cortex. The involvement of this broader brain region implies that subcortical regions and complex neural activity organizations play a key role that has not been fully understood. This complexity is what the corresponding population, especially the MDD population, needs for the potential effect of correcting impaired inhibitory control.

[0003] Therefore, tools that can interfere with multi-region neural activity should be used to implement targeted stimulation on the relevant cortical / subcortical brain regions related to emotion processing and cognitive control that are strongly correlated with inhibitory control, with the expectation of effectively improving impaired inhibitory control. The dorsolateral prefrontal cortex (DLPFC) is usually a key region for brain stimulation treatment of MDD. Its functional connectivity (FC) with the subgenual anterior cingulate cortex (sgACC) has been proven by research to reflect the cognitive and emotional recovery of MDD patients: the DLPFC-sgACC connection is the basis for emotion regulation and cognitive-emotion integration and helps with inhibitory control. In addition, the amygdala (Amyg) is one of the most critical regions in the development of MDD, responsible for emotion processing, decision-making, reward processing, attention, and perception. Due to its significant ability to regulate emotions and cognition, the amygdala is also a beneficial part of the neural network related to inhibitory control. The ventral striatum (VS) is another subcortical region involved in the process of MDD. Existing research has shown that deep targeted stimulation of the VS has beneficial effects on emotion recovery.

[0004] Although the above research has revealed the organization of inhibitory control over emotional and cognitive functions in complex neural networks and how the neural network is affected in the process of MDD, however, the current non-invasive brain stimulation regulation technology has limited ability to affect the regulatory neural network composed of cortical and subcortical brain regions because they do not penetrate deep into the brain and have not been verified for multi-deep brain region stimulation. Invasive neuroelectrical stimulation is a viable option, but for MDD patients, the need for surgical implantation of electrodes is costly and unnecessary.

[0005] Time Interference (TI) stimulation is a novel brain stimulation technique, known for its non-invasiveness and deep brain accessibility. It has started to be used as an alternative tool to Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS) in cognitive research and clinical practice. Its existing applications include disrupting the reinforcement learning of motor skills by targeting and effectively interfering with the neural activities in the striatum or hippocampus, and enhancing episodic memory and motor skill learning by stimulating brain regions. TI stimulation involves applying multiple electric fields to the brain at different high frequencies (>2kHz) and setting these electric fields to intersect at the target site to generate an interference pattern, producing a low-frequency envelope modulation amplitude waveform, and regulating the deep brain neural activities through the generated difference frequency waveform. At the current intensity used in humans, high-frequency kHz frequency fields do not affect neural activities, so this technique has also been proven to be safe. However, although TI has high feasibility in improving emotional control and cognitive-emotional regulation, there is still a lack of inhibitory control regulation or intervention means based on TI stimulation.

[0006] Therefore, there is a need for a time interference electrical stimulation system that can adjust multiple subcortical brain regions and targetedly adjust the stimulation pattern based on the stimulation effect to effectively improve the inhibitory control function. Summary of the Invention

[0007] To solve the problems existing in the prior art, the purpose of this application is to provide a time interference electrical stimulation system for inhibitory control regulation, which has an image acquisition module, a stimulation module, an evaluation module, and a control module. The stimulation module is used to provide time interference electrical stimulation waveforms with adjustable parameters such as intensity and frequency to multiple deep brain stimulation regions. Before and after stimulation, the image acquisition module and the evaluation module are used to collect functional connectivity data and emotional evaluation data of the corresponding target regions in the deep brain to evaluate the regulatory effect of the stimulation on the inhibitory control ability and adjust the stimulation parameters accordingly to achieve personalized adjuvant treatment for people with impaired inhibitory control.

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

[0009] A time interference electrical stimulation system for inhibitory control regulation, comprising: a stimulation module that generates time interference electrical stimulation waveforms in multiple stimulation regions of the test population to stimulate the corresponding stimulation regions and adjusts the stimulation parameters of the time interference electrical stimulation waveforms; a control module electrically connected to the stimulation module, used to control the stimulation module to adjust the stimulation parameters based on the regulation results of the emotional and cognitive neural circuits; wherein, the multiple stimulation regions include the dorsolateral prefrontal cortex region, the subgenual anterior cingulate cortex region, and / or the amygdala region; the stimulation parameters include stimulation intensity, stimulation time, and / or stimulation frequency; the regulation results of the emotional and cognitive neural circuits include efficient regulation and inefficient regulation.

[0010] According to some embodiments of the present application, the stimulation module includes: a first stimulation unit that generates a first stimulation waveform in the dorsolateral prefrontal cortex region using two pairs of electrodes. The stimulation parameters of the first stimulation waveform include: stimulation intensity, ranging from 0 to 5 mA; stimulation time, ranging from 15 min to 30 min; stimulation frequency, ranging from 5 Hz to 20 Hz; a second stimulation unit that generates a second stimulation waveform in the subgenual anterior cingulate cortex region using two pairs of electrodes. The stimulation parameters of the second stimulation waveform include: stimulation intensity, ranging from 0 to 5 mA; stimulation time, ranging from 15 min to 30 min; stimulation frequency, ranging from 20 Hz to 200 Hz; a third stimulation unit that generates a third stimulation waveform in the amygdala region using two pairs of electrodes. The stimulation parameters of the third stimulation waveform include: stimulation intensity, ranging from 0 to 5 mA; stimulation time, ranging from 15 min to 30 min; stimulation frequency, ranging from 50 Hz to 200 Hz.

[0011] According to some embodiments of the present application, a temporal interference electrical stimulation system for inhibitory control regulation further includes: an image acquisition module that acquires functional magnetic resonance images of the test population to obtain functional connectivity data of multiple target regions of the test population; an evaluation module that is electrically connected to the image acquisition module and the stimulation module respectively, acquires cognitive-emotional evaluation data of the test population and receives the functional connectivity data of multiple target regions, and obtains the emotional and cognitive neural circuit regulation results of the test population based on the emotional evaluation data and the functional connectivity data of multiple target regions, so as to be used as an evaluation index for the inhibitory control ability of the test population.

[0012] According to some embodiments of the present application, the image acquisition module acquiring the functional magnetic resonance images of the test population includes: the image acquisition module acquires the functional magnetic resonance images of the test population before and after the temporal interference electrical stimulation of the stimulation module respectively; the image acquisition module obtaining the functional connectivity data of multiple target regions of the test population includes: preprocessing and denoising the functional magnetic resonance images; calculating the time series correlation data between multiple target regions based on the functional magnetic resonance images; using the Fisher transform bivariate correlation coefficient of the time series correlation data between multiple target regions as the functional connectivity data of multiple target regions.

[0013] According to some embodiments of the present application, the multiple target regions include: USCBrain Atlas 113, corresponding to the dorsolateral prefrontal cortex region among the multiple stimulation regions; Brainnetome Atlas 179 and Brainnetome Atlas 187, corresponding to the subgenual anterior cingulate cortex region among the multiple stimulation regions; and Brainnetome Atlas 212 and Brainnetome Atlas 214, corresponding to the amygdala region among the multiple stimulation regions.

[0014] According to some embodiments of the present application, the plurality of stimulation regions further includes a ventral striatum region; the stimulation module further includes a fourth stimulation unit, which generates a fourth stimulation waveform in the ventral striatum region by using two pairs of electrodes. The stimulation parameters of the fourth stimulation waveform include: a stimulation intensity, which ranges from 0 to 5 mA; a stimulation time, which ranges from 15 min to 30 min; and a stimulation frequency, which ranges from 20 Hz to 200 Hz.

[0015] According to some embodiments of the present application, the evaluation module includes: an interaction unit, configured to provide an interaction interface to the test population for cognitive-emotional evaluation and obtain cognitive-emotional evaluation data; an analysis unit, based on the cognitive-emotional evaluation data of the test population and the functional connectivity data of the plurality of target regions, determines the regulatory results of the time-interference electrical stimulation of each stimulation region in the plurality of stimulation regions and / or the time-interference electrical stimulation of a combination of different stimulation regions on the emotions and cognitive neural circuits of the test population before and after stimulation, and transmits the regulatory results of the emotions and cognitive neural circuits to the control module.

[0016] According to some embodiments of the present application, the interaction unit provides an interaction interface to the test population for cognitive-emotional evaluation, including: the interaction interface provides a mood Stroop test, a Hamilton Depression Scale evaluation, and / or a Hamilton Anxiety Scale evaluation to the test population before and after the time-interference electrical stimulation of the stimulation module on the test population.

[0017] According to some embodiments of the present application, the regulatory results of the emotions and cognitive neural circuits being highly efficient regulation include: for (a) the first emotion significance value of the regulatory results of the emotions and cognitive neural circuits obtained before and after the time-interference electrical stimulation of the stimulation module on the stimulation region < α1; (b) the second emotion significance value of the regulatory results of the emotions and cognitive neural circuits obtained before and after the time-interference electrical stimulation of the stimulation module on the stimulation region < α2; (c) the functional connectivity significance value of the functional connectivity data of the regulatory results of the emotions and cognitive neural circuits obtained before and after the time-interference electrical stimulation of the stimulation module on the stimulation region < α3, satisfying at least two of the conditions (a), (b), and (c); the regulatory results of the emotions and cognitive neural circuits being inefficient regulation include: only satisfying one of the conditions (a), (b), and (c).

[0018] According to some embodiments of the present application, controlling the stimulation module based on the regulatory results of the emotions and cognitive neural circuits to adjust the stimulation parameters includes: adjusting the stimulation time of the corresponding stimulation region based on the regulatory results of the emotions and cognitive neural circuits being inefficient regulation.

[0019] A time-interference electrical stimulation system for inhibitory control regulation provided by the present application can use multiple stimulation units of a stimulation module to apply stimuli with specific intensities and frequencies at different times in four brain regions related to inhibitory control regulation, so that the intensity of neural network regulation of inhibitory control between these brain regions and / or between these brain regions and other related brain regions changes, thereby providing a complete improvement plan for inhibitory control regulation for MDD subjects in order to improve MDD symptoms; in addition, the system described in the present application can also actively obtain stimulation results and evaluate stimulation effects by using an evaluation module and an image acquisition module, which is conducive to timely adjusting the usage strategies of multiple stimulation units, thereby facilitating the iterative optimization of the entire system. Brief Description of the Drawings

[0020] Figure 1 The figure illustrates an exemplary block diagram of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0021] Figure 2 The figure illustrates a schematic structural diagram of any stimulation unit of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0022] Figure 3 The figure illustrates exemplary results of an emotional Stroop test of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0023] Figure 4 The figure illustrates exemplary HAMD test results and HAMA test results of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0024] Figure 5A The figure illustrates a schematic diagram of functional connections of an exemplary Brainnetome Atlas 179 of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0025] Figure 5B The figure illustrates a schematic diagram of functional connections of an exemplary Brainnetome Atlas 187 of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0026] Figure 6 The figure illustrates a schematic diagram of functional connections of exemplary Brainnetome Atlas 212 and Brainnetome Atlas 214 of a time-interference electrical stimulation system for inhibitory control regulation according to an embodiment of the present application.

[0027] Figure 7AIllustrated is an exemplary schematic diagram of the stimulation electric field power of the stimulation waveform of a time interference electrical stimulation system for suppressing control regulation according to an embodiment of the present application.

[0028] Figure 7B Illustrated is an exemplary schematic diagram of the stimulation frequency of the stimulation waveform of a time interference electrical stimulation system for suppressing control regulation according to an embodiment of the present application.

[0029] Figure 8 Illustrated is a schematic diagram of the electrode positions and the stimulation waveform generation positions of a time interference electrical stimulation system for suppressing control regulation according to an embodiment of the present application. Detailed implementation manners

[0030] The present application will be further described below in conjunction with embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application, and are not used to limit the present application.

[0031] Unless otherwise defined, the technical and scientific terms in this specification have the same meaning as those commonly understood by those skilled in the art. Although methods and materials similar or identical to those described herein may be used in experiments or practical applications, the materials and methods are still described below. In case of conflict, the present specification, including the definitions therein, shall prevail. In addition, the materials, methods and examples are for illustrative purposes only and not restrictive. The present application will be further described below in conjunction with specific embodiments, but not used to limit the scope of the present application.

[0032] Definitions

[0033] Inhibitory control

[0034] Inhibitory control is one of the core parts of the brain's executive function. Its essence is the individual's ability to actively suppress, interrupt or delay dominant responses (such as instinctive impulses or habitual behaviors) to adapt to environmental changes. According to different inhibitory objects, inhibitory control is divided into multiple types: conflict inhibition, which is used to inhibit the interference of competing stimuli, and response inhibition, which is used to inhibit behaviors that do not conform to the current goal. The realization of an individual's inhibitory control function mainly involves multiple brain regions such as its prefrontal cortex, such as the dorsolateral prefrontal cortex region (DLPFC), inferior frontal gyrus, anterior cingulate cortex (ACC) and basal ganglia, and shows correlations with both single brain regions and the neural network between brain regions.

[0035] Insufficient inhibitory ability may lead to an increase in impulsive behaviors and a decrease in adaptability, thereby triggering negative emotions. On the contrary, anxiety, fear or depressive emotions will also weaken the inhibitory function. For example, individuals with trait anxiety are more vulnerable to distraction stimuli. Therefore, inhibitory control has a high degree of correlation with an individual's emotional control and regulation ability; in addition, inhibitory control is also the basis of higher cognitive functions such as working memory and reading comprehension, and changes in an individual's cognitive ability can also be used to characterize their ability to inhibit dominant responses.

[0036] Functional connectivity

[0037] Functional connectivity (FC) is the statistical dependence of activity patterns between different brain regions or neuronal populations, typically measured by metrics such as correlation and synchrony of time series signals (e.g., the BOLD signal of fMRI, EEG / MEG signals, or neuronal firing activity). It reflects the dynamic coordination of neural activity in space and time, rather than direct anatomical connections. For example, regions with indirect polysynaptic connections may also form functional coupling through synchronous activity, which is difficult to distinguish anatomically but can be identified through FC analysis. Brain networks related to inhibitory control, such as the prefrontal-basal ganglia loop, etc., the strength of their functional connectivity is directly related to the related behavioral manifestations of inhibitory control. For example, the enhanced functional connectivity between the prefrontal cortex and the inferior frontal lobe is related to the improvement of motor response inhibition ability. In addition, fMRI-based studies have also shown that the abnormal enhancement of the connection in brain regions such as PreSMA-IFG in patients with obsessive-compulsive disorder reflects the impairment of the compensatory inhibitory control mechanism, and there is a significant correlation between the FC strength between brain regions and the excitatory-inhibitory ratio of multiple cortical and subcortical regions. Therefore, the intensity change of FC can play a role in characterizing inhibitory control in terms of both microscopic chemical structure and macroscopic functional network and their associations.

[0038] Application overview

[0039] As mentioned above, although existing studies have confirmed that stimulating target regions such as DLPFC and ACC can improve the inhibitory control disorder performance of MDD to a certain extent, they are not (or not only) due to the improvement of a single region, but rather through the enhancement / weakening of the connections between different neural pathways. For example, stimulating sgACC can lead to a decrease in the FC strength of the frontal lobe, which reflects the normalization of some hyperconnections in the complex cognitive control pathway. And previously reported that the amygdala-hippocampus neural pathway plays a crucial role in memory and positive emotion formation, which indicates that the improvement of cognitive and emotional regulation is the basis for the enhanced inhibitory control observed after stimulating related regions such as the amygdala. All these illustrate that the intervention and regulation of inhibitory control require the participation of multiple brain regions to achieve good results.

[0040] In particular, MDD severely disrupts inhibitory control, making the cognitive processes necessary for regulating automatic responses and achieving goal-directed behaviors increasingly chaotic. The disorder of inhibitory control is closely related to persistent low mood. Compared with healthy people, those with inhibitory control disorders have always shown deficiencies in emotion, memory, and attention control. Therefore, TI stimulation can become an effective non-invasive electrical stimulation method for regulating deep brain activity and behavioral performance and improving inhibitory control. Compared with invasive methods such as DBS, TI stimulation avoids the inconvenience and potential risks brought by implanting electrodes while ensuring the effectiveness of stimulation, and has higher practical value for improving MDD symptoms.

[0041] Based on the feasibility of TI stimulation technology in the regulation of deep neural pathways, the present application provides a time interference electrical stimulation system for inhibitory control regulation, which includes an image acquisition module, a stimulation module, an evaluation module, and a control module. The image acquisition module is used to collect functional magnetic resonance images of the test population to obtain functional connectivity data of multiple target regions of the test population, so as to evaluate the functional connectivity changes in the stimulation regions. The stimulation module generates time interference electrical stimulation waveforms in multiple stimulation regions of the test population to stimulate the corresponding stimulation regions, and adjusts the stimulation mode by adjusting the stimulation parameters of the time interference electrical stimulation waveforms to optimize the stimulation schemes for different individuals. The evaluation module is electrically connected to the image acquisition module and the stimulation module respectively, and is used to obtain functional connectivity data and collect cognitive emotion evaluation data, so as to combine multiple modal data to obtain the regulation results of the emotion and cognitive neural circuits of the test population, and evaluate the improvement degree of inhibitory control ability. The control module is electrically connected to the stimulation module and the evaluation module, and adjusts the stimulation parameters of the stimulation module based on the regulation results of the emotion and cognitive neural circuits to optimize the regulation effect of the system.

[0042] For the deep brain regions where stimulation is applied, the present application selects multiple regions that show effectiveness in improving emotion and / or cognitive functions, or regions that show high correlation with known effective regions in the functional connectivity network during the improvement of emotion and / or cognitive functions, as the stimulation targets for inhibitory control regulation, including: the dorsolateral prefrontal cortex region, which is a key region involved in emotion regulation and cognitive functions related to depression; the subgenual anterior cingulate cortex region, which is a brain region related to the emotion and reward network; and the amygdala region, which appears frequently in the pathophysiological studies of depression. Based on the consideration of the deep connections of complex neural networks, the amygdala is also a potential target for improving inhibitory control.

[0043] Furthermore, for the TI stimulation of the selected stimulation regions, the stimulation parameters may include stimulation intensity, stimulation time, and / or stimulation frequency, etc. For different selected stimulation regions, the stimulation parameters required for the stimulation waveforms are also different. The stimulation module can control and adjust each stimulation parameter according to the instructions of the control module to improve the interference effectiveness for each selected brain region. The regulation results of the emotion and cognitive neural circuits are calculated by the evaluation module based on multi-modal evaluation data, and are divided into three results: high-efficiency regulation, low-efficiency regulation, and ineffective regulation. The control module can send different stimulation parameter adjustment instructions to the stimulation module based on different results.

[0044] The system described in this application can be applied to the test population with inhibitory control disorders. Through targeted TI stimulation of specific regions, relevant test evaluations of inhibitory control, such as clinical scale tests and neuroimaging tests for mood-cognitive improvement, are provided before and after stimulation, and a certain interval is set for the stimulation protocols between different target regions. Subsequently, this application induces characteristic FC changes related to the potential network mechanism of inhibitory control through the selective stimulation of specific targets by TI, enhances the inhibitory control function of the test population, and thus achieves the alleviation of symptoms of mental health disorders such as MDD and autism.

[0045] Finally, the system described in this application also verifies the authenticity of the generation and effect of the TI stimulation waveform of the stimulation module in the selected stimulation region, and this part will be detailed in a specific example below.

[0046] After introducing the basic principle of this application, various non-limiting embodiments of this application will be specifically introduced with reference to the accompanying drawings.

[0047] Exemplary System

[0048] Figure 1 The exemplary block diagram of a time interference electrical stimulation system for inhibitory control regulation according to an embodiment of this application is illustrated.

[0049] As Figure 1 shown, the time interference electrical stimulation system for inhibitory control regulation according to an embodiment of this application includes the following modules.

[0050] A stimulation module that generates time interference electrical stimulation waveforms in multiple stimulation regions of the test population to stimulate the corresponding stimulation regions, and adjusts the stimulation parameters of the time interference electrical stimulation waveforms; a control module, electrically connected to the stimulation module, for controlling the stimulation module based on the regulation results of the emotion and cognitive neural circuits to adjust the stimulation parameters. In addition, an evaluation module and an image acquisition module can be further configured to evaluate the effect after the test subject receives the TI stimulation of the system described in this application.

[0051] Among them, the multiple stimulation regions include at least two of the dorsolateral prefrontal cortex region, the subgenual anterior cingulate cortex region, and the amygdala region; the stimulation parameters include stimulation intensity, stimulation time, and / or stimulation frequency, that is, the envelope modulation amplitude, duration, and envelope modulation frequency of the time interference electrical stimulation waveform; the regulation results of the emotion and cognitive neural circuits include efficient regulation and inefficient regulation. It can be understood that there may be regions (i.e., inefficient regions) in the multiple stimulation regions that do not show significant improvement in inhibitory control-related emotion and cognitive functions after being individually stimulated (i.e., inefficient regulation), so the significance of inhibitory control improvement can be increased by extending the stimulation time.

[0052] Specifically, during the actual treatment process, part of the stimulation area does regulate and improve the symptoms of inhibitory control disorder exhibited by MDD. However, this effect may not be specific and immediate, and may show the result of inefficient regulation during a complete treatment process. Therefore, according to the example of the present application, the stimulation module can further adjust the stimulation time, such as increasing the stimulation time. The stimulation module can also be configured with a clock timing control unit. After adjusting the stimulation time applied by one or more of the stimulation modules in the corresponding stimulation area, the clock timing control unit can keep the stimulation intervals of each stimulation unit and the stimulation time of the stimulation units whose stimulation time has not been adjusted unchanged by adjusting the stimulation program time axis, so that the entire stimulation program can be implemented normally.

[0053] The stimulation module includes a first stimulation unit that generates a first stimulation waveform in the DLPFC area using two pairs of electrodes. The stimulation parameters of the first stimulation waveform include: stimulation intensity, whose range is 0 to 5 mA; stimulation time, whose range is 15 min to 30 min; stimulation frequency, whose range is 5 Hz to 20 Hz. Since the left DLPFC (LDLPFC) has a greater correlation with positive emotion regulation, preferably, the first stimulation unit generates a first stimulation waveform in the (LDLPFC) using two pairs of electrodes.

[0054] The stimulation module further includes a second stimulation unit that generates a second stimulation waveform in the sgACC area using two pairs of electrodes. The stimulation parameters of the second stimulation waveform include: stimulation intensity, whose range is 0 to 5 mA; stimulation time, whose range is 15 min to 30 min; stimulation frequency, whose range is 20 Hz to 200 Hz. In MDD patients, the metabolic activity of the left sgACC (LsgACC) is usually overactive and is strongly correlated with the responsiveness to antidepressant treatment. Preferably, the second stimulation unit generates a second stimulation waveform in the LsgACC using two pairs of electrodes. It should be noted that electrical stimulation of the sgACC usually affects the adjacent pregenual part (pgACC), and the performance of this part in inhibitory control function is considered to be highly consistent with that of the sgACC. Therefore, when selecting the target area to evaluate the stimulation effect of the sgACC, the corresponding target area should also be selected to evaluate the stimulation effect of the pgACC.

[0055] The third stimulation unit uses two pairs of electrodes to generate a third stimulation waveform in the Amyg region. The stimulation parameters of the third stimulation waveform include: stimulation intensity, with a range of 0 to 5 mA; stimulation time, with a range of 15 min to 30 min; and stimulation frequency, with a range of 50 Hz to 200 Hz. The left and right sides of the Amyg region, namely the left Amyg (LAmyg) and the right Amyg (RAmyg), are respectively related to conscious-level emotional memory and subconscious-level emotional memory, and selective stimulation can be performed according to the actual feasibility of TI stimulation implementation.

[0056] Advantageously, the plurality of stimulation regions further includes the VS region; the stimulation module further includes a fourth stimulation unit that uses two pairs of electrodes to generate a fourth stimulation waveform in the VS region. The stimulation parameters of the fourth stimulation waveform include: stimulation intensity, with a range of 0 to 5 mA; stimulation time, with a range of 15 min to 30 min; and stimulation frequency, with a range of 20 Hz to 200 Hz. Both the left and right sides of the VS region, namely the left VS (LVS) and the right VS (RVS), are related to anhedonia and somatic symptoms exhibited by MDD patients, and selective stimulation can be performed according to the actual feasibility of TI stimulation implementation.

[0057] Reference Figure 2 is used to illustrate the structure of any one of the first stimulation circuit to the fourth stimulation circuit. The control module can be, for example, Figure 2 the control board shown in, which is a device with a processor, a memory, and an input / output interface, and can be respectively connected to a power adapter, a group of stimulation boards, an electrode adapter, and a battery. Additionally, an output indicator light and a display touch screen are attached. Among them, the control board controls a group of stimulation boards, that is, the stimulation boards that generate different frequency waveforms, to generate a modulation waveform of the stimulation waveform, and then the electrode adapter conveys the modulation waveform to the corresponding electrode pair to generate a low-frequency envelope in a specific stimulation region, that is, the required stimulation waveform.

[0058] Two stimulation boards form a group of stimulation boards to serve as any one of the first stimulation circuit to the fourth stimulation circuit. The intensity of the interference waveform is adjusted through their respective operational amplifiers and load resistors, and the control board controls the operation time of each group of stimulation boards as the stimulation time. Each stimulation board can include a waveform generation circuit, an amplification circuit, etc., to generate different frequency waveforms and amplify them to an available level.

[0059] In addition, the control board, the stimulation board, the electrode adapter, etc. can be powered by the power supply through the power adapter or by the battery. The control board also has a USB interface, which can receive the results of emotional and cognitive neural circuit regulation transmitted by the evaluation module, or directly connect to the image acquisition module and the evaluation module to receive the functional connection data of the image acquisition module and / or the cognitive and emotional evaluation data of the evaluation module. It can be understood that the evaluation module can be an independent module, such as an electronic device (such as a single-chip microcomputer, MCU, PLC, etc.) similar to the control board with a processor and input / output interfaces, or a part of the control board. For example, it is a partial processing unit of the processor of the control board that is only used to calculate the results of emotional and cognitive neural circuit regulation of the test population based on the emotional evaluation data and the functional connection data.

[0060] The control board can transmit stimulation parameters to electronic devices (such as intelligent mobile devices, servers, Internet of Things devices, etc.) and computer storage devices (such as desktop computers, laptop computers, etc.), which is conducive to the user obtaining stimulation-related data on these devices for further analysis; the trigger interface can be used to control the start and interruption of the control board, and the output indicator light can light up to give a warning when the control board controls the stimulation board to generate interference waveforms or a failure occurs; the control board can be electrically connected to the display touch screen, so that the user can observe the stimulation dynamics in real time through the display touch screen. The user can also manually transmit control instructions to the control board through the display touch screen, such as manually adjusting the current intensity, frequency, etc. of the stimulation waveform.

[0061] The time interference electrical stimulation system for inhibitory control regulation further includes the following modules: an image acquisition module, which collects functional magnetic resonance images of the test population to obtain functional connection data of multiple target regions of the test population; an evaluation module, which is electrically connected to the image acquisition module and the stimulation module respectively, collects the cognitive and emotional evaluation data of the test population and receives the functional connection data of the multiple target regions, and obtains the results of emotional and cognitive neural circuit regulation of the test population based on the emotional evaluation data and the functional connection data of the multiple target regions, so as to be used as an evaluation index for the inhibitory control ability of the test population. The image acquisition module can be an electronic device similar to the control board with a processor and input / output interfaces, which is used to obtain functional magnetic resonance image data from a functional magnetic resonance device (such as fMRI) or a computer storage device connected to the functional magnetic resonance device, and send the data to the evaluation module or the control module.

[0062] The image acquisition module is used to collect functional magnetic resonance images of the test population, including: the image acquisition module collects functional magnetic resonance images of the test population before and after the stimulation of the test population by the time interference electrical stimulation of the stimulation module; the image acquisition module obtains the functional connectivity data of multiple target regions of the test population, including: preprocessing and denoising the functional magnetic resonance images; calculating the time series correlation data between the multiple target regions based on the functional magnetic resonance images; using the Fisher transform bivariate correlation coefficient of the time series correlation data between the multiple target regions as the functional connectivity data of the multiple target regions.

[0063] The multiple target regions include: USCBrain Atlas 113, corresponding to the DLPFC region among the multiple stimulation regions, preferably corresponding to the LDLPFC region among the multiple stimulation regions; Brainnetome Atlas 179 and Brainnetome Atlas 187, corresponding to the sgACC region among the multiple stimulation regions, preferably corresponding to the LsgACC region among the multiple stimulation regions; and Brainnetome Atlas 212 and Brainnetome Atlas 214, corresponding to the Amyg region among the multiple stimulation regions. In addition, the multiple target regions may further include Brainnetome Atlas 224, corresponding to the VS region. In particular, Brainnetome Atlas 179 is the target region for evaluating pgACC, and Brainnetome Atlas 187 is the target region for evaluating sgACC.

[0064] The evaluation module is used to multi-dimensionally evaluate the TI electrical stimulation effect of the stimulation module by using the obtained cognitive emotion data and the neuroimaging data obtained by the image acquisition module. Therefore, the evaluation module may further include: an interaction unit, used to provide an interaction interface to the test population for cognitive emotion evaluation and obtain the cognitive emotion evaluation data. In the case where the evaluation module is a part of the control module, the interaction unit may be, for example, an input / output interface on the control panel connected to the display touch screen and the processor of the control panel connected to this interface.

[0065] The evaluation module further includes an analysis unit that, based on the cognitive emotion evaluation data of the subject population and the functional connectivity data of the multiple target regions, determines the results of the modulation of the emotion and cognitive neural circuits before and after the stimulation of the subject population by the temporal interference electrical stimulation of each stimulation region in the multiple stimulation regions and / or the temporal interference electrical stimulation of a combination of different stimulation regions, and transmits the results of the modulation of the emotion and cognitive neural circuits to the control module. Similarly, the analysis unit can be the processor of the control board and the corresponding memory for storing the results of the modulation of the emotion and cognitive neural circuits.

[0066] The interaction unit provides an interaction interface to the subject population for cognitive emotion evaluation, including: the interaction interface provides a mood Stroop test, a Hamilton Depression Scale (HAMD) evaluation, and / or a Hamilton Anxiety Scale (HAMA) evaluation to the subject population before and after the temporal interference electrical stimulation of the stimulation module on the subject population.

[0067] The mood Stroop test is a psychological experimental paradigm that studies the effect of emotion on cognitive control by introducing emotion-related stimuli (such as emotion words or pictures), and can be used to evaluate an individual's attentional bias and inhibitory control ability towards emotional information. Its scores, such as reaction time and error rate, reflect the strength of inhibitory control ability. HAMD (such as HAMD-17) and HAMA are commonly used evaluation tools in clinical psychology, which are used to measure the severity of depressive and anxiety symptoms respectively. Both depressive and anxiety symptoms can affect the emotion regulation ability, which is a manifestation of inhibitory control, as well as other behaviors such as inattention and mental retardation, which are also typical manifestations of impaired inhibitory control.

[0068] The results of the modulation of the emotion and cognitive neural circuits being efficient modulation or inefficient modulation are determined by the following three evaluation indicators:

[0069] (a) The first emotion significance value of the results of the modulation of the emotion and cognitive neural circuits obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation region is < α1. In some examples, it can be that the p-value of the repeated measures analysis of variance result of the results of the modulation of the emotion and cognitive neural circuits obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation region is < 0.05, making the improvement of the results significant;

[0070] (b) The second emotion significance value of the results of the modulation of the emotion and cognitive neural circuits obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation region is < α 2，In some examples, the p-value of the one-tailed Wilcoxon signed-rank test result of the emotional and cognitive neural circuit regulation results obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area can be 0.05 to further improve the credibility of index (a); and

[0071] (c) The functional connection significance value of the functional connection data of the emotional and cognitive neural circuit regulation results obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area is < α3. In some examples, it can be the p-value of the multiple comparison correction cluster level of the functional connection data of the target area obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area is 0.05, so as to prove that the functional connection of the target area has changed significantly in the desired direction.

[0072] For the stimulation unit corresponding to the emotional and cognitive neural circuit regulation result that satisfies at least two of the conditions (a), (b), and (c), the result of this stimulation unit in this independent stimulation is efficient regulation. For the stimulation unit corresponding to the emotional and cognitive neural circuit regulation result that only satisfies one of the conditions (a), (b), and (c), the result of this stimulation unit in this independent stimulation is inefficient regulation; in addition, when the temporal interference electrical stimulation of the stimulation module on the stimulation area makes the test population feel uncomfortable, the result of this independent stimulation is also set to inefficient regulation.

[0073] Controlling the stimulation module based on the emotional and cognitive neural circuit regulation result to adjust the stimulation parameter includes: adjusting the stimulation time of the corresponding stimulation area based on the inefficient regulation of the emotional and cognitive neural circuit regulation result. Adjusting the stimulation time of the corresponding stimulation area may include increasing the stimulation time because for at least some stimulation areas, a relatively longer adjustment time is required to show the effect compared to other areas, such as the DLPFC brain area; in addition, when the test population feels uncomfortable, the stimulation time, stimulation intensity, etc. can also be reduced to prevent their emotional state from being further reduced due to the influence of the physiological state. This is because the physical discomfort of the MDD population will aggravate the emotional depression, and the emotional depression will reduce their tolerance to discomfort. Therefore, the control of the comfort level during the stimulation process is more important for them than for other patients.

[0074] Next, various examples for verifying the effectiveness of TI stimulation implemented in the stimulation area and comparing the emotional and cognitive neural circuit regulation results obtained from different stimulation areas in the temporal interference electrical stimulation system for inhibitory control regulation according to the embodiments of the present application will be described in detail.

[0075] This application provides a general and / or specific description of the test methods used in the tests. For the instruments used, if the manufacturer is not specified, they are all conventional raw material products or instruments that can be obtained commercially.

[0076] Example 1 Verification of the effectiveness of applying TI stimulation to the stimulation area

[0077] The applicant recruited two patients with drug - refractory epilepsy (both right - handed, a 23 - year - old male and a 22 - year - old female). The two patients had stereotactic electroencephalogram (SEEG) depth electrodes implanted for about one month to determine the seizure area and to determine whether the target TI stimulation was generated in specific brain regions. The depth electrodes had 5 - 20 contacts, and their implantation positions were completely based on clinical criteria and verified by the fusion of post - implantation CT images and pre - implantation T1 - weighted MR images. The TI stimulation procedure was consistent with the procedure for TI - stimulating MDD subjects using the stimulation module in the subsequent examples, and the initial stimulation parameters were the same. The targeting positions of TI stimulation were determined based on the patients' T1 - weighted MRI images, and two pairs of scalp electrodes in the 10 - 10 system were selected for each TI - stimulation area.

[0078] According to the electrode positions, Patient 1 set the stimulation area as LsgACC (frequency 100 Hz) during one stimulation process, and Patient 2 set the stimulation areas as LDLPFC (frequency 10 Hz), RAmyg (frequency 100 Hz), and RVS (frequency 100 Hz) during three separate stimulation processes, respectively.

[0079] The voltage and intensity of the TI electric field in the stimulation area were recorded from the patients' implanted SEEG depth electrodes, and the electrode implantation was completely based on clinical criteria. For TI stimulation, an alternating current with a fixed frequency and intensity was delivered to the scalp electrodes of the two patients within 10 minutes, and the stimulation parameters were the same as those for the formal stimulation, as shown in Table 2. The target stimulation area was selected based on the minimum physical distance to the center of the selected brain region, and the non - target stimulation area was set to have the same depth as the target stimulation area and the maximum distance. In all four selected brain regions, compared with the non - target stimulation area, the envelope - modulated amplitude waveform of the potential at the target stimulation area was significantly larger, as shown in Table 1. This indicates that the envelope - modulated amplitude waveform generated by the stimulation module successfully reached the maximum value at the stimulation area in the center of the selected brain region, rather than having the maximum value at other positions, which makes the TI stimulation of the stimulation area accurate and helps to evaluate its true effect.

[0080] Table 1 Envelope voltage and electric - field power of four brain regions under TI stimulation

[0081]

[0082] Next, the envelope electric field power and envelope frequency within one second of the stimulation area were calculated. The results showed that the magnitudes of the envelope electric field power of LsgACC, RAmyg, and RVS were basically the same, and the electric field power of LDLPFC was relatively large. Their mean ± standard deviation were: LsgACC = 0.12 ± 0.00 V / m; RAmyg = 0.20 ± 0.00 V / m; RVS = 0.17 ± 0.01 V / m; LDLPFC = 1.39 ± 0.13 V / m. The envelope electric field power of all four stimulation areas was scaled to the value at a current intensity of 1 mA for comparison, as Figure 7A shown, the stability of the envelope electric field power of electrical stimulation in all areas was good. The mean ± standard deviation of the envelope frequency of all stimulation areas were: LsgACC = 100.08 ± 0.11 Hz; RAmyg = 100.01 ± 0.09 Hz; RVS = 100.01 ± 0.02 Hz; LDLPFC = 10.01 ± 0.03 Hz, as Figure 7B shown, all were stable at the set frequency.

[0083] The above results indicate that the stimulation module can deliver the TI stimulation waveform to all selected brain regions with stable spatial position, electric field power, and frequency.

[0084] Example 2: The stimulation module provides TI electrical stimulation to four stimulation areas

[0085] A control board, a stimulation board, and an electrode adapter as shown in Figure 2 were used to cooperate with the 10 - 10 standard electrodes to generate the stimulation waveform. The control board was Xilinx Virtex. Among them, the evaluation module was also integrated in the control board. The image acquisition module was a computer connected to the fMRI device, which transmitted the functional connectivity data to the control board through the USB interface.

[0086] The applicant recruited 15 subjects diagnosed with MDD (aged 18 - 53 years, with an average age of 35.1 ± 10.9 years, 2 males). All subjects experienced five TI stimulations within five weeks. For each subject, one of the stimulations and control stimulations of the four stimulation areas was randomly assigned without replacement each week. At the baseline assessment, T1 - weighted structural MRI of all subjects was obtained; before each TI stimulation or control stimulation and two weeks after the last stimulation, the HAMD test and HAMA test were performed on the subjects respectively to evaluate the improvement of mood in real - time; before and after each TI stimulation or control stimulation, rsfMRI imaging and the emotional Stroop test were performed respectively to evaluate the changes in functional connectivity and emotional cognition in real - time. The specific test results are detailed in Examples 3 and 4 later.

[0087] Five stimulation areas and a control stimulation were set, including:

[0088] (1) LDLPFC stimulation with a frequency of 10 Hz and a duration of 20 min,

[0089] (2) LsgACC stimulation with a frequency of 100 Hz and a duration of 20 min,

[0090] (3) RAmyg stimulation with a frequency of 100 Hz and a duration of 20 min,

[0091] (4) RVS stimulation with a frequency of 100 Hz and a duration of 20 min, and

[0092] (5) The stimulation module applies two 2 kHz currents to the electrode pairs of each stimulation unit as control stimulation.

[0093] As shown in Table 2, the initial stimulation frequency is set to 100 Hz because of its high stability and safety. Electrodes in all stimulation areas use a fundamental frequency of 2 kHz, generating a 10 Hz difference frequency for the electrode pairs of LDLPFC, and a 100 Hz difference frequency for LsgACC, RVS, and RAmyg. The control stimulation has a 0 Hz difference frequency and a random stimulation area.

[0094] The initial intensity of the current delivered by the electrodes is 1 mA to ensure the comfort of the subjects. If the subjects have no discomfort, the current intensity will be steadily increased in steps of 0.2 mA every two seconds to a stimulation current level of 4 mA. Once the stimulation current intensity is fixed, the subjects will receive 20 minutes of TI stimulation, where the field strength at the target site is the maximum. After the stimulation, the current applied by the electrodes is steadily decreased to zero in the same manner. All electrode positions are based on the existing 10 - 10 electrode system, as Figure 8 illustrates the electrode placement in different stimulation areas of one subject (Subject 14) and the TI electric fields generated in the corresponding stimulation areas.

[0095] Table 2 Stimulation parameter settings for stimulation areas

[0096]

[0097] The control stimulation is used to compare and verify whether the TI stimulation performed for the first time in the five stimulation areas has a significant effect on the emotional - cognitive function and / or functional connectivity strength of the subjects. Its 0 Hz envelope frequency does not contain any envelope - modulated amplitude waveform and does not drive additional neural activity in the stimulation area.

[0098] Example 3 Acquisition and analysis of functional connectivity data of brain images in the target area

[0099] Based on the stimulation protocol of Example 2, before and after each TI stimulation, rsfMRI functional images of the subjects were acquired using a 3T UIHu MR780 scanner. T1w images were acquired using a 3D GRE sequence with a repetition time (TR) = 7 ms, an echo time (TE) = 3 ms, a flip angle = 9°, the number of slices = 160, a voxel size = 1×1×1 mm, and a field of view (FOV) = 256 mm. Resting-state functional images were acquired using an EPI sequence with the following parameters: TR = 2 s, TE = 30 ms, flip angle = 80°, the number of slices = 36, voxel size = 3.59×3.59×3.50 mm, and FOV = 230 mm.

[0100] The functional and anatomical data were preprocessed using a modular pipeline, including realignment, outlier detection, indirect segmentation, MNI space normalization, and smoothing. In addition, the functional images were denoised using a standardized pipeline. Subsequently, first-order analysis and group analysis were performed on the preprocessed and denoised resting-state MRI data of the four TI stimulations and the control stimulation of the LsgACC. The specific steps are as follows:

[0101] A connectivity graph was used to characterize the spatial layout of the FC with the target regions. Considering the precision of the TI stimulation, the target regions included two regions of interest (ROIs) of the left anterior cingulate cortex (LACC) based on the Brainnetome Atlas (BNA): BNA 179, corresponding to the left pregenual anterior cingulate cortex (LpgACC) part of the LACC, and BNA187 corresponding to the subgenual part of the same region, i.e., LsgACC. This is because TI stimulation of the LsgACC usually also affects the nearby LpgACC and influences its neural activity. Therefore, the FC analysis of the target region of the LpgACC can also reflect the overall changes of the LACC to improve the evaluation accuracy of the LsgACC receiving stimulation.

[0102] The FC intensity was represented by the bivariate correlation coefficient of the Fisher transformation of the time series data between related regions. The weighted general linear model (weighted GLM) was used to perform first-order analysis estimation for each target region and the corresponding target voxel respectively, simulating the relationship between their BOLD signal time series. Next, a general linear model (GLM) was used for group analysis. The results were corrected at the voxel level with a threshold of p < 0.001, and significant clusters were considered only when the data existed at p < 0.05 (corrected cluster level for multiple comparisons).

[0103] Subsequently, the functional image data before and after stimulation of RAmyg, RVS, and LDLPFC, as well as before and after control stimulation, were also subjected to the same preprocessing, denoising, first-order analysis, and group analysis. The target regions of RAmyg were the combination of BNA 212 (medial RAmyg) and BNA 214 (lateral RAmyg); BNA 224 was selected as the target region of RVS; USCBrain 113 was used as the target region of LDLPFC. The evaluation method was the same as above. Since BNA212 and BNA214 were not considered to have differentiated functions in the art, they were combined and regarded as a whole region for evaluating the TI stimulation of RAmyg.

[0104] By performing a 2 (time: before and after stimulation) x 2 (stimulation: real stimulation and control stimulation) analysis of variance, the neuroimaging changes in all four stimulated regions were analyzed. No significant neuroimaging changes were found in the separate before-and-after analyses of LDLPFC and RVS. A significant interaction was observed in LpgACC, as Figure 5A shown. Compared with the control stimulation, the FC intensity between LpgACC and the left superior frontal gyrus (LSFG) and the left middle frontal gyrus (LMFG) decreased after TI stimulation, and the connection strength after testing was significantly lower than that before testing. For LsgACC, as Figure 5B shown, compared with the control stimulation, the FC intensity between LsgACC and the right superior frontal gyrus (RSFG) decreased, and the connection strength after testing was significantly lower than that before testing. For RAmyg, as Figure 6 shown, compared with the control stimulation, the FC intensity between RAmyg and the bilateral hippocampi (LHIP, RHIP) increased after TI stimulation, and the connection strength after testing was significantly higher than that before testing.

[0105] The above results indicate that structural and functional changes occurred in LsgACC and RAmyg before and after a single TI stimulation, specifically manifested as changes in the FC of their target regions and other specific regions, and the change trends were all consistent with the reported enhancement of inhibition.

[0106] Example 4 Acquisition and Analysis of Cognitive-Emotional Assessment Data

[0107] Based on the stimulation protocol of Example 2, first, before and after each TI stimulation, an emotional Stroop test was conducted. The difference in response time (RT) in the Stroop test is a marker of inhibitory control ability. Specifically, the test consisted of a total of 80 trials in random order. In each trial, a face with a red emotional word was displayed on the screen for 1000 ms, followed by a blank screen with a cross in the middle for 3000 - 5000 ms. In congruent trials, the emotion expressed by the face was consistent with the emotion expressed by the word, while in incongruent trials they were opposite. When the cross appeared, the subject was required to press a button as quickly as possible to classify the emotional valence of the word as positive or negative; non - response was regarded as an error trial and was ignored in subsequent analyses. The RT of each trial was recorded.

[0108] Then, the RT and response accuracy of all trials were recorded, and the test results of the subjects were averaged. To test the effect of TI stimulation, a 2 (time: before and after the overall trials) x 5 (stimulation: LDLPFC, LsgACC, RAmyg, RVS, control stimulation) repeated - measures analysis of variance was conducted. A significant interaction was found, F(4,11) = 3.784, p = 0.036, η2 = 0.579, indicating that the stimulation trials had an effect on the performance of the subjects' Stroop test, that is, it improved the cognitive ability of emotions, but there was no significant main effect of time or region, and no particularly significant time points or stimulation regions with differences were obtained.

[0109] To further explore which stimulation regions were significantly affected by TI stimulation, four 2 (time: before and after stimulation) x 2 (condition: stimulation region stimulation, control stimulation) repeated - measures analyses of variance were conducted by comparing the stimulation under each stimulation region with the control stimulation. The results showed that there was a significant interaction in LsgACC, F(1,14) = 14.059, p = 0.002, η2 = 0.501; a significant interaction was also found in RAmyg, F(1,14) = 11.573, p = 0.004, η2 = 0.453. For LDLPFC, there was no significant interaction, F(1,14) = 1.168, p = 0.224, η2 = 0.104. For the RVS region, no significant interaction was found, F(1,14) = 1.149, p = 0.302, η2 = 0.076. Figure 3 The results showed a significant difference in RT values before and after the stimulation trials. Compared with the control stimulation, the RT values produced by TI stimulation of LsgACC and RAmyg after the test were lower than those before the test and were included in the RT values of the overall stimulation trials.

[0110] Second, before each TI stimulation or control stimulation and two weeks after the last stimulation, the HAMD test and the HAMA test were conducted. AsFigure 4 As shown, significant improvements in both HAMD and HAMA were observed before and after the stimulation test: HAMD p < 0.001, HAMA p < 0.001, indicating that the stimulation test had an effect on the performance of the two emotional tests of the subjects and the emotions of the subjects were improved. To explore the triggering effect of TI stimulation in the four stimulation regions on the emotional state of the subjects, a repeated measures analysis of variance was also performed on the changes in the HAMD / HAMA test results after each treatment. The results showed that, except for the LsgACC stimulation and the control stimulation, the HAMD of all target groups was significantly reduced: using the one-tailed Wilcoxon signed-rank test, LDLPFC V = 98, p = 0.0047; LsgACC V = 76.5, p = 0.14; RAmyg V = 112.5, p = 0.003; RVS V = 107.5, p = 0.0074; control group V = 73.5, p = 0.2). The HAMA evaluation results of LDLPFC and RAmyg were also significantly reduced: using the one-tailed Wilcoxon signed-rank test, LDLPFC V = 94, p = 0.0099; LsgACC V = 74, p = 0.44; RAmyg V = 112.5, p = 0.0031; RVS V = 47, p = 0.23; control V = 68, p = 0.26. In addition, based on the test result data, the changes in the HAMD / HAMA test results before and after the overall stimulation test and single stimulation were obtained respectively, as shown in Tables 3 and 4:

[0111] Table 3 Changes in HAMD / HAMA test results before and after the TI stimulation test

[0112]

[0113] Table 4 Changes in HAMD / HAMA test results before and after TI stimulation in a single region

[0114]

[0115] As can be seen from the above, the improvement in the HAMD / HAMA test results of the subjects caused by the stimulation of a single stimulation region was much lower than that of the overall plan including all stimulation regions, and like some stimulation regions and the control stimulation, no significant effect was produced, so its stimulation effect has no reference significance; in addition, two weeks after the end of the stimulation test, the subjects could still maintain a gratifying improvement in cognitive-emotional function. This indicates that the stimulation plan including 4 stimulation regions has a more positive and effective significance for the improvement of the subjects' emotions compared with single-region stimulation, and after receiving the treatment of this stimulation process, the inhibitory control ability of the subjects maintained a good improvement effect within a certain period after the stimulation.

[0116] In summary, by using TI stimulation, significant changes in the functional connectivity of the LsgACC and Amyg with the RSFG and bilateral HIPs occurred in the expected direction related to enhanced orientation and inhibitory control, significantly improving the subjects' emotional cognitive ability in the emotional Stroop test, and this cognitive ability is involved in the process of brain inhibitory control. In addition, for the overall stimulation paradigm of the four stimulation regions included in the system of the present application, it showed better effects than single-region TI stimulation in improving the subjects' cognitive-emotional ability and emotional state. This indicates that the brain regions that did not produce an improved inhibitory control effect had deep connections with other effective / ineffective brain regions before / after stimulation, thereby helping to optimize the stimulation effects of other effective / ineffective brain regions, or perhaps making their own stimulation effects more significant, and the reasons thereof are worthy of further exploration.

[0117] Therefore, the system described in the present application provides a promising deep-brain multi-region TI stimulation paradigm, which can be used to systematically regulate or study the cognitive behaviors or their neural mechanisms of deep brain regions, can effectively perturb and analyze multiple neural circuits, and can adjust the stimulation parameters in real time according to the stimulation effects or the subjects' feedback, thereby providing a stable and convincing solution for the regulation and improvement of higher-level neural activities in specific cognitive functions including inhibitory control.

[0118] The basic principles of the present application have been described above in conjunction with specific embodiments. However, it should be noted that the advantages, benefits, effects, etc. mentioned in the present application are only examples and not limitations, and it cannot be considered that these advantages, benefits, effects, etc. are essential for each embodiment of the present application. In addition, the above-disclosed specific details are only for illustrative and easy-to-understand purposes, rather than limitations, and the above details do not limit the present application to necessarily adopt the above specific details for implementation.

[0119] The block diagrams of the devices, apparatuses, equipment, and systems involved in the present application are only illustrative examples and do not intend to require or imply that they must be connected, arranged, and configured in the manner shown in the block diagrams. As those skilled in the art will recognize, these devices, apparatuses, equipment, and systems can be connected, arranged, and configured in any manner. Words such as "including", "comprising", "having", etc. are open-ended terms, meaning "including but not limited to", and can be used interchangeably with each other. The words "or" and "and" used herein refer to the word "and / or", and can be used interchangeably with each other, unless the context clearly indicates otherwise. The word "such as" used herein refers to the phrase "such as but not limited to", and can be used interchangeably with each other.

[0120] It should also be noted that in the devices, equipment, and methods of the present application, each component or each step can be decomposed and / or recombined. These decompositions and / or recombinations should be regarded as equivalent solutions of the present application.

[0121] The foregoing description of the disclosed aspects is provided to enable any person skilled in the art to make or use the present application. Various modifications to these aspects will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other aspects without departing from the scope of the present application. Thus, the present application is not intended to be limited to the aspects shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

[0122] The foregoing description has been presented for purposes of illustration and description. Furthermore, this description is not intended to limit the embodiments of the present application to the form disclosed herein. Although numerous example aspects and embodiments have been discussed above, those skilled in the art will recognize some variations, modifications, alterations, additions, and subcombinations thereof.

Claims

1. A time-interference electrical stimulation system for suppressing control regulation, comprising: A stimulation module that generates time-interference electrical stimulation waveforms in multiple stimulation regions of a subject population to stimulate the corresponding stimulation regions, and adjusts the stimulation parameters of the time-interference electrical stimulation waveforms; A control module electrically connected to the stimulation module, for controlling the stimulation module to adjust the stimulation parameters based on the regulation results of emotional and cognitive neural circuits; Wherein, the multiple stimulation regions include the dorsolateral prefrontal cortex region, the subgenual anterior cingulate cortex region, and / or the amygdala region; the stimulation parameters include stimulation intensity, stimulation time, and / or stimulation frequency; the regulation results of emotional and cognitive neural circuits include efficient regulation and inefficient regulation.

2. The time interference electrical stimulation system for suppressing control regulation according to claim 1, wherein, The stimulation module includes: A first stimulation unit that generates a first stimulation waveform in the dorsolateral prefrontal cortex region using two pairs of electrodes, and the stimulation parameters of the first stimulation waveform include: stimulation intensity, with a range of 0 to 5 mA; stimulation time, with a range of 15 min to 30 min; stimulation frequency, with a range of 5 Hz to 20 Hz; A second stimulation unit that generates a second stimulation waveform in the subgenual anterior cingulate cortex region using two pairs of electrodes, and the stimulation parameters of the second stimulation waveform include: stimulation intensity, with a range of 0 to 5 mA; stimulation time, with a range of 15 min to 30 min; stimulation frequency, with a range of 20 Hz to 200 Hz; A third stimulation unit that generates a third stimulation waveform in the amygdala region using two pairs of electrodes, and the stimulation parameters of the third stimulation waveform include: stimulation intensity, with a range of 0 to 5 mA; stimulation time, with a range of 15 min to 30 min; stimulation frequency, with a range of 50 Hz to 200 Hz.

3. The time-interference electrical stimulation system for suppressing control regulation according to claim 1, further comprising: An image acquisition module that acquires functional magnetic resonance images of the subject population to obtain functional connectivity data of multiple target regions of the subject population; An evaluation module electrically connected to the image acquisition module and the stimulation module respectively, acquires cognitive-emotional evaluation data of the subject population and receives the functional connectivity data of the multiple target regions, and obtains the regulation results of emotional and cognitive neural circuits of the subject population based on the emotional evaluation data and the functional connectivity data of the multiple target regions, as an evaluation index of the inhibitory control ability of the subject population.

4. The time-interference electrical stimulation system for suppressing control regulation according to claim 3, wherein, The image acquisition module acquiring functional magnetic resonance images of the subject population includes: The image acquisition module acquires functional magnetic resonance images of the subject population before and after the time-interference electrical stimulation of the stimulation module on the subject population respectively; The image acquisition module obtaining functional connectivity data of multiple target regions of the subject population includes: Performing preprocessing and denoising on the functional magnetic resonance images; Calculating the time series correlation data between the multiple target regions based on the functional magnetic resonance images; Use the Fisher-transformed bivariate correlation coefficient of the time-series correlation data between the multiple target regions as the functional connectivity data of the multiple target regions.

5. The time interference electrical stimulation system for suppressing control regulation according to claim 4, wherein, The multiple target regions include: USCBrain Atlas 113, corresponding to the dorsolateral prefrontal cortex region among the multiple stimulation regions; Brainnetome Atlas 179 and Brainnetome Atlas 187, corresponding to the subgenual anterior cingulate cortex region among the multiple stimulation regions; and Brainnetome Atlas 212 and Brainnetome Atlas 214, corresponding to the amygdala region among the multiple stimulation regions.

6. The time-interference electrical stimulation system for inhibitory control regulation according to claim 1, wherein the multiple stimulation regions further include a ventral striatum region; the stimulation module further includes a fourth stimulation unit, which generates a fourth stimulation waveform in the ventral striatum region using two pairs of electrodes. The stimulation parameters of the fourth stimulation waveform include: stimulation intensity, ranging from 0 to 5 mA; stimulation time, ranging from 15 min to 30 min; and stimulation frequency, ranging from 20 Hz to 200 Hz.

7. The time interference electrical stimulation system for suppressing control regulation according to claim 3, wherein, The evaluation module includes: an interaction unit, configured to provide an interaction interface to the test population for cognitive-emotional evaluation and obtain the cognitive-emotional evaluation data; an analysis unit, based on the cognitive-emotional evaluation data of the test population and the functional connectivity data of the multiple target regions, determines the regulation results of the time-interference electrical stimulation of each stimulation region in the multiple stimulation regions and / or the time-interference electrical stimulation of combinations of different stimulation regions on the emotions and cognitive neural circuits of the test population before and after stimulation, and transmits the regulation results of the emotions and cognitive neural circuits to the control module.

8. The time-interference electrical stimulation system for inhibitory control regulation according to claim 7, wherein the interaction unit providing an interaction interface to the test population for cognitive-emotional evaluation includes: the interaction interface provides a mood Stroop test, Hamilton Depression Scale evaluation, and / or Hamilton Anxiety Scale evaluation to the test population before and after the time-interference electrical stimulation of the stimulation module on the test population, respectively.

9. The time-interference electrical stimulation system for inhibitory control regulation according to claim 1, wherein the regulation results of the emotions and cognitive neural circuits being efficient regulation include: For (a) the first emotional significance value of the emotional and cognitive neural circuit regulation results obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area < α1; (b) the second emotional significance value of the emotional and cognitive neural circuit regulation results obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area < α2; (c) the functional connection significance value of the functional connection data of the emotional and cognitive neural circuit regulation results obtained before and after the temporal interference electrical stimulation of the stimulation module on the stimulation area < α3, satisfying at least two of the conditions (a), (b), and (c); The emotional and cognitive neural circuit regulation result being an inefficient regulation includes: Only satisfying one of the conditions (a), (b), and (c).

10. The temporal interference electrical stimulation system for inhibitory control regulation according to claim 1, wherein, Controlling the stimulation module based on the emotional and cognitive neural circuit regulation result to adjust the stimulation parameter includes: Based on the emotional and cognitive neural circuit regulation result being the inefficient regulation, adjusting the stimulation time of the corresponding stimulation area.

Images