Parameter optimization system and method for transcranial time interference stimulation

Abstract

The invention discloses a transcranial time interference stimulation parameter optimization system and method, and belongs to the technical field of nerve regulation and control. The system comprises a tTIS stimulator, an electrode array, a control module and a calculation module. According to the system, two paths of high-frequency carrier current with a specific frequency difference generated by the tTIS stimulator interfere in a target brain region to generate a low-frequency envelope electric field, so that accurate non-invasive regulation and control on a deep brain region are realized. The system constructs a personalized head model based on head image data of a subject, and optimizes an electrode application position; the control module executes a preset stimulation protocol, preferentially fixes the stimulation duration and the envelope frequency, allows the current intensity to be adjusted within a safe range, and is provided with an automatic stop mechanism to prevent excessive treatment. The invention is particularly suitable for treating human chronic pain through targeted regulation of the ventral prefrontal cortex (vmPFC), the regulation principle is verified in a mouse model, and the drug has the characteristics of accurate stimulation, high safety, lasting curative effect and the like.

Description

Technical Field

[0001] This invention relates to the field of neuromodulation technology, and specifically discloses a transcranial time-interference stimulation parameter optimization system and method, which is particularly suitable for non-invasive deep brain region stimulation therapy for neurological diseases such as chronic pain. Background Technology

[0002] Chronic pain is a common neurological disorder, and its occurrence is closely related to the adaptive plasticity of the central nervous system. Currently, non-invasive neuromodulation techniques such as transcranial magnetic stimulation and transcranial electrical stimulation are widely used in clinical practice, but they mainly affect superficial cortical areas and have limited ability to precisely modulate deep brain regions such as the ventromedial prefrontal cortex or dorsolateral prefrontal cortex in humans.

[0003] Transcranial temporal stimulation (tTIS) is an emerging non-invasive neuromodulation technique that uses two high-frequency currents to interfere with deep brain regions, generating a low-frequency envelope electric field to selectively activate target brain areas. However, the therapeutic effect of tTIS is highly dependent on the combination of stimulation parameters, such as current intensity, duration, and envelope frequency. Existing tTIS systems lack parameter optimization mechanisms based on efficacy data, and parameter settings rely on experience, making it difficult to ensure the consistency and safety of treatment. Currently, there is a lack of systematic parameter optimization schemes, which limits the precision and safety of its clinical application. Summary of the Invention

[0004] The present invention aims to provide a transcranial time-interference stimulation parameter optimization system and method to solve the problems of inaccurate deep brain region stimulation, parameter setting dependence on experience, and lack of personalized optimization in the prior art.

[0005] The transcranial time-interference stimulation parameter optimization system provided by this invention includes:

[0006] tTIS stimulator: used to generate two high-frequency carrier current signals with a specific frequency difference; Electrode array: Connected to the tTIS stimulator, used to apply electrical signals to the subject's scalp; Control module: Communicates with the tTIS stimulator to execute preset stimulation protocols and control output parameters; Calculation module: Used to construct a finite element model of the head based on the subject's head imaging data, and to optimize the electrode placement position through electric field simulation.

[0007] Furthermore, the control module is configured to limit the stimulation duration to between 15 and 30 minutes and has an automatic stop or current ramp-up function.

[0008] Furthermore, the system stores parameter priority configuration logic based on efficacy verification, in which stimulation duration and envelope frequency are fixed first, while current intensity is a user-adjustable variable.

[0009] Furthermore, the electrode array consists of four independent electrodes, used in conjunction with Ag / AgCl electrode sheets and conductive gel, with an area preferably ranging from 3 cm × 3 cm to 5 cm × 5 cm.

[0010] Furthermore, the output current intensity of the tTIS stimulator ranges from 0 to 4 mA, with a preferred operating range of 1 to 2 mA.

[0011] This invention also provides a method for optimizing transcranial time-interference stimulation parameters, comprising the following steps: Acquire head imaging data of the subject and construct a finite element model of the head; Determine the coordinates of the target brain region and optimize the electrode placement position through electric field simulation; Configure and optimize the stimulation protocol, including continuous stimulation mode, duration of 15 to 30 minutes, and envelope frequency of 10 to 40 Hz; The tTIS stimulus is applied based on the optimization results and automatically stops when the time limit is reached.

[0012] Furthermore, the optimized stimulation protocol is determined based on parameter weighting analysis, in which stimulation duration contributes the most to the therapeutic effect, followed by envelope frequency.

[0013] Furthermore, the preferred protocol is: continuous stimulation mode, 20 Hz envelope frequency, 2 mA current, and 20 minutes duration.

[0014] Compared with the prior art, the beneficial technical effects of the present invention include: 1. By utilizing the principle of high-frequency carrier waves penetrating shallow layers and low-frequency envelopes interfering with deep layers, this method overcomes the limitations of traditional techniques in stimulating deep brain regions. Combined with personalized head models and electric field simulation, it achieves precise localization and activation of target brain regions in human vmPFC.

[0015] 2. Based on experimentally validated parameter weights (duration > envelope frequency > current intensity), the system has a built-in optimization protocol that prioritizes fixing key parameters and features automatic duration control and current creepage function, which effectively prevents overstimulation while improving the consistency of therapeutic efficacy.

[0016] 3. The electrode design and current output are optimized for human applications, taking into account both safety and comfort; the induced sustained analgesic effect makes it possible as a long-term management solution for chronic pain, and the system as a whole provides a complete and reliable solution for the clinical translation of tTIS technology. Attached Figure Description

[0017] Figure 1 This document presents the tTIS system structure, electric field simulation diagram, and tTIS targeted intervention verification. Figure 2 The results of pain behavior tests in mice under different stimulus patterns and states of consciousness; Figure 3 An analysis of the effects of current intensity and stimulation duration on therapeutic efficacy; Figure 4 Analysis of the impact of envelope frequency and carrier frequency on therapeutic efficacy; Figure 5 A heatmap for comprehensive evaluation of the treatment effect of tTIS; Figure 6 A graph showing the weighted analysis of the contribution of the tTIS parameter to the treatment outcome. Detailed Implementation

[0018] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings. It should be noted that these descriptions are for the purpose of aiding understanding the present invention, but do not constitute a limitation thereof. Furthermore, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0019] The tTIS parameter optimization system and method of the present invention will be described in detail below with reference to embodiments. The present invention aims to provide a system and method for safe, effective and precise non-invasive neuromodulation of deep brain regions (such as the mouse medial prefrontal cortex mPFC or its human homologous brain region vmPFC), which is particularly suitable for the treatment of chronic pain, and ensures maximum efficacy through system parameter optimization.

[0020] System Overview The transcranial time-interference stimulation parameter optimization system provided in this invention mainly includes: a tTIS stimulator, an electrode array, a control module, and a calculation module. By integrating biophysical principles, personalized computational modeling, and a validated optimized stimulation protocol, the system achieves precise, safe, and effective electrical stimulation of target deep brain regions.

[0021] 1. tTIS stimulator The tTIS stimulator is the core hardware of the system, essentially a sophisticated dual-channel isolated AC current source. It is configured to generate two independent high-frequency (typically in the kHz range, e.g., 1000 Hz to 6000 Hz, preferably 2000 Hz) sinusoidal carrier current signals (S1, S2), with a specific, small frequency difference between the two carriers. (e.g., 20 Hz). This frequency difference ( The effective neuromodulation electric field envelope frequency (e.g., 20 Hz) generated in the intracranial interference area is determined by this. The key to the stimulator is ensuring electrical isolation and precise synchronization of the two current paths in the hardware circuitry, preventing direct coupling of currents at the scalp electrodes, thereby ensuring that interference occurs only in the physical field of the target intracranial brain region (e.g., ...). Figure 1 (As shown). The stimulator's output current intensity is designed to be adjustable from 0 to 4 mA, with fine-tuning within the 0 to 0.5 mA range and step-wise adjustment (step size) for values ​​greater than 0.5 mA to accommodate the needs of different body sizes and tissue impedances, from rodents to humans. For human clinical applications, considering the high impedance of the scalp and skull, the software protocol typically recommends using a current intensity of 1 to 2 mA and integrates a current ramp-up / ramp-down function to smoothly change the current at the start and end of stimulation, improving patient comfort.

[0022] 2. Electrode array The electrode array is connected to the output channel of the tTIS stimulator, responsible for safely and effectively delivering two high-frequency carrier currents to the subject's scalp. According to a preferred embodiment of the invention, the electrode array comprises four independent electrodes, divided into two pairs (Pair 1: electrodes A1, B1; Pair 2: electrodes A2, B2). This four-electrode configuration represents the minimum and most effective hardware requirement for achieving the formation of a focused electric field through the interference of two currents, and is particularly suitable for stimulation of a single target (such as the vmPFC).

[0023] Electrode Structure Details: To minimize the risk of skin burns and improve tolerance to long-term stimulation while conscious, the electrodes are specially designed. Preferably, Ag / AgCl (silver chloride) electrode pads are used, a material with stable electrochemical properties and low polarization resistance. A conductive gel or a saline-soaked sponge pad is used between the electrode pad and the scalp to ensure good electrical contact and significantly reduce contact resistance. The electrode pad area is designed to be sufficiently large (e.g., circular or square, approximately 3 cm × 3 cm to 5 cm × 5 cm) to distribute the current density below a safe threshold, avoiding localized stinging or thermal damage. The electrodes can be disposable patches or integrated into an adjustable headgear to ensure stable, non-displacement during a typical 20–30 minute treatment.

[0024] 3. Control Module The control module communicates with the tTIS stimulator (wired or wireless) and is responsible for the intelligent management and execution of the entire stimulation process. Its core functions include: Parameter control: Precisely control the output parameters of the tTIS stimulator according to the preset or user-defined stimulation protocol, including: stimulation mode (continuous / intermittent), current intensity, carrier frequency, frequency difference (envelope frequency), duration of a single stimulation, etc.

[0025] Pre-defined stimulation protocol execution: The module stores optimal treatment protocols that have been systematically optimized and validated in previous animal experiments (such as mouse chronic pain models). These protocols specify at least: continuous stimulation (rather than intermittent stimulation); stimulation duration fixed within a preferred range (e.g., 15 to 30 minutes, preferably 20 minutes); and envelope frequency fixed within a specific frequency band (e.g., the β band from 10 Hz to 40 Hz, preferably 20 Hz). Figure 2 , 4 (As shown).

[0026] Parameter Priority and Locking Logic: Based on the parameter weight analysis derived from experiments, the control module implements a parameter priority configuration logic. This priority configuration logic is based on systematic parameter scanning experimental data from 62 chronic pain mouse models. It was derived using multiple linear regression analysis and a random forest model for weight fitting. The core finding is that the priority order of parameter influence on treatment effect (duration > envelope frequency > current intensity > carrier frequency) exhibits a universal pattern across species. Specifically, in the mouse model, the contribution weight of stimulation duration to treatment effect is 39.58%, envelope frequency is 31.45%, current intensity is 22.04%, and carrier frequency is 6.93% (e.g.,...). Figure 6 As shown, this weighted percentage serves only as core evidence for validating the effectiveness of the priority order in animal experiments and is not directly used as an absolute quantitative basis for human clinical operations. This weighted model exhibits stable predictive consistency in cross-validation (R²>0.85). Its core value lies in validating the optimization logic that "duration is the key influencing factor, and carrier frequency has the least impact." This optimization logic has been integrated into the firmware of the control module for automatically executing parameter priority configuration and locking logic in clinical applications. Under this logic, stimulation duration is given the highest priority and is usually set to a fixed value or selected within a strictly defined range to prevent overtreatment (experiments have shown that exceeding 30 minutes may lead to decreased efficacy or neuronal fatigue). Envelope frequency is given secondary priority and is also usually set to a fixed value or limited to the optimal frequency band (e.g., 20 Hz). Current intensity can be used as a variable that physicians can fine-tune according to patient tolerance within a safe range (e.g., 0.5 ~ 2 mA). Carrier frequency has the least impact and can be set to a fixed value within a certain range (e.g., 2000 Hz).

[0027] Safety and Time Limit Control: The control module is equipped with a mandatory time limit module. This module integrates a dual protection mechanism: a hardware watchdog timer and a software timing interrupt program. The hardware watchdog timer runs independently of the main control program, accumulating the stimulation duration in real time and is unaffected by software failures. The software timing interrupt program verifies the stimulation duration at fixed intervals (e.g., 10 ms), providing redundant verification with the hardware timer. When the duration of a single stimulation reaches a preset upper limit threshold (e.g., 30 minutes), the module will automatically trigger a stop current output or initiate a "soft stop" program that slowly reduces the current to zero. This "soft stop" program refers to linearly or exponentially decaying the output current from its current value to zero within 3 to 10 seconds, fundamentally preventing potential risks caused by unexpectedly prolonged stimulation time (e.g., ...). Figure 3 (As shown). This invention eliminates the risk of overstimulation due to operational errors by locking key parameters and setting a forced stop mechanism.

[0028] Status monitoring: In some embodiments, the control module can also receive real-time impedance detection signals from the stimulator or external sensors to monitor the electrode-skin contact quality and issue an alarm when the contact is poor to prevent ineffective stimulation or skin discomfort caused by uneven current distribution.

[0029] 4. Calculation Module The computational module is key to achieving personalized and precise localization. Its core task is to optimize and determine the placement of the electrode array on the scalp based on individual anatomical structure, ensuring that the generated interference envelope electric field can cover the target brain region to the greatest extent.

[0030] Input: Obtain magnetic resonance imaging (MRI) data of the subject's head structure.

[0031] Modeling and Simulation: Based on MRI data, a personalized finite element model (FEM) of the head is constructed using image segmentation and 3D reconstruction techniques. This model distinguishes between different tissues such as the scalp, skull, cerebrospinal fluid, gray matter, and white matter, assigning each corresponding conductivity parameter. Simultaneously, the 3D coordinates of the target brain region (e.g., for chronic pain, the human target is the ventromedial prefrontal cortex (vmPFC), which needs to be mapped from its standard brain atlas coordinates to the individual brain space) are determined within the model.

[0032] Optimized calculations: Computational electromagnetics methods (such as the finite element method) are used to simulate the distribution of low-frequency envelope electric fields generated within the skull when two pairs of electrodes are placed at different positions on the surface of a scalp model. Figure 1 As shown in the figure. By using optimization algorithms (such as gradient descent, genetic algorithm, etc.) to maximize the envelope electric field intensity or electric field coverage volume within the target brain region (vmPFC) as the objective function, the optimal application coordinates of the four electrodes on the scalp surface are solved in reverse.

[0033] Output optimization results: The system provides the user with the calculated optimal electrode coordinates, which are quantified using relative distances (in millimeters) in the anterior-posterior and mediolateral directions, with anatomical landmarks (such as the root of the nose, left and right tragus, or external auditory canal) as reference points. Furthermore, the system supports converting these anatomical coordinates into standard electrode sites (such as Fz, C3, P4, etc.) or their interpolated positions on a head-mounted EEG acquisition cap (such as the 10–20 system or the 10–10 system), outputting them as channel numbers on the cap or spherical coordinates (θ, φ). This enables rapid electrode deployment and guides the operator in accurately attaching the electrodes.

[0034] System Workflow and Methods The transcranial time-interference stimulation parameter optimization method of the present invention specifically includes the following steps: S1: Personalized positioning preparation. Obtain head structural MRI data of subjects who will undergo tTIS treatment.

[0035] S2: Calculate the optimal electrode placement. The calculation module loads MRI data and constructs a personalized finite element model of the head. The operator inputs or selects the target brain region (e.g., vmPFC). The calculation module automatically runs electric field simulation and optimization algorithms to calculate the four scalp electrode placement positions that will maximize the envelope electric field of the target brain region.

[0036] S3: Configure stimulation parameters. The operator selects or confirms a preset "Chronic Pain Optimization Protocol" through the user interface of the control module. This protocol is automatically set: mode "Continuous", envelope frequency "20 Hz", and duration "20 minutes". The current intensity can be set according to a preset range (e.g., 1 ~ 2 mA) and the patient's initial treatment tolerance (usually starting from a lower value). Other parameters such as carrier frequency (e.g., 2000 Hz) are built-in.

[0037] S4: Electrode Application and Connection. Based on the coordinates provided by the calculation module, accurately attach four prepared electrodes (Ag / AgCl electrode pads + conductive gel) to the subject's scalp. Connect the electrode leads to the two independent output channels of the tTIS stimulator.

[0038] S5: Stimulation is initiated. The operator activates the control module. The stimulator begins outputting two high-frequency carrier currents with a 20 Hz frequency difference. The current passes through the scalp and skull, interfering in the deep brain region (target vmPFC area), generating a low-frequency modulated electric field with a frequency of 20 Hz. This electric field is sufficient to depolarize neurons in this region and generate a neural response, while the overlying cortex, due to the "low-pass filtering" property of the neuronal membrane to the high-frequency carrier, is not abnormally activated. This biophysical mechanism was verified by c-Fos immunofluorescence staining in animal experiments: after stimulation, c-Fos protein expression significantly increased in the target brain region (e.g., mouse mPFC), while expression was very low in the superficial cortical region (e.g., ...). Figure 1 (As shown).

[0039] S6: Safety Monitoring and Automatic Termination. During stimulation, the control module continuously times the circuit. When the stimulation time reaches the preset 20 minutes (or the set upper limit), the control module automatically sends a command to the stimulator to stop the current output, completing a single treatment.

[0040] S7: Treatment Management. Based on the optimal protocol used in animal studies, the above treatment can be administered once daily for several consecutive days (e.g., 7 days) to constitute a treatment course, in order to induce sustained analgesia and changes in neuroplasticity (e.g., Figure 5 (As shown).

[0041] Technical adaptation optimization and core details explanation Guarantee of specificity for deep stimulation: This invention ensures that stimulation is limited to the deep target area through a triple mechanism: (a) Principle level: Utilizing the capacitance characteristics of neuronal cell membranes (low-pass filter), high-frequency carrier waves (such as 2000 Hz) are insufficient to induce action potentials when penetrating superficial tissues; (b) Engineering level: Hardware isolation of dual-channel current sources prevents non-interference coupling; (c) Validation level: Targeting can be confirmed by detecting biomarkers (such as c-Fos) after stimulation.

[0042] Scientific basis for parameter optimization: The "optimal parameter combination" (continuous, awake, 20 Hz, 0.05 mA (mice), 2 mA (humans), 20 minutes) and parameter priorities (duration 39.58%, envelope frequency 31.45%, current intensity 22.04%, carrier frequency 6.93%) are derived from systematic parameter scanning and multiple linear regression analysis of a chronic pain mouse model, and are supported by solid experimental data (e.g., Figure 6 (As shown).

[0043] Human application adaptation: Target mapping: The mouse mPFC corresponds to the human vmPFC in terms of structure and function.

[0044] Current adaptation: The effective current verified in mouse experiments is 0.05 mA. Based on the principle of safety first and preliminary field strength simulation estimation, considering the larger tissue volume and higher impedance difference between the skull and scalp in the human body, the recommended clinical starting current intensity range is 0.5 to 2 mA (this range is not an exact physical conversion value). The specific value needs to be determined dynamically based on the electric field simulation results of the aforementioned personalized head finite element model and the individual patient's tolerance.

[0045] Necessity of localization: Due to significant individual differences in human skull shape and frontal sinus size, the aforementioned personalized modeling and electrode placement optimization are necessary. Simply pasting standard positions may cause the focal point to shift, affecting the therapeutic effect.

[0046] Safety features: Time safety: Based on the experimental conclusion that "40 minutes may lead to overtreatment," the system has a built-in mandatory time limit module (e.g., Figure 3 (As shown).

[0047] Physical safety: The use of large-area Ag / AgCl electrodes and conductive gel greatly reduces the risk of skin burns.

[0048] Electrical safety: Current output range limited (0 ~ 4 mA), the software defaults to the safe range.

[0049] Application Examples Example 1: Treatment of chronic pain in human patients A patient with chronic neuropathic pain underwent treatment. A head MRI scan was performed first. Based on the MRI data, a computational module calculated the optimal four electrode placement points (e.g., two on the forehead and two on the parietal lobe) for the individual patient's vmPFC. The therapist applied the electrodes and set the control module to "standard pain protocol" (continuous mode, 20 Hz, 20 minutes, 1.0 mA initial current). The patient received 20 minutes of tTIS treatment once daily for one week. During treatment, the patient experienced only mild tingling sensations on the skin, without pain. Post-treatment pain scores significantly decreased, and the effect persisted for a period of time after treatment (e.g., 24–72 hours). Figure 5 (As shown).

[0050] Example 2: Scientific Research and Parameter Exploration Researchers can use the system to explore new disease models or brain regions. They can temporarily "unlock" the parameter fixing function of the control module, systematically adjust variables such as duration and envelope frequency, and at the same time use the system's personalized positioning function to ensure targeting accuracy, thereby efficiently exploring the optimal parameters for new application scenarios.

[0051] In summary, the transcranial time-interference stimulation parameter optimization system and method provided by this invention, by integrating personalized precise positioning, experimentally validated parameter optimization protocols, intelligent safety control, and humanized electrode design, achieves safe, effective, and convenient non-invasive neuromodulation of deep brain regions, and provides an innovative solution for the treatment of diseases such as chronic pain.

[0052] The embodiments of the present invention have been described in detail above with reference to the accompanying drawings, but the present invention is not limited to the described embodiments. For those skilled in the art, various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and these variations still fall within the protection scope of the present invention.

Claims

1. A transcranial temporal interferometry stimulation parameter optimization system, characterized in that, include: The tTIS stimulator is used to generate two high-frequency carrier current signals with a specific frequency difference. An electrode array, connected to the tTIS stimulator, is used to apply the two high-frequency carrier current signals to the subject's scalp to generate a low-frequency envelope electric field in the target brain region through interference. The control module is communicatively connected to the tTIS stimulator and configured to control the output parameters of the tTIS stimulator and execute a preset stimulation protocol. The stimulation protocol includes a continuous stimulation mode, a preset current intensity range, a preset stimulation duration range, and a preset envelope frequency range. The control module stores a parameter priority configuration model trained based on previous animal experimental efficacy data, wherein the stimulation duration is set to a fixed value, the envelope frequency is limited to 20 ± 10 Hz, and the current intensity is a variable that the user can adjust within a safe range. The calculation module is configured to construct a finite element model of the head based on the subject's head imaging data, and optimize the placement of the electrode array on the scalp surface by electric field simulation calculation according to the coordinates of the target brain region. This includes optimizing the relative spacing and angle of the two pairs of electrodes to maximize the low-frequency envelope electric field intensity and spatial focusing within the target brain region.

2. The system according to claim 1, characterized in that, The control module is configured to execute a preset stimulation protocol, limiting the stimulation duration to between 15 and 30 minutes, and automatically stopping the current output or starting a current ramp-down program when the preset upper limit of the single stimulation duration is reached.

3. The system according to claim 1 or 2, characterized in that, The control module stores priority configuration logic based on efficacy verification, wherein the stimulation duration is configured as a fixed parameter with the highest priority, the envelope frequency is configured as a fixed parameter with the second highest priority or limited to a specific frequency band, and the current intensity is configured as a variable that the user can adjust within a safe range.

4. The system according to claim 1, characterized in that, The target brain region is the ventromedial prefrontal cortex; the preset envelope frequency range is 10 Hz to 40 Hz.

5. The system according to claim 1, characterized in that, The electrode array includes four independent electrodes, divided into two pairs; the tTIS stimulator is a dual-channel isolated current source, ensuring that the two high-frequency carrier currents are isolated from each other in hardware and only interfere through physical fields within the cranium.

6. The system according to claim 1 or 5, characterized in that, The electrode includes an Ag / AgCl electrode sheet, which is used in conjunction with conductive gel or saline sponge, and the electrode sheet area is from 3 cm × 3 cm to 5 cm × 5 cm.

7. The system according to claim 1, characterized in that, The output current intensity of the tTIS stimulator ranges from 0 to 4 mA.

8. A method for optimizing transcranial temporal interferometry stimulation parameters, characterized in that, Applied to the system as described in any one of claims 1-7, the method comprises: Obtain head imaging data of the subjects; Based on the head imaging data, a finite element model of the head is constructed, and the coordinates of the target brain region are determined; Based on the aforementioned finite element model of the head and the coordinates of the target brain region, the application position of the electrodes for applying two high-frequency carrier currents on the scalp surface is optimized and determined through electric field simulation calculations. Configure tTIS parameters according to a preset optimized stimulation protocol, wherein the optimized stimulation protocol includes at least: adopting a continuous stimulation mode, setting the stimulation duration to between 15 and 30 minutes, and setting the envelope frequency to between 10 Hz and 40 Hz; Based on the determined electrode locations and configured tTIS parameters, tTIS stimulation is applied to the target brain region of the subject.

9. The method according to claim 8, characterized in that, The parameters of the optimized stimulation protocol are determined based on the parameter priority configuration logic as described in claim 3 or the weight order revealed by the parameter priority configuration model as described in claim 1, wherein the stimulation duration has the highest contribution weight to the therapeutic effect, followed by the envelope frequency, then the current intensity, and the carrier frequency has the lowest contribution weight; the target brain region is the ventromedial prefrontal cortex, and the optimized stimulation protocol is applicable to the treatment of chronic neuropathic pain.

10. The method according to claim 8, characterized in that, The optimized stimulation protocol specifically includes: continuous stimulation mode, 20 Hz envelope frequency, 2 mA current intensity, and 20-minute stimulation duration.

11. The method according to claim 8, characterized in that, During stimulation, the stimulation time is monitored in real time. When the duration of a single stimulation reaches the preset upper limit, the stimulation is automatically stopped or the output current is gradually reduced.

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