Portable brain-limb cooperative tremor regulation and control method and system and related products

Abstract

The invention relates to the technical field of medical treatment, and provides a portable brain-limb cooperative tremor regulation and control method, which comprises the following steps: collecting motion data of a hand of a user; identifying individualized tremor frequency of the user in real time based on the motion data of the hand of the user; based on the identified individualized tremor frequency, band-pass filtering with the individualized tremor frequency as the center is carried out on the tremor signal after high-pass filtering, and the current tremor phase is detected; based on the individualized tremor frequency and the tremor phase, generating percutaneous introduction mode stimulation parameters and starting stimulation; generating transcranial time domain interference stimulation parameters and starting stimulation at a specific time point after the transcranial introduction mode stimulation is started; the transcranial time domain interference stimulation and the transcutaneous afferent mode stimulation are cooperatively controlled for intervention; the tremor intensity change is monitored in real time, stimulation parameters are dynamically adjusted, and closed-loop control is formed. According to the technical scheme, through the integrated design of real-time sensing, dual-mode cooperation and closed-loop regulation, tremor efficient suppression and portable treatment are achieved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical treatment, in particular to a portable brain-limb coordinated tremor regulation method and system and related products. BACKGROUND

[0002] Essential tremor (ET) is the most common movement disorder in adults, with a global prevalence of about 0.9%. Its main manifestations are action tremors in the hands, head, or voice, which severely limit the daily activities of patients (e.g., eating, writing, etc.). Current clinical treatments mainly include drugs (propranolol, etc.) and surgery (deep brain stimulation, DBS). However, drug treatment is ineffective for about 50% of patients and is accompanied by side effects such as drowsiness, while DBS, although effective, requires craniotomy and electrode implantation, which carries the risk of infection, bleeding, and high costs, making it difficult to meet the needs of daily family management.

[0003] Existing non-invasive treatment options mainly include two categories: 1) single peripheral nerve stimulation, i.e., acting on the wrist nerve through transcutaneous electrical stimulation (e.g., TENS), using a fixed frequency or a simple tremor frequency following mode, such as applying an electrical pulse at the same frequency after detecting tremors through electromyography (EMG); 2) open-loop central regulation, i.e., a conceptual scheme based on transcranial time-domain interference stimulation (tTIS), which applies two high-frequency currents through scalp electrodes to form a low-frequency envelope in the deep brain, but the stimulation parameters are fixed and run independently, and cannot be linked with peripheral intervention.

[0004] The above-mentioned existing non-invasive treatment options have the following main defects: 1) insufficient neural modulation efficiency, specifically, the fixed frequency mode of single peripheral stimulation easily causes neural adaptation, while simple frequency following only produces a masking effect, lacks the strong recruitment ability of high-frequency pulses for nerve fibers, and has poor persistence of inhibition effect; 2) lack of coordination mechanism, mainly manifested in that the central tTIS stimulation is in an open-loop state, cannot dynamically adjust the starting time and parameters according to the real-time tremor state, and thus is difficult to form a brain-limb coordinated intervention in terms of timing; 3) lack of portability and closed loop, mainly manifested in that traditional devices lack integrated tremor sensing and adaptive control modules, rely on external sensors, and cannot build a wearable rapid closed-loop system. SUMMARY

[0005] The present application provides a portable brain-limb coordinated tremor regulation method, system and related products, which realizes efficient tremor suppression and portable treatment through real-time sensing-dual-mode coordination-closed-loop regulation integrated design.

[0006] In one aspect, the present application provides a portable brain-limb coordinated tremor regulation system, which comprises: a main control module; A tremor perception module, in communication connection with the main control module, is configured to collect motion data of a user's hand; A transcranial time-domain interference stimulation module, in connection with the main control module, is configured to generate two high-frequency currents to form a low-frequency envelope stimulation signal in a deep area of the user's brain; A transcutaneous afferent pattern stimulation module, in connection with the main control module, is configured to generate a specific mode of electrical pulse to stimulate the user's wrist nerve; A power management module is configured to supply power to the above-mentioned modules; The main control module is configured to: identify the individualized tremor frequency of the user in real time based on the motion data collected by the tremor perception module; control the transcutaneous afferent pattern stimulation module to generate a composite stimulation mode with high-frequency pulses and alternating stimulation of different nerves at the individualized tremor frequency based on the tremor phase and the individualized tremor frequency; control the transcranial time-domain interference stimulation module to generate optimized stimulation parameters at a specific time point after the transcutaneous afferent pattern stimulation is started; cooperatively control the transcranial time-domain interference stimulation module and the transcutaneous afferent pattern stimulation module to intervene, and dynamically adjust the stimulation parameters according to the change in tremor intensity feedback by the tremor perception module, forming a closed-loop control.

[0007] In another aspect, the present application provides a portable brain-limb coordinated tremor regulation method, which uses the above-mentioned portable brain-limb coordinated tremor regulation system, and the method comprises: Collecting motion data of a user's hand; Identifying the individualized tremor frequency of the user in real time based on the motion data; Based on the identified individualized tremor frequency, performing band-pass filtering on the high-pass filtered tremor signal centered at the individualized tremor frequency, and detecting the current tremor phase; Based on the individualized tremor frequency and the tremor phase, generating transcutaneous afferent pattern stimulation parameters and starting stimulation; At a specific time point after the transcutaneous afferent pattern stimulation is started, generating transcranial time-domain interference stimulation parameters and starting stimulation; Cooperatively controlling the transcranial time-domain interference stimulation and the transcutaneous afferent pattern stimulation to intervene; Real-time monitoring of the change in tremor intensity, and dynamic adjustment of the stimulation parameters, forming a closed-loop control.

[0008] In a third aspect, the present application provides a storage medium storing a computer program, which is executed by a processor to implement the steps of the technical solution of the above-mentioned portable brain-limb coordinated tremor regulation method.

[0009] As can be seen from the technical solution provided in this application, on the one hand, by integrating a tremor sensing module to collect hand movement data in real time and dynamically generating stimulation parameters based on individualized tremor frequencies, the neural adaptability defects of fixed-frequency stimulation are overcome, thereby improving neural modulation efficiency. On the other hand, a timing protocol is adopted in which the transcutaneous afferent stimulation module (TAPS) is activated first and the transcranial temporal interference stimulation module (tTIS) is activated later: TAPS uses high-frequency pulses to alternately stimulate the two nerves at individualized tremor frequencies to enhance the nerve fiber recruitment ability. tTIS is triggered 1 / 4 of the tremor cycle after TAPS is activated, and generates an envelope targeting deep brain nuclei through two high-frequency current interferences. The two complement each other in time and space, producing a synergistic enhancement effect. On the third hand, the alternating frequency of TAPS and the stimulation intensity of tTIS are dynamically adjusted based on tremor sensing feedback to form a "sensing-decision-stimulation" closed loop, solving the defect that open-loop systems cannot respond to dynamic changes in tremor. Furthermore, through a power management module and integrated hardware architecture, tremor sensing, dual-mode stimulation, and control logic are integrated into a wearable device, breaking through the size limitations of traditional devices and making it suitable for daily management in home scenarios. In summary, the technical solution of this application achieves efficient tremor suppression and portable treatment through an integrated design of real-time perception, dual-mode collaboration, and closed-loop control. Attached Figure Description

[0010] To more clearly illustrate the technical solutions in the embodiments of this application or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0011] Figure 1 This is a schematic diagram of the structure of the portable brain-limb coordinated tremor modulation system provided in the embodiments of this application; Figure 2 These are different views of the physical object corresponding to the portable brain-limb co-tremor modulation system provided in the embodiments of this application, namely the portable brain-limb co-tremor modulation device. Figure 3 This is a structural diagram of the portable brain-limb sympathetic tremor modulation device based on type-C stimulation electrode adapter cable type 1 provided in the embodiments of this application; Figure 4 This is a structural diagram of the portable brain-limb sympathetic tremor modulation device based on type-C stimulation electrode adapter cable type 2 provided in the embodiments of this application; Figure 5 This is the constant current source topology provided in the embodiments of this application; Figure 6This application provides a single-group, 2000Hz complementary output constant current sinusoidal current output waveform based on the AD8226 instrumentation amplifier combined with the AD820 precision operational amplifier. Figure 7 This is a schematic diagram of a resistive network test simulating a human head provided in an embodiment of this application; Figure 8 The embodiments provided in this application are based on Figure 7 Schematic diagram of simulated waveforms in different regions of the test network; Figure 9 This is a flowchart of a portable brain-limb coordinated tremor modulation method provided in the embodiments of this application; Figure 10 This is a schematic diagram showing changes in baseline metabolism of the tremor network as displayed in a PET scan image provided in an embodiment of this application; Figure 11 This is a schematic diagram illustrating the improvement of tremor power in four typical clinical tasks using the technical solution of this application. Detailed Implementation

[0012] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0013] In this specification, adjectives such as "first" and "second" are used only to distinguish one element or action from another, without necessarily requiring or implying any actual such relationship or order. Where circumstances permit, reference to an element or component or step (etc.) should not be construed as being limited to only one of the elements, components, or steps, but may be one or more of the elements, components, or steps, etc.

[0014] For ease of description, the dimensions of the various parts shown in the accompanying drawings are not drawn to actual scale.

[0015] Existing non-invasive treatment options mainly fall into two categories: 1) Single peripheral nerve stimulation, which involves applying transcutaneous electrical stimulation (e.g., TENS) to the wrist nerve, using a fixed frequency or a simple tremor-following pattern, such as applying electrical pulses at the same frequency after detecting tremors via electromyography (EMG); 2) Open-loop central modulation, which is a conceptual approach based on transcranial time-domain interference stimulation (tTIS), where two high-frequency currents are applied through scalp electrodes to form a low-frequency envelope deep in the brain, but its stimulation parameters are fixed and operate independently, and cannot be linked with peripheral interventions. The existing non-invasive treatment methods have the following main defects: 1) Insufficient neural modulation efficiency, specifically, the fixed frequency pattern of a single peripheral stimulus is prone to induce neural adaptation, while simple frequency following only produces a masking effect and lacks the strong recruitment ability of nerve fibers from high-frequency pulses, resulting in poor persistence of inhibitory effects; 2) Lack of synergistic mechanism, mainly manifested in the fact that central tTIS stimulation is mostly in an open-loop state, and cannot dynamically adjust the initiation timing and parameters according to the real-time tremor state, resulting in a temporal disconnect with peripheral stimulation and making it difficult to form brain-limb synergistic intervention; 3) Lack of portability and closed-loop, mainly manifested in the fact that traditional devices lack an integrated tremor sensing and adaptive control module, rely on external sensors, and cannot build a wearable rapid closed-loop system.

[0016] To address the problems of the prior art, this application proposes a portable brain-limb coordinated tremor modulation system. Before introducing the system, the technical terms involved in this application are explained as follows: 1. Deep Brain Stimulation (DBS): Commonly known as a brain pacemaker, DBS typically involves implanting stimulating electrodes into specific brain nuclei through stereotactic surgery. Weak electrical pulses are delivered to the target nuclei via electrode contacts, directly modulating brain nucleus function and effectively treating neurological disorders. A DBS device generally consists of three parts: a pulse generator, an extension cable, and a probe.

[0017] 2. Traditional Transcranial Electrical Stimulation (TCS): Traditional TCS devices use low-intensity current (±2mA) to stimulate target areas of the cerebral cortex, thereby regulating neuronal excitability, modulating brain wave rhythms, promoting neural remodeling and repair, and improving cerebral blood supply. Traditional TCS mainly includes four modes: transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial pulsed current stimulation (tPCS), and transcranial random noise stimulation (tRNS). 2.1) Transcranial Direct Current Stimulation (tDCS): This involves the constant release of a weak direct current (1-2 mA) onto the scalp via two or more electrodes. tDCS consists of two surface electrode pads: a cathode and an anode. Cathode stimulation reduces cortical excitability through neuronal hyperpolarization, while anode stimulation increases cortical excitability through subthreshold neuronal depolarization. Neurophysiological studies have shown that tDCS works by modulating neurotransmitters such as glutamate, GABA, dopamine, serotonin, and cholinesterase.

[0018] 2.2) Transcranial Alternating Current Stimulation (tACS): Unlike tDCS, which is constant throughout the cycle, tACS omits the directional voltage component, and its phase curve alternates periodically between positive and negative voltages.

[0019] 2.3) Transcranial Pulse Current Stimulation (tPCS): Weak pulse currents are transmitted to the cerebral cortex through the anode and cathode with fixed stimulation amplitude and specific time intervals.

[0020] 2.3) Transcranial Random Noise Stimulation (tRNS): A weak alternating current oscillating at a random frequency is delivered through the scalp using a pair of electrodes.

[0021] 3. Transcranial temporal interference stimulation (tTIS): By applying two high-frequency currents with a frequency difference to the scalp surface, the interference principle is used to generate a low-frequency envelope waveform inside the brain, thereby achieving precise stimulation of deep nuclei without affecting the neural activity of the cerebral cortex.

[0022] 4. Transcutaneous Electrical Nerve Stimulation (TENS): TENS, also known as peripheral nerve fiber electrical stimulation, is an electrotherapy method that delivers specific low-frequency pulsed currents through the skin to treat pain. It excites coarse fibers, indirectly closing the pain transmission gate, activating endogenous morphine-like neurons in the brain, and thus triggering the release of endogenous morphine-like peptides, exerting an analgesic effect. It can also improve local blood circulation and promote edema absorption by inducing slight muscle tremors and contractions, thereby enhancing the analgesic effect. As a routine treatment method applicable to rehabilitation interventions for various motor and sensory disorders, it has obtained multiple certifications from the U.S. Food and Drug Administration (FDA).

[0023] 5. Direct Digital Synthesizer (DDS): DDS is a frequency synthesis technique that directly synthesizes the desired waveform based on the concept of phase. It is a frequency synthesis method that directly generates various frequencies and waveforms by controlling the rate of phase change.

[0024] 6. Microcontroller Unit (MCU): Also known as a single-chip microcomputer, it is a chip-level computer that integrates a central processing unit (CPU) with a reduced frequency and specifications, along with peripheral interfaces such as memory, timer, USB, A / D converter, UART, and even LCD driver circuitry, all onto a single chip. This allows for different control combinations for various applications. MCUs are found in everything from mobile phones and PC peripherals to remote controls, automotive electronics, and industrial applications such as stepper motor and robotic arm control.

[0025] 7. Integrated Circuit (IC): refers to a silicon chip containing integrated circuits. It is very small and is often part of a computer or other electronic device.

[0026] 8. The Inertial Measurement Unit (IMU), also known as a six-axis sensor module (including a three-axis accelerometer and a three-axis gyroscope), is used to accurately measure the angular velocity and acceleration of the wrist in three-dimensional space. It is the core sensing element for real-time monitoring and identification of tremor movements.

[0027] like Figure 1 The diagram shown is a schematic of a portable brain-limb coordinated tremor modulation system provided in this application embodiment. It mainly includes a main control module 101, a tremor sensing module 102, a transcranial temporal interference stimulation module 103, a transcutaneous afferent mode stimulation module 104, and a power management module 105, which are described in detail below: The tremor sensing module 102 is communicatively connected to the main control module 101 and is used to collect motion data of the user's hand. The transcranial time-domain interference stimulation module 103 is connected to the main control module 101 and is used to generate two high-frequency currents to form a low-frequency envelope stimulation signal in the deep region of the user's brain. The transcutaneous afferent stimulation module 104, connected to the main control module 101, is used to generate electrical pulses of a specific pattern to stimulate the user's wrist nerves. Power management module 105 is used to supply power to the above modules; The main control module 101 is configured to: identify the user's individualized tremor frequency in real time based on the motion data collected by the tremor sensing module 102; control the transcutaneous afferent stimulation module 104 to generate a composite stimulation mode with high-frequency pulses and alternating stimulation of different nerves at the individualized tremor frequency based on the tremor phase and individualized tremor frequency; control the transcranial temporal interference stimulation module 103 to generate optimized stimulation parameters at a specific time point after the transcutaneous afferent stimulation is initiated; coordinate the control of the transcranial temporal interference stimulation module 103 and the transcutaneous afferent stimulation module 104 to intervene, and dynamically adjust the stimulation parameters according to the tremor intensity changes fed back by the tremor sensing module 102 to form a closed-loop control.

[0028] The aforementioned portable brain-limb coordinated tremor modulation system may also include human-computer interaction modules such as buttons and an LCD display. The functions of these buttons are as follows: Figure 2This will be explained in the description. Specifically, the power management module 105 manages and protects the charging and discharging of the power supply tubes; the main control module 101 controls the entire system; the interactive modules such as buttons / LCD displays handle input and output system interactions; the transcranial time-domain interference stimulation module 103 includes a direct digital frequency synthesizer (DDS) and a complementary output voltage-controlled constant current circuit. The DDS outputs the original signal of the predetermined signal, and the complementary output voltage-controlled constant current circuit converts the input voltage into a constant current output. Together, they complete the transcranial time-domain interference stimulation function. The transcutaneous afferent mode stimulation module 104 mainly includes a power drive unit, an H-bridge module, and a boost circuit. The power drive unit drives the H-bridge, the H-bridge module outputs bipolar voltage, and the boost circuit boosts the voltage. The power drive unit, H-bridge module, and boost circuit work together to complete transcutaneous afferent mode stimulation (TAPS). In general, transcranial time-domain interference stimulation and transcutaneous afferent mode stimulation will ultimately stimulate the human body through electrodes according to the corresponding outputs under the system's control timing.

[0029] The main control module 101 can be a microcontroller unit (MCU), which drives the hardware peripherals of the entire portable brain-limb tremor modulation system. Through proper embedded software design, it can drive the LCD display, buttons, direct digital frequency synthesizer (DDS), power management module, and internal peripherals of the MCU, such as the ADC analog-to-digital converter and timer module. Furthermore, the MCU implements the sequential execution and task scheduling of the application-level business logic of the entire product. Specifically, it can schedule tasks related to LCD interactive display, button interactive logic, stimulation electrode impedance acquisition and analysis, DDS arbitrary waveform generation, and power management module processing. A specific example of the main control module 101 is illustrated using the AT32F403ACGT7 as the main control MCU. The AT32F403A series uses a high-performance ARM® Cortex®-M4F 32-bit RISC core with an operating frequency of 240 MHz. The Cortex®-M4F core includes a single-precision floating-point unit (FPU), supporting all ARM® single-precision data processing instructions and data types. This device includes three 12-bit ADCs, two 12-bit DACs, eight general-purpose 16-bit timers, two general-purpose 32-bit timers, and up to two PWM timers. It also includes standard and advanced communication interfaces: up to three I2C interfaces, four SPI interfaces (multiplexed as I2S interfaces), two SDIO interfaces, eight USART / UART interfaces, one USB interface, and two CAN interfaces. The peripherals of this MCU are sufficient to meet the peripheral resource requirements of this portable brain-limb tremor control system. The MCU is not limited to AT32F403ACGT. Other Artery MCUs that can meet the peripheral resource requirements are also acceptable, such as mainstream ones like GigaDevice GD32xxx series MCUs and STMicroelectronics STM32XXX series MCUs.

[0030] from Figure 1The portable brain-limb coordinated tremor modulation system exemplifies two key advantages. First, by integrating a tremor sensing module to collect hand movement data in real time and dynamically generating stimulation parameters based on individualized tremor frequencies, it overcomes the neural adaptability limitations of fixed-frequency stimulation, thereby improving neural modulation efficiency. Second, it employs a timing protocol that prioritizes the transcutaneous afferent mode stimulation module (TAPS) and delays the transcranial temporal interference stimulation module (tTIS): TAPS alternately stimulates both nerves with high-frequency pulses at individualized tremor frequencies, enhancing nerve fiber recruitment; tTIS, in turn, delays the activation of the transcutaneous afferent mode stimulation module (TAPS) and the transcranial temporal interference stimulation module (tTIS). Triggered after initiating a 1 / 4 tremor cycle, the system generates an envelope targeting deep brain nuclei through two high-frequency current interferences. These two components are complementary in both time and space, producing a synergistic enhancement effect. Thirdly, based on tremor perception feedback, the alternating frequency of TAPS and the intensity of tTIS stimulation are dynamically adjusted, forming a "perception-decision-stimulation" closed loop. This overcomes the limitation of open-loop systems in responding to dynamic changes in tremor. Furthermore, through a power management module and integrated hardware architecture, tremor perception, dual-mode stimulation, and control logic are integrated into a wearable device, overcoming the size limitations of traditional devices and making it suitable for daily management in home settings. In summary, the technical solution of this application achieves efficient tremor suppression and portable treatment through an integrated design of real-time perception, dual-mode collaboration, and closed-loop regulation.

[0031] Figure 2 The image shows different views of the portable brain-limb tremor modulation system, corresponding to the actual device. The functions of each component are described below: Label A as the display, mainly for realizing interactive functions such as stimulus parameters and status display; Mark B is a status indicator light, whose core function is to identify states such as charging in progress, charging complete, and fault indication. Mark C indicates electrode jack 1, which is the jack for the circular electrode, i.e., the transcutaneous TAPS stimulation electrode. Mark D is the electrode socket 2, which is the socket for the Type-C morphological electrode, namely the transcranial time-domain interference electrical stimulation (tTIS) electrode; The button marked E is the "Mode" button: It is mainly used to switch modes. A short press switches modes, which mainly include three modes: 1) "tTIS" mode, which works alone in the transcranial time-domain interference electrical stimulation (tTIS) mode; 2) "TAPS" mode, which works alone in the transcutaneous afferent electrical stimulation mode; 3) "Auto" mode, in which clicking the "Start" button will automatically work according to the workflow described above. This is the system default, and this application is also written and described in this mode. The button marked F is the "Intensity Reduction" button, which reduces the intensity of the stimulus. A short press increases the intensity by 1 step, and a long press reduces it quickly. The button marked G is the "Intensity Increase" button, which increases the stimulation intensity. A short press increases the intensity by 1 step, and a long press increases it rapidly. The button marked H is the "Start / Pause" button, which controls the stimulation output. Specifically, it can start, pause, and restart after pausing. The button marked 'I' is the 'Power On / Off' button, which controls the power on / off of the device. The J symbol indicates a Type-C interface, which can be used as a charging interface, as well as for serial communication and program downloading. Mark K indicates the Velcro attachment point, meaning the handheld device is worn on the wrist by attaching the Velcro.

[0032] In this embodiment, the Type-C morphological electrode mainly includes Type-C-based stimulation electrode adapter cable type 1 and Type-C-based stimulation electrode adapter cable type 2, wherein, Type-C-based stimulation electrode adapter cable type 1 is as follows: Figure 3 As shown. The Type-C based stimulation electrode adapter cable (Type 1) has two interfaces: one is the input interface, as shown... Figure 3 As indicated by label A, this interface is a Type-C interface, primarily used for connecting the stimulation jack 2 of a portable brain-limb sympathetic tremor modulation device. Figure 2 At point D, another interface is a port connector. The standard port connector has a 1.5mm hole diameter (the hole diameter can be customized). The core of this port connector is to connect various types of stimulation electrodes, such as disc-shaped silver / silver chloride powder electrodes, gel electrodes, and sponge electrodes. This type of electrode adapter cable facilitates the expansion of the device into various application scenarios. Type-C-based stimulation electrode adapter cable type 2, as shown... Figure 4 As shown, one end of this type of stimulation adapter cable is a Type-C interface, mainly used to connect to the stimulation output interface of portable brain-limb sympathetic tremor modulation devices, such as... Figure 2 The electrode is marked D at one end, and the other end is a standard, commonly used disc-shaped silver or silver chloride powder electrode. Most deep brain stimulation (TBS) electrodes are of this type. This allows the electrode adapter to be placed directly on the desired stimulation site on the EEG cap, greatly facilitating portable deep brain stimulation. TAPS electrodes can be hydrogel electrodes.

[0033] Figure 1The example tremor sensing module 102 includes an inertial measurement unit (IMU). As previously mentioned, the IMU includes a triaxial accelerometer and a triaxial gyroscope. In this embodiment, the triaxial accelerometer primarily uses an LSM303D (STMicroelectronics) to collect real-time motion data of the user's hand for tremor detection and frequency analysis. The LSM303D accelerometer is a low-power, high-precision triaxial accelerometer suitable for motion detection, with a sensitivity of 0.061 mg / LSB (±2g) and a sampling rate of not less than 100 Hz. Its high sampling rate (100 Hz) and sensitivity enable it to accurately capture tremor signals.

[0034] The transcranial time-domain interference stimulation module 103 mainly includes a direct digital frequency synthesizer (DDS) and a complementary output voltage-controlled constant current source. The DDS generates four isolated high-frequency sine wave signals with an adjustable frequency range of 900Hz to 1430Hz. Specifically, the core of the DDS is to output four preset stimulation waveforms, primarily achieved by the microcontroller unit (MCU) sending corresponding instructions to the DDS chip via a communication bus. One specific example (other similar DDS chips with four-channel isolated output are also acceptable) is as follows: The AD9959 is selected as the digital frequency synthesis chip. The AD9959 has an internal clock frequency of up to 500 MHz and integrates four DDS cores. The channels are isolated from each other, with an isolation degree greater than 65 dB. Therefore, the four internal synchronous output channels can be independently programmed, allowing for independent output of analog sine wave signals up to 200 MHz. The amplitude of each channel's output signal can reach 500 mV, with an amplitude resolution of 0.5 mV, and a minimum frequency adjustment step of approximately 1 Hz.

[0035] In this embodiment, the complementary output voltage-controlled constant current source mainly includes two sets of constant current sources, each set of constant current sources driving a pair of stimulation electrodes, such as... Figure 1 As shown, the first set of constant current sources drives stimulation electrodes 1 and 2, and the second set of constant current sources drives stimulation electrodes 3 and 4. The current amplitude of the constant current source output is adjustable, and the current output error is ±1%. The complementary output type voltage-controlled constant current source can also adopt the Howland topology, which is implemented by combining an instrumentation amplifier and an operational amplifier. The complementary output type voltage-controlled constant current source is described in detail below.

[0036] The core of a complementary output type voltage-controlled constant current source is to convert the voltage signals from four DDS outputs into four constant current source signal outputs. Specifically, such as... Figure 1As shown, stimulation electrode 1 and stimulation electrode 2 are constructed as a set of complementary output voltage-controlled constant current sources, and stimulation electrode 3 and stimulation electrode 4 are constructed as another set of complementary output voltage-controlled constant current sources.

[0037] Constant current source topology such as Figure 5 As shown. Based on whether the constant voltage / constant current source is a low-impedance or high-impedance path relative to ground, constant current source topologies can be categorized into several types, including floating-ground output constant current source topologies, ground-output constant current source topologies, and complementary output constant current source topologies. If... Figure 5 The diagram shows a floating-ground constant current source topology. Stimulating electrodes 1 and 3 are constant voltage sources, while stimulating electrodes 2 and 4 are constant current sources. The constant voltage sources are low-impedance channels relative to ground, while the constant current sources are high-impedance channels. Therefore, stimulating electrodes 1 and 3 have low impedance relative to ground, while stimulating electrodes 2 and 4 have high impedance relative to ground. This floating-ground constant current source can cause unnecessary interference because the current input to stimulating electrode 2 can either return to ground via the low-impedance channel through stimulating electrode 1 or form a loop to ground via the low-impedance channel through stimulating electrode 3. Similarly, the current input to stimulating electrode 4 can form a loop via either stimulating electrode 1 or stimulating electrode 3.

[0038] like Figure 5 The diagram shows the topology of a ground-output constant current source. Stimulating electrodes 1 and 3 are constant current sources, while stimulating electrodes 2 and 4 are directly grounded. Since the constant current source is a high-impedance path relative to ground, stimulating electrodes 1 and 3 have high impedance relative to ground, while stimulating electrodes 2 and 4 have low impedance relative to ground. This causes unnecessary interference in the floating-ground type constant current source, because the current flowing from stimulating electrode 1 to the receptor can either form a closed loop from stimulating electrode 2 to ground or from stimulating electrode 4 to ground. Similarly, the current flowing from stimulating electrode 3 to the receptor can also form a closed loop from stimulating electrodes 2 and 4 to ground.

[0039] like Figure 5 The diagram shows the topology of a complementary output constant current source. Stimulating electrodes 1, 2, 3, and 4 are all constant current sources. Since each constant current source is a high-impedance path relative to ground, all four electrodes are high-impedance relative to ground. This prevents unnecessary interference from the complementary output constant current source, as the current input to the receptor from stimulating electrode 1 can only pass through stimulating electrode 2 to ground; similarly, the current input to the receptor from stimulating electrode 3 can only pass through stimulating electrode 4 to ground. The current distribution in the receptor is also similarly determined by… Figure 5Based on the current flow direction in the diagram, it can be analyzed that no unnecessary interference will occur near the stimulation electrode; only phase interference will occur in the central region a. The area where interference occurs is as follows: Figure 5 As shown in the shaded area a, both the floating-ground output constant current source topology and the ground output constant current source topology will produce some unnecessary interference in other non-shaded areas, in addition to the temporal interference in the central region a.

[0040] In summary, to ensure that unnecessary time-domain transcranial electrical stimulation is not output, the constant current source in this embodiment uses a complementary output voltage-controlled constant current source topology. For example... Figure 5 As shown, ultimately, stimulation electrode 1 and stimulation electrode 2 form a set of high-frequency sinusoidal currents such as 2000Hz, and stimulation electrode 3 and stimulation electrode 4 form another set of high-frequency sinusoidal currents. In this way, the two high-frequency sinusoidal currents will meet in the shaded area a to form a low-frequency envelope wave of 10Hz, thereby realizing the function of deep stimulation by time-domain interference.

[0041] As mentioned earlier, a complementary output voltage-controlled constant current source can be implemented using a Howland topology, combining an instrumentation amplifier and an operational amplifier. Specifically, a complementary output voltage-controlled constant current source with a Howland topology is constructed by combining the AD8226 instrumentation amplifier and the AD820 precision operational amplifier. It should be noted that the AD8226 instrumentation amplifier and AD820 precision operational amplifier are only one design to meet the requirements; the AD8226 instrumentation amplifier combined with the OPA180 can also be used to construct other suitable designs, etc. The AD8226 instrumentation amplifier is a low-cost, wide-supply-voltage instrumentation amplifier that requires only one external resistor to set any gain between 1 and 1000. The AD8226 instrumentation amplifier supports a variety of signal voltages. Its wide input range and rail-to-rail output allow signals to fully utilize the power rails. Because the input range also includes the ability to operate below the negative supply voltage, small signals close to ground voltage can be amplified without a dual supply. The AD8226 instrumentation amplifier can be powered by a dual supply from ±1.35 V to ±18 V, or by a single supply from 2.2 V to 36 V. The AD820 precision operational amplifier is a precision, low-power, FET-input operational amplifier that can be powered from a single 5 V to 36 V supply or from a dual ±2.5 V to ±18 V supply. This amplifier features single-supply capability and an input voltage range extending below the negative supply rail, thus handling input signals below ground voltage in single-supply mode. The output voltage swing extends to within 10 mV on each supply rail for maximum output dynamic range. The following is an analysis of a complementary output voltage-controlled constant current source based on a Howland topology constructed using the AD8226 instrumentation amplifier and the AD820 precision operational amplifier: The gain expression for the AD8226 instrumentation amplifier is: G = Vout / Vin = (V7 - V6) / (Vi+ - Vi-) = (49.4KΩ / Rg) + 1.

[0042] Where Vout represents the output voltage of the AD8226 instrumentation amplifier, Vin represents the differential input voltage difference of the AD8226 instrumentation amplifier, G represents the gain of the AD8226 instrumentation amplifier, V7 represents the output voltage at pin 7 of the AD8226 instrumentation amplifier, V6 represents the input voltage at pin 6 of the AD8226 instrumentation amplifier, Rg represents the gain setting resistor, the core purpose of which is to accurately set and control the voltage gain of the AD8226 instrumentation amplifier, and Vi+ and Vi- are the differential inputs of the AD8226 instrumentation amplifier.

[0043] By utilizing the virtual shorting of the two input pins of the AD820 precision operational amplifier, the relationship between the output current I0 of the voltage-controlled current source circuit and the input voltages Vi+ and Vi- can be derived as follows: I0 = (V7 - V6) / R0 = G*(Vi+ - Vi-) / R0.

[0044] Where G represents the gain of the AD8226 instrumentation amplifier, V7 represents the output voltage at pin 7 of the AD8226 instrumentation amplifier, V6 represents the input voltage at pin 6 of the AD8226 instrumentation amplifier, R0 represents the sampling resistor, which is the core and reference of the entire complementary output voltage-controlled constant current source, and its purpose is to provide an accurate current feedback signal so that the load current is stabilized at a set value. Vi+ and Vi- are the differential inputs of the AD8226 instrumentation amplifier.

[0045] In this circuit, the current frequency depends only on the signal input terminal, and the current magnitude depends only on the signal input difference and the value of the sampling resistor. This current source can adapt well to the characteristics of the wide range of stimulation frequencies, wide range of currents, and large load changes in the phase interference stimulation experiment, and can continuously and stably output current through the feedback circuit.

[0046] The AD8226 instrumentation amplifier, combined with the AD820 precision operational amplifier, produces a complementary output constant current source waveform with a 2000Hz output, as shown in the diagram below. Figure 8 As shown. Figure 6 The simulated waveform is actually based on a single-group, 2000Hz complementary output constant current sinusoidal current output waveform of the AD8226 instrumentation amplifier combined with the AD820 precision operational amplifier. In the figure, I(R1) and I(R4) are actually equivalent to Figure 5The stimulation electrodes 1 and 2, along with two sets of AD8226 instrumentation amplifiers combined with AD820 precision operational amplifiers, form a complementary output constant current source that can realize tTIS time-domain interference electrical stimulation, thereby achieving the design of deep brain stimulation.

[0047] A transcranial time-domain interferometric stimulation (tTIS) system, constructed using complementary output voltage-controlled constant current sources based on two sets of AD8226 instrumentation amplifiers and AD820 precision operational amplifiers, simulates the impedance of the human head through a test network as follows: Figure 7 As shown. Figure 7 The region between markers A and B is the central region, i.e., the pre-defined stimulus target area; markers C and D are non-central regions. Figure 8 In the first set of constant current sources, the output waveform is a sinusoidal current with a peak current of 2mA and a frequency of 2008Hz. The output waveform of the second set of constant current sources is a sinusoidal current with a peak current of 2mA and a frequency of 2000Hz. These two sets of high-frequency sinusoidal currents serve as the input to the final tTIS time-domain interferometric electrostimulation system. Because their envelope waveform is 2008Hz-2000Hz=8Hz, a standard 8Hz envelope is ultimately generated in the central region (between marker A and marker B), as shown below. Figure 8 As shown in V(A, B), since a complementary output voltage-controlled constant current source is selected, no low-frequency envelope waveform is generated in regions other than the central stimulation target region, such as... Figure 8 The V(C,D) waveform in the data also proves that there is no interference in the non-stimulation target region, and verifies the effectiveness of the complementary output voltage-controlled constant current source.

[0048] The constant voltage stimulation output circuit utilizes a Texas Instruments LM27313 boost converter to boost the 3.7V lithium battery voltage to a maximum of 20V, providing sufficient stimulation voltage. Two electronically switched MOSFETs alternately conduct to generate biphasic stimulation pulses. The stimulation amplitude is adjusted by an Analog Devices ADS162 digital potentiometer, controlled by an MCU via an SPI interface. The LM27313 boost converter is a high-efficiency, small-package chip that boosts the lithium battery voltage to 20V, providing sufficient operating voltage for electrical stimulation. The ADS162 digital potentiometer adjusts the stimulation amplitude and is controlled by the MCU via the SPI interface, enabling precise adjustment of the stimulation intensity.

[0049] Figure 1The example transcutaneous afferent mode stimulation (TAPS) module 104 includes a boost converter circuit, an electronic switch, and a digital potentiometer. The electronic switch can be a MOSFET, and the digital potentiometer is controlled by the main control module 101 via an SPI interface. The boost converter circuit can boost the 3.7V lithium battery voltage to a maximum of 20V. The TAPS module 104 uses high-frequency pulses at a base frequency of 150 Hz to enhance nerve fiber recruitment and alternately stimulates the ulnar and median nerves at the wrist with an identified individualized tremor frequency (f_t). The system employs preset precise timing logic for phase-delayed triggering (TAPS is initiated first, tTIS is delayed), forming a closed-loop intervention. TAPS technology is a non-invasive neuromodulation therapy for essential tremor (ET). It applies burst-like alternating electrical stimulation with synchronized individualized tremor frequencies to the median and radial nerves via an electrode array attached to the wrist, thereby activating and modulating the central tremor network (especially the key node VIM in the ventral intermediate nucleus of the thalamus), effectively interfering with pathological oscillations. The following explains the mechanism by which TAPS resolves ET and the settings of related parameters.

[0050] First, let's explain the mechanism of TAPS in addressing tremor effusion (ET). TAPS uses non-invasive electrical stimulation of the median nerve and the superficial branch of the radial nerve at the wrist, alternating between these two nerves in a patterned burst stimulation manner. The stimulation frequency is synchronized with the patient's own tremor frequency. Its main mechanisms of action include: modulation of the central tremor network: Studies have shown that peripheral nerve stimulation can activate nodes in the central tremor network, such as the ventral intermediate nucleus of the thalamus (VIM), interfering with pathological neural oscillations. Induction of synaptic plasticity: Burst-like stimulation may induce sustained changes in neural plasticity, allowing the tremor-relieving effect to persist even after stimulation stops. Sensory afferent modulation: High-intensity sensory input inhibits motor output, similar to a "noise-overwhelmed signal" or "reset oscillation" mechanism.

[0051] The following explains the stimulation parameters, location, and rationale for TAPS: (1) Stimulation location: Electrode placement: Four hydrogel electrodes are placed on the palmar side of the wrist (target median nerve and radial nerve) and the dorsal side (counter electrode); Stimulation targets: superficial branches of the median nerve and radial nerve, which are closely related to the tremor because they are responsible for hand sensation and some motor control.

[0052] (2) Stimulation parameters: Waveform: charge-balanced biphasic pulses, pulse width: 300 µs / phase, frequency: 150 Hz (pulse frequency), alternation frequency = individual patient tremor frequency (4–12 Hz), amplitude: gradually increased to the highest comfortable level where the patient feels anesthesia but without muscle contraction, duration: each stimulation lasts 40 minutes.

[0053] (3) Rationale for parameter settings: 150 Hz: High-frequency stimulation can effectively activate Aβ fibers, providing strong sensory input without causing pain or motor response; Alternating stimulation: Simulates tremor frequency, which may more effectively interfere with central oscillations; Individualized frequency: Adjusted according to the tremor frequency of each patient to improve the specificity of treatment; 40-minute duration: Based on efficacy data from previous clinical trials. Table 1 below is the parameter table for transcutaneous transducer stimulation (TAPS).

[0054] Table 1. Parameters of Transcutaneous Afferent Pattern Stimulation (TAPS)

[0055] Figure 1 The example system or device may include a human-computer interaction module, which includes an LCD display and buttons, and may also include a Type-C interface for charging, communication, or program downloading; the system or device can be worn on the user's wrist via Velcro.

[0056] Figure 1 The electrode montage configuration of the example transcranial time-domain interferometry stimulation module 103 is as follows: For the target point on the medial part of the globus pallidus, the electrode pairs are located at CP3-CP6 and F3-F6; for the target point on the substantia nigra, the electrode pairs are located at F5-P5 and F6-PO8. The mechanism of transcranial temporal interferometry (tTIS) in addressing ET, as well as the stimulation sites, stimulation parameters, and settings for tTIS in addressing ET, will be explained below.

[0057] First, let's explain the mechanism by which tTIS addresses tremor effusion (ET). tTIS generates a low-frequency envelope signal (e.g., 10–130 Hz) in deep brain regions (e.g., the basal ganglia, substantia nigra, subthalamic nucleus, etc.) by applying two slightly different high-frequency alternating currents (e.g., 2000 Hz and 2010 Hz). Due to their low-pass filtering properties, neurons respond only to this low-frequency envelope signal, thus achieving selective neural modulation. In ET, tTIS may function through the following mechanisms: Modulating pathological oscillations: ET is associated with abnormal beta oscillations (12–30 Hz) or gamma oscillations; tTIS can interfere with or inhibit these abnormal activities through an envelope signal of a specific frequency (e.g., 130 Hz). Simulating DBS effects: The 130 Hz envelope frequency used by tTIS is consistent with the frequency commonly used in deep brain stimulation (DBS), and may improve tremor through a similar mechanism. Enhancing neuroplasticity: tTIS may promote the normalization of motor control circuits by modulating synaptic strength and neural network connectivity.

[0058] The tTIS solution addresses the stimulation sites, stimulation parameters, and rationale for ET as follows: (1) Stimulation target: Globus Pallidus internus (GPi); Stimulation parameters: 130 Hz envelope frequency, carrier frequency 1300 / 1430 Hz, current intensity 2.5 mA / 2 mA; 10-20 system electrode montage: Channel 1: CP3 (left central parietal point) and CP6 (behind the right central parietal point); Channel 2: F3 (left frontal point) and F6 (in front of the right frontal point). This montage is designed to allow the two electric fields to interfere in the right GPi (target) region.

[0059] (2) Stimulation target: Substantia Nigra (SN); Stimulation parameters: 130 Hz envelope frequency, carrier frequency 900 / 1030 Hz, current intensity 0.75-1 mA; 10-20 system electrode montage: Channel 1: F5 (between F3 and F7) and P5 (between P3 and P7, close to the PO8 region); Channel 2: F6 (between F4 and F8) and PO8 (right occipital point), this montage is designed to form an interference field in the bilateral substantia nigra regions.

[0060] (3) Reasons for parameter settings: 130 Hz envelope: consistent with the commonly used frequency for DBS treatment of tremor, which can effectively inhibit abnormal nerve discharges; high-frequency carrier (≥2 kHz): avoids activation of surface neurons, ensuring stimulation depth and focus; medium current intensity (1~2 mA): maximizes the intensity of the deep electric field within a safe range, taking into account both tolerance and effectiveness; multi-channel montage: optimizes the electric field distribution through multi-electrode configuration, improving targeting. Table 2 below is the parameter table for transcranial time-domain interferometry (tTIS).

[0061]

[0062] Table 2 Parameters of transcranial time-domain interferometry (tTIS)

[0063] As previously described, the power management module 105 supplies power to the main control module 101, the tremor sensing module 102, the transcranial temporal interferometry stimulation module 103, and the transcutaneous afferent mode stimulation module 104. Further details are provided below.

[0064] In this embodiment, the power management module 105 is a battery management subsystem (BMS). The core of this subsystem is to implement the charging and discharging management of the system, and to implement undervoltage protection, overcurrent protection, short circuit protection, etc., based on the collected signals such as current, voltage, and temperature. A specific example of a BMS is to build the entire battery management system based on BQ27220+DW01 (of course, there are many ICs that can build a single-cell lithium battery management system, not limited to BQ27220+DW01). BQ27220 implements battery management, specifically achieving the following functions: (1) Battery status monitoring: BQ27220 can monitor the battery's power, voltage, temperature and other parameters in real time, thereby realizing the monitoring and management of the battery status; (2) Charging control: BQ2722 can realize the charging control of the battery, specifically including the setting of parameters such as charging speed and charging cut-off voltage, to ensure the safe and effective charging of the battery; (3) Battery capacity estimation: by obtaining the battery-related parameters, the battery capacity is estimated based on a specific algorithm, so that the user knows the battery's available power and charging status; (4) Temperature control: BQ27220 can realize the monitoring and control of the battery temperature, and can realize over-temperature protection, etc. through settings. DW01 is generally combined with MOSFETs such as 8205A to realize battery protection, and its main functions are as follows: (1) Overcharge protection: protects against overcharging of lithium batteries; (2) Over-discharge protection: protects against over-discharging of lithium batteries; (3) Overcurrent protection: protects against excessive current; (4) Short circuit protection: protects the battery in the event of a short circuit.

[0065] Figure 1The working process of this portable brain-limb synergistic tremor modulation system is briefly described below: By integrating two non-invasive stimulation techniques, transcranial temporal interference stimulation (tTIS) and percutaneous peripheral nerve pattern stimulation (TAPS), it achieves synergistic intervention and adaptive closed-loop control of essential tremor (ET). After system startup, electrode contact detection is first performed. Then, the built-in IMU is used to identify the patient's individualized tremor frequency (f_t) in real time, and TAPS stimulation parameters are automatically generated accordingly: the median nerve and the superficial branch of the radial nerve are alternately stimulated at a pulse frequency of 150 Hz according to f_t, thereby inhibiting tremor by modulating the central tremor network and sensory afferent mechanisms. After TAPS initiates a quarter tremor cycle, the system synchronously triggers algorithm-optimized tTIS stimulation. Based on preset target points (e.g., GPi or substantia nigra), a 130 Hz envelope interference electric field is generated by two high-frequency carrier waves (e.g., 900 / 1030 Hz or 1300 / 1430 Hz). This intervenes in deep brain regions by modulating pathological oscillations and simulating DBS effects. During the dual-mode stimulation, the IMU continuously monitors tremor intensity and dynamically adjusts the alternating frequency of TAPS and the intensity of tTIS stimulation, forming a closed-loop control until tremor suppression or manual cessation by the user.

[0066] refer to Figure 9 This application provides a portable brain-limb coordinated tremor modulation method, which employs... Figure 9 The example of a portable brain-limb coordinated tremor modulation system mainly includes steps S901 to S907, which are detailed below: Step S901: Collect motion data of the user's hand.

[0067] In this embodiment, the motion data of the user's hand can be collected in real time in three orthogonal directions (X, Y, Z) using a triaxial accelerometer (LSM303D) in the IMU at a sampling frequency of 100 Hz. , , .

[0068] Step S902: Based on the user's hand movement data, identify the user's individualized tremor frequency in real time.

[0069] Based on the user's hand movement data, the user's individualized tremor frequency can be identified in real time through the following sub-steps S9021 to S9023: Step S9021: Calculate the quadratic mean of the triaxial acceleration data. This triaxial acceleration data is a core component of the user's hand motion data.

[0070] For each sampling point (every 10 ms), the triaxial acceleration data are combined into a scalar representing the overall motion intensity in order to eliminate the influence of hand posture and sensor orientation on the measurement of tremor amplitude.

[0071] Step S9022: Filter out low-frequency components using a 10th-order Butterworth high-pass filter to obtain a high-pass filtered signal.

[0072] High-pass filtering calculates... The sequence is passed through a 10th-order Butterworth high-pass filter (>3 Hz). This step is crucial, as it aims to filter out low-frequency (typically <3 Hz) components generated by voluntary movement (such as reaching out or scooping beans), retaining only the high-frequency tremor signal.

[0073] Step S9023: Perform a fast Fourier transform on the high-pass filtered signal and detect the peak power spectral density in the range of 4~12Hz.

[0074] First, the high-pass filtered signal is divided into multiple time windows for analysis. In one specific example, the window length is 2.5 seconds (corresponding to 250 sampling points). Then, a Fast Fourier Transform (FFT) is performed, that is, an FFT is performed on the data in each 2.5-second time window to transform it from the time domain to the frequency domain. The FFT result is then calculated to obtain the power spectral density, which shows the distribution of signal power at different frequencies. Finally, within the typical frequency range of jitter (4~12 Hz), the highest peak in the PSD is found. The frequency corresponding to this peak is identified as the individualized jitter frequency f_t for that time window.

[0075] Step S903: Based on the identified individualized tremor frequency, perform bandpass filtering on the high-pass filtered tremor signal centered on the individualized tremor frequency, and detect the current tremor phase.

[0076] In this embodiment, detecting the current tremor phase includes performing a Hilbert transform on the bandpass-filtered tremor signal to generate an analytical signal, and determining the starting phase of the tremor cycle by detecting the rising zero-crossing point. Detecting the tremor phase is crucial for achieving phase-locked closed-loop stimulation. It requires determining the current position within a tremor cycle in real time (e.g., 0°, 90°, 180°, 270°). It mainly includes the following four steps (1) to (4): (1) Data preparation: The initial steps are shared with the frequency identification process. First, the data after high-pass filtering is obtained. The signal mainly contains the tremor component after voluntary movement has been removed.

[0077] (2) Bandpass Filtering: In order to further improve the signal-to-noise ratio and obtain a purer periodic oscillation signal, the system will use a narrow bandpass filter centered on the currently estimated individualized jitter frequency f_t (e.g., 5 Hz). For example, the passband of the filter can be set to [4Hz, 6 Hz]. This step can filter out noise outside this frequency range and obtain a jitter signal in a near-perfect sine wave form.

[0078] (3) Phase Extraction: The Hilbert Transform is the standard method for extracting the instantaneous phase and amplitude of a signal. By applying the Hilbert Transform to the above bandpass filtered signal, an analytic signal can be constructed.

[0079] (4) Calculate the instantaneous phase: The instantaneous phase corresponding to each sampling point can be directly calculated from this analytical signal. The range is usually from -π to π or from 0 to 2π.

[0080] Zero-crossing detection is another simpler method that detects the rising zero-crossing points (from negative to positive) of a filtered signal. Each rising zero-crossing point is defined as the start of a jitter cycle (phase 0° or 0π). The time between one zero-crossing point and the next is a jitter cycle. The points in between can be estimated by linear interpolation (e.g., 25% of the cycle is 90° or π / 2).

[0081] Step S904: Based on individualized tremor frequency and tremor phase, generate transcutaneous afferent stimulation parameters and initiate stimulation.

[0082] In the embodiments of this application, the percutaneous afferent stimulation parameters include: a base pulse frequency of 150 Hz, a biphasic pulse width of 300 μs / phase, an alternation frequency consistent with the individualized tremor frequency, and a stimulation intensity that increases to the comfort threshold in 0.25 mA increments.

[0083] Step S905: At a specific time point after the initiation of transcutaneous afferent stimulation, generate transcranial temporal interference stimulation parameters and initiate stimulation.

[0084] In this embodiment of the application, the specific time point is the 1 / 4 tremor cycle moment after the initiation of transcutaneous afferent stimulation. The transcranial time-domain interference stimulation parameters include: the difference between the two carrier frequencies is in the range of 10~130Hz, the envelope frequency is fixed at 130Hz; the current intensity is 0.75~2.5mA, and the target points include the medial part of the globus pallidus or the substantia nigra.

[0085] Step S906: Intervene by synergistically controlling transcranial temporal interference stimulation and transcutaneous afferent pattern stimulation.

[0086] Specifically, after TAPS initiates a quarter tremor cycle, the system synchronously triggers algorithm-optimized tTIS stimulation. Based on preset target points (e.g., GPi or substantia nigra), a 130 Hz envelope interference electric field generated by two high-frequency carrier waves (e.g., 900 / 1030 Hz or 1300 / 1430 Hz) is applied, intervening in deep brain regions by modulating pathological oscillations and simulating DBS effects. During the dual-mode stimulation, the IMU continuously monitors the tremor intensity and dynamically adjusts the alternating frequency of TAPS and the intensity of tTIS stimulation, forming a closed-loop control until tremor suppression or manual cessation by the user.

[0087] Step S907: Monitor tremor intensity changes in real time and dynamically adjust stimulation parameters to form a closed-loop control.

[0088] In this embodiment of the application, the dynamic adjustment of stimulation parameters includes: when the tremor intensity decreases but does not reach the threshold, increasing the tTIS current intensity in 0.25mA increments; when the tremor frequency changes by more than ±1Hz, adjusting the TAPS alternation frequency synchronously.

[0089] From the above appendix Figure 9The portable brain-limb synergistic tremor modulation method exemplifies several advantages. First, by collecting hand movement data in real time and dynamically generating stimulation parameters based on individualized tremor frequencies, it overcomes the neural adaptability defects of fixed-frequency stimulation, thereby improving neural modulation efficiency. Second, it employs a temporal protocol of priority initiation of transcutaneous afferent mode stimulation (TAPS) and delayed intervention of transcranial temporal interference stimulation (tTIS): TAPS uses high-frequency pulses to alternately stimulate both nerves at individualized tremor frequencies, enhancing nerve fiber recruitment capabilities; tTIS is triggered 1 / 4 of the tremor cycle after TAPS initiation, generating an envelope targeting deep brain nuclei through two high-frequency current interferences. The two complement each other temporally and spatially, producing a synergistic enhancement effect. Third, based on tremor perception feedback, it dynamically adjusts the alternating frequency of TAPS and the intensity of tTIS stimulation, forming a "perception-decision-stimulation" closed loop, solving the defect of open-loop systems that cannot respond to dynamic changes in tremor. Furthermore, through a power management module and integrated hardware architecture, tremor perception, dual-mode stimulation, and control logic are integrated into a wearable device, breaking through the size limitations of traditional devices and making it suitable for daily management in home settings. In summary, the technical solution of this application achieves efficient tremor suppression and portable treatment through an integrated design of real-time perception, dual-mode collaboration, and closed-loop control.

[0090] To further verify the clinical efficacy of this invention, this application conducted several experimental studies. Clinical data were collected from a patient population with essential tremor after intervention using this system, as detailed below: Project 1: Duration of Tremor Relief. Through testing on multiple patients, the tremor relief effect lasted for a considerable period after the systemic stimulation was discontinued. Data showed that the average relief time reached 94.8 minutes, a significant improvement compared to the traditional 60 minutes (traditional protocol referenced clinical standards). Specific data are shown in Table 3.

[0091] Table 3: Duration of Tremor Relief Effect

[0092] Project Two: Metabolic Evidence Demonstration via Positron Emission Tomography (PET). For example... Figure 10 As shown, PET scan images reveal changes in baseline metabolism in the tremor network, which are correlated with clinical improvement (correlation coefficient r=0.7). Figure 11 This is a schematic diagram illustrating the improvement in tremor power of the technical solution provided in this application across four typical clinical tasks. This demonstrates that TAPS + tTIS treatment induces neural plasticity or neural remodeling, resulting in more durable improvement. Figure 10 The example PET scan image shows the baseline metabolic status. Figure 11 The changes shown after the intervention further support the deep brain region modulation effect of this application.

[0093] Project 3: Clinical Assessment. Through tasks such as posture maintenance, spiral drawing, finger-to-nose test, and water pouring, the technical solution described in this application significantly improved patients' motor function. The posture maintenance task showed the most significant improvement, with a median improvement of 5.9 times. Specific data are summarized below: Posture maintenance task: median improvement of 5.9 times; Drawing a spiral: Median improvement factor 2.4 times; Finger-to-nose test: Median improvement 1.6 times; Water pouring task: Median improvement multiple 2.5 times.

[0094] The above results indicate that the technical solution of this application can effectively improve the quality of life of patients in a variety of daily activities.

[0095] This application implements all or part of the processes in the methods of the above embodiments, which can also be accomplished by a computer program instructing related hardware. The computer program for the portable brain-limb coordinated tremor modulation method can be stored in a storage medium. When executed by a processor, the computer program can implement the steps of the various method embodiments described above, namely: collecting motion data of the user's hand; identifying the user's individualized tremor frequency in real time based on the user's hand motion data; performing bandpass filtering on the high-pass filtered tremor signal centered on the individualized tremor frequency based on the identified individualized tremor frequency, and detecting the current tremor phase; generating transcutaneous afferent mode stimulation parameters and initiating stimulation based on the individualized tremor frequency and tremor phase; generating transcranial temporal interference stimulation parameters and initiating stimulation at a specific time point after the initiation of transcutaneous afferent mode stimulation; coordinating the control of transcranial temporal interference stimulation and transcutaneous afferent mode stimulation for intervention; and monitoring changes in tremor intensity in real time and dynamically adjusting stimulation parameters to form a closed-loop control. The computer program includes computer program code, which can be in the form of source code, object code, executable files, or certain intermediate forms. Storage media can include: any entity or device capable of carrying computer program code, recording media, USB flash drives, portable hard drives, magnetic disks, optical disks, computer memory, read-only memory (ROM), random access memory (RAM), electrical carrier signals, telecommunication signals, and software distribution media, etc. It should be noted that the contents of storage media can be appropriately added to or removed according to the requirements of legislation and patent practice in a jurisdiction. For example, in some jurisdictions, according to legislation and patent practice, storage media may not include electrical carrier signals and telecommunication signals.

[0096] The above embodiments are only used to illustrate the technical solutions of this application, and are not intended to limit it. Although this application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. These modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of this application, and should all be included within the protection scope of this application. The specific embodiments described above further illustrate the purpose, technical solutions, and beneficial effects of this application. It should be understood that the above descriptions are merely specific embodiments of this application and are not intended to limit the protection scope of this application. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of this application should be included within the protection scope of this invention.

Claims

1. A portable brain-limb coordinated tremor modulation system, characterized in that, The system includes: Main control module; The tremor sensing module is communicatively connected to the main control module and is used to collect motion data of the user's hand. The transcranial time-domain interference stimulation module, connected to the main control module, is used to generate two high-frequency currents to form a low-frequency envelope stimulation signal in the deep region of the user's brain. The transcutaneous afferent stimulation module, connected to the main control module, is used to generate electrical pulses of a specific pattern to stimulate the nerves in the user's wrist. The power management module is used to supply power to the above modules; The main control module is configured to: identify the user's individualized tremor frequency in real time based on the motion data collected by the tremor sensing module; control the transcutaneous afferent stimulation module to generate a composite stimulation mode with high-frequency pulses that alternately stimulate different nerves at the individualized tremor frequency based on the tremor phase and the individualized tremor frequency; control the transcranial temporal interference stimulation module to generate optimized stimulation parameters at a specific time point after the transcutaneous afferent stimulation is initiated; coordinate the control of the transcranial temporal interference stimulation module and the transcutaneous afferent stimulation module to intervene, and dynamically adjust the stimulation parameters according to the tremor intensity changes fed back by the tremor sensing module, forming a closed-loop control.

2. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The vibration sensing module includes an inertial measurement unit.

3. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The transcranial time-domain interference stimulation module includes a direct digital frequency synthesizer and a complementary output voltage-controlled constant current source.

4. The portable brain-limb coordinated tremor modulation system according to claim 3, characterized in that, The direct digital frequency synthesizer generates four isolated high-frequency sine wave signals.

5. The portable brain-limb coordinated tremor modulation system according to claim 3, characterized in that, The complementary output voltage-controlled constant current source includes two sets of constant current sources, each set of constant current sources drives a pair of stimulation electrodes.

6. The portable brain-limb coordinated tremor modulation system according to claim 5, characterized in that, The constant current source outputs an adjustable current amplitude, and the current output error is ±1%.

7. The portable brain-limb coordinated tremor modulation system according to claim 5, characterized in that, The complementary output voltage-controlled constant current source adopts a Howland topology and is implemented by combining an instrumentation amplifier and an operational amplifier.

8. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The transcutaneous afferent stimulation module includes a boost converter circuit, an electronic switch, and a digital potentiometer.

9. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The system also includes a human-computer interaction module, which includes an LCD display and buttons.

10. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The system is worn on the user's wrist via Velcro.

11. The portable brain-limb coordinated tremor modulation system according to claim 1, characterized in that, The electrode montage configuration of the transcranial time-domain interferometry stimulation module is as follows: For the target point on the inner side of the globus pallidus, the electrode pair is located at CP3-CP6 and F3-F6; For the substantia nigra target, the electrode pair is located at F5-P5 and F6-PO8.

12. A portable method for modulating brain-limb coordinated tremor, characterized in that, The method using the system according to any one of claims 1 to 11 comprises: Collect user hand movement data; Based on the motion data, the user's individualized tremor frequency can be identified in real time. Based on the identified individualized tremor frequency, the high-pass filtered tremor signal is subjected to band-pass filtering centered on the individualized tremor frequency, and the current tremor phase is detected. Based on the individualized tremor frequency and tremor phase, transcutaneous afferent stimulation parameters are generated and stimulation is initiated. At a specific time point after the initiation of transcutaneous afferent stimulation, transcranial temporal interference stimulation parameters are generated and stimulation is initiated. Intervention was performed by synergistic control of transcranial temporal interference stimulation and transcutaneous afferent pattern stimulation; Real-time monitoring of tremor intensity changes and dynamic adjustment of stimulation parameters form a closed-loop control.

13. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The real-time identification of the user's individual tremor frequency includes: Calculate the second mean of the triaxial acceleration data The triaxial acceleration data is a core component of the motion data; The low-frequency components are filtered out by a tenth-order Butterworth high-pass filter to obtain the high-pass filtered signal; The high-pass filtered signal is subjected to a fast Fourier transform, and the peak power spectral density is detected in the range of 4~12Hz.

14. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The specific time point is the moment when 1 / 4 of the tremor cycle has been initiated after the transcutaneous afferent stimulation mode.

15. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The transcutaneous afferent stimulation parameters include: The basic pulse frequency is 150Hz, and the biphase pulse width is 300μs / phase. The alternation frequency was consistent with the individualized tremor frequency, and the stimulation intensity was increased in 0.25mA increments to the comfort threshold.

16. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The transcranial time-domain interferometry stimulation parameters include: The frequency difference between the two carriers is 10~130Hz, and the envelope frequency is fixed at 130Hz. The current intensity is 0.75~2.5mA, and the target points include the inner part of the globus pallidus or the substantia nigra.

17. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The dynamically adjusted stimulation parameters include: When the tremor intensity decreases but does not reach the threshold, the tTIS current intensity is increased in 0.25mA increments. When the vibration frequency changes by more than ±1Hz, the TAPS alternation frequency is adjusted synchronously.

18. The portable brain-limb coordinated tremor modulation method according to claim 12, characterized in that, The detection of the current tremor phase includes: The bandpass filtered flutter signal is subjected to Hilbert transform to generate an analytical signal; The starting phase of the tremor cycle is determined by detecting the zero-crossing point.

19. A storage medium having a computer program stored thereon, characterized in that, When the program is executed by a processor, it implements the steps of the method according to any one of claims 12 to 18.

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