Closed-loop vagus nerve stimulation system capable of cooperating with rehabilitation exercise

Abstract

The invention discloses a closed-loop vagus nerve stimulation system capable of cooperating with rehabilitation exercise. The closed-loop controller is used for collecting an external signal related to animal movement as a gating signal, processing the signal and generating a control instruction; the vagus nerve stimulator is used for receiving the control instruction of the closed-loop controller, adjusting stimulation parameters and outputting vagus nerve stimulation pulses; the wireless communication module is used for realizing wireless connection between the closed-loop controller and the vagus nerve stimulator and ensuring rapid transmission of a control instruction; the motion signal acquisition device is used for acquiring external signals related to animal motion; according to the invention, the problem of output misalignment of existing small equipment under a high load is obviously improved through a four-stage cascaded constant-current pulse generation architecture; meanwhile, based on a naked pulse infrared direct drive protocol and an MCU highly integrated processing chain, the timing sequence matching precision requirement of vagus nerve stimulation pulses and rat rehabilitation exercise actions is ensured.

Description

Technical Field

[0001] This invention belongs to the field of neuromodulation medical device technology, specifically relating to a closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises in animal experiments, suitable for motor function rehabilitation research in animal models of ischemic stroke. Background Technology

[0002] Ischemic stroke is a leading cause of disability worldwide, and current rehabilitation methods have limited effectiveness in restoring motor function. Studies have shown that timing-matching vagus nerve stimulation (VNS) with rehabilitation exercise training can enhance neural plasticity and improve stroke rehabilitation outcomes. However, the exact mechanisms underlying the combination of vagus nerve stimulation and exercise rehabilitation, and its benefits for brain diseases, are not fully understood and require further experimental research. However, current technologies have the following limitations:

[0003] 1) Output capability deficiency: Existing miniaturized vagus nerve stimulation devices have significant limitations under high impedance conditions (typically 8-10KΩ), which manifests as insufficient output driving capability and difficulty in maintaining accurate constant current output, thus limiting the effectiveness and stability of vagus nerve stimulation in practical applications.

[0004] 2) Real-time control delay: Current mainstream vagus nerve stimulation devices used in experimental research generally rely on Bluetooth-based wireless communication links for control. This technology architecture has inherent communication delays (usually exceeding 200ms), which makes it impossible to meet the control requirements of precise synchronization with rehabilitation movements. Existing systems cannot achieve high-precision time synchronization matching between stimulation pulses and rehabilitation movements (required delay threshold <75ms).

[0005] 3) Defects in closed-loop control: Existing closed-loop vagus nerve stimulation systems rely primarily on the monitoring of endogenous physiological signals (such as electromyography (EMG) and electrocardiography (ECG) signals) for their closed-loop triggering gating mechanism. This mechanism is essentially limited to feedback from the body's internal state and lacks effective coordination with external rehabilitation exercises, thus failing to truly achieve the synergistic rehabilitation effect of vagus nerve stimulation and rehabilitation exercises. Summary of the Invention

[0006] To address the aforementioned problems, this invention provides a closed-loop vagus nerve stimulation system that can coordinate with rehabilitation exercises. This system solves the problems of insufficient output capacity, high control delay, and lack of effective coordination with external rehabilitation exercises under high impedance conditions. It achieves millisecond-level synchronous coordination between rehabilitation exercises and vagus nerve stimulation, and ensures the effectiveness and safety of stimulation under high impedance conditions.

[0007] This invention includes:

[0008] Closed-loop controller: used to collect external signals related to animal movement as gating signals, process the signals and generate control commands;

[0009] Vagus nerve stimulator: used to receive control commands from the closed-loop controller, adjust stimulation parameters and output vagus nerve stimulation pulses;

[0010] Wireless communication module: used to realize the wireless connection between the closed-loop controller and the vagus nerve stimulator, ensuring the rapid transmission of control commands;

[0011] Motion signal acquisition device: used to acquire external signals related to animal movement, which are directly related to the animal's rehabilitation movement and serve as input signals for the closed-loop controller;

[0012] The system uses the motion signal acquisition device to sense the animal's rehabilitation exercise status in real time. The closed-loop controller generates control commands based on the external signals and transmits them quickly to the vagus nerve stimulator through the wireless communication module. The vagus nerve stimulator adjusts the stimulation parameters according to the control commands and outputs vagus nerve stimulation pulses that match the timing of the rehabilitation exercise, thereby achieving coordinated control of rehabilitation exercise and vagus nerve stimulation.

[0013] The beneficial effects of this invention are as follows: Through the optimized design of a four-stage cascaded constant current pulse generation architecture, this invention achieves a constant current output deviation of ≤±5% under high tissue impedance conditions of 8-10kΩ, significantly improving the output inaccuracy problem of existing small devices under high loads. Simultaneously, based on the bare pulse infrared direct drive protocol and a highly integrated MCU processing chain, an end-to-end instruction delay of ≤10ms is achieved, ensuring that the timing matching accuracy of vagal nerve stimulation pulses and rat rehabilitation movements is far below the <75ms threshold requirement. This achieves millisecond-level precise synchronization between rehabilitation movements and nerve stimulation. This precise timing synchronization is a crucial factor in inducing synaptic plasticity reconstruction and obtaining optimal rehabilitation effects. The miniaturized stimulator design, combined with a harness assembly scheme, effectively adapts to the free-behavioral state of experimental animals, alleviating the synchronization failure problem caused by physical restraint and movement interference in traditional devices. Attached Figure Description

[0014] Figure 1 The diagram shown is a schematic block diagram of the closed-loop vagus nerve stimulator of the present invention.

[0015] Figure 2 The diagram shown is a schematic of the application of the closed-loop vagus nerve stimulator with motor coordination of the present invention.

[0016] Figure 3 The diagram shown is a schematic of the four-stage cascaded constant current pulse circuit of this invention.

[0017] Figure 4The diagram shown is a schematic of the boost circuit of this invention.

[0018] Figure 5 The diagram shown is a schematic of the pressure sensor of the present invention. Detailed Implementation

[0019] This invention employs a wearable rat closed-loop vagus nerve stimulation system, comprising a closed-loop controller and a vagus nerve stimulator. The closed-loop controller and the vagus nerve stimulator are wirelessly connected via infrared technology. The closed-loop controller collects pressure signals from the rat's forelimbs as gating signals, processes these signals, generates control commands, and transmits them to the vagus nerve stimulator via infrared technology. The vagus nerve stimulator receives commands from the closed-loop controller, flexibly adjusts stimulation parameters, and outputs vagus nerve stimulation pulses. The system achieves closed-loop control of motion perception, signal processing, and electrical stimulation output, ensuring synchronous timing pairing between vagus nerve stimulation and rat bar-pressing training.

[0020] Furthermore, the closed-loop controller includes a pressure sensing module and a main control MCU unit; the pressure sensing module adopts a thin-film pressure sensor (range 2g-1.5kg), which is fixed to the pressure bar area of ​​the rat's forelimb; the main control MCU unit has a built-in ADC sampling module, which is used to linearize and convert the original pressure signal, and perform dual dynamic threshold determination (duration ≥20ms and amplitude ≥ preset threshold), and then drive the infrared emitting tube to output a bare pulse control signal.

[0021] Furthermore, the infrared communication uses an unmodulated bare pulse protocol, with an end-to-end delay of ≤10ms for command transmission.

[0022] Furthermore, a thin-film pressure sensor is placed below the pressure bar training device and connected to the pressure sensor via a wire.

[0023] Furthermore, the vagus nerve stimulator includes: an infrared receiving unit that captures raw pulse signals via a high-speed phototransistor, shapes them using a voltage comparator, and inputs them into the MCU unit; an MCU unit that parses pulse width parameters and generates stimulation parameter instructions; and a constant current pulse generation module that, based on a four-level circuit architecture (DC offset / signal superposition / programmable gain amplification / Howland current source), outputs a biphase constant current pulse that is adjustable from 0.1 to 1 mA and from 0 to 500 Hz, maintaining a constant current accuracy of ±5% under an 8-10 kΩ load.

[0024] Furthermore, the vagus nerve stimulator integrates a high-efficiency boost circuit, using a TPS61093 chip to boost the lithium polymer battery to +12V, and generates a -12V symmetrical power supply through a charge pump inverter to power the operational amplifier.

[0025] Furthermore, the vagus nerve stimulator was secured to the back of the experimental animal using a harness.

[0026] Furthermore, the vagus nerve stimulator is equipped with a Cuff-type implantable electrode, with platinum-iridium alloy contacts orthogonally surrounding the vagus nerve, and the stimulation direction is orthogonal to the direction of the nerve fibers to reduce the activation threshold.

[0027] Furthermore, the cuff-type implantable electrode is connected to the stimulator via a wire.

[0028] Example:

[0029] like Figure 1 and Figure 2 As shown in this embodiment, a backpack-type closed-loop vagus nerve stimulation system consists of two main functional units: a vagus nerve stimulator and a closed-loop controller. These two parts operate independently. The vagus nerve stimulator is connected to a Cuff electrode via a wire. The Cuff electrode is implanted and directly coupled to the rat's vagus nerve. The overall dimensions of the stimulator are 36mm × 32mm × 8mm. The miniaturized design of the stimulator, combined with a harness assembly, secures it to the rat's back. The closed-loop controller includes a pressure sensor and is fixed to the outside of the rat incubator via a pressure rod device. Its overall dimensions are 50mm × 60mm.

[0030] The closed-loop controller includes an STM32 microcontroller unit, a pressure sensing unit, and an infrared communication unit. The pressure sensing unit uses an FSR402 thin-film pressure sensor, see [link to relevant documentation]. Figure 5 Its measurement range covers 2g-1.5Kg. It is placed under the pressure bar of the rat pressure bar training device and connected to the input terminal of the microcontroller unit via a wire. The pressure signal is digitized by the built-in analog-to-digital converter of the STM32 microcontroller, and a dual-verification algorithm is used to determine the motion state: when the pressure value is ≥50g and the duration exceeds 20ms, a trigger command is sent to the stimulator via the infrared communication unit. The infrared communication unit adopts a microwatt-level static power consumption design, uses bare pulse signals for signal transmission, and has a communication response time of less than 10ms, establishing a wireless connection with the stimulator.

[0031] The vagus nerve stimulator includes an STM32 microcontroller unit, a four-stage cascaded constant current pulse circuit, and a power management module. The infrared communication unit's receiver is connected to the input of the STM32 microcontroller, and the microcontroller's output controls the stimulation circuit via a PWM signal.

[0032] The four-stage cascaded constant current pulse circuit consists of a DC offset module, a signal superposition module, a programmable gain amplifier module, and a constant current output module cascaded together. It is built using a TL072C dual operational amplifier. See [link / reference needed]. Figure 3 .

[0033] First stage: Input offset circuit: A TL072C op-amp unit and resistors R11 and R12 are connected in series between the +3V3 power supply and GNDD ground to form a precision voltage divider network to generate a reference voltage Vref. This voltage is buffered and output through a voltage follower circuit composed of U1A. The non-inverting input (pin 3) of the op-amp is directly connected to the midpoint of the voltage divider, and the inverting input (pin 2) is shorted to the output (pin 1), achieving high input impedance and low output impedance characteristics, effectively isolating the load interference of the subsequent stage. The TL072C op-amp performs signal synthesis. The input signal PWMA is injected into the inverting input terminal (pin 6) of U1B through resistor R32; the pre-stage The non-inverting input (pin 5) is fed in through resistor R17. The non-inverting input is grounded via resistor R19 (10kΩ), and the feedback resistor R18 (10kΩ) connects the output (pin 7) to the inverting input. These four 10kΩ resistors form a symmetrical subtractor topology to perform the operation:

[0034] The output generates complementary differential signals (+1 / 2PWMA and -1 / 2PWMA) with ±1 / 2 amplitude characteristics.

[0035] The TL072C (U2A) unit is used to process the PWMB signal. The input PWMB is directly connected to the non-inverting input (pin 3) of the op-amp via resistor R13. The inverting input (pin 2) and the output (pin 1) are directly connected to form a unity-gain buffer, and a stable low-impedance 1 / 2 PWMB signal is output.

[0036] Second stage: Differential signal superposition circuit: The core superposition unit is composed of TL072C: The ±1 / 2 PWMA differential signal and 1 / 2 PWMB signal output from the front stage are injected into the U2B input terminal through a resistor network to realize the preset logic: PWMA high level + PWMB low level → output positive high level; PWMA low level + PWMB low level → output reverse high level; PWMA high level + PWMB high level → output zero level.

[0037] Third stage: Amplification circuit: The superimposed signal is used to form an inverting amplifier through TL072C. The gain is set by the input resistor R24 ​​and the feedback resistor R26 to complete the signal amplification process.

[0038] Fourth stage: Constant current circuit: The final stage adopts an improved Howland current pump architecture. Through a precision resistor network and operational amplifier control, the amplified voltage signal is converted into a stable current to drive the Cuff electrode, which meets the high-precision biphase constant current pulse stimulation output required under high impedance (1-10KΩ).

[0039] like Figure 4As shown, the stimulator's power management module is powered by a lithium polymer battery pack, with a 300mAh battery capacity that can sustain operation for two weeks. The system uses an RT9013-33 chip to convert 3.7V to 3.3V to power the microcontroller and sensing unit, while a TPS61093 chip provides ±12V boost conversion for the operational amplifier. The stimulator circuit board measures 31mm × 36mm and connects to the battery pack via a quick-plug interface.

[0040] In a preferred example, the system integrates an OLED display unit connected to the output of an STM32 microcontroller to update stimulation intensity, threshold parameters, and pulse sequence status in real time. The modular design allows for rapid replacement of the sensor, battery pack, and bioelectrodes; the measured delay from pressure sensing to stimulus release is ≤50ms. The stimulation electrode is connected to a constant current output module via an extension wire, outputting biphasic constant current pulses with parameters ranging from 0-500Hz frequency, 0.1-1ms pulse width, and 0.1mA-1.2mA amplitude, meeting the requirements for vagus nerve rehabilitation experiments.

[0041] In summary, this application provides a closed-loop vagus nerve stimulation system employing lever motion detection combined with infrared wireless transmission technology for use in experimental animal motor rehabilitation combined with vagus nerve stimulation. Compared to stimulation circuits that do not employ cascaded constant current topology, the four-stage cascaded design ensures effective and safe output of stimulation current even under high contact impedance. Compared to closed-loop control systems that use endogenous physiological signals as gating signals, this system drives closed-loop stimulation through real-time lever motion detection, achieving synergy between vagus nerve stimulation and rehabilitation exercises, resulting in better vagus nerve stimulation rehabilitation effects. Compared to systems using Bluetooth technology for wireless communication, this system, through infrared wireless technology and bare pulse signal transmission, significantly reduces control latency, achieving millisecond-level precise synergy between rehabilitation exercises and nerve stimulation.

[0042] The above description describes specific embodiments of the present invention and the technical principles employed. Any changes made in accordance with the concept of the present invention that do not exceed the spirit of the specification and drawings should still fall within the protection scope of the present invention.

Claims

1. A closed-loop vagus nerve stimulation system that can coordinate rehabilitation exercises, characterized in that, include: Closed-loop controller: used to collect external signals related to animal movement as gating signals, process the signals and generate control commands; Vagus nerve stimulator: used to receive control commands from the closed-loop controller, adjust stimulation parameters and output vagus nerve stimulation pulses; Wireless communication module: used to realize the wireless connection between the closed-loop controller and the vagus nerve stimulator, ensuring the rapid transmission of control commands; Motion signal acquisition device: used to acquire external signals related to animal movement, which are directly related to the animal's rehabilitation movement and serve as input signals for the closed-loop controller; The system uses the motion signal acquisition device to sense the animal's rehabilitation exercise status in real time. The closed-loop controller generates control commands based on the external signals and transmits them quickly to the vagus nerve stimulator through the wireless communication module. The vagus nerve stimulator adjusts the stimulation parameters according to the control commands and outputs vagus nerve stimulation pulses that match the timing of the rehabilitation exercise, thereby achieving coordinated control of rehabilitation exercise and vagus nerve stimulation.

2. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The wireless communication module uses infrared communication technology, and the end-to-end delay of the infrared communication command transmission is less than or equal to 10 milliseconds.

3. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The motion signal acquisition device is a pressure sensing module, which uses a thin-film pressure sensor to collect pressure signals generated by animal limb movement as gating signals.

4. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 3, characterized in that: The thin-film pressure sensor has a range of 2 grams to 1.5 kilograms, and the pressure sensing module is fixed to the animal's limb movement area for real-time detection of the animal's movement status.

5. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The closed-loop controller includes a main control MCU unit, which has a built-in ADC sampling module for linearizing the acquired motion signal and performing dual dynamic threshold determination. The determination conditions include duration and amplitude.

6. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 5, characterized in that: The conditions for determining the dual dynamic threshold are: duration ≥ 20 milliseconds and amplitude ≥ preset threshold.

7. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The vagus nerve stimulator includes a constant current pulse generation module, which is based on a four-level circuit architecture and is capable of outputting adjustable biphasic constant current pulses.

8. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 7, characterized in that: The constant current pulse generator module can maintain a constant current accuracy of ±5% under an 8-10 kΩ load.

9. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The vagus nerve stimulator is fixed to the back of the experimental animal by a harness to accommodate the animal's free-movement state.

10. The closed-loop vagus nerve stimulation system for coordinated rehabilitation exercises according to claim 1, characterized in that: The vagus nerve stimulator is equipped with implantable electrodes. The implantable electrodes use platinum-iridium alloy contacts that orthogonally surround the vagus nerve. The stimulation direction is orthogonal to the direction of the nerve fibers to reduce the activation threshold.

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