Ear and neck percutaneous vagus nerve stimulation device based on internal perception signal

Abstract

The invention discloses an ear and neck percutaneous vagus nerve stimulation device based on an internal feeling signal, which belongs to the related technical field of percutaneous vagus nerve stimulation and is composed of a physiological signal acquisition module, a data transmission module, a signal processing and analyzing module, a control module, ear and neck integrated stimulation equipment, an interaction module and a power supply. The device supports neck or ear vagus nerve stimulation and a stimulation mode of combined use of the neck and the ear vagus nerve. And the same or different stimulation parameters can be used for the vagus nerves of the ears and the neck. According to the non-invasive design, the electrode does not need to be placed in a human body through an operation, nerves are stimulated through an external stimulator, and the risk of injury to the human body is reduced; and meanwhile, the output of two stimulation parameters taVNS and tcVNS can be adjusted adaptively through physiological signals and internal feeling indexes, and the fusion effect is improved.

Description

Technical Field

[0001] The present invention relates to the technical field related to transcutaneous vagus nerve stimulation, and in particular to an ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals. Background Art

[0002] Vagus nerve stimulation: The vagus nerve is the longest and most widely distributed pair of cranial nerves, extending from the brainstem medulla to the colon, and mainly innervating the chest and abdominal organs. The vagus nerve involves the autonomic nervous system, cardiovascular, respiratory, gastrointestinal, immune and endocrine systems. In 1988, the world's first implantation of vagus nerve stimulation (VNS) surgery was successfully performed, and VNS began to be used in the treatment of other diseases. After more than 30 years of development, VNS has now been approved by the FDA for adjuvant treatment of epilepsy, refractory depression, cluster headache, migraine and stroke rehabilitation. Vagus nerve stimulation can be divided into invasive vagus nerve stimulation and non-invasive vagus nerve stimulation. Since invasive vagus nerve stimulation requires surgery, patients face greater safety risks and bear a heavier economic burden. Therefore, relatively safe, convenient, cheap, non-invasive and painless non-invasive vagus nerve stimulation came into being. The most common ways to activate vagus nerve afferent fibers through non-invasive vagus nerve stimulation are transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS). With the development of non-invasive vagus nerve stimulation, taVNS and tcVNS have shown broad prospects in clinical applications. In recent years, taVNS has achieved a lot of research results in controlling inflammatory responses and treating mental illnesses such as depression, schizophrenia, and insomnia, showing good clinical effects. The tcVNS technology, represented by the handheld stimulator developed in the United States, has also shown significant improvement in the treatment of migraine, epilepsy, and improving alertness. In the future, taVNS and tcVNS are expected to play an important role in the treatment of more diseases, provide patients with more effective treatment options, and further improve clinical treatment effects.

[0003] Similarities between transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation: Currently, a large number of studies on taVNS and tcVNS have shown that the two have similar effects in physiological regulation, such as cognitive function and cardiac autonomic nerve function. In addition, there is overlap in the regulation of some diseases. For example, taVNS and tcVNS both show improvement effects on migraine. In 2018, in a clinical application study of tcVNS for acute treatment of migraine, it was found that the percentage of pain-free attacks at 60 minutes and 120 minutes in the tcVNS group was significantly higher than that in the sham stimulation group, and the decrease in pain scores from baseline to 60 minutes in the tcVNS group was significantly greater than that in the sham stimulation group. In 2021, a functional magnetic resonance imaging study on the treatment of migraine found that taVNS can relieve headache symptoms and regulate the thalamocortical circuits of migraine patients. Similarly, taVNS and tcVNS also have regulatory effects on gastrointestinal diseases. A large number of clinical double-blind studies have found that 4 weeks of taVNS treatment of functional dyspepsia is effective and safe, accompanied by improvements in dyspepsia symptoms and quality of life; 4 weeks of tcVNS also showed an effective effect on patients with idiopathic gastroparesis, with improvements in their main symptoms and gastric emptying. In addition, taVNS and tcVNS also have an improvement effect on Parkinson's symptoms. taVNS treatment can effectively alleviate gait disorders in Parkinson's patients and reshape sensory motor integration; tcVNS also significantly improves the key gait parameters (speed, standing time, and step length) of Parkinson's patients, and significantly increases glutathione and brain-derived neurotrophic factor levels. All of the above indicate that taVNS and tcVNS are effective VNS intervention targets. The overlap in indications between the two, coupled with their similar neural conduction pathways, such as regulating brain function through the solitary nucleus and parabrachial nucleus, suggests that the combined action of taVNS and tcVNS is likely to have the potential for synergistic enhancement. In the field of neuroregulation, studies have found that the multi-nerve combination approach does have a synergistic effect. For example, the combined stimulation of taVNS and transcranial direct current stimulation (tDCS) significantly increases the activation range of the cerebral cortex and subcortex, which is significantly greater than the superposition effect of tDCS and taVNS. And the combined effect of the two on the improvement rate of working memory is also significantly higher than that of taVNS or tDCS alone. Therefore, considering that taVNS and tcVNS have the same indications and similar regulatory pathways, the combined effect of the two transcutaneous vagus nerve stimulation methods is likely to have a stronger activation of the vagus nerve.

[0004] Differences between transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation: The transcutaneous auricular vagus nerve and the transcutaneous cervical vagus nerve are slightly different in terms of anatomical structure and fiber structure. In terms of anatomical structure, the auricular vagus nerve originates from the superior ganglion, distributes to the back of the auricle and the skin of the external auditory canal, innervates the ear and connects to the main trunk of the vagus nerve; the cervical vagus nerve starts from the medulla oblongata of the brainstem, and is closer to the main trunk of the vagus nerve because it does not branch out many terminal branches in the neck. In terms of fiber structure, the auricular vagus nerve is all afferent fibers, while the cervical vagus nerve contains both afferent fibers and efferent fibers, and the content of Aβ fibers is much higher than that of the auricular vagus nerve. Due to differences in anatomical structure and fiber structure, there may be differences in the regulatory effects of taVNS and tcVNS. The latest studies have shown that stimulating the auricular vagus nerve and the cervical vagus nerve of rats has different effects on single neurons. Specifically, taVNS may transmit more regulatory signals to the cerebral cortex, thereby producing a wider range of cognitive regulatory effects, such as enhancing working memory, improving alertness, and regulating work motivation. Since the stimulation site of tcVNS is closer to the trunk of the vagus nerve, the regulatory function of viscera such as cardiac activity and gastrointestinal activity is relatively strong. In addition, taVNS and tcVNS may have different indications, or have lateralization for the treatment of the same type of diseases. For example, for the treatment of migraine, taVNS is mainly used for preventive treatment, while tcVNS is more used for acute treatment. Therefore, a single taVNS or tcVNS treatment method may not be sufficient to meet the diverse needs of patients. The present invention proposes a taVNS and tcVNS integrated treatment device, which aims to strengthen the activation of the vagus nerve and enhance the treatment effect from different aspects, thereby providing patients with a more comprehensive and effective treatment plan. In addition, considering that taVNS and tcVNS have different regulatory effects on the brain and viscera, the interoceptive signals (such as heart-brain coupling and stomach-brain coupling indicators) reflect the interaction between the brain and viscera, and can reflect the synergistic stimulation effect of the two. Therefore, in order to better promote the organic combination of taVNS and tcVNS, this system monitors the patient's physiological signals such as ECG, EEG and GEG in real time during the treatment process, calculates interoceptive indicators such as heart-brain coupling and stomach-brain coupling, and provides real-time feedback based on these indicators to achieve closed-loop regulation, thereby achieving ideal treatment effects.

[0005] The widely used vagus nerve stimulation technology at present is single taVNS stimulation or single tcVNS stimulation. At present, there are many patents that have protected the upgraded and optimized versions of these two stimulation devices. For example, Chinese patent CN210020867U "Ear vagus nerve electrical stimulation device" is an ear vagus nerve electrical stimulation device, including a stimulation module, a battery, an interactive interface, and at least one pair of stimuli for stimulating the projection area of ​​the ear vagus nerve. The device can be used at home without the supervision of trained health care professionals, and is very convenient to use. Chinese invention CN202311501308.X "A portable transcutaneous cervical vagus nerve stimulator" is a portable transcutaneous cervical vagus nerve stimulation device. The device includes an electrode replacement unit and a fixed locking unit, which can realize the replacement and installation of vagus nerve stimulation electrodes, thereby facilitating the use of the device. Chinese invention CN201910780585.6 "A non-invasive vagus nerve stimulation device for activating immune anti-inflammatory pathways" is a non-invasive vagus nerve stimulation device for activating immune anti-inflammatory pathways. The device includes a signal transmission module, a main control chip module, a stimulation signal generation module, and a power management module. This invention patent is the first non-invasive vagus nerve stimulation device for activating immune anti-inflammatory pathways. It avoids the risk of implantation, is safe and efficient, and the device is small and easy to carry, meeting the daily needs of patients. However, there is currently no integrated treatment device on the market that integrates taVNS devices and tcVNS devices, which greatly limits the treatment technology and regulation scheme selection of vagus nerve regulation.

[0006] There are also some utility model patents that focus on improving or improving the therapeutic effect or appearance of one of the technologies. For example, the Chinese utility model patent CN202320314248.X "Ear vagus nerve electrode" improves the electrode shape of ear vagus nerve stimulation, and the Chinese utility model patent CN202223520675.8 "An ear vagus nerve stimulator" improves the appearance of the ear vagus nerve stimulation device to a certain extent. However, there is currently no control device that can integrate the two stimulation methods.

[0007] In addition, the vagus nerve stimulation devices on the market that can perform closed-loop control are mainly based on single-modal signal calculations of electrocardiogram, electroencephalogram or other signals, but there is no closed-loop control based on internal sensory indicators such as heart-brain coupling and gastro-brain coupling. Chinese invention CN109529193B "Vagus nerve stimulator and system based on closed-loop control" monitors and sends the patient's heart rate data to an external device, and receives adjustable parameters fed back by the external device based on the patient's heart rate data, and then controls the action of the transcutaneous ear vagus nerve stimulator according to the adjustable parameters, thereby realizing closed-loop control of the transcutaneous ear vagus nerve stimulator; Chinese invention CN114082102A "A closed-loop vagus nerve stimulator based on scalp EEG" processes the scalp EEG signal through a scalp EEG signal processing module and determines whether epilepsy occurs, and transmits the epilepsy occurrence signal to the vagus nerve stimulator. After receiving the signal, the vagus nerve stimulator automatically generates a stimulation pulse in time to form a closed-loop stimulation; Chinese invention CN117618772 A "Targeted vagus nerve stimulation system" includes a vagus stimulation central control module, a targeting module, a feedback module, a stimulation module and an electrode module. The targeting module in the system transmits the human body's intestinal electrical signals, respiratory signals, and electromyographic signals to the vagus stimulation central control module. The vagus stimulation central control module generates ear vagus stimulation signals and / or neck vagus stimulation signals through a targeted analysis method and outputs them to the target area of ​​the human body via the electrode module. The feedback module transmits the heart rate signal and the electroencephalogram signal to the vagus stimulation central control module. The vagus stimulation central control module confirms the vagus stimulation effect through a feedback analysis method and adjusts the ear vagus stimulation signals and / or neck vagus stimulation signals, thereby realizing closed-loop regulation of vagus stimulation assisted by targeted information.

[0008] However, there are the following disadvantages in the prior art:

[0009] 1. The existing technology is limited to the independent research and development and improvement of taVNS technology and tcVNS technology, and has not considered the integration of taVNS and tcVNS intervention methods, which limits the further development and application of vagus nerve stimulation technology.

[0010] 2. Since taVNS and tcVNS have similar indications, but have certain differences and complementarities in their specific conduction neural pathways and mechanisms of action, the combined stimulation of taVNS and tcVNS may have a better regulatory effect, which is not taken into account in existing technologies.

[0011] 3. The existing technologies only modify the individual taVNS and individual tcVNS stimulation electrodes, and there is no electrode device that can achieve integrated stimulation of the two.

[0012] 4. Considering that taVNS and tcVNS have different effects on single neurons, the regulatory effects will also be different, and the treatment effects on some diseases of the same type will have different laterality. Therefore, the integrated device of taVNS and tcVNS can meet the needs of patients for treatment of different conditions. The existing technology has not taken this into consideration.

[0013] 5. The existing taVNS devices and tcVNS devices are both independent stimulation systems, which makes it impossible for the two to perform effective synchronized stimulation. At the same time, the simultaneous use of the two devices increases the equipment procurement cost, placement space and promotion difficulty, which is not conducive to the further development and application of vagus nerve stimulation technology.

[0014] 6. The existing technology does not have objective physiological indicators that can organically integrate the two regulation methods of taVNS and tcVNS, and achieve synergistic effects (i.e., the effect of 1+1>2).

[0015] 7. Due to the differences in anatomical and fiber structures between the transcutaneous auricular vagus nerve and the transcutaneous cervical vagus nerve, taVNS mainly transmits signals to the cerebral cortex, while tcVNS is more prominent in regulating visceral activity. The integration of the two requires a comprehensive assessment indicator that can simultaneously reflect the linkage changes in the activity levels of the cerebral cortex and visceral networks, such as the neuro-cardiac coupling (NCC) level and heart-evoked potential (HEP). However, the existing technology does not have an indicator that can comprehensively evaluate the central-visceral regulatory effects of taVNS and tcVNS.

[0016] 8. The existing technology mainly provides closed-loop control of taVNS alone or tcVNS alone, and there is no integrated device of taVNS and tcVNS that can perform closed-loop control.

[0017] 9. Existing closed-loop vagus nerve stimulation devices are mainly based on a single physiological signal, such as the calculation of electrocardiogram, electroencephalogram or other signals for feedback. There is no integrated taVNS and tcVNS device that can provide feedback based on multiple central-visceral nerve activity coupling level indicators such as heart-brain coupling and stomach-brain coupling.

[0018] Therefore, there is an urgent need to design a new technology for vagus nerve stimulation to overcome at least one disadvantage of the prior art. Summary of the invention

[0019] In order to solve the above problems, the present invention provides an ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals, which is composed of a physiological signal acquisition module, a data transmission module, a signal processing and analysis module, a control module, an ear and neck integrated stimulation device, an interaction module and a power supply;

[0020] Physiological signal acquisition module, used to collect physiological signals from different parts of the human body;

[0021] A data transmission module, used to transmit the collected physiological signals of different parts of the human body to the signal processing and analysis module, and obtain the internal perception index of the mutual coupling between different parts of the human body through the signal processing and analysis module;

[0022] The signal processing and analysis module calculates relevant physiological indicators based on the collected physiological signals such as electrocardiogram, electroencephalogram and gastric electricity, further obtains the internal perception index, and is also used to generate a first control signal based on the obtained internal perception index through a preset threshold value;

[0023] an interactive module, used to display the ear vagus nerve and / or the cervical vagus nerve that needs to be electrically stimulated, and provide control options for electrically stimulating the ear vagus nerve and / or the cervical vagus nerve, and generate a second control signal according to the selection of the control option and send it to the control module, wherein the interactive module is also used to display the waveform of the physiological signal and related physiological indicators in real time;

[0024] The control module is used to control the pulse stimulation module according to the first control signal and the second control signal to electrically stimulate the ear vagus nerve and / or the cervical vagus nerve corresponding to the internal perception index below the threshold, wherein the ear-neck integrated stimulation device is an integrated neck and ear design and is connected to the control module by a wire.

[0025] Preferably, the physiological signal acquisition module is also used to collect ECG signals through three leads in the Mason-Likar correction method, wherein the three leads are respectively located below the left clavicle, below the right clavicle, and in the left lower abdomen;

[0026] And, for EEG signal collection: F3 and F4 leads of the 10-20 international standard lead system, with FCz as the reference during collection, and grounded at the center of the forehead;

[0027] For gastric electrical signal collection: the electrodes include seven points, five of which are gastric electrical signal collection electrodes, and the remaining two are reference electrodes and ground electrodes respectively. The first gastric electrical collection site 1 is located at the xiphoid process of the human body, the second gastric electrical collection site 2 is located at the midpoint between the xiphoid process and the navel, the fourth gastric electrical collection site 4 and the fifth gastric electrical collection site 5 are located at the intersection of the horizontal line of the first gastric electrical collection site 1 and the second gastric electrical collection site 2 and the longitudinal line of the midclavicular line respectively, and the third gastric electrical collection site 3 is located at the intersection of the diagonal lines of the rectangle formed by the remaining four gastric electrical collection sites 1, 2, 4, and 5; the ground electrode is located on the left abdomen, above the iliac crest, and the reference electrode and the third gastric electrical collection site 3 are placed symmetrically.

[0028] Preferably, the data processing and analysis module is also used to measure the R peak of the ECG signal to obtain the RR interval sequence, delete the abnormal sequence, form the NN interval sequence, and then perform time domain analysis and frequency domain analysis on the sequence to calculate the heart rate and indicators reflecting the parasympathetic nerve activity.

[0029] Preferably, the data processing and analysis module is also used to analyze the EEG of F3 and F4, remove data segments with abnormal amplitudes, and also remove eye movement artifacts and electrocardiographic field artifacts in the EEG, divide the continuous EEG data into several overlapping or non-overlapping segments, apply a window function to each data segment to reduce the spectrum leakage effect, and then perform a fast Fourier transform on each windowed data segment, take the square of the modulus of the spectrum of each segment to obtain the power spectrum of each segment; average the power spectra of all segments to obtain the final power spectral density estimate, and extract the power values ​​corresponding to the δ band (0.5-4Hz), θ band (4-8Hz), α band (8-13Hz), β band (13-30Hz), and γ band (30-50Hz) from the PSD, so that the above indicators reflect the neural activity of the brain in different states.

[0030] Preferably, the data processing and analysis module is also used to analyze each lead of the gastric electrogram, perform fast Fourier transform on the signal for spectral analysis, and obtain relevant indicators that can reflect gastric activity, including: main frequency (DF), main frequency power (DP) corresponding to the main frequency, slow wave power and percentage.

[0031] Preferably, the data processing and analysis module obtains the heart-brain coupling parameter in the interoception index, which is used to sort the intervals RRi between all r peaks in the ECG records of the same time period by size, and those in the upper third are defined as long heartbeats, and those in the lower third are defined as short heartbeats; the EEG data is divided between -600ms and 600ms relative to the r peak, and the power spectral density PSD value of each segment is determined by fast Fourier transform, the PSD value is logarithmically transformed, and the average is taken at the δ frequency; and a general linear regression model is used, and the δ power is used as a predictor in the logistic model to predict the subsequent RRi of each r peak, thereby determining the heart-brain coupling parameter.

[0032] Preferably, the data processing and analysis module obtains the stomach-brain coupling parameter in the interoceptive index, which is used to determine the corresponding marginal probability distribution and joint probability distribution according to the gastric electrical vector and the EEG vector; and after calculating the conditional entropy and the joint entropy according to the marginal probability distribution and the joint probability distribution, the transfer entropy is determined, and then the stomach-brain coupling parameter is determined, wherein,

[0033] The conditional entropy is expressed as:

[0034]

[0035] The joint entropy is expressed as:

[0036]

[0037] The transfer entropy is expressed as:

[0038]

[0039] Where p(x) represents the marginal probability distribution of the last vector of the gastric electrical vector, p(y) represents the marginal probability distribution of the last vector of the EEG vector, and p(x, y) represents the joint probability distribution of the last vector and current value of the gastric electrical vector and the EEG vector. is the joint entropy of the current value of the EEG vector and the last vector of the gastric EEG vector, is the conditional entropy of the current value of the EEG vector under the condition of the last vector of the given gastric electrical vector, and M represents the length of the vector.

[0040] Preferably, the ear-neck integrated stimulation device comprises electrodes and a stimulation pulse generator;

[0041] The electrodes include multiple modes, including ear electrodes and neck electrodes, which can use patch electrodes respectively and are connected to the output end of the stimulation device through wires; or the neck stimulation device uses a device to press the skin surface for output, and the ear stimulation electrode is connected to the stimulation device through a wire for output; or the stimulation electrode is designed as an integrated neck and ear stimulation electrode, which is connected to the device host through a wire; and the stimulation electrode has an impedance detection function, which detects the human body impedance in real time during the stimulation process and stops the stimulation when the human body resistance is too large;

[0042] The stimulation pulse generator is used to provide pulse waves for electrical stimulation of the ear vagus nerve and the cervical vagus nerve, wherein the user selects and controls the frequency, pulse width, single / double phase and stimulation duration of the pulse wave through the interactive module.

[0043] Preferably, the interactive module is also used to display the waveform of the collected physiological signals and the calculated physiological indicators, and to provide feedback to the user on the physiological state of the body.

[0044] Preferably, the method for using the device comprises the following steps:

[0045] Set stimulation parameters: First, select the stimulation method, select taVNS alone or tcVNS alone, select taVNS and tcVNS before and after stimulation, or select both stimulation at the same time. Then set appropriate stimulation parameters for taVNS and tcVNS respectively, and then measure the sensory thresholds of transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation respectively, where the stimulation current value is set at about 150% of the sensory threshold;

[0046] Connecting physiological signal acquisition electrodes: According to the electrode position diagram for collecting each signal, connect the electrodes for collecting ECG, EEG and GEG signals, and select to collect one or more physiological signals;

[0047] Clean and stimulate the skin area: According to the stimulation positions of the transcutaneous auricular vagus nerve and the transcutaneous cervical vagus nerve, use a scrub to scrub the skin to reduce impedance, clean it with an alcohol cotton pad, and then apply conductive cream on the electrode or directly attach it to the skin. The stimulation position of the transcutaneous auricular vagus nerve is the tragus and cymba auricularis in the ear, and the stimulation position of the transcutaneous cervical vagus nerve is between the Adam's apple and the sternocleidomastoid muscle.

[0048] Start stimulation: The device starts and performs slight current stimulation on the vagus nerve according to the set parameters;

[0049] Adjust parameters: During the stimulation process, if the user feels uncomfortable, has abnormal reactions, or has abnormal changes in physiological signals, adjust the stimulation parameters or stop using it immediately;

[0050] End of stimulation: To stop stimulation, make sure the device is turned off and remove the electrodes or electrical stimulation patches used for stimulation from the surface of the skin.

[0051] The present invention discloses the following technical effects:

[0052] The present invention is non-invasive and does not require surgery to place electrodes inside the human body. The nerves are stimulated by an external stimulator, reducing the risk of damage to the human body.

[0053] The present invention can support stimulation of the vagus nerve in the neck or ear, as well as the stimulation method, stimulation system and stimulation device used in combination with the vagus nerve in the ear and neck. The device supports the use of the same or different stimulation parameters for the vagus nerve in the ear and neck;

[0054] The present invention can first perform ear / neck vagus nerve stimulation, and then perform neck / ear vagus nerve stimulation; first perform ear / neck vagus nerve stimulation for a fixed duration, and then perform neck / ear vagus nerve stimulation; and a combined stimulation setting method and an integrated stimulation setting system or stimulation system that use both at the same time;

[0055] The present invention designs an electrode design that integrates ear vagus nerve stimulation electrodes and neck vagus nerve stimulation electrodes in different forms (such as ear-hanging type, neck-hanging type, hand-held type, electroacupuncture type, patch type, head-mounted type, etc.);

[0056] The present invention adds a stimulation output interface to stimulate the vagus nerve of the ear while performing a pressing-type neck vagus nerve stimulation; and uses electrode patches to stimulate the vagus nerve of the ear and neck respectively;

[0057] The present invention uses a clamp, a hook, a foldable bracket and other methods to connect the ear stimulation electrode and the neck stimulation electrode to form an integrated stimulation electrode;

[0058] The present invention supports the design of large medical integrated equipment, small household integrated equipment, and various equipment forms that can be put into a pocket, hung around the waist, or tied to the chest or arm;

[0059] The present invention supports both USB charging and battery replacement for the ear and neck integrated stimulation device;

[0060] The present invention develops mobile phone applications and computer software to allow users to control devices wirelessly or wired via Bluetooth, data cables, etc., and browse device usage history, understand device parameter usage suggestions, etc.;

[0061] The present invention simultaneously monitors ECG, EEG, gastric electrogram and other physiological signals (such as respiration, electromyography, intestinal electrogram, etc.) in real time and calculates relevant physiological indicators for closed-loop feedback of the ear-neck integrated vagus nerve regulation system and stimulation method;

[0062] The present invention can calculate various coupling parameters such as heart-brain coupling, stomach-brain coupling, heart-lung coupling, heart-stomach coupling, heart-brain-lung coupling, and other interoceptive indicators (such as lung-brain coupling, gut-brain coupling, etc.) in real time, and use these indicators as feedback information to perform closed-loop electrical stimulation on the human body, a closed-loop feedback system, and a stimulation device;

[0063] The present invention can adaptively adjust the output of two stimulation parameters, taVNS and tcVNS, respectively through physiological signals and interoceptive indicators to improve the fusion effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0064] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0065] Figure 1 Schematic diagrams of different styles of ear-neck integrated stimulation electrodes / devices according to embodiments of the present invention, wherein (A) is a schematic diagram of a handheld neck nerve stimulation electrode combined with an ear vagus nerve stimulation device; (B) is a schematic diagram of a neck-hanging neck nerve stimulation electrode combined with an ear vagus nerve stimulation device; different forms can be connected to a central control system or a cloud service end to achieve closed-loop feedback regulation, or directly set parameters for non-closed-loop neural regulation;

[0066] Figure 2Schematic diagram of the integrated transcutaneous vagus nerve stimulation device for the ear and neck according to an embodiment of the present invention;

[0067] Figure 3 It is the electrocardiogram, electroencephalogram and gastric electrogram collection position map described in the embodiment of the present invention;

[0068] Figure 4 is a structural diagram of a physiological signal acquisition module according to an embodiment of the present invention;

[0069] Figure 5 is a flow chart of an electrical stimulation method based on interoceptive signals according to an embodiment of the present invention;

[0070] Figure 6 These are the operating steps of the stimulation device described in the embodiment of the present invention. DETAILED DESCRIPTION

[0071] To make the purpose, technical scheme and advantages of the embodiments of the present application clearer, the technical scheme in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all of the embodiments. The components of the embodiments of the present application generally described and shown in the drawings here can be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of the present application provided in the drawings is not intended to limit the scope of the application claimed for protection, but merely represents the selected embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without making creative work belong to the scope of protection of the present application.

[0072] like Figure 1-6 As shown, the present invention provides an integrated transcutaneous vagus nerve stimulation device for the ear and neck based on interoceptive signals. The specific contents are as follows:

[0073] 1. Device Overview:

[0074] The present invention proposes an integrated transcutaneous vagus nerve stimulation device for the ear and neck based on interoceptive signals, which is a closed-loop stimulation system that can monitor physiological signals such as electrocardiogram, electroencephalogram and gastric electricity in real time, calculate relevant physiological indicators, and further calculate interoceptive parameters such as heart-brain coupling and stomach-brain coupling, and perform feedback regulation. First, the physiological signal acquisition module collects physiological signals such as electrocardiogram, electroencephalogram, gastric electricity, myoelectricity, intestinal electricity, and respiration of the human body and performs simple preprocessing. After that, these preprocessed signals are transmitted to the data processing and analysis module in real time through a data line or Bluetooth. The data processing and analysis module analyzes the received signals, calculates indicators such as electrocardiogram, electroencephalogram, gastric electricity, myoelectricity, intestinal electricity, and respiration, and further calculates indicators such as heart-brain coupling, cardiopulmonary coupling, heart-stomach coupling, stomach-brain coupling, gastrointestinal coupling, and myoelectric evoked potential, and compares these parameters with pre-set thresholds. When multiple indicators such as heart-brain coupling and / or stomach-brain coupling are lower than or higher than the pre-set threshold, the pulse stimulator is immediately started. Before using the device, users can choose to use taVNS alone or tcVNS alone, or choose to use taVNS and tcVNS in a certain order for front and back stimulation, or choose to stimulate both at the same time. The device achieves better therapeutic effects by integrating transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation. The stimulation system incorporates a regulation method based on interoceptive signal feedback. The collection method is non-invasive and can understand the user's physiological state in real time during the stimulation process.

[0075] 2. System Implementation:

[0076] The device is mainly composed of a physiological signal acquisition module, a data transmission module, a signal processing and analysis module, a control module, an ear-neck integrated stimulation device, an interactive module and a power supply. It can realize the acquisition, transmission, processing and analysis of physiological signals such as electrocardiogram, electroencephalogram and gastric electricity, and perform electrical stimulation. The system can monitor the user's physiological state in real time during the stimulation process, which is convenient for timely adjustment.

[0077] The physiological signal acquisition module collects physiological signals such as ECG, EEG and gastric electrocardiogram of the human body, including signal amplifiers, filters and analog-to-digital converters, and is embedded in the data transmission module. The data transmission algorithm is embedded in the physiological signal acquisition device, and the data can be transmitted to the signal processing and analysis module via a data cable or Bluetooth to improve the computing efficiency. The ECG signal acquisition uses the three leads in the Mason-Likar correction method, and the three leads are respectively below the left clavicle, below the right clavicle, and in the left lower abdomen. The EEG signal acquisition uses the F3 and F4 leads of the 10-20 international standard lead system. FCz is used as a reference during acquisition, and the center of the forehead is grounded. The gastric electrogram signal acquisition electrode includes 7 points, five of which are gastric electrogram signal acquisition electrodes, and the remaining two are reference electrodes and ground electrodes. The first gastric electrogram acquisition site 1 is located at the xiphoid process of the human body, the second gastric electrogram acquisition site 2 is located at the midpoint between the xiphoid process and the navel, the fourth gastric electrogram acquisition site 4 and the fifth gastric electrogram acquisition site 5 are located at the intersection of the horizontal line of the first gastric electrogram acquisition site 1 and the second gastric electrogram acquisition site 2 and the longitudinal line of the midclavicular line, respectively, and the third gastric electrogram acquisition site 3 is located at the intersection of the diagonal lines of the rectangle formed by the remaining four gastric electrogram acquisition sites 1, 2, 4, and 5. The ground electrode (GND) is located on the left abdomen, above the iliac crest, and the reference electrode (REF) is placed symmetrically with the third gastric electrogram acquisition site 3. The above physiological signals are collected on a hardware device, and several of them can be selectively collected during collection. Before collection, the skin of the electrode area needs to be scrubbed and cleaned to enhance the conductivity of the skin.

[0078] The data processing and analysis module receives physiological signals and analyzes and calculates each signal. The data processing and analysis module measures the R peak of the ECG signal to obtain the RR interval sequence, deletes the abnormal sequence, forms the NN interval sequence, and then performs time domain analysis and frequency domain analysis on this sequence to calculate the heart rate and indicators reflecting parasympathetic nerve activity: RMSDD, pNN50 and HF, etc. The data processing and analysis module analyzes the EEG of F3 and F4 leads respectively, removes the data segments with abnormal amplitude, and also removes the eye movement artifacts and cardiac field artifacts in the EEG, divides the continuous EEG data into several overlapping or non-overlapping segments, applies a window function (such as a Hamming window) to each data segment to reduce the spectrum leakage effect, and then performs a fast Fourier transform on each windowed data segment, takes the square of the modulus of the spectrum of each segment, and obtains the power spectrum of each segment. The power spectra of all segments are averaged to obtain the final power spectrum density estimate, and the power values ​​corresponding to the δ band (0.5-4Hz), θ band (4-8Hz), α band (8-13Hz), β band (13-30Hz), and γ band (30-50Hz) are extracted from the PSD. The above indicators can reflect the neural activity of the brain in different states. The data processing and analysis module analyzes each lead of the gastric electricity separately, performs fast Fourier transformation on the signal for spectrum analysis, and obtains relevant indicators that can reflect gastric activity: main frequency (DF), main frequency power (DP) corresponding to the main frequency, slow wave power and percentage, etc.

[0079] After that, the data processing and analysis module further calculated interoceptive indicators such as heart-brain coupling and gastro-brain coupling. To calculate the heart-brain coupling parameters, the intervals between all r peaks (RRi) in the ECG records of the same period were sorted by size. Those in the upper third were defined as long heartbeats, and those in the lower third were defined as short heartbeats. The EEG data were segmented from -600ms to 600ms relative to the r peak, and the power spectral density (PSD) of each segment was determined using the fast Fourier transform (FFT). The PSD values ​​were logarithmically transformed and averaged over the delta frequency. Using the general linear regression model, the logistic model was applied for analysis. The delta power was used as a predictor in the logistic model to predict whether the subsequent RRi of each r peak belonged to a short heartbeat or a long heartbeat of all RRi. The formula was:

[0080] RRi (long heartbeat = 1, short heartbeat = 0) ~ ln (delta power);

[0081] The parameter estimation of regression is used as a measure of the strength and direction of heart-brain coupling. To calculate the gastro-brain coupling parameters, first determine the corresponding marginal probability distribution and joint probability distribution based on the gastric electrical vector and the EEG vector; calculate the conditional entropy and joint entropy based on the marginal probability distribution and the joint probability distribution. The calculation formulas for the joint entropy H(x) and conditional entropy H(x|y) are:

[0082]

[0083] Among them, p(x) represents the marginal probability distribution of the last vector of the gastric electric vector, p(y) represents the marginal probability distribution of the last vector of the EEG vector, and p(x, y) represents the joint probability distribution of the last vector and current value of the gastric electric vector and the EEG vector. Finally, the transfer entropy is determined. The calculation formula of the transfer entropy is:

[0084]

[0085] in, is the joint entropy of the current value of the EEG vector and the last vector of the gastric EEG vector, is the conditional entropy of the current value of the EEG vector under the condition of the last vector of the given gastric electrical vector, and M represents the length of the vector.

[0086] This module compares the calculated interoceptive index with a preset threshold value, and immediately activates the pulse stimulator when the interoceptive index is lower than the preset threshold value.

[0087] The control module is based on a single-chip microcomputer / microprocessor, which processes the command information from the interaction module and the information from the signal processing and analysis module, and transmits the corresponding instructions to the vagus nerve stimulation module to output content that meets the user's requirements.

[0088] The main core components of the ear-neck integrated stimulation device are electrodes and stimulation pulse generators. The stimulation electrodes include multiple modes, such as ear electrodes and neck electrodes, which can use patch electrodes respectively and are connected to the output end of the stimulation device through wires; it can also be used that the neck stimulation device presses the skin surface for output, and the ear stimulation electrode is connected to the stimulation device through a wire for output; it is also possible to design a neck-ear integrated stimulation electrode, which is connected to the device host through a wire. At the same time, the stimulation electrode has an impedance detection function, which can detect the human body impedance in real time during the stimulation process, and stop the stimulation when the human body resistance is too large to ensure safety and stimulation effect. The stimulation pulse generator can output pulse waves, including two electrical stimulation generators, which are used for electrical stimulation of the ear vagus nerve and the neck vagus nerve respectively. Users can set the stimulation parameters of the ear stimulation and neck stimulation, such as frequency (Hz), pulse width (us), single / double phase and stimulation duration.

[0089] The interactive module is mainly equipped with a user interface on the host, which is used to receive the user's settings for stimulation parameters and feedback physiological information to the user. Simpler devices may have physical buttons, while more modern devices will provide LCD displays or touch screens to allow users to adjust parameters such as frequency, stimulation time and intensity. The stimulation parameters of taVNS and tcVNS are set independently and do not affect each other. Users can choose a separate taVNS or a separate tcVNS, or they can choose taVNS and tcVNS before and after stimulation, or choose to stimulate both at the same time. The interactive interface can display the waveform of the collected physiological signals and the calculated physiological indicators in real time, and feedback the physiological state of the body to the user. The interactive interface also has a time setting function, allowing users to set the duration of the two stimulations. Users can use vagus nerve stimulation within a specific time interval according to specific needs to ensure the safety and effectiveness of the stimulation.

[0090] The power supply is provided by batteries. Common battery types include rechargeable lithium-ion batteries or regular replaceable batteries (such as AA or AAA batteries). The power consumption of the device is low, so a single charge can usually last from a few hours to a few days. The device is equipped with a USB port or wireless charging function, which allows users to charge the device at any time. It can also be designed to be replaced by a battery.

[0091] The main designs of the devices include large devices for hospital use, small portable devices for home use, and various forms that can be hung on a belt and put into a pocket. The devices can also have supporting mobile phone applications or computer software that allow users to control the devices through wired or wireless methods such as Bluetooth or data cables. These software can record the user's usage history, adjust the stimulation parameters, and provide feedback or reports to help users understand the treatment effect. At the same time, through the software, users can also choose different stimulation modes, frequencies and intensities to meet different treatment needs.

[0092] 3. Operation steps:

[0093] The operation steps of this method mainly include setting stimulation parameters, connecting physiological signal acquisition electrodes, cleaning the stimulation skin area, starting stimulation, adjusting stimulation parameters, and ending stimulation.

[0094] Set stimulation parameters: First, select the stimulation method. You can choose taVNS alone or tcVNS alone, or you can choose taVNS and tcVNS before and after stimulation, or choose to stimulate both at the same time. Then set the appropriate stimulation parameters of taVNS and tcVNS, such as stimulation frequency, intensity, pulse width, stimulation time, etc. Then measure the sensory threshold of transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation respectively. The stimulation current value can be set at about 150% of the sensory threshold.

[0095] Connecting electrodes for collecting physiological signals: You can refer to the electrode position diagram for collecting various signals in the device manual, connect electrodes for collecting ECG, EEG and GEG signals, and you can choose to collect one or more physiological signals.

[0096] Clean and stimulate the skin area: The location of transcutaneous ear vagus nerve stimulation is mainly the tragus and cymba concha in the ear, and the location of transcutaneous neck vagus nerve stimulation is mainly between the Adam's apple and the sternocleidomastoid muscle. First, the user uses a scrub to scrub the skin to reduce impedance, cleans it with an alcohol pad, and then applies conductive cream on the electrode or directly attaches it to the user's skin.

[0097] Start stimulation: The device starts and performs slight current stimulation on the vagus nerve according to the parameters set by the user.

[0098] Adjust parameters: During the stimulation process, if the user feels uncomfortable, has abnormal reactions, or has abnormal changes in physiological signals, the stimulation parameters can be adjusted or use can be stopped immediately.

[0099] End stimulation: Stop stimulation appropriately according to the treatment plan or recommendation. Make sure the device is turned off and remove the electrodes or electrical stimulation patches from the skin surface. This treatment is over.

[0100] The present invention is described with reference to flowcharts and / or block diagrams of methods, devices (systems), and computer program products according to embodiments of the present invention. It should be understood that each process and / or block in the flowchart and / or block diagram, as well as the combination of processes and / or blocks in the flowchart and / or block diagram, can be implemented by computer program instructions. These computer program instructions can be provided to a processor of a general-purpose computer, a special-purpose computer, an embedded processor, or other programmable data processing device to produce a machine, so that the instructions executed by the processor of the computer or other programmable data processing device generate instructions for implementing the processes in the flowchart and / or block diagram. Figure 1 A process or multiple processes and / or boxes Figure 1 A device that provides the functions specified in a block or multiple blocks.

[0101] In the description of the present invention, it should be understood that the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defined as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0102] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. An ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals, characterized in that: It consists of a physiological signal acquisition module, a data transmission module, a signal processing and analysis module, a control module, an ear-neck integrated stimulation device, an interaction module and a power supply; The physiological signal acquisition module is used to acquire physiological signals from different parts of the human body; The data transmission module is used to transmit the collected physiological signals of different human body parts to the signal processing and analysis module, and obtain the internal perception index of the mutual coupling between different human body parts through the signal processing and analysis module; The signal processing and analysis module calculates relevant physiological indicators based on the collected physiological signals such as electrocardiogram, electroencephalogram and gastric electricity, further obtains the internal perception index, and is also used to generate a first control signal based on the obtained internal perception index through a preset threshold value; The interactive module is used to display the ear vagus nerve and / or the cervical vagus nerve that needs to be electrically stimulated, and provide control options for electrically stimulating the ear vagus nerve and / or the cervical vagus nerve, and generate a second control signal according to the selection of the control option and send it to the control module, wherein the interactive module is also used to display the waveform of the physiological signal and related physiological indicators in real time; The control module is used to control the ear-neck integrated stimulation device according to the first control signal and the second control signal, and electrically stimulate the ear vagus nerve and / or the neck vagus nerve corresponding to the internal perception index below the threshold, wherein the ear-neck integrated stimulation device is an integrated neck and ear design and is connected to the control module via a wire.

2. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 1, characterized in that: The physiological signal acquisition module is also used to collect electrocardiogram signals through three leads in the Mason-Likar correction method, wherein the three leads are respectively located below the left clavicle, below the right clavicle, and in the left lower abdomen; And, for EEG signal collection: F3 and F4 leads of the 10-20 international standard lead system, with FCz as the reference during collection, and grounded at the center of the forehead; For gastric electrical signal collection: the electrodes include seven points, five of which are gastric electrical signal collection electrodes, and the remaining two are reference electrodes and ground electrodes respectively. The first gastric electrical collection site 1 is located at the xiphoid process of the human body, the second gastric electrical collection site 2 is located at the midpoint between the xiphoid process and the navel, the fourth gastric electrical collection site 4 and the fifth gastric electrical collection site 5 are located at the intersection of the horizontal line of the first gastric electrical collection site 1 and the second gastric electrical collection site 2 and the longitudinal line of the midclavicular line respectively, and the third gastric electrical collection site 3 is located at the intersection of the diagonal lines of the rectangle formed by the remaining four gastric electrical collection sites 1, 2, 4, and 5; the ground electrode is located on the left abdomen, above the iliac crest, and the reference electrode and the third gastric electrical collection site 3 are placed symmetrically.

3. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 2, characterized in that: The data processing and analysis module is also used to measure the R peak of the ECG signal to obtain the RR interval sequence, delete the abnormal sequence, form the NN interval sequence, and then perform time domain analysis and frequency domain analysis on the sequence to calculate the heart rate and indicators reflecting the parasympathetic nerve activity.

4. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 3, characterized in that: The data processing and analysis module is also used to analyze the EEG of F3 and F4, remove data segments with abnormal amplitudes, and also remove eye movement artifacts and electrocardiographic field artifacts in the EEG, divide the continuous EEG data into several overlapping or non-overlapping segments, apply a window function to each data segment to reduce the spectrum leakage effect, then perform a fast Fourier transform on each windowed data segment, take the square of the modulus of the spectrum of each segment to obtain the power spectrum of each segment; average the power spectra of all segments to obtain the final power spectrum density estimate, extract the power values ​​corresponding to the δ band (0.5-4Hz), θ band (4-8Hz), α band (8-13Hz), β band (13-30Hz), and γ band (30-50Hz) from the PSD, so that the above indicators reflect the neural activity of the brain in different states.

5. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 4, characterized in that: The data processing and analysis module is also used to analyze each lead of the gastric electrogram, perform fast Fourier transform on the signal for spectrum analysis, and obtain relevant indicators that can reflect gastric activity, including: main frequency (DF), main frequency power (DP) corresponding to the main frequency, slow wave power and percentage.

6. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 5, characterized in that: The data processing and analysis module obtains the heart-brain coupling parameter in the interoception index, and is used to sort the intervals RRi between all r peaks in the electrocardiogram records of the same time period by size, and those in the upper third are defined as long heartbeats, and those in the lower third are defined as short heartbeats; the EEG data is divided between -600ms and 600ms relative to the r peak, and the power spectral density PSD value of each segment is determined using fast Fourier transform, the PSD value is logarithmically transformed, and the average is taken at the δ frequency; and a general linear regression model is used, and the δ power is used as a predictor in the logistic model to predict the subsequent RRi of each r peak, thereby determining the heart-brain coupling parameter.

7. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 6, characterized in that: The data processing and analysis module obtains the stomach-brain coupling parameter in the interoceptive index, which is used to determine the corresponding marginal probability distribution and joint probability distribution according to the gastric electrical vector and the EEG vector; and after calculating the conditional entropy and the joint entropy according to the marginal probability distribution and the joint probability distribution, the transfer entropy is determined, and then the stomach-brain coupling parameter is determined, wherein, The conditional entropy is expressed as: The joint entropy is expressed as: The transfer entropy is expressed as: Where p(x) represents the marginal probability distribution of the last vector of the gastric electrical vector, p(y) represents the marginal probability distribution of the last vector of the EEG vector, and p(x, y) represents the joint probability distribution of the last vector and current value of the gastric electrical vector and the EEG vector. is the joint entropy of the current value of the EEG vector and the last vector of the gastric EEG vector, is the conditional entropy of the current value of the EEG vector under the condition of the last vector of the given gastric electrical vector, and M represents the length of the vector.

8. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 7, characterized in that: The ear-neck integrated stimulation device comprises electrodes and a stimulation pulse generator; The electrodes include multiple modes, including ear electrodes and neck electrodes, which can use patch electrodes respectively and are connected to the output end of the stimulation device through wires; or the neck stimulation device uses a device to press the skin surface for output, and the ear stimulation electrode is connected to the stimulation device through a wire for output; or the neck and ear integrated stimulation electrode is connected to the device host through a wire, and the stimulation electrode has an impedance detection function, which detects the human body impedance in real time during the stimulation process, and stops the stimulation when the human body resistance is too large; The stimulation pulse generator is used to provide pulse waves for electrical stimulation of the ear vagus nerve and the cervical vagus nerve, wherein the user selects and controls the frequency, pulse width, single / double phase and stimulation duration of the pulse wave through the interactive module.

9. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 8, characterized in that: The interactive module is also used to display the waveform of the collected physiological signals and the calculated physiological indicators, and to provide feedback to the user on the physiological state of the body.

10. The ear and neck transcutaneous vagus nerve stimulation device based on interoceptive signals according to claim 9, characterized in that: The method for using the device comprises the following steps: Set stimulation parameters: First, select the stimulation method, select taVNS alone or tcVNS alone, select taVNS and tcVNS before and after stimulation, or select both stimulation at the same time; then set appropriate stimulation parameters for taVNS and tcVNS respectively, and then measure the sensory thresholds of transcutaneous auricular vagus nerve stimulation and transcutaneous cervical vagus nerve stimulation respectively, where the stimulation current value is set at about 150% of the sensory threshold; Connecting physiological signal acquisition electrodes: According to the electrode position diagram for collecting each signal, connect the electrodes for collecting ECG, EEG and GEG signals, and select to collect one or more physiological signals; Clean and stimulate the skin area: According to the stimulation positions of the transcutaneous auricular vagus nerve and the transcutaneous cervical vagus nerve, use a scrub to scrub the skin to reduce impedance, clean it with an alcohol cotton pad, and then apply conductive cream on the electrode or directly attach it to the skin. The stimulation position of the transcutaneous auricular vagus nerve is the tragus and cymba auricularis in the ear, and the stimulation position of the transcutaneous cervical vagus nerve is between the Adam's apple and the sternocleidomastoid muscle. Start stimulation: The device starts and performs slight current stimulation on the vagus nerve according to the set parameters; Adjust parameters: During the stimulation process, if the user feels uncomfortable, has abnormal reactions, or has abnormal changes in physiological signals, adjust the stimulation parameters or stop using it immediately; End of stimulation: To stop stimulation, make sure the device is turned off and remove the electrodes or electrical stimulation patches used for stimulation from the surface of the skin.

Images