Peripheral nerve stimulation control system and method

Abstract

Provided is a peripheral nerve stimulation system comprising: a device for electrically stimulating a peripheral nerve and measuring an evoked compound action potential (ECAP) from the peripheral nerve; a control unit for receiving feedback of the ECAP measured after stimulating the peripheral nerve and determining a threshold value of the ECAP; and a stimulation determination unit for determining, according to the threshold value, a stimulation intensity of an electrode that stimulates the peripheral nerve.

Description

Peripheral nerve stimulation control system and method

[0001] The present invention relates to a peripheral nerve stimulation control system and method, and more specifically, to a peripheral nerve stimulation control system and method capable of measuring therapeutic effects and appropriate intensity within the peripheral nervous system through a feedback control system based on induced complex potential.

[0002] Neuromodulation is a clinical approach that inhibits or excites target neurons to regulate abnormal neural activity through artificial stimulation using electrical, magnetic, or ultrasonic energy according to established clinical protocols. To date, various neuromodulation therapies, including deep brain stimulation (DBS) for Parkinson's disease, transcranial magnetic stimulation (TMS) for psychiatric disorders, and epidural spinal cord stimulation (SC) for chronic pain management, have received FDA approval and demonstrated statistically significant patient outcomes in modern clinical settings.

[0003] Traditionally, neuromodulation techniques have been primarily applied to the central nervous system, resulting in limited accessibility. However, there is growing interest in peripheral neuromodulation, which offers greater accessibility and serves as a critical pathway for neural signals that directly regulate various organs. Consequently, research related to peripheral nerve stimulation (PNS) for chronic diseases such as hypertension and bladder dysfunction is actively underway. Current research aims to expand the clinical application of PNS to address diverse medical needs and improve patient outcomes. These advancements suggest that further improvements in PNS can lead to more accurate and effective therapeutic solutions, offering significant potential for personalized treatment.

[0004] Currently, PNS protocols are periodically determined by medical professionals who analyze the patient's condition and adjust the treatment regimen by modifying factors such as duration, intensity, and stimulation frequency. However, the optimal treatment protocol can continuously fluctuate due to individual physiological conditions, drug interactions, and changes in the stage of disease progression. Furthermore, variations in the electrode-neurointerface can significantly impact physiological equilibrium, potentially hindering the attainment of meaningful results from applied stimulation. Despite the administration of standardized protocols across patient groups, achieving consistent outcomes for every individual remains a challenge. This variability is evident in specific studies, which report differences in efficacy between equivalent groups. Additionally, there are documented cases where excessive electrical stimulation was applied to some individuals within the control group, putting them at risk of tissue and nerve damage. Despite these risks, methods utilizing maximum stimulation intensity at the patient's tolerance level are still being practiced. Consequently, the resulting inefficiencies or side effects sometimes outweigh the benefits of neuromodulation. This instability has driven the development of control methods that continuously incorporate relevant physiological feedback, rather than relying on empirical observations or periodic adjustments based on experience.

[0005] The technological landscape of neuromodulation is rapidly evolving, driven by the development of bioelectronic systems that enable real-time signal recording and closed-loop control. Capturing comprehensive physiological signals allows for quantitative analysis, which can improve the precision of therapeutic interventions. In particular, neural signal monitoring has brought significant advancements to DBS and SCS. The use of local in-situ potential (LFP) and spike analysis for closed-loop control has greatly improved the management of diseases mediated by central nervous system disorders. However, while these established interventions have advanced in treating conditions such as epilepsy and even hypertension, LFP and spike analysis face challenges in adaptation and application because they are not effectively delivered to the peripheral nervous system. To address the current limitations of the PNS, attention must shift to control systems that utilize measurable and effective functions within the peripheral nervous system to maximize the outcomes of neuromodulation.

[0006] Among these PNS therapies, transcutaneous tibial nerve stimulation (PTNS) is recognized as having the potential to provide high scalability across various PNS treatments. This potential stems from the fact that it relies on neural signal feedback, particularly evoked compound action potentials (ECAPs) observed across nerve strands, rather than being limited to specific physiological parameters of chronic diseases. Therefore, for PTNS, the development of custom-designed devices for measurement and stimulation that are fully implantable is essential, but a system for this purpose has not yet been developed. Overactive bladder (OAB) refers to a condition characterized by urinary urgency (a strong and sudden urge to urinate) in the absence of other clear causes, such as urinary tract infections, commonly accompanied by daytime frequent urination and nocturia. Although PNS is being studied as a non-pharmacological intervention for adults with overactive bladder syndrome, a tibial nerve stimulation system and electrodes for the aforementioned bladder activity control have not yet been developed.

[0007] Therefore, the problem that the present invention aims to solve is to provide a tibial nerve stimulation system that integrates measurement and stimulation for PNS treatment.

[0008] To solve the above problem, the present invention provides a peripheral nerve stimulation control system comprising: an implantable device for electrically stimulating a peripheral nerve and measuring an evoked compound action potential (ECAP) from the peripheral nerve; a control unit that receives feedback of the measured evoked compound action potential (ECAP) after stimulating the peripheral nerve and determines a threshold value of the evoked compound action potential (ECAP); and a stimulation determination unit that determines a stimulation intensity for stimulating the peripheral nerve according to the threshold value.

[0009] In one embodiment of the present invention, the peripheral nerve stimulation system is implantable in vivo.

[0010] In one embodiment of the present invention, the peripheral nerve stimulation system further includes a wireless charging unit for wirelessly supplying power to the device.

[0011] In one embodiment of the present invention, the control unit integrates the measured evoked compound action potential (ECAP) value.

[0012] In one embodiment of the present invention, the control unit determines the point at which the second derivative of the integrated evoked compound action potential (ECAP) value shows a significant increase exceeding twice the previous result value as the threshold value.

[0013] In one embodiment of the present invention, the peripheral nerve is a transcutaneous tibial nerve.

[0014] The present invention also provides a peripheral nerve stimulation control system for treating an overactive bladder (OAB) comprising a peripheral nerve stimulation system.

[0015] The present invention also provides a method for controlling peripheral nerve stimulation, comprising the steps of: electrically stimulating a peripheral nerve; measuring an evoked compound action potential (ECAP) from the peripheral nerve; receiving feedback of the measured evoked compound action potential (ECAP) to determine a threshold value of the evoked compound action potential (ECAP); and determining a stimulation intensity for stimulating the peripheral nerve according to the threshold value.

[0016] In one embodiment of the present invention, the step of determining the threshold value of the evoked compound action potential (ECAP) is to integrate the measured evoked compound action potential (ECAP), and the threshold value is the point where the second derivative of the integrated evoked compound action potential (ECAP) value exceeds twice the previous result value and shows a significant increase.

[0017] In one embodiment of the present invention, the peripheral nerve is a transcutaneous tibial nerve.

[0018] In one embodiment of the present invention, the determined stimulation intensity is the electrical stimulation intensity that stimulates the peripheral nerve at the point where the threshold value is determined.

[0019] Unlike conventional technology, which has the problem that it cannot be assured that the electrical stimulation induces a desired neuromodulation effect beyond motor reflexes, the present invention can optimize stimulation parameters by using ECAP as quantitative neural feedback.

[0020] Figure 1 is a diagram illustrating an ECAP-based stimulation intensity regulation mechanism for PNS stimulation.

[0021] Figure 2 is a schematic design diagram for the application of the TNS of the present invention.

[0022] Figure 3 is a summary of the threshold test steps performed to evaluate the motion threshold and ECAP threshold of each subject.

[0023] Figure 4 presents the results of threshold analysis of representative data obtained during the test, and the top figure shows the electromyogram and neural signal response to the applied stimulation intensity.

[0024] Figure 5 shows the motion threshold and ECAP threshold measured in 8 mice.

[0025] Figure 6 shows the results of a representative urination pattern measured at this stage.

[0026] Figure 7 presents the analyzed immaturity interval results of steady state, motor threshold stimulation, and ECAP threshold stimulation for 8 rats.

[0027] Figure 8 is an experimental design for system testing after transplantation into a behavioral rat.

[0028] Figure 9 is a diagram illustrating the experimental protocol timeline for experimenting on autonomous rats.

[0029] Figure 10 is a diagram illustrating the threshold analysis process performed on a rat in autonomous behavior.

[0030] FIG. 11 is a step diagram illustrating an ECAP-based control method according to an embodiment of the present invention.

[0031] Hereinafter, preferred embodiments of the present invention will be described in detail with reference to the attached drawings.

[0032] Before describing the present invention in detail, the terms and words used in this specification should not be interpreted as being unconditionally limited to their ordinary or dictionary meanings, and the inventor of the present invention may appropriately define and use the concepts of various terms to best describe their invention.

[0033] Furthermore, it should be understood that these terms or words should be interpreted in a meaning and concept consistent with the technical spirit of the present invention.

[0034] In other words, the terms used in this specification are used merely to describe preferred embodiments of the invention and are not intended to specifically limit the content of the invention.

[0035] It should be noted that these terms are defined in consideration of the various possibilities of the present invention.

[0036] Additionally, in this specification, singular expressions may include plural expressions unless the context clearly indicates a different meaning.

[0037] In addition, you should be aware that even if it is expressed in the plural, it may contain a singular meaning.

[0038] Throughout this specification, where it is stated that a component "includes" another component, unless specifically stated otherwise, this may mean that it does not exclude any other component but may include any other component.

[0039] Furthermore, in cases where it is stated that a component "exists inside or is installed in connection with" another component, this component may be installed in direct connection with or in contact with the other component.

[0040] In addition, they may be installed spaced apart at a certain distance, and in the case where they are installed spaced apart at a certain distance, there may be a third component or means for fixing or connecting the component to another component.

[0041] Meanwhile, it should be noted that the description of the third component or means mentioned above may be omitted.

[0042] On the other hand, if it is stated that one component is "directly connected" or "directly connected" to another component, it should be understood that there is no third component or means.

[0043] Likewise, other expressions describing the relationship between each component, such as “between” and “right between”, or “adjacent to” and “directly adjacent to”, should be interpreted as having the same intent.

[0044] In addition, terms such as “one side,” “other side,” “one side,” “other side,” “first,” “second,” etc., in this specification are used to ensure that one component can be clearly distinguished from another component.

[0045] However, it should be noted that the meaning of the component is not used restrictively by such terminology.

[0046] In addition, positional terms such as "top," "bottom," "left," and "right" used in this specification should be understood as indicating the relative position of the corresponding component in the drawing.

[0047] Furthermore, unless an absolute location is specified regarding their positions, terms related to these locations should not be understood as referring to absolute locations.

[0048] Furthermore, in the specification of the present invention, terms such as “…part,” “…unit,” “module,” and “device,” if used, refer to a unit capable of handling one or more functions or operations.

[0049] You should be aware that this can be implemented in hardware, software, or a combination of hardware and software.

[0050] In the drawings attached to this specification, the size, location, connection relationships, etc., of each component constituting the present invention may be described in a partially exaggerated, reduced, or omitted manner for the convenience of explanation or to sufficiently clearly convey the concept of the present invention, and therefore, the proportions or scale may not be strictly accurate.

[0051] In addition, in describing the present invention below, detailed descriptions of components that are deemed to unnecessarily obscure the essence of the invention, such as known technologies including prior art, may be omitted.

[0052] To solve the aforementioned problem, the present invention monitors ECAP from a stimulus to evaluate neural activation, and the control system accordingly [determines] stimulus parameters

[0053] Furthermore, to evaluate the in vivo performance and feasibility of the system according to the present invention, tibial nerve stimulation (TNS) was selected as an application of this closed-loop neural modulation method, and a closed-loop PNS control system is provided that optimizes stimulation parameters using ECAP as quantitative neural feedback.

[0054] The system and method according to the present invention exhibit excellent accuracy and adaptability to direct neural interfaces and can provide high scalability across various PNS treatments, because the system according to the present invention is not limited to specific physiological parameters of chronic diseases and relies on neural signal feedback, particularly ECAP observed across neural strands.

[0055] The present invention provides an integrated device designed to be fully implantable and custom-developed for ECAP measurement and peripheral nerve stimulation, and provides feedback to enable a control system to adjust stimulation parameters accordingly by monitoring ECAP from aspiration to nerve activation evaluation.

[0056] To evaluate the in vivo performance and feasibility of the integrated system according to one embodiment of the present invention, tibial nerve stimulation (TNS) was selected as an application of this closed-loop neuromodulation method, but the scope of the present invention is not limited thereto.

[0057] A TNS to which a system according to one embodiment of the present invention is applied is a new treatment for alleviating symptoms of an overactive bladder (OAB), and the effect of the system according to the present invention was evaluated by monitoring controlled bladder activity.

[0058]

[0059] The present invention will be explained in more detail through the following preferred embodiments.

[0060] Examples

[0061] Device firmware

[0062] The system according to the present invention operates with a CC1350 microcontroller unit (Texas Instruments) controlling an RHS2116 electrophysiology interface (Intan Technologies). The firmware is written in Code Composer Studio (v12, Texas Instruments) and is controlled via a LabView GUI (National Instruments Corporation). A wireless connection for PC control of the device was established using a development kit (Texas Instruments Inc.). On the host PC, the GUI allowed for controlling device functions and adjusting stimulation parameters, displayed measurement results, and enabled data transmission for further analysis.

[0063]

[0064] Circuit development

[0065] The system according to the present invention was designed to withstand implantation conditions and was powered by a 3.7V Li-Po battery with a WPT charging option. A 3.3V low dropout regulator (ADP151, Analog Devices Inc.) was integrated to ensure proper operation of the main chip. Additionally, a ±5V buck-boost converter (LT3582, Analog Devices Inc.) was used to generate the two-phase signal required for stimulation. A 433MHz antenna (ANT1204, Pulse Electronics) was integrated for wireless communication. A functional diagram of the circuit design is shown in Supplementary Figure 2. The PCB size was 15mm × 18mm.

[0066]

[0067] Electrode implantation

[0068] In the present invention, the measurement electrode implanted in vivo is a mesh-type gold electrode coated with a polymer such as GelMA. This electrode is positioned on the sciatic nerve to measure nerve signals, specifically measuring response signals to stimulation applied to the tibial nerve and extracting evoked complex potential signals. On the other hand, the stimulation electrode for applying electrical stimulation to peripheral nerves is positioned on the tibial nerve, and in one embodiment of the present invention, tibial nerve stimulation was performed using a bio-implantable nerve cuff electrode from Microprobe.

[0069]

[0070] Wireless Power Transfer Design

[0071] The peripheral nerve stimulation system according to the present invention is charged via a wireless charging method, and the wireless power unit (system) for this purpose is designed with a dedicated WPT Rx coil for the device. A WPT Tx coil is integrated into a cylindrical cage, and both coils are tuned to a frequency of 6.78 MHz. The system according to the present invention incorporates a linear voltage regulator (XCM414, Torex Semiconductor Ltd.) to enable WPT charging of the battery. The WPT Rx coil is designed to wrap around the edge of the PCB, optimizing space utilization with a size of 17 mm × 20 mm. The WPT Tx coil is connected to a wireless power amplifier (EPC9512, Efficient Power Conversion Corp.) and a DC power supply for WPT charging (PWS4305, Tektronix Inc.).

[0072]

[0073] Packaging case

[0074] This packaging is composed of biocompatible materials, ceramic and Kovar, which are brazed together to facilitate seamless welding of the implanted conditions. This design prioritizes non-metallic (ceramic) components covering more than 80% of the case surface area to improve wireless connectivity efficiency. The case lid is also made of Kovar material with an integrated feedthrough (SA271082 Rev3, Morgan Advanced Materials) for electrode connection. The case was laser welded after assembly for a hermetic seal. The dimensions of the packaging case, including the lid, are 20mm × 25mm × 8mm.

[0075]

[0076] Mouse preparation

[0077] All procedures were approved by the Pohang University of Science and Technology Animal Care and Use Committee (POSTECH IACUC). Sprague-Dowley rats (270–300 g body weight, 8 weeks old, male) were used in the study. These rats were administered short-term anesthesia with isoflurane (Pyramal Critical Care, Inc.) for the surgical procedure (isoflurane 2%, flow rate 0.5–0.6 L / min, 30–40 min). Postoperatively, anesthesia was switched to urethane (Sigma-Aldrich) via intraperitoneal injection (urethane saline 20%, body weight 1.0–1.2 g / kg) to maintain autonomic system function for the micturition reflex.

[0078] The sciatic nerve was accessed through the lateral thigh and measured by placing a custom-developed cuff electrode. Similarly, the tibial nerve was accessed through the ankle region and stimulated using a nerve cuff electrode (NC-1-2-250SS-1-2-Sut-20SS, microprobe for life sciences). The rat bladder was exposed, and IBP was controlled by inserting a catheter connected to a pressure transducer (BP-100, iWorx System Inc.) and a syringe pump (Pump 11 Elite I / W Dual, v3.0.6, Harvard Device) for IBP control. A DAQ module (IX-RA-834, iWorx System Inc.) and Labscribe (v3, iWorx System Inc.) were used for physiological measurements.

[0079] For freely moving mice, additional surgical procedures were required. The catheter was expanded and connected to a neck button (Instech Laboratories, Inc.) to minimize interference with movement and secure the catheter connection from inside the body to the external environment. The system according to the present invention was implanted in the subcutaneous lumbar region to maintain a connection with the electrode. The incision made during the surgery was sutured and disinfected before the mouse recovered from isoflurane anesthesia.

[0080]

[0081] analyze

[0082] ECAP threshold analysis and stimulus control

[0083] Figure 1 is an ECAP-based stimulation intensity control mechanism for PNS stimulation, and Figure 2 is a design schematic for the application of the present invention to TNS, showing the results of comparing the effectiveness of urination inhibition between the control method based on the motor response of TNS and the control method of the present system.

[0084] Referring to FIGS. 1 and 2, the measurement results transmitted from the device were analyzed to capture the ECAP response for ECAP threshold evaluation. The ECAP signals were integrated to quantify neural activation, and the ECAP threshold was determined as the point where the second derivative of the integrated ECAP signal exceeded twice the previous result value, indicating a significant increase.

[0085] The ECAP threshold (i.e., the electrical stimulation intensity of the stimulating electrode at the point where the threshold is reached) was selected as the stimulation intensity, and the neural signal was continuously monitored to maintain the ECAP signal level throughout the stimulation. This protocol is illustrated in FIG. 2, etc., and in this way, the stimulation intensity becomes the electrical stimulation intensity that stimulates the peripheral nerve at the point where the threshold is determined.

[0086]

[0087] System evaluation through TNS applications

[0088] In a clinical setting, TNS therapy is commonly used to alleviate symptoms of urinary disorders such as urinary incontinence and OAB. TNS aims to reduce detrusor overactivity and relieve symptoms of bladder urgency and frequency. Although the exact mechanism of TNS is still uncertain, it is thought that these effects occur due to the modulation of afferent signals induced by bladder distension, thereby maintaining bladder persistence. A quantitative analysis of the increased resection interval achieved by applied stimulation was performed according to Figures 1 and 2 by monitoring bladder activity through intravesical pressure (IBP) measurements.

[0089] The bioelectronic system according to the present invention is specifically designed for TNS with an implantable device and electrode configuration customized to meet the requirements of TNS treatment. This system evaluates nerve activity by delivering electrical stimulation to the tibial nerve while simultaneously measuring response signals from the sciatic nerve.

[0090] Using the ECAP analysis described in FIGS. 1 and 2, the system adjusts the stimulation intensity to ensure accurate control and effective neural modulation. Conventional TNS uses toe tremors as a criterion for determining stimulation intensity, whereas the system according to the present invention uses ECAP as a feedback function to analyze the increase in neural activation as a selection criterion. To evaluate the performance of the feedback-based stimulation optimization system according to the present invention, motor responses (foot tremors) were monitored via electromyography for comparison with existing methods.

[0091]

[0092] Threshold evaluation for stimulus intensity control

[0093] The experimental protocol shown in Figure 3 summarizes the threshold test steps performed to evaluate the motion threshold and ECAP threshold of each subject. During this test, the stimulation intensity was gradually increased (in 5 μA steps from 20 to 255 μA within a safe range for direct neural stimulation), and neural signals and electromyographic responses were continuously measured.

[0094] Figure 4 presents the results of threshold analysis of representative data obtained during the test, and the top figure shows the electromyogram and neural signal response to the applied stimulation intensity.

[0095] In Figure 4, the motion threshold was defined as the stimulus intensity at which EMG activation occurs, and the ECAP threshold was determined by a significant increase in ECAP amplitude, as analyzed through the rate of change of the integrated ECAP. The threshold test ensured accurate measurement and verification of both thresholds, with the motion threshold averaging 94 ± 2.2 μA and the ECAP threshold averaging 117 ± 4.5 μA. Figure 5 shows the motion threshold and ECAP threshold measured in eight rats, where the motion threshold was consistently lower than the ECAP threshold.

[0096] The tibial nerve, branching from the sciatic nerve, consists of motor and sensory nerves encompassing various types of nerve fibers. These fibers possess distinct physical and electrophysiological characteristics. As fiber diameter decreases and myelination declines, progressively higher stimulation intensities are required in the following order to activate and propagate activity potential: Aα-, Aβ-, Aδ, and C fibers. Afferent nerves of the urinary tract and bladder primarily consist of Aδ and C fibers, while motor responses originate from Aα fibers. An ECAP threshold higher than the motor threshold suggests that additional nerve fibers are activated upon reaching the ECAP threshold. This approach enables more precise intensity tuning using ECAP as a specific physiological marker, providing superior quantitative control compared to existing methods.

[0097]

[0098] Comparison of TNS effects for system evaluation

[0099] Reducing urination frequency is one of the important factors for OAB treatment. In a major experiment, the effect of increasing voiding intervals was compared between a group stimulated at the exercise threshold and the ECAP threshold intensity.

[0100] Figure 6 shows the results illustrating representative voiding patterns measured at this stage. The exercise threshold stimulus was administered first, followed by the ECAP threshold stimulus, with a minimum rest period of one hour between tests to minimize residual effects. IBP was monitored throughout the experiment to assess voiding activity and compare the results of the stimulus tests with the steady state. The bottom figure shows the results of the voiding interval analysis. The exercise threshold stimulus slightly increased the voiding interval, whereas the ECAP threshold stimulus increased it by 38% compared to the steady state (Normal: 171.1 ± 21.6 seconds, Exercise Threshold: 179.2 ± 20.2 seconds, ECAP Threshold: 237 ± 69.9 seconds).

[0101] Figure 7 presents the analyzed immaturity interval results for 8 rats under steady state, motor threshold stimulation, and ECAP threshold stimulation. Motor threshold stimulation increased the immaturity interval by less than 10%, while ECAP threshold stimulation achieved a significant increase. In addition to this profound effect, an immaturity inhibition pattern was observed only with ECAP threshold stimulation.

[0102] Previous studies (Non-patent Literatures 1 to 6) described changes in electrophysiological characteristics and functional roles according to specific types of nerve fibers. Neural responses after stimulation pulses were consistently observed within the signal window and increased progressively with increasing stimulation intensity. The significant increase in ECAP amplitude observed at the ECAP threshold appears to be attributed to the activation of additional nerve fibers during the propagation of action potentials. At the stimulation intensity reaching the ECAP threshold, more nerve fibers are activated, leading to a cumulative increase in ECAP amplitude as the activation threshold is progressively met. However, variations among the types of activated nerve fibers suggest that the stimulation intensity at the motor threshold may not be sufficient to achieve the desired neuromodulatory effect, as the fibers necessary to generate the desired therapeutic outcome may not be adequately engaged. These findings highlight the limitations of existing methods. Motor responses often do not correlate with optimal therapeutic outcomes, resulting in inappropriate neuromodulatory effects. If the initial stimulation intensity is insufficient, the intensity must be increased to reach the therapeutic threshold. However, motor responses lack precision in this adjustment process.

[0103] On the other hand, the approach according to the present invention incorporates quantitative feedback from ECAP analysis to enable more precise adjustments, thereby inducing more targeted neuromodulation. Our experimental results demonstrated that the system according to the present invention achieves better alignment with desired results than existing methods.

[0104]

[0105] Device verification for operation under implant conditions

[0106] The circuitry of the custom implantable device consists of a microcontroller unit and an electrophysiological interface, enabling integrated operation of neural stimulation and signal measurement. It also features wireless communication and wireless power transfer (WPT) usable under implanted conditions.

[0107] The device according to the present invention was assembled in a custom packaging case containing a WPT transmission coil and a Li-Po battery. This case was designed to allow both hermetically sealed and radio frequency signal penetration. Prior to implantation experiments, wireless control, data transmission, and WPT were successfully tested in vivo.

[0108] In the present invention, temperature tests were performed during maximum amplitude stimulation and WPT charging. At this time, the temperature increased by 0.7°C after 30 minutes and by 1.2°C after 1 hour. Under idle conditions, the temperature increased by 0.6°C after 6 hours. During implantation surgery, the temperature rose by 1.1°C according to the protocol and was maintained below 2°C, which is the safety limit for implantable medical devices.

[0109] Power consumption is primarily attributed to the operation of the electrophysiological interface. Power consumption during total operation (generating stimulation pulse signals at maximum amplitude) was measured at 86.8 mW, while idle consumption was 48.5 mW. The system operated fully for 5 hours and could maintain idle mode for 2 days without recharging. During WPT charging, the system operated for more than 12 hours, as charging during operation was unnecessary because the TNS protocol required stimulation for only 30 minutes.

[0110]

[0111] Evaluation of the transplanted free-moving mouse system

[0112] The custom-developed devices and electrodes were meticulously designed to meet the requirements for fully implantable systems. This process involved optimizing both functional capabilities and physical properties to achieve effective neuromodulation while ensuring stable performance in an in vivo environment. The validation process included rigorous testing and improvements to ensure the devices and electrodes could withstand implantation, thereby guaranteeing the successful implementation of selected TNS applications.

[0113] The system was assembled according to the procedure summarized in the method section and implanted into a free-moving mouse.

[0114] Figure 8 shows the experimental design for system testing after transplantation into behavioral mice, and Figure 9 is a diagram explaining the experimental protocol timeline for testing on autonomous behavioral mice.

[0115] In addition, Fig. 10 is a diagram illustrating the threshold analysis process performed on a rat in autonomous behavior.

[0116] In this experimental example, after a recovery period of 3 days following implantation, the mice underwent the experimental protocol summarized in Fig. 9 to be evaluated while in a free-moving state. The neural signals measured under implantation conditions successfully distinguished the ECAP threshold.

[0117] The threshold test and excision interval were compared in freely moving rats, and the results showed that the effect was greater when the movement threshold was lower (movement threshold: 48 ± 2.7 μA, ECAP threshold: 71 ± 2.2 μA) and stimulated by the ECAP threshold (change in ECAP excision interval: 140.9 ± 13.9 seconds → 235.0 ± 64.7 seconds).

[0118] These results, which are closely consistent with those observed in previous acute tests, demonstrate the robustness and adaptability of the system under dynamic conditions. The successful differentiation of ECAP thresholds and the consistent effects on free-moving rats strongly indicate the reliability of the system in more natural and real-world environments. The effective performance of the fully implanted system suggests its applicability to other PNS applications, highlighting the scalability of our approach.

[0119] As explained above, the present invention is intended to regulate electrical stimulation protocols in neuromodulation and aims to solve the problems of conventional techniques that rely on waiting for a desired response after stimulation or on direct responses to stimulation, such as sensory perception or motor reflexes. In other words, unlike conventional techniques that suffer from the problem of being time-consuming in cases where a response appears only after a certain period of stimulation, or in cases of motor reflexes where there is no certainty that the electrical stimulation will go beyond the reflex to induce the desired neuromodulation effect, this invention examines the degree of electrical stimulation actually applied to the tibial nerve and the nervous system connected to it through evoked complex potentials, identifies the appropriate range for electrical stimulation application, and proceeds with regulation.

[0120] As a result, in the case of tibial nerve stimulation, the new method shows a higher neuromodulation effect compared to the conventional method of modulation through motor reflexes, and for example, in a stimulation system for the treatment of overactive bladder (OAB), appropriate stimulation intensity and therapeutic effect can be monitored by receiving feedback on peripheral nerve stimulation based on evoked complex potentials.

[0121] The present invention also provides a control method using the system described above.

[0122] FIG. 11 is a step diagram illustrating an ECAP-based control method according to an embodiment of the present invention.

[0123] Referring to FIG. 11, a peripheral nerve stimulation control method according to one embodiment of the present invention comprises: a step of electrically stimulating a peripheral nerve through an electrode or the like; a step of measuring an evoked compound action potential (ECAP) from the peripheral nerve that occurs after the electrical stimulation; a step of receiving feedback on the measured evoked compound action potential (ECAP) and determining a threshold value of the evoked compound action potential (ECAP); and a step of determining a stimulation intensity that stimulates the peripheral nerve according to the threshold value.

[0124] In particular, in one embodiment of the present invention, the step of determining the threshold value of the evoked compound action potential (ECAP) is to integrate the measured evoked compound action potential (ECAP), and the threshold value is the point where the second derivative of the integrated evoked compound action potential (ECAP) value exceeds twice the previous result value and shows a significant increase.

[0125] As explained above, unlike the prior art which has the problem that it cannot be assured that electrical stimulation induces a desired neuromodulation effect beyond motor reflexes, the present invention can optimize stimulation parameters by using ECAP as quantitative neural feedback.

[0126] The present invention relates to a peripheral nerve stimulation control system and method, and is recognized as having industrial applicability.

Claims

1. As a peripheral nerve stimulation control system, An implantable device for electrically stimulating a peripheral nerve and measuring an evoked compound action potential (ECAP) from the peripheral nerve; A control unit that receives feedback on the evoked compound action potential (ECAP) measured after stimulating the peripheral nerve and determines a threshold value of the evoked compound action potential (ECAP); and A peripheral nerve stimulation control system comprising a stimulation determining unit that determines the stimulation intensity for stimulating the peripheral nerve according to the above threshold value.

2. In Paragraph 1, The above peripheral nerve stimulation system is a peripheral nerve stimulation control system characterized by being implantable in vivo.

3. In Paragraph 1, The peripheral nerve stimulation system described above is a peripheral nerve stimulation control system characterized by further including a wireless charging unit for wirelessly supplying power to the device.

4. In Paragraph 1, A peripheral nerve stimulation control system characterized by the above-mentioned control unit integrating the measured evoked compound action potential (ECAP) value.

5. In Paragraph 4, A peripheral nerve stimulation control system characterized by the above-described control unit determining the point at which the second derivative of the integrated evoked compound action potential (ECAP) value shows a significant increase exceeding twice the previous result value as the threshold value.

6. In any one of paragraphs 1 through 5, A peripheral nerve stimulation control system characterized in that the above peripheral nerve is a transcutaneous tibial nerve.

7. A peripheral nerve stimulation control system for treating an overactive bladder (OAB) comprising a peripheral nerve stimulation system according to claim 6.

8. As a method for controlling peripheral nerve stimulation, Step of electrically stimulating peripheral nerves; A step of measuring an evoked compound action potential (ECAP) from the peripheral nerve; A step of determining a threshold value of the evoked compound action potential (ECAP) by receiving feedback of the measured evoked compound action potential (ECAP); and A peripheral nerve stimulation control method comprising the step of determining the stimulation intensity for stimulating the peripheral nerve according to the above threshold value.

9. In Paragraph 8, The step of determining the threshold value of the above-mentioned evoked compound action potential (ECAP) comprises integrating the measured evoked compound action potential (ECAP), and A peripheral nerve stimulation control method characterized by the fact that the threshold value is the point where the second derivative of the integrated evoked compound action potential (ECAP) value exceeds twice the previous result value and shows a significant increase.

10. In Paragraph 9, A method for controlling peripheral nerve stimulation characterized in that the above-mentioned peripheral nerve is a transcutaneous tibial nerve.

11. In Paragraph 9, A peripheral nerve stimulation control method characterized in that the above-determined stimulation intensity is an electrical stimulation intensity that stimulates the peripheral nerve at the point where the above-determined threshold is determined.

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