Implantable closed-loop neurostimulation system and its charge energy management method

Abstract

This application provides an implantable closed-loop neurostimulation system and its charge energy management method. The charge energy management method includes: determining the electrostatic energy stored on the electrode-tissue interface based on the net charge amount at the electrode-tissue interface and the current double-layer capacitance; determining a safe energy threshold based on the current double-layer capacitance, the current temperature, and the impedance value of the adjacent tissue surrounding the electrode; determining a compensation charge amount when the electrostatic energy exceeds the safe energy threshold; and applying a compensation charge to the electrode within a safe time period determined based on the compensation charge amount and patient physiological signals.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to an implantable closed-loop neurostimulation system and its charge energy management method. Background Technology

[0002] Implantable closed-loop neurostimulation systems apply electrical pulses to specific neural nuclei via intracranial electrodes to modulate abnormal neural activity. To ensure long-term safe operation, implantable closed-loop neurostimulation systems must strictly adhere to the charge balance principle: that is, within any given time window, the net charge at the electrode-tissue interface should approach zero to avoid irreversible electrochemical reactions at the electrode-tissue interface (such as water electrolysis, metal corrosion, drastic pH changes, etc.), thereby preventing tissue damage or electrode failure.

[0003] In existing technologies, symmetrical bidirectional pulses (such as a cathode phase followed immediately by an equal amount of anode phase) are typically used to achieve charge balance in a single stimulation. However, in closed-loop systems, stimulation parameters (frequency, amplitude, pulse width) are dynamically adjusted based on the patient's physiological signals (such as epileptic premonitory signals), causing changes in the net charge accumulation rate. Compensation strategies using fixed waveforms are difficult to accurately match the actual charge imbalance, easily leading to problems such as undercompensation or overcompensation.

[0004] Therefore, there is an urgent need for an implantable closed-loop neurostimulation system that can adaptively adjust charge energy based on the state of the electrode-tissue interface. Summary of the Invention

[0005] This application addresses the shortcomings of existing methods by proposing an implantable closed-loop neurostimulation system and its charge energy management method, aiming to solve the problem that the charge balance strategy of existing implantable systems cannot adaptively adjust charge energy based on the state of the electrode-tissue interface.

[0006] In a first aspect, embodiments of this application provide an implantable closed-loop neurostimulation system, comprising:

[0007] Electrodes implanted in the brain;

[0008] The signal output circuit is used to output compensation charge, and to output stimulation current during each stimulation pulse output and test current during stimulation intervals.

[0009] A current acquisition module is used to acquire the stimulation current;

[0010] A voltage measurement module is used to measure the response voltage on the electrode during the stimulation interval;

[0011] A temperature sensor, integrated in the region adjacent to the electrode, is used to measure the current temperature of the electrode-tissue interface;

[0012] An impedance calculation module is used to calculate the impedance value of the tissue adjacent to the electrode based on the test current and the response voltage during the stimulation interval.

[0013] The controller is used to perform the following operations:

[0014] Based on the stimulation current, the net charge at the electrode-tissue interface is obtained;

[0015] The current double-layer capacitance is determined based on the aging factor of the electrode, the current temperature, and the historical accumulated charge.

[0016] Based on the net charge and the current double-layer capacitance, determine the electrostatic energy stored at the electrode-tissue interface;

[0017] The safe energy threshold is determined based on the current double-layer capacitance, the current temperature, and the impedance value output by the impedance calculation module.

[0018] When the electrostatic energy exceeds the safe energy threshold, a compensation charge is determined so that the compensated electrostatic energy does not exceed the target energy threshold, where the target energy threshold is a preset proportion of the safe energy threshold.

[0019] Based on the amount of compensation charge, within a safe time period determined based on the patient's physiological signals, the signal output circuit is controlled to apply compensation charge to the electrode.

[0020] In a second aspect, embodiments of this application provide a charge energy management method, wherein the charge energy management method is performed by an implantable closed-loop neurostimulation system as described in the first aspect, the implantable closed-loop neurostimulation system comprising electrodes implanted in the cranium, and the method comprising:

[0021] The electrostatic energy stored on the electrode-tissue interface is determined based on the net charge at the electrode-tissue interface and the current double-layer capacitance, wherein the current double-layer capacitance is determined based on the aging factor of the electrode, the current temperature of the electrode-tissue interface, and the historical accumulated charge.

[0022] The safe energy threshold is determined based on the current double-layer capacitance, the current temperature, and the impedance value of the adjacent tissue around the electrode.

[0023] When the electrostatic energy exceeds the safe energy threshold, a compensation charge is determined so that the compensated electrostatic energy does not exceed the target energy threshold, where the target energy threshold is a preset proportion of the safe energy threshold.

[0024] Based on the amount of compensation charge, a compensation charge is applied to the electrode within a safe time period determined based on the patient's physiological signals.

[0025] Thirdly, embodiments of this application also disclose a signal processing system, including the implantable closed-loop neurostimulation system as described in the second aspect.

[0026] Fourthly, embodiments of this application also disclose a computer-readable storage medium storing a computer program that, when executed by a processor, implements one or more of the charge energy management methods described in the embodiments of the first aspect of this application.

[0027] Fifthly, embodiments of this application also disclose a computer program product, including a computer program that, when executed by a processor, implements one or more charge energy management methods as described in the embodiments of the first aspect of this application.

[0028] The beneficial technical effects of the technical solutions provided in this application include:

[0029] The solution in this application utilizes the net charge at the electrode-tissue interface and the current double-layer capacitance to calculate the electrostatic energy stored at the electrode-tissue interface in real time. It then dynamically adjusts the current double-layer capacitance based on aging factors, temperature, and impedance values. This allows for early prediction of electrochemical instability risks and triggers safety warnings, thus avoiding delays in fault warnings. Furthermore, by adaptively determining the safe energy threshold based on the current double-layer capacitance, electrode-tissue interface temperature, and the impedance of the tissue adjacent to the electrode, safety and robustness are significantly improved.

[0030] In addition, in other embodiments, charge compensation is implemented by using an asymmetric bidirectional pulse with an adjustable positive-to-negative amplitude ratio, and the positive-to-negative amplitude ratio can be dynamically optimized according to the net charge accumulation rate, thereby avoiding compensation overshoot, improving charge neutralization efficiency, and shortening compensation time.

[0031] Additional aspects and advantages of this application will be set forth in part in the description which follows, and will become apparent from the description or may be learned by practice of this application. Attached Figure Description

[0032] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the following description of the embodiments taken in conjunction with the accompanying drawings, wherein:

[0033] Figure 1 This is a flowchart illustrating a charge energy management method for an implantable closed-loop neurostimulation system.

[0034] Figure 2 This is a schematic diagram of the structure of an implantable closed-loop neurostimulation system provided in an embodiment of this application;

[0035] Figure 3This is a schematic diagram of the signal processing system provided in an embodiment of this application. Detailed Implementation

[0036] The embodiments of this application are described below with reference to the accompanying drawings. It should be understood that the embodiments described below with reference to the accompanying drawings are exemplary descriptions for explaining the technical solutions of the embodiments of this application, and do not constitute a limitation on the technical solutions of the embodiments of this application.

[0037] Those skilled in the art will understand that, unless specifically stated otherwise, the terms "described" and "the" as used herein may also include plural forms. It should be further understood that the term "comprising" as used in this application's specification means the presence of the stated features, integers, steps, operations, elements, and / or components, but does not exclude implementations of other features, information, data, steps, operations, elements, components, and / or combinations thereof supported by this art. It should be understood that when we say an element is "connected" or "coupled" to another element, the element may be directly connected or coupled to the other element, or it may mean that the element and the other element are connected through an intermediate element. Furthermore, "connected" or "coupled" as used herein may include wireless connections or wireless coupling. The term "and / or" as used herein refers to at least one of the items defined by the term; for example, "A and / or B" may be implemented as "A," or as "B," or as "A and B."

[0038] To make the objectives, technical solutions, and advantages of this application clearer, the embodiments of this application will be described in further detail below with reference to the accompanying drawings.

[0039] In existing technologies, symmetrical bidirectional pulses (such as a cathode phase followed immediately by an equal amount of anode phase) are typically used to achieve charge balance in a single stimulation. However, in a closed-loop system, stimulation parameters (frequency, amplitude, pulse width) are dynamically adjusted based on the patient's physiological signals (such as pre-epileptic aura), causing changes in the net charge accumulation rate. Using a fixed waveform compensation strategy makes it difficult to accurately match the actual charge imbalance, easily leading to the following problems:

[0040] 1. Insufficient compensation: The continuous accumulation of residual net charge causes the interface voltage to drift outside the water window;

[0041] 2. Overcompensation: Introducing a reverse net charge also poses a safety hazard;

[0042] 3. Ignoring interface state changes: The impact of electrode aging, temperature fluctuations, or changes in tissue impedance on the safety boundary is not considered, resulting in rigid energy threshold settings.

[0043] Furthermore, traditional methods often rely on current integration to determine charge balance, but they fail to reflect the true energy state of the electrode-tissue interface. In fact, even with zero net charge, if the double-layer capacitance decreases significantly due to aging, the electrostatic energy corresponding to the same charge will be significantly higher. It may still exceed the safety limit and cause potential breakdown.

[0044] Therefore, this application proposes an implantable closed-loop neurostimulation system capable of adaptively adjusting charge energy based on the electrode-tissue interface state. It aims to solve the following technical problems:

[0045] 1. Existing charge balance strategies cannot dynamically adjust the compensation amount according to the net charge accumulation rate, resulting in insufficient or over-compensation and a lack of adaptability;

[0046] 2. Existing charge balance strategies do not dynamically set energy safety thresholds in conjunction with real-time parameters such as electrode aging, temperature changes, and tissue impedance.

[0047] 3. Existing charge balance strategies rely solely on current or voltage thresholds, which cannot predict the potential energy overrun risk caused by capacitor degradation in advance, resulting in delayed fault warnings.

[0048] 4. Using a fixed symmetrical pulse as the compensation waveform cannot achieve precise charge neutralization, which is not only inefficient, but also increases interface disturbance and energy consumption.

[0049] The technical solution of this application and how it solves the above-mentioned technical problems are described in detail below with specific embodiments. It should be noted that the following embodiments can be referenced, borrowed, or combined with each other, and the same terms, similar features, and similar implementation steps in different embodiments will not be described again.

[0050] The implantable closed-loop neurostimulation system and its charge energy management method proposed in this application will be described in detail below with reference to the accompanying drawings.

[0051] In some embodiments, a method for charge energy management of an implantable closed-loop neurostimulation system is provided. The implantable closed-loop neurostimulation system includes electrodes implanted intracranially, and the method is performed by the implantable closed-loop neurostimulation system. Figure 1 As shown, the method includes:

[0052] S1. Determine the electrostatic energy stored at the electrode-tissue interface based on the net charge at the electrode-tissue interface and the current double-layer capacitance.

[0053] In some embodiments, the electrostatic energy stored at the electrode-tissue interface can be calculated using the following formula:

[0054] ,

[0055] in, Q net Net charge C dl (t) represents the current double-layer capacitance.

[0056] Optionally, the net charge is obtained by time integration of the stimulation current during each stimulation pulse output.

[0057] In some embodiments, net charge Q net It can be calculated using the following formula:

[0058] Q net = ,

[0059] in, j (n) is the nth n The current value at each sampling point, Δ t This is the sampling interval. Optionally, the sampling frequency is... f s Sampling interval Δ t =1 / f s Acquired during a single stimulation pulse N A current value.

[0060] Optionally, the current double-layer capacitance is determined based on the electrode aging factor, the current temperature of the electrode-tissue interface, and the historical accumulated charge.

[0061] In some embodiments, the current double-layer capacitance C dl (t) can be calculated using the following formula:

[0062] ,

[0063] in, C 0 represents the initial capacitance. f ( t ) represents the aging factor of the electrode. f ( T ) is a compensation factor for the current temperature of the electrode-tissue interface. f ( U ) is a factor related to the historical cumulative charge.

[0064] Optional, electrode aging factor .in, t This represents the cumulative operating time since electrode implantation. βThis is the aging rate coefficient, used to characterize the long-term stability of electrode materials. f ( t It is used to characterize the rate of decay of the double-layer capacitance of the electrode material over time. f ( t () is greater than 0 and less than 1.

[0065] Optional, compensation factor for the current temperature of the electrode-tissue interface. .in, T This represents the current temperature of the electrode-tissue interface. T 0 represents the reference body temperature, for example: 37℃. γ This is the temperature sensitivity coefficient, used to characterize the linear proportionality of capacitance changes with temperature. f ( T It is used to correct the effect of interface temperature on double-layer capacitance. f ( T () Greater than or equal to 0.95 and less than or equal to 1.1.

[0066] Optional, correlation factor for historical cumulative charge .in, Q This refers to the historical cumulative charge injection amount (total charge, not net charge). α A sensitivity coefficient is used to characterize the degree of capacitance decay caused by a unit of accumulated charge. f ( U This is used to reflect the degradation of interface properties caused by cumulative charge injection. f ( U () is greater than 0 and less than or equal to 1.

[0067] S2. Determine the safe energy threshold based on the current double-layer capacitance, current temperature, and impedance value of the adjacent tissue around the electrode.

[0068] Optionally, the impedance value is obtained by applying a test current to the electrode during the stimulation interval and measuring the response voltage. The impedance value can characterize the electrical properties of the microenvironment surrounding the electrode.

[0069] In some embodiments, the test current can be a weak AC test current. Optionally, the magnitude of the weak AC test current can be 1~10 µA peak-to-peak value, preferably 5 µA peak-to-peak value, to ensure that the applied charge density is below the neuron's electrical activation threshold, thereby achieving perturbation-free impedance monitoring.

[0070] Optional, impedance value .in, j The amplitude of the test current applied to the electrodes during the stimulation interval. v The steady-state response voltage at the electrode-tissue interface during the application of the test current is measured.

[0071] Optionally, the current temperature is measured by a temperature sensor integrated into the region adjacent to the electrodes.

[0072] Optionally, the tissue adjacent to the electrode can be understood as the biological tissue region that is in direct contact with the electrode.

[0073] In some embodiments, the safe energy threshold can be calculated using the following formula:

[0074] ,

[0075] in, E 0 represents electrostatic energy. g ( C dl ) is the capacitance-related factor. h ( T ) represents a temperature-related factor. f For tissue health factors.

[0076] Optional, capacitance correlation factor g ( C dl It can be calculated using the following formula:

[0077] ,

[0078] in, C dl (t) represents the current double-layer capacitance. C 0 represents the initial capacitance.

[0079] Optional, temperature-related factor h ( T It can be calculated using the following formula:

[0080] ,

[0081] in, T (t) represents the current temperature of the electrode-tissue interface. T 0 represents the reference body temperature, for example: 37℃.

[0082] Optional, tissue health factors Where Z(t) is the impedance value of the adjacent tissue around the electrode, and Z0 is the reference impedance.

[0083] S3. When the electrostatic energy exceeds the safe energy threshold, determine the amount of compensation charge so that the compensated electrostatic energy does not exceed the target energy threshold.

[0084] In some embodiments, the electrostatic energy can be compared with a safe energy threshold to determine whether the electrostatic energy exceeds the safe energy threshold. If the electrostatic energy exceeds the safe energy threshold, a compensation charge is further determined and charge compensation is performed to ensure that the compensated electrostatic energy is within the safe energy range.

[0085] Optionally, the target energy threshold is a preset proportion of the safe energy threshold. That is, in this embodiment of the application, the net charge at the electrode-tissue interface is adjusted by applying a compensating charge, thereby reducing (or increasing) the electrostatic energy stored at the electrode-tissue interface, so that the stored electrostatic energy does not exceed a preset proportion (i.e., the safe upper limit) of the current safe energy threshold, for example, not exceeding 80% of the current safe energy threshold.

[0086] In some embodiments, determining the amount of compensation charge includes: determining the amount of compensation charge based on the difference between the target amount of charge and the net amount of charge.

[0087] Optionally, if the difference between the target charge and the net charge is greater than zero, a negative compensation charge is applied; otherwise, a positive compensation charge is applied.

[0088] Optionally, the target charge can be calculated using the following formula:

[0089] ,

[0090] in, Q net Net charge E target The target energy threshold, C dl (t) represents the current double-layer capacitance.

[0091] S4. Based on the amount of compensating charge, apply compensating charge to the electrodes within a safe time period determined based on the patient's physiological signals.

[0092] In some embodiments, a compensating charge can be applied to the electrodes using an asymmetric bidirectional pulse waveform.

[0093] Optionally, the positive and negative amplitude ratio of the asymmetric bidirectional pulse waveform is dynamically adjusted according to the accumulation rate of net charge. It should be understood that, in the scheme of this application embodiment, adjusting the positive and negative amplitudes can improve charge neutralization efficiency, shorten compensation time, and reduce the risk of secondary stimulation.

[0094] Optional, positive and negative amplitude ratio Dynamic adjustments are made based on the following formula:

[0095] ,

[0096] Where λ is an empirical coefficient. This represents the rate of accumulation of net charge.

[0097] It should be understood that if A value greater than 0 indicates that the accumulation of the positive phase (anodic phase) is dominant. ρ If the value is greater than 1, a negative phase (cathode phase) needs to be added to accelerate neutralization. Otherwise, a positive phase needs to be added.

[0098] In some embodiments, the safe time period is a time period determined by any of the following methods:

[0099] When the electrode acquires a local field potential signal with a signal-to-noise ratio higher than a preset threshold, the time period in which the phase angle of the periodic oscillation in the 4-8 Hz frequency band of the local field potential is between π and 2π is selected.

[0100] When the signal-to-noise ratio of the local field potential signal is lower than the preset threshold, the second third of the diastolic phase of the ECG cycle is selected.

[0101] In some embodiments, the above method may further include updating the safe energy threshold under any of the following conditions:

[0102] After the application of one electrical stimulation pulse is completed;

[0103] After the operation of applying the compensating charge is completed;

[0104] When a temperature change at the electrode-tissue interface exceeding a preset threshold is detected;

[0105] After obtaining the new impedance value;

[0106] When the preset cycle is reached.

[0107] Optionally, the safety energy threshold can be updated after an electrical stimulation pulse is applied, or after a compensation charge is applied. Since the safety energy threshold is related to the double-layer capacitance, and each application of an electrical stimulation pulse or compensation charge to the electrode causes a change in the double-layer capacitance, updating the safety energy threshold after each application of an electrical stimulation pulse or compensation charge ensures its accuracy.

[0108] Optionally, the safety energy threshold can be updated when a temperature change at the electrode-tissue interface is detected to exceed a preset threshold. Since the safety energy threshold is related to the temperature of the electrode-tissue interface, updating the safety energy threshold when a temperature change at the electrode-tissue interface is detected to exceed the preset threshold ensures the accuracy of the safety energy threshold.

[0109] Optionally, the safe energy threshold can be updated after a new impedance value is obtained. Since the safe energy threshold is related to the impedance value, it can be updated each time a new impedance value is obtained, thereby ensuring the accuracy of the safe energy threshold.

[0110] Optionally, the safe energy threshold can be updated when a preset period is reached. That is, the safe energy threshold can be updated periodically based on a preset period. For example, the preset period could be 12 hours, 24 hours, a week, etc., but is not limited to these. For instance, the safe energy threshold can be updated every 12 hours.

[0111] In some embodiments, the above method may further include:

[0112] After applying a compensating charge to the electrode and delaying for at least a first time period, it is determined whether the electrode has experienced a sudden failure based on the impedance deviation or energy residual.

[0113] Optionally, the duration of the first time period can range from 5 ms to 200 ms. The specific value depends on the electrode material, tissue type, etc., but is not limited to this.

[0114] Optionally, the impedance deviation is the deviation between the current impedance value of the adjacent tissue and the historical baseline value. The historical baseline value is the moving average of the impedance values ​​measured over the past M effective measurement periods. An effective measurement period can be understood as a compensation operation period that meets preset conditions. These preset conditions may include: the standard deviation of the measured impedance value is lower than a preset value (to exclude motion artifacts or circuit interference), and the corresponding energy residual does not exceed a preset range (to avoid fault data affecting the historical baseline value).

[0115] For example, if 20 compensation operations were performed in the past 24 hours, and 3 of them were marked as "invalid" due to impedance measurement jumps caused by violent head shaking of the patient, then the "valid measurement period" is 17. If M=10 is set, then the impedance values ​​of the most recent 10 valid periods are used to calculate the moving average.

[0116] In some embodiments, time can be calculated using the following formula. k Moving average:

[0117] ,

[0118] in, Z i It is the first i The impedance value measured this time.

[0119] It should be understood that with each new measurement, the measurement cycle "slides" forward once, discarding the oldest measurement value and adding the latest one. For example, assuming M=5, the impedance values ​​(in Ω) of the most recent 6 measurements are: [980, 1010, 990, 1005, 1020, 1500]. Then, the moving average of the 5th measurement (the previous 5 measurements) is: (980+1010+990+1005+1020) / 5 = 1001Ω, and the moving average of the 6th measurement (the last 5 measurements) is: (1010+990+1005+1020+1500) / 5 = 1105Ω. Because the 6th measurement shows an abnormally high value (1500 Ω), the moving average increases significantly, thus triggering an "impedance surge" alarm.

[0120] In other words, the current impedance value of the adjacent tissue can be measured after a delay of at least the first time period (e.g., 10 ms) following the application of the compensating charge. This is because after applying a charge to the electrode, the electrode-tissue interface temporarily exhibits high impedance (due to ion depletion). Immediately performing impedance measurement could easily lead to a misjudgment due to a "sudden impedance change." Therefore, after applying the compensating charge, it is necessary to wait at least 10 ms until the interface voltage stabilizes before performing impedance measurement to ensure the accuracy of fault diagnosis.

[0121] Optionally, the energy residual is the difference between the calculated first compensation energy and the actually measured second compensation energy. The first compensation energy is calculated based on the net charge before compensation, the net charge after compensation, and the current double-layer capacitance. The second compensation energy is obtained by integrating the voltage and current at the electrode-tissue interface, which are measured during the compensation period.

[0122] In other words, the calculation of the energy residual can be initiated at least a short time interval (e.g., 10 ms) after the application of the compensation charge. This is because after applying a charge to the electrode, there is a millisecond-level electrochemical relaxation process at the electrode-tissue interface. Immediate energy measurement would include unsteady-state responses, leading to residual distortion. Therefore, after applying the compensation charge, it is necessary to wait at least 10 ms until the interface voltage stabilizes before performing the energy residual calculation to ensure the accuracy of fault diagnosis.

[0123] Optionally, the first compensation energy can be calculated using the following formula:

[0124] ,

[0125] in, C dl For the current electric double-layer capacitance, Q after Q is the cumulative net charge after applying compensation charge. before This represents the cumulative net charge before the application of compensating charge.

[0126] Optionally, the second compensation energy can be calculated using the following formula:

[0127] E 2= ,

[0128] in, v ( t () represents the instantaneous voltage at the electrode-tissue interface during the compensation period. j ( t t0 represents the instantaneous current flowing through the electrode during the compensation period, t0 represents the start time of the compensation, and t1 represents the end time of the compensation.

[0129] In some embodiments, determining whether an electrode has experienced a sudden failure based on impedance deviation or energy residual includes:

[0130] A sudden electrode failure is determined to occur under any of the following conditions:

[0131] The energy residual exceeds a first threshold, and this energy residual shows an increasing trend in consecutive compensation operations; or,

[0132] The impedance deviation exceeded the second threshold during the second time period.

[0133] Optionally, if the energy residual exceeds the first threshold multiple times consecutively and the energy residual shows an upward trend, then it is determined that the electrode has experienced a sudden failure.

[0134] Optionally, the impedance deviation is the relative change of the current impedance value compared to a historical reference value. Optionally, the impedance deviation can be expressed as a percentage (%). For example, if the historical reference value is 1000 Ω, and the current impedance value is 1010 Ω, then the impedance deviation is +1%. Or, if the current impedance value is 995 Ω, then the impedance deviation is -0.5%.

[0135] Optionally, impedance deviation exceeding the second threshold within the second time period can be understood as impedance deviation decreasing or increasing beyond the second threshold within the second time period. For example, if the second threshold is 30%, and the current impedance value (e.g., 650 Ω) decreases by 35% compared to the historical reference value (e.g., 1000 Ω) within 24 hours, then the second threshold is exceeded, and in this case, a sudden electrode failure can be determined.

[0136] In some embodiments, the above method may further include:

[0137] When a sudden electrode failure is detected, a fault alarm or safety protection mechanism is triggered.

[0138] Optionally, if the energy residual exceeds a first threshold (e.g., 5 × 10⁻⁶), -8J), and shows an increasing trend for N consecutive times (e.g., N=3) (e.g., the energy residuals for the 3 times are 6.2×10). -8 J, 7.5 × 10 -8 J, 9.0×10 -8 If the impedance deviation exceeds 30% within 24 hours, it is determined that the electrode has experienced a sudden failure, and a fault alarm or safety protection mechanism needs to be triggered; otherwise, it is determined that the electrode is undergoing normal aging, and no alarm needs to be triggered.

[0139] In summary, the embodiments of this application provide a method for adaptively adjusting charge energy based on the state of the electrode-tissue interface, which can achieve the following technical effects:

[0140] 1. By utilizing the net charge at the electrode-tissue interface and the current double-layer capacitance, the electrostatic energy stored at the electrode-tissue interface is calculated in real time. Combined with aging factors, temperature, and impedance, the current double-layer capacitance is dynamically adjusted to predict electrochemical instability risks in advance, trigger safety warnings, and avoid the lag in fault warnings.

[0141] 2. By comprehensively considering the current double-layer capacitance (reflecting the material state), the electrode-tissue interface temperature (affecting electrochemical properties), and the impedance value of the tissue adjacent to the electrode (reflecting the stability of the biological environment), the safe energy threshold can be adaptively determined, which can significantly improve safety and robustness.

[0142] 3. Within a safe time period allowed by physiological signals (such as during non-ictal periods), charge compensation is implemented using an asymmetric bidirectional pulse with an adjustable positive-to-negative amplitude ratio. The positive-to-negative amplitude ratio can be dynamically optimized according to the net charge accumulation rate, thereby avoiding compensation overshoot and reducing additional stimulation interference to nerve tissue.

[0143] Based on the same inventive concept, embodiments of this application provide an implantable closed-loop neurostimulation system, such as... Figure 2 As shown, the implantable closed-loop neurostimulation system 10 includes: an electrode 11 implanted in the cranium, a signal output circuit 12, a current acquisition module 13, a voltage measurement module 14, a temperature sensor 15, an impedance calculation module 16, and a controller 17. The signal output circuit 12 and the voltage measurement module 14 are respectively connected to the electrode 11. The signal output circuit 12 is also connected to the current acquisition module 13 and the controller 17. The current acquisition module 13 is also connected to the impedance calculation module 16 and the controller 17. The voltage measurement module 14 is also connected to the impedance calculation module 16, and the impedance calculation module 16 is also connected to the controller 17. The temperature sensor 15 is connected to the input terminal of the controller 17.

[0144] In some embodiments, the signal output circuit 12 is configured to output a compensation charge, and to output a stimulation current during each stimulation pulse output and a test current during the stimulation interval. A current acquisition module 13 is used to acquire the stimulation current. A voltage measurement module 14 is used to measure the response voltage on the electrode during the stimulation interval. A temperature sensor 15 is integrated in the region adjacent to the electrode for measuring the current temperature at the electrode-tissue interface. An impedance calculation module 16 is used to calculate the impedance value of the tissue adjacent to the electrode based on the test current applied by the signal output circuit during the stimulation interval and the response voltage measured by the voltage measurement module.

[0145] Controller 17 is configured to perform the following operations:

[0146] The net charge at the electrode-tissue interface is obtained by integrating the stimulation current output by the signal output circuit 12 over time.

[0147] The current double-layer capacitance is calculated based on the aging factor of the electrode, the current temperature output by the temperature sensor 15, and the historical accumulated charge.

[0148] Calculate the electrostatic energy stored at the electrode-tissue interface based on the net charge and the current electric double layer capacitance.

[0149] The safe energy threshold is determined based on the current double-layer capacitance, the current temperature, and the impedance value output by the impedance calculation module 16.

[0150] When the electrostatic energy exceeds the safe energy threshold, the amount of compensation charge is determined so that the compensated electrostatic energy does not exceed the target energy threshold, which is a preset ratio of the safe energy threshold.

[0151] Based on the amount of compensating charge, within a safe time period determined based on the patient's physiological signals, the control signal output circuit 12 applies compensating charge to the electrodes.

[0152] In some embodiments, when the controller 17 controls the signal output circuit 12 to apply compensation charge to the electrode, it specifically uses the control signal output circuit 12 to apply compensation charge to the electrode through an asymmetrical bidirectional pulse waveform.

[0153] Optionally, the positive and negative amplitude ratio of the asymmetric bidirectional pulse waveform can be dynamically adjusted according to the accumulation rate of net charge.

[0154] In some embodiments, the controller 17 is further configured to: update the safe energy threshold under any of the following conditions:

[0155] After the application of one electrical stimulation pulse is completed;

[0156] After the operation of applying the compensating charge is completed;

[0157] When a temperature change at the electrode-tissue interface exceeding a preset threshold is detected;

[0158] After obtaining the new impedance value;

[0159] When the preset cycle is reached.

[0160] In some embodiments, the controller 17 is further configured to: determine whether a sudden failure has occurred in the electrode based on impedance deviation or energy residual, after a delay of at least a first time period following the application of a compensation charge to the electrode.

[0161] Optionally, the impedance deviation is the deviation between the current impedance value of the adjacent tissue and a historical reference value.

[0162] Optionally, the energy residual is the difference between the calculated first compensation energy and the actually measured second compensation energy.

[0163] Optionally, the first compensation energy is calculated based on the net charge before compensation, the net charge after compensation, and the current double-layer capacitance.

[0164] Optionally, the second compensation energy is obtained by integrating the voltage and current at the electrode-tissue interface, which are measured during the compensation period.

[0165] In some embodiments, when the controller 17 determines whether an electrode has experienced a sudden failure based on impedance deviation or energy residual, it is specifically configured to: determine that an electrode has experienced a sudden failure in any of the following situations:

[0166] The energy residual exceeds the first threshold, and the energy residual shows an increasing trend in consecutive compensation operations; or,

[0167] The impedance deviation exceeded the second threshold during the second time period.

[0168] In some embodiments, the controller 17 is further configured to: trigger a fault alarm or safety protection mechanism when it is determined that a sudden failure has occurred in the electrode.

[0169] In some embodiments, the safe time period is a time period determined by any of the following methods:

[0170] When the electrode acquires a local field potential signal with a signal-to-noise ratio higher than a preset threshold, the time period in which the phase angle of the periodic oscillation in the 4-8 Hz frequency band of the local field potential is between π and 2π is selected.

[0171] When the signal-to-noise ratio of the local field potential signal is lower than the preset threshold, the second third of the diastolic phase of the ECG cycle is selected.

[0172] The implantable closed-loop neurostimulation system provided in this application embodiment can achieve the above-mentioned... Figure 1The various processes implemented in the method embodiments shown will not be described again here to avoid repetition.

[0173] The implantable closed-loop neurostimulation system provided in this application calculates the electrostatic energy stored at the electrode-tissue interface in real time by utilizing the net charge and current double-layer capacitance at the electrode-tissue interface. It then dynamically adjusts the current double-layer capacitance in conjunction with aging factors, temperature, and impedance, thereby enabling early prediction of electrochemical instability risks and triggering safety warnings, thus avoiding delays in fault warnings. Simultaneously, based on the current double-layer capacitance, electrode-tissue interface temperature, and impedance of the tissue adjacent to the electrode, it adaptively determines the safe energy threshold, significantly improving safety and robustness. Furthermore, by employing asymmetric bidirectional pulses with an adjustable positive-to-negative amplitude ratio for charge compensation, and with this ratio dynamically optimized according to the net charge accumulation rate, it avoids compensation overshoot, improves charge neutralization efficiency, and shortens compensation time.

[0174] The implantable closed-loop neurostimulation system of this application embodiment can execute the charge energy management method provided in the embodiments of this application. The implementation principle is similar. The actions performed by each module and unit in the implantable closed-loop neurostimulation system in each embodiment of this application correspond to the steps in the charge energy management method in each embodiment of this application. For detailed functional descriptions of each module of the implantable closed-loop neurostimulation system, please refer to the descriptions in the corresponding charge energy management methods shown above. They will not be repeated here.

[0175] Based on the same principles as the methods shown in the embodiments of this application, the embodiments of this application also provide a signal processing system, which includes the implantable closed-loop neurostimulation system provided in the above embodiments.

[0176] In an alternative embodiment, a signal processing system, such as Figure 3 As shown, Figure 3 The signal processing system 20 shown includes a processor 21 and a memory 23. The processor 21 is communicatively connected to the memory 23, for example, via a bus 22.

[0177] Processor 21 may be a CPU (Central Processing Unit), general-purpose processor, DSP (Digital Signal Processor), ASIC (Application Specific Integrated Circuit), FPGA (Field-Programmable Gate Array), or other programmable logic device, transistor logic device, hardware component, or any combination thereof, including the chip or implantable closed-loop neurostimulation system described in any of the above embodiments. It can implement or execute the various exemplary logic blocks, modules, and circuits described in conjunction with the disclosure of this application. Processor 21 may also be a combination that implements computational functions, such as including one or more microprocessor combinations, a combination of DSP and microprocessor, etc.

[0178] Bus 22 may include a pathway for transmitting information between the aforementioned components. Bus 22 may be a PCI (Peripheral Component Interconnect) bus or an EISA (Extended Industry Standard Architecture) bus, etc. Bus 22 may be divided into address bus, data bus, control bus, etc. For ease of representation, Figure 3 The bus is represented by a single thick line, but this does not mean that there is only one bus or one type of bus.

[0179] The memory 23 may be a ROM (Read-Only Memory) or other type of static storage device capable of storing static information and instructions, RAM (Random Access Memory) or other type of dynamic storage device capable of storing information and instructions, or it may be an EEPROM (Electrically Erasable Programmable Read Only Memory), a CD-ROM (Compact Disc Read-Only Memory) or other optical disc storage, optical disc storage (including compressed optical discs, laser discs, optical discs, digital universal optical discs, Blu-ray discs, etc.), magnetic disk storage media or other magnetic storage devices, or any other medium capable of carrying or storing desired program code in the form of instructions or data structures and accessible by a computer, but not limited thereto.

[0180] The memory 23 is used to store computer programs that execute the embodiments of this application, and the execution is controlled by the processor 21. The processor 21 is used to execute the computer programs stored in the memory 23 to implement the steps shown in the foregoing method embodiments.

[0181] This application provides a computer-readable storage medium storing a computer program. When the computer program is executed by a processor, it can implement the steps and corresponding content of the aforementioned method embodiments.

[0182] This application also provides a computer program product, including a computer program that, when executed by a processor, can implement the steps and corresponding content of the aforementioned method embodiments.

[0183] In the description of this application, the terms "center," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," and "outer," etc., indicate directions or positional relationships based on the exemplary directions or positional relationships shown in the accompanying drawings. They are used to facilitate the description or simplification of the embodiments of this application and are not intended to indicate or imply that the device or component referred to must have a specific orientation or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this application.

[0184] The terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. In the description of this application, unless otherwise stated, "a plurality of" means two or more.

[0185] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "joining" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal communication between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0186] In the description of this specification, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0187] The above description is only a partial implementation of this application. It should be noted that for those skilled in the art, other similar implementation methods based on the technical concept of this application, without departing from the technical concept of this application, also fall within the protection scope of the embodiments of this application.

Claims

1. An implantable closed-loop neurostimulation system, characterized in that, include: Electrodes implanted in the brain; The signal output circuit is used to output compensation charge, and to output stimulation current during each stimulation pulse output and test current during stimulation intervals. A current acquisition module is used to acquire the stimulation current; A voltage measurement module is used to measure the response voltage on the electrode during the stimulation interval; A temperature sensor, integrated in the region adjacent to the electrode, is used to measure the current temperature of the electrode-tissue interface; An impedance calculation module is used to calculate the impedance value of the tissue adjacent to the electrode based on the test current and the response voltage during the stimulation interval. The controller is used to perform the following operations: Based on the stimulation current, the net charge at the electrode-tissue interface is obtained; The current double-layer capacitance is determined based on the aging factor of the electrode, the current temperature, and the historical accumulated charge. Based on the net charge and the current double-layer capacitance, determine the electrostatic energy stored at the electrode-tissue interface; The safe energy threshold is determined based on the current double-layer capacitance, the current temperature, and the impedance value output by the impedance calculation module. When the electrostatic energy exceeds the safe energy threshold, a compensation charge is determined so that the compensated electrostatic energy does not exceed the target energy threshold, where the target energy threshold is a preset proportion of the safe energy threshold. Based on the amount of compensation charge, within a safe time period determined based on the patient's physiological signals, the signal output circuit is controlled to apply compensation charge to the electrode.

2. The implantable closed-loop neurostimulation system according to claim 1, characterized in that, When the controller controls the signal output circuit to apply compensation charge to the electrode, it is specifically used for: The signal output circuit is controlled to apply compensating charge to the electrode through an asymmetrical bidirectional pulse waveform, wherein the positive and negative amplitude ratio of the asymmetrical bidirectional pulse waveform is dynamically adjusted according to the accumulation rate of the net charge.

3. The implantable closed-loop neurostimulation system according to claim 1, characterized in that, The controller is also configured to update the safe energy threshold under any of the following conditions: After the application of one electrical stimulation pulse is completed; After the operation of applying the compensating charge is completed; When the temperature change at the electrode-tissue interface exceeds a preset threshold; After obtaining the new impedance value; When the preset cycle is reached.

4. The implantable closed-loop neurostimulation system according to claim 1, characterized in that, The controller is also used for: After a delay of at least a first time period following the application of the compensation charge to the electrode, it is determined whether the electrode has experienced a sudden failure based on the impedance deviation or energy residual. Wherein, the impedance deviation is the deviation between the current impedance value of the adjacent tissue and the historical reference value; the energy residual is the difference between the calculated first compensation energy and the actually measured second compensation energy; The first compensation energy is calculated based on the net charge before compensation, the net charge after compensation, and the current double-layer capacitance; The second compensation energy is obtained by integrating the voltage and current at the electrode-tissue interface, which are measured during the compensation period.

5. The implantable closed-loop neurostimulation system according to claim 4, characterized in that, When determining whether the electrode has experienced a sudden failure based on impedance deviation or energy residual, the controller is specifically used for: The electrode is determined to have experienced a sudden failure under any of the following circumstances: The energy residual exceeds a first threshold, and the energy residual shows an increasing trend in consecutive compensation operations; or, The impedance deviation exceeds the second threshold during the second time period.

6. The implantable closed-loop neurostimulation system according to claim 5, characterized in that, The controller is also used for: When a sudden failure is detected in the electrode, a fault alarm or safety protection mechanism is triggered.

7. The implantable closed-loop neurostimulation system according to any one of claims 1-6, characterized in that, The safe time period is a time period determined by any of the following methods: When the electrode acquires a local field potential signal with a signal-to-noise ratio higher than a preset threshold, the time period in which the phase angle of the periodic oscillation in the 4-8 Hz frequency band of the local field potential is between π and 2π is selected. When the signal-to-noise ratio of the local field potential signal is lower than the preset threshold, the latter third of the diastolic phase of the electrocardiogram cycle is selected.

8. A signal processing system, characterized in that, Including the implantable closed-loop neurostimulation system as described in any one of claims 1 to 7.

Images