Implantable nerve stimulation system

Abstract

The invention relates to the technical field of medical equipment, in particular to an implantable nerve stimulation system which comprises a controller, the controller is configured to execute closed-loop stimulation output, judge whether a physiological signal accords with a preset state or not according to the physiological signal, set a plurality of preset states according to priority, and set a corresponding closed-loop stimulation rule for each state, and executing a corresponding adaptive stimulation rule according to the confirmed preset state, and executing a motion adaptive stimulation rule if the system is not in any preset state, thereby realizing more accurate and meticulous closed-loop regulation and control.

Description

Technical Field

[0001] The present invention relates to the technical field of medical equipment, and in particular to an implantable neural stimulation system. Background Art

[0002] Deep brain stimulation therapy is an effective means of treating Parkinson's disease, essential tremor, dystonia, obsessive-compulsive disorder and other diseases. This therapy requires sending electrical pulses to specific areas of the brain to control disease symptoms. After implanting the stimulation device, the doctor will program it based on experience and the patient's response to determine a set of fixed parameters for continuous stimulation.

[0003] However, continuous stimulation consumes a lot of power and reduces the service life of non-rechargeable products. On the other hand, when the intensity requirement is low, continuous high-frequency stimulation will affect the normal neural circuits to a certain extent, and have a certain impact on the patient's cognition, behavior, psychology and other aspects. Summary of the invention

[0004] In view of this, the present invention provides an implantable neural stimulation system, including a controller, wherein the controller is configured to perform closed-loop stimulation output, including:

[0005] S11, obtaining physiological signals;

[0006] S12, judging a plurality of preset states with priorities according to the physiological signal;

[0007] S13, if it is determined that the state is in a preset state, adjusting the stimulation output according to the closed-loop stimulation rule corresponding to the state, at least one of the preset states includes multiple categories, and the multiple closed-loop stimulation rules include adaptive parameter adjustment according to the category;

[0008] S14, if it is determined that the state is not in any of the preset states, adjusting the stimulation output according to the motion adaptive stimulation rule;

[0009] S15, the motion adaptive stimulation rule or the closed-loop stimulation rule ends and waits for a preset time, and then executes the closed-loop stimulation output again.

[0010] Preferably, the preset state includes a sleep state, the sleep state includes a plurality of sleep categories, and the closed-loop stimulation rule corresponding to the sleep state is an adaptive parameter adjustment according to the sleep category;

[0011] The controller is configured to perform adaptive parameter adjustment according to the sleep category by:

[0012] Determine the sleep category, wherein the sleep categories include wakefulness, sleep stage N1, sleep stage N2, sleep stage N3 and REM stage;

[0013] Controlling the stimulation amplitude of the wakefulness period to be greater than the stimulation amplitude of the sleep N1 period and the sleep N2 period;

[0014] The stimulation amplitudes of the sleep stage N1, the sleep stage N2 and the REM stage are controlled to be greater than the stimulation amplitude of the sleep stage N3.

[0015] Preferably, the preset state includes gait freezing, and the closed-loop stimulation rule corresponding to the gait freezing is to adjust the stimulation output according to a variable frequency stimulation rule.

[0016] Preferably, the motion adaptive stimulation rule comprises adjusting the stimulation output according to the symptom category, and the controller is configured to adjust the stimulation output according to the symptom category by taking the following steps:

[0017] identifying a symptom category based on the physiological signal;

[0018] Stimulation amplitude was adjusted within the parameters associated with the identified symptom category.

[0019] Preferably, the motion adaptive stimulation rule includes adaptive parameter adjustment according to energy values ​​of preset frequency bands in the physiological signal;

[0020] The controller is configured to perform adaptive parameter adjustments using the following steps:

[0021] comparing the energy value to an energy threshold range;

[0022] If the energy value is within the energy threshold range, maintaining the current stimulation;

[0023] If the energy value is outside the energy threshold range, the stimulation amplitude is adjusted in the same direction or in the opposite direction relative to the energy value.

[0024] Preferably, the motion adaptive stimulation rule includes an upper limit of a parameter range;

[0025] Setting the upper limit of the parameter range includes:

[0026] Set the upper limit of stimulation parameters and fix stimulation parameter P0;

[0027] Under the drug on-time and fixed stimulation parameter P0 stimulation output state, the energy threshold lower limit of the physiological signal is collected and calculated;

[0028] In the drug off period and the fixed stimulation parameter P0 stimulation output state, the stimulation parameter is increased, and the stimulation parameter P1 is recorded when the difference between the energy value and the lower limit of the energy threshold is within the first preset range;

[0029] The smaller one of the two values ​​of the stimulation parameter upper limit and the stimulation parameter P1 is used as the upper limit of the parameter range for regulating the stimulation output by the motion adaptive stimulation rule.

[0030] Preferably, the motion adaptive stimulation rule includes a lower limit of a parameter range;

[0031] Setting the lower limit of the parameter range includes:

[0032] Set the lower limit of stimulation parameters and fix the stimulation parameter P0;

[0033] In the drug-off period and when the stimulation output is turned off, the energy threshold upper limit of the physiological signal is collected and calculated;

[0034] In the drug on-period and fixed stimulation parameter P0 stimulation output state, reducing the stimulation parameter, and recording the stimulation parameter P2 when the difference between the energy value and the upper limit of the energy threshold is within the second preset range;

[0035] The larger of the two values ​​of the stimulation parameter lower limit and the stimulation parameter P2 is used as the lower limit of the parameter range for regulating the stimulation output by the motion adaptive stimulation rule.

[0036] Preferably, the motion adaptive stimulation rule includes a parameter range lower limit and an energy threshold upper limit;

[0037] Setting the lower limit of the parameter range and the upper limit of the energy threshold includes:

[0038] Within the preset parameter range, the stimulation output is gradually increased according to the preset step size;

[0039] Collect physiological signals during stimulation output and calculate the energy value of the preset frequency band;

[0040] If a first instruction is received during the stimulation output period, the stimulation parameters and the preset frequency band energy value corresponding to the first instruction are used as the lower limit of the parameter range and the upper limit of the energy threshold for adjusting the stimulation output by the motion adaptive stimulation rule.

[0041] Preferably, the motion adaptive stimulation rule includes an upper limit of a parameter range and a lower limit of an energy threshold;

[0042] Setting the upper limit of the parameter range and the lower limit of the energy threshold includes:

[0043] After receiving the first instruction, continue to gradually increase the stimulation output according to the preset step length;

[0044] If a second instruction is received during the stimulation output period, the stimulation parameter corresponding to the second instruction minus the preset step size is used as the upper limit of the parameter range for adjusting the stimulation output by the motion adaptive stimulation rule, and the preset frequency band energy value under the stimulation parameter corresponding to the second instruction is used as the lower limit of the energy threshold for adjusting the stimulation output by the motion adaptive stimulation rule.

[0045] Preferably, if the second instruction is not received, and the current stimulation parameter + the preset step length > the stimulation parameter P4, the third instruction is executed;

[0046] The third instruction includes setting the current stimulation parameter as the upper limit of the adaptive parameter range, and the current preset frequency band energy value as the lower limit of the energy threshold.

[0047] The implantable neural stimulation system provided by the present invention has the following beneficial effects:

[0048] The controller is configured to perform closed-loop stimulation output. Multiple preset states are set according to priority. Physiological signals are used to determine whether the state is in any preset state. Each state has a corresponding closed-loop stimulation rule. The corresponding adaptive stimulation rule is executed according to the confirmed preset state. If the state is not in any preset state, the motion adaptive stimulation rule is executed, thereby achieving more accurate and detailed closed-loop control. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The above and other objects, features and advantages of the present invention will become more apparent through the following description of the embodiments of the present invention with reference to the accompanying drawings, in which:

[0050] Figure 1 Schematic diagram of an implantable neural stimulation system in an embodiment of the present invention.

[0051] Figure 2 1 is a schematic diagram of a closed-loop stimulation output process in an embodiment of the present invention.

[0052] Figure 3 It is a schematic diagram of closed-loop stimulation output in combination with a specific state in an embodiment of the present invention.

[0053] Figure 4 It is a schematic diagram of the flow of regulating stimulation output by motion adaptive stimulation rules in an embodiment of the present invention.

[0054] Figure 5 It is a schematic diagram of the parameter configuration process before executing closed-loop stimulation output in an embodiment of the present invention.

[0055] Figure 6 It is a schematic diagram of the first process flow of parameter configuration in an embodiment of the present invention.

[0056] Figure 7 It is a schematic diagram of the second process of parameter configuration in an embodiment of the present invention.

[0057] Figure 8 It is a schematic diagram of the second process of parameter configuration in an embodiment of the present invention.

[0058] Description of reference numerals:

[0059] 10-terminal; 20-programmable control device; 30-pulse generator; 40-extension wire; 50-electrode;

[0060] 31 - acquisition module; 32 - processing module; 33 - storage module; 34 - communication module. DETAILED DESCRIPTION

[0061] The present invention is described below based on embodiments, but the present invention is not limited to these embodiments. In the detailed description of the present invention below, some specific details are described in detail. It is possible for a person skilled in the art to fully understand the present invention without the description of these details. In order to avoid confusing the essence of the present invention, well-known methods, processes, procedures, components and circuits are not described in detail. Unless the context clearly requires, the words "including", "comprising" and the like in the entire application document should be interpreted as including rather than exclusive or exhaustive meanings; that is, "including but not limited to" meanings.

[0062] Figure 1 Schematic diagram of the structure of an implantable neural stimulation system in an embodiment of the present invention.

[0063] like Figure 1 , the implantable neurostimulation system includes a terminal 10, a programmable device 20, a pulse generator 30, an extension wire 40 and an electrode 50. The programmable device 20 is located outside the patient's body, the pulse generator 30, the extension wire 40 and the electrode 50 are located inside the patient's body, and the pulse generator 30 is connected to one or more electrodes 50 through the extension wire 40. The pulse generator 30 can also be directly connected to the electrode 50. In some other embodiments, the implantable neurostimulation system can be composed of the programmable device 20, the pulse generator 30, the extension wire 40 and the electrode 50, or the pulse generator 30, the extension wire 40 and the electrode 50 can perform closed-loop stimulation output.

[0064] The terminal 10 can analyze the patient data collected by the program-controlled device 20, thereby optimizing and iterating the internal algorithm of the pulse generator 30 through the program-controlled device 20. The program-controlled device 20 can be used to adjust the stimulation parameters of the patient, read the patient's EEG, acceleration and other data, configure the pulse generator 30 for adaptive stimulation, and read the records stored in the pulse generator 30. The program-controlled device 20 can be a doctor-controlled device or a patient-controlled device, and the hardware platform of the program-controlled device 20 can be a PC, a tablet, a mobile phone, a self-developed platform, etc.

[0065] The pulse generator 30 includes a controller, which includes an acquisition module 31, a processing module 32, a storage module 33 and a communication module 34. The processing module 32 has a stimulation unit, which is used to output electric pulses to electrically stimulate the target point at the stimulation end of the electrode 50. The acquisition module 31 collects signals such as local field potential (LFP) and acceleration in the deep brain, and the pulse generator 30 determines the stimulation parameters and outputs stimulation based on LFP, acceleration and its internal algorithm. The storage module 33 can store and record physiological signals related to the stimulation parameters and status, and the communication module 34 is used to communicate with external devices such as the programmable device 20. The programmable device 20 can also program the pulse generator 30 to use a fixed stimulation parameter P0 stimulation or a closed-loop adaptive stimulation. The fixed stimulation parameter P0 is a pre-set stimulation parameter and is also a stimulation parameter in the open-loop state.

[0066] In the present invention, the pulse generator 30 also has monitoring and recording functions, and can perform state recording and stimulation parameter recording through the processing module 32 and the storage module 33. State recording: showing changes in the patient's state over time, such as changes in sleep stages, changes in the energy value of the preset frequency band (β band), etc.; stimulation parameter recording: showing changes in the patient's stimulation parameters, which can reflect the adaptive adjustment of the stimulation parameters as the state changes. When the pulse generator 30 identifies different states and gives different stimulation parameters, the storage module 33 records them for subsequent viewing and analysis. Unlike existing EEG acquisition, the monitoring records are stored in the pulse generator 30. In order to reduce the demand for storage space, the pulse generator 30 does not record the time domain data of the original physiological signal.

[0067] The implantable neural stimulation system of the present invention can also remotely transmit physiological signals and power spectra. During the physiological signal acquisition process, the patient-controlled device is connected to the pulse generator 30 to collect and record physiological signals in real time for a certain period of time, and the patient-controlled device retains the original time domain data. The physiological signal is stored in the patient-controlled device, uploaded to the terminal 10 (doctor server) through the patient-controlled device, and analyzed by the doctor. For example, physiological signals can be collected for a certain period of time after taking the medicine in different months after implantation, and the relationship between stimulation parameters and drug metabolism fluctuations in different periods after implantation can be observed.

[0068] When recording the power spectrum, the patient can use the patient programmable device to mark the event after the event occurs. The pulse generator 30 automatically records the EEG signal of the order of tens of seconds, and can calculate the power spectrum within the frequency band according to the pre-set frequency band range, and save it in the pulse generator 30. The records in the pulse generator 30 can be read by the patient programmable device and uploaded to the terminal 10 for analysis by the doctor. Or the doctor programmable device can read the records when you go to the hospital next time. This method does not need to maintain a long-term connection between the pulse generator 30 and the patient programmable device, and can be activated at any time, providing a shorter signal power spectrum without original time domain data.

[0069] Figure 2 1 is a schematic diagram of a closed-loop stimulation output flow of a pulse generator in an embodiment of the present invention. The pulse generator includes at least one controller, and at least one controller is configured to Figure 2 The flow shown implements a closed-loop stimulus output:

[0070] S11, obtaining physiological signals;

[0071] Acquiring physiological signals includes collecting physiological signals and receiving physiological signals. The pulse generator can collect physiological signals through electrodes. There are multiple contacts on the electrodes. There are differences in the local field potential (LFP) collected by different contacts. Selecting a suitable acquisition channel for data acquisition and monitoring helps to achieve more accurate and detailed closed-loop parameter adjustment. In the present invention, the pulse generator can collect data from multiple acquisition channels (contacts and contacts, contacts and the housing of the pulse generator) and calculate the power spectrum, which is convenient for comparing the signal differences under different acquisition channels. The sampling rate preferably ranges between 200Hz-500Hz, and a suitable sampling rate can also be selected according to demand to optimize the acquisition. Further analyze the EEG signal amplitude or power spectrum calculation results of each acquisition channel, and select an acquisition channel with a larger signal strength in the preset frequency band, no obvious ECG artifacts, and no obvious stimulation artifacts by comparison. The pulse generator is connected to two electrodes, and the two electrodes are respectively used to be implanted on the left and right sides of the brain. Through one acquisition channel, the stimulation output of one electrode can be controlled, and the stimulation output of the electrodes on both sides can also be controlled. In some other embodiments, a collection channel may be provided for each side of the electrode to collect the EEG signal of the corresponding side.

[0072] In the present invention, the acquisition contacts are tested before the closed-loop stimulation begins, so as to select a suitable acquisition channel to ensure the stimulation accuracy of the closed-loop stimulation output. Physiological signals may include acceleration, electrocardiogram, electroencephalogram, etc. When the pulse generator is implanted in the chest, the acquisition channel is set to the outer shell and contacts of the pulse generator, so as to realize the acquisition of electrocardiogram signals. Acceleration can be collected by the built-in sensor of the pulse generator. In some embodiments of the invention, myoelectric, acceleration, angular velocity, electrocardiogram, eye movement and other signals collected by external devices can also be used, and the external device transmits the collected parameters to the pulse generator to assist in the recognition and judgment of the state.

[0073] S12, judging a plurality of preset states with priorities according to the physiological signal;

[0074] The preset states set in the pulse generator are: sleep state, gait freezing state, walking state in gait recognition, and body position state switching. There are many combinations of preset states that do not overlap, such as the combination of sleep state and gait freezing state, enabling sleep monitoring to judge the sleep state, adjusting the corresponding stimulation parameters according to the difference in sleep state, enabling gait monitoring to determine whether gait freezing occurs, and outputting variable frequency stimulation if it occurs, etc. The activation time of different preset state judgments can be the same or different, such as different activation times for sleep state and gait freezing judgment, or turning on all state monitoring throughout the day. According to the configured priority, the pulse generator will execute the recognition and judgment of each preset state one by one. For example, if the sleep state recognition priority is set to be greater than the gait freezing priority, if the recognition is in the sleep state, gait freezing recognition will not be performed.

[0075] The pulse generator judgment interval is between 0.5-10 minutes, such as: a judgment is performed every 30 seconds, 1 minute, 5 minutes or 10 minutes. The maximum interval for executing the judgment is 10 minutes. The larger the judgment interval, the longer the physiological signal time that can be recorded, but if the judgment interval is too large, the change of the intermediate state may be missed. In some other embodiments, the judgment interval can be set according to various factors such as the patient's condition and age, such as 15 minutes, 20 minutes, 25 minutes or longer time intervals.

[0076] S13, if it is determined to be in a certain preset state, adjusting the stimulation output according to the closed-loop stimulation rule corresponding to the state;

[0077] For example, different program groups correspond to the walking state, body position state switching and the static state. The program group for the walking state and body position state switching is variable frequency stimulation (the stimulation parameters are the same or different from the variable frequency stimulation rules corresponding to the gait freezing state), and the body position state switching includes the switching between the lying position, the sitting position and the standing position respectively. The static state includes the lying position, the sitting position and the standing position. The program group of the static state is to adjust the stimulation output according to the motion adaptive stimulation rules, and the preset state does not include static state recognition. In the present invention, at least one preset state includes multiple categories, and multiple closed-loop stimulation rules include adaptive parameter adjustment corresponding to the category. For example, the sleep state includes multiple sleep categories, namely, the awake period, the sleep N1 period, the sleep N2 period, the sleep N3 period and the REM period, and the parameter adjustment method for each sleep category can be pre-set.

[0078] In the present invention, after completing a parameter adjustment according to the closed-loop stimulation rule, the current closed-loop stimulation rule can be regarded as ended, and a program group that can be executed cyclically can also be set in the closed-loop stimulation rule. The program group includes continuing to obtain physiological signals, judging the current state according to the physiological signals, and making the pulse generator judge the current state when executing the closed-loop stimulation rule to adjust the stimulation output. If the recognition state changes, the current closed-loop stimulation rule is ended.

[0079] S14, if it is determined that the state is not in any of the preset states, adjusting the stimulation output according to the motion adaptive stimulation rule;

[0080] The motion adaptive stimulation rule includes adaptive parameter adjustment according to the preset frequency band energy value in the physiological signal, and the pulse generator adaptively adjusts the stimulation parameters. Taking the β frequency band as an example, if it exceeds the upper energy threshold, the stimulation parameters are increased, and if it is lower than the lower energy threshold, the stimulation parameters are reduced.

[0081] S15, the motion adaptive stimulation rule or the closed-loop stimulation rule ends and waits for a preset time, and then executes the closed-loop stimulation output again;

[0082] The motion adaptive stimulation rule or the closed-loop stimulation rule ends and waits for a preset time, and then executes the closed-loop stimulation output again, that is, executes S11 again to obtain the physiological signal, and re-executes the preset state judgment. In the present invention, the delay waiting time is between 1min-60min, and the preferred time range is 5min-20min. If the delay waiting time is too long, some states may be missed. In some other embodiments, the pulse generator can continuously acquire the physiological signal, and after S15 delays and waits for a preset time, S12 is executed.

[0083] Figure 3 FIG. 1 is a schematic diagram of a pulse generator according to an embodiment of the present invention performing closed-loop stimulation output in combination with a specific state. Figure 3As shown, the multiple preset states include a sleep state and a gait freezing state, and the sleep state has a higher priority than the gait freezing state. If it is determined to be a sleep state, the controller of the pulse generator is configured to adjust the stimulation output according to the adaptive stimulation rule of the sleep category. If it is determined to be a gait freezing state, the closed-loop stimulation rule corresponding to the gait freezing is to adjust the stimulation output according to the variable frequency stimulation rule. The specific procedures include:

[0084] S21, obtaining physiological signals;

[0085] S22, determining whether the device is in a sleeping state;

[0086] S23, if yes, adjust the stimulation output according to the sleep adaptive stimulation rule.

[0087] The controller is configured to adjust the stimulation output according to the sleep adaptive stimulation rule using the following steps:

[0088] Determine the sleep category. The sleep state includes multiple sleep categories. Determine the sleep category and adaptively adjust the stimulation output according to the sleep category. The sleep category is divided into awake period, sleep N1 period, sleep N2 period, sleep N3 period and REM period. The controller is configured to adjust the stimulation output according to the sleep category, that is, control the stimulation amplitude of the awake period to be greater than the stimulation amplitude of the sleep N1 period, sleep N2 period and sleep N3 period, and control the stimulation amplitude of the sleep N1 period, the sleep N2 period and the REM period to be greater than the stimulation amplitude of the sleep N3 period.

[0089] Sleep stage N1 is the initial stage of falling asleep, sleep stage N2 is light sleep, and brain activity is intense during sleep REM, all of which require a higher stimulation amplitude than N3. The pulse generator is preset with stimulation parameters corresponding to each sleep stage. In some other embodiments, the pulse generator is preset with nuclei corresponding to each contact of the electrode. If the sleep stage is judged to be stage N2, the contacts of the STN nuclei corresponding to the same electrode are controlled to adjust the amplitude parameters according to the stimulation ratio, and the frequency is kept high frequency, and the contacts corresponding to the SNr nuclei output low-frequency stimulation. The output mode of different-frequency stimulation of two contacts of the same electrode can induce more N3 deep sleep in patients and reduce micro-awakening of patients during sleep. If not in a sleeping state, execute S24.

[0090] Furthermore, the controller adjusts the stimulation output according to the sleep adaptive stimulation rules, and the program group that can be executed cyclically includes: obtaining physiological signals, judging the sleep state and category, and adjusting to preset stimulation parameters according to changes in sleep category until the sleep state is exited.

[0091] S24, determining whether the gait is frozen;

[0092] Specifically, the physiological signal includes gait monitoring information, and gait monitoring is used to identify whether the gait is frozen. If yes, S25 is executed, and if no, S26 is executed.

[0093] S25, executing variable frequency stimulation rules.

[0094] Specifically, gait freezing is monitored when standing up (body position switching) and starting to walk (or walking state). If gait freezing occurs, the controller is configured to adjust the stimulation output according to the variable frequency stimulation rules. Variable frequency stimulation is alternating low-frequency and high-frequency stimulation, for example, a low frequency of 60 to 90 Hz is combined with a high frequency of 130 to 185 Hz. In some other embodiments, when gait freezing is detected during body position switching, the contacts of the same electrode corresponding to the STN nucleus can also be controlled to output high-frequency stimulation, and the contacts of the corresponding SNr nucleus can be controlled to output low-frequency stimulation, forming hetero-frequency stimulation. The low frequency optional range is between 50Hz-90Hz, and the high frequency range is between 100Hz-185Hz. In some other embodiments, the high and low frequency ranges in the variable frequency stimulation overlap or partially overlap with the high and low frequency ranges in the hetero-frequency stimulation.

[0095] S26, adjust the stimulation output according to the motion adaptive stimulation rule. The motion adaptive stimulation rule has two stimulation adjustment methods. Method 1: According to the symptom category corresponding to the physiological signal identification, the state recognition model can determine the symptom category according to the physiological signal, and adjust the stimulation amplitude within the parameter range associated with the identified symptom category. The state categories include states such as obvious dyskinesia symptoms, obvious Parkinson's disease, and suppressed Parkinson's disease, and the corresponding stimulation adjustment programs are pre-set respectively. Method 2: Adaptive parameter adjustment based on the energy value of the preset frequency band in the physiological signal.

[0096] In method 1, the pulse generator is pre-configured with the upper limit of the first parameter range, the lower limit of the first parameter range, the step length S1, the step length S2 and the time t1, the step length S1 and the step length S2 can be equal, and the time t1 is greater than 10 minutes. The controller executes the motion adaptive stimulation rule and adjusts the stimulation output according to method 1.

[0097] Example 1: If the physiological signal is identified as obvious dyskinesia, the stimulation amplitude is reduced according to the preset step size S1 between the upper limit of the first parameter range and the lower limit of the first parameter range. If the state changes to dyskinesia suppression or the stimulation amplitude reaches the lower limit of the first parameter range, the stimulation output is stopped from being reduced.

[0098] Example 2: If Parkinson's disease is obvious according to the physiological signal, the stimulation amplitude is increased according to the preset step size S2 between the upper limit of the first parameter range and the lower limit of the first parameter range. If the state changes to Parkinson's disease suppression or reaches the upper limit of the first parameter range, the stimulation amplitude is stopped from being increased.

[0099] Example 3: If Parkinson's disease suppression is identified according to the physiological signal (symptoms are eliminated after increasing the stimulation amplitude), and the duration reaches the preset time t1, the stimulation amplitude is reduced between the upper limit of the first parameter range and the lower limit of the first parameter range according to the preset step S2. If the state changes to obvious Parkinson's disease or reaches the lower limit of the first parameter range, the reduction of the stimulation amplitude is stopped, and the motion adaptive stimulation rule adjustment is terminated.

[0100] In the embodiment of the present invention, acceleration information, angular velocity, electromyographic information, etc. can be collected by the acceleration sensor inside the pulse generator, or the external acceleration sensor / electromyographic acquisition sensor. The acceleration sensor calculates the power spectrum after filtering, extracts the characteristics of each channel, such as peak power, peak power frequency, angular velocity root mean square, angle root mean square, etc., and judges the symptoms and severity through a classification model (such as a state recognition model), and identifies whether the abnormal movement symptoms are obvious / suppressed, and whether Parkinson's disease is obvious / suppressed. It is also possible to combine the existing technology to judge the electromyography through a classification model. Further, if an external acceleration sensor is used, the acceleration sensor can be set on the left and right limbs of the human body respectively. According to the acceleration and angular velocity information collected by the acceleration sensors on the left and right sides, if it is identified that the human body has midline symptoms and unilateral Parkinson's disease is obvious, the pulse generator adjusts the stimulation frequency of the left and right electrodes to a different frequency, and the electrode on the side corresponding to the midline symptoms is a low-frequency stimulation output.

[0101] Specifically, if it is judged that the Parkinson's disease in the left limbs is obvious, the Parkinson's disease in the right limbs is not obvious, and there are midline symptoms, the pulse generation will adjust the stimulation frequency of the electrode implanted in the left brain side to a low frequency, and the stimulation frequency of the electrode in the right brain side to a high frequency; if it is judged that the Parkinson's disease in the left limbs is not obvious, but the Parkinson's disease in the right limbs is obvious, and there are midline symptoms, the pulse generation will adjust the stimulation frequency of the electrode implanted in the right brain side to a low frequency, and the stimulation frequency of the electrode in the left brain side to a high frequency. The low frequency range is between 50Hz-90Hz, the high frequency range is between 100Hz-185Hz, the difference range between the high frequency and the low frequency is between 10Hz-135Hz, and the preferred difference range is between 30Hz-95Hz. For example, the low frequency is 50Hz, and the high frequency is between 100Hz-145Hz; for example, the low frequency is 90Hz, and the high frequency is between 120Hz-185Hz. This design can not only improve Parkinson's disease corresponding to high-frequency stimulation, but also use low frequency to improve midline symptoms. The pulse generator outputs a wider range of electrical stimulation parameters, which improves the effect of electrical stimulation therapy.

[0102] Figure 4It is a flow chart of adjusting the stimulation output according to the motion adaptive stimulation rule in an embodiment of the present invention. The present invention pre-configures the second parameter range upper limit, the second parameter range lower limit, the step length S3, the energy threshold upper limit, and the energy threshold lower limit for the pulse generator through a program-controlled device. Physiological signals include local field potentials (Local Field Potential, LFP). There is a correlation between the β and γ frequency bands in the local field potential and the hypokinetic tonic state of Parkinson's. When the β frequency band signal is stronger, the hypokinetic tonic symptoms are often stronger. When the β frequency band signal decreases, the symptoms are alleviated. When the γ frequency band signal is stronger, the relationship with the hypokinetic tonic symptoms is opposite to that of the β frequency band. In an embodiment of the present invention, the β frequency band in the physiological signal is used as a preset frequency band and an energy value is calculated. The controller performs adaptive parameter adjustment according to the preset frequency band energy value (method two), including calculating the energy value of the preset frequency band (β frequency band), comparing the energy value of the preset frequency band with the upper and lower limits of the energy threshold, and according to the comparison result, executing to maintain the current stimulation or adjust the stimulation amplitude according to the preset step length S3. S26 adjusts the stimulation output according to the motion adaptive stimulation rule, such as Figure 4 As shown, specifically including:

[0103] S261 calculates the energy value of a preset frequency band (β frequency band);

[0104] When the high energy value of the β band is outside the energy threshold range, the symptoms of hypokinetic rigidity are obvious, and the stimulation amplitude can be adjusted to increase the stimulation, or when the energy value of the β band is small and outside the energy threshold range, the stimulation can be reduced, that is, the stimulation amplitude is adjusted in the same direction as the energy value. In some other embodiments, the preset frequency band can also be the γ band, and the hypokinetic rigidity symptoms are suppressed when the energy value of the γ band is high. The judgment logic for adjusting the stimulation amplitude is opposite to that of the β band, that is, the stimulation amplitude is adjusted in the opposite direction relative to the energy value. Therefore, this embodiment adjusts the stimulation parameters by comparing the energy value of the preset frequency band with the energy threshold range.

[0105] S262 determines whether the energy threshold upper limit is exceeded;

[0106] If yes, S263 adjusts the stimulation parameter = min (current stimulation parameter + preset step length S3, upper limit of the second parameter range), completing a parameter adjustment;

[0107] If not, then determine whether the energy is below the lower limit of the energy threshold at S264;

[0108] If it is lower than the lower limit of the energy threshold, adjust the stimulation parameter to max (current stimulation parameter - preset step length S3, lower limit of the second parameter range), and complete a parameter adjustment;

[0109] S266 maintains the current stimulation parameters. At this time, the energy value of the current preset frequency band is between the upper limit of the energy threshold and the lower limit of the energy threshold, that is, within the energy threshold range;

[0110] S267 The motion adaptive stimulation rule adjustment is completed. After a delay of a preset time, the closed-loop stimulation output is executed again to execute S11 to collect physiological signals.

[0111] In some other embodiments, the controller can also adjust the stimulation output according to the preset frequency band energy value in the following manner:

[0112] First, the controller is preset with: energy reference value BVR (Band Value Reference), stimulation output reference value SVR (Stim Value Reference), stimulation upper limit value SVMax (Stim Value Max), stimulation lower limit value SVMin (Stim Value Min);

[0113] Then, calculate the temporary stimulation reference value SVT (Stim Value Temp) = current energy value / preset energy reference value BVR×stimulation output reference value SVR;

[0114] Finally, determine the current stimulation parameter = min(max(temporary stimulation reference value SVT, stimulation lower limit value SVMin), stimulation upper limit value SVMax), the stimulation output reference value SVR can be a fixed stimulation parameter P0 (stimulation parameter in open-loop state) between the stimulation upper limit value and the stimulation lower limit value.

[0115] Figure 5 1 is a flow chart of parameter configuration of the pulse generator before executing closed-loop stimulation output in an embodiment of the present invention. The pulse generator can also perform parameter configuration before executing closed-loop stimulation output, such as Figure 5 As shown, the controller performs the following steps to configure parameters:

[0116] S31 selects the acquisition channel;

[0117] According to the acquisition parameters (left and right sides of the brain, sampling rate, acquisition time), test signals are collected for all acquisition channels. Test signals refer to ECG and EEG signals. The signals collected by each channel are analyzed and compared, and the acquisition channel is selected based on the β-band signal strength, ECG, stimulation artifacts, etc. The pulse generator can be implanted in the chest, and can also be selected as the acquisition channel between the shell and the contact to realize the acquisition of ECG signals.

[0118] S32 real-time physiological signal acquisition, optimization of personalized model parameters;

[0119] The controller is embedded with a general state recognition model. After collecting real-time signals, it can also obtain personalized model parameters for the current patient through automated calculation or manual training optimization to optimize adaptive stimulation.

[0120] The S33 closed-loop stimulation output function configuration can be set through the programmable device.

[0121] The settings include:

[0122] a) State selection: determine the state, such as sleep, exercise, etc.

[0123] b) Judgment rules: use only one state to judge, or judge multiple states according to the rules. The present invention judges multiple states according to the priority rules;

[0124] c) Monitoring interval: how often the status is judged. The pulse generator judgment interval is between 0.5-10 minutes;

[0125] d) Monitoring period: when the monitoring function is enabled, no monitoring will be performed when it is not enabled;

[0126] e) Biomarker selection: Select the frequency band of interest, such as the β band, and use the EEG signal of the corresponding frequency band for analysis and identification.

[0127] S34 configures stimulation rules and stimulation parameters, including configuring upper and lower limits of parameter ranges and upper and lower limits of energy thresholds.

[0128] S35 obtains confirmation information;

[0129] According to the configured stimulation rules and stimulation parameters, the controller performs closed-loop control for a period of time. If there is no abnormality, the configuration is confirmed.

[0130] S36 sets the modification permission;

[0131] For example, whether the patient-controlled device is allowed to adjust parameters within a certain range, whether parameter optimization is allowed, etc.

[0132] S37 completes parameter configuration.

[0133] Figure 6 FIG. 1 is a first flow chart of parameter configuration of a pulse generator in an embodiment of the present invention. Figure 6 As shown, the controller is configured with parameters in the first manner (e.g., S34 configures stimulation parameters). In some other embodiments, S34 configures stimulation rules and stimulation parameters can be executed before the closed-loop stimulation output program, or can be executed during the closed-loop stimulation output, such as before S11 obtains physiological signals or before S13 adjusts stimulation output, to ensure that the controller can extract the upper and lower limits of the parameter range and the upper and lower limits of the energy threshold when adjusting the stimulation output.

[0134] The controller performs the following steps:

[0135] S41 configures the stimulation parameter lower limit Plow, the stimulation parameter upper limit Pup, and the fixed stimulation parameter P0.

[0136] S42 obtains drug metabolism information and calculates the energy threshold of the physiological signal. The energy threshold calculation of the physiological signal can be obtained in the following manner. In the drug off period and when the stimulation output is turned off, the upper limit of the energy threshold of the physiological signal is collected and calculated; in the drug on period and the fixed stimulation parameter P0 stimulation output state, the lower limit of the energy threshold of the physiological signal is collected and calculated.

[0137] S43, when the drug is off and the stimulation parameter P0 is fixed, the stimulation parameter is increased, and the difference between the current energy value and the lower limit of the energy threshold is within the first preset range, and the current stimulation parameter P1 is recorded; when the drug is on and the stimulation parameter P0 is fixed, the stimulation parameter is reduced, and the difference between the current energy value and the upper limit of the energy threshold is within the second preset range, and the current stimulation parameter P2 is recorded. The energy value of the preset frequency band of the physiological signal is in a fluctuating state. It is difficult to require it to be exactly the same as the upper and lower limits of the energy threshold during the judgment process. Therefore, the first preset range and the second preset range are pre-set in the pulse generator, and when the difference between the current energy value and the upper and lower limits of the energy threshold is within the preset range, it is used as the judgment result.

[0138] S44 determines the parameter range lower limit of the motion adaptive rule-regulated stimulation output = max(Plow, P2), the parameter range upper limit = min(Pup, P1), sets the parameter range lower limit to the first parameter range lower limit and / or the second parameter range lower limit, sets the parameter range upper limit to the first parameter range upper limit and / or the second parameter range upper limit, and the calculated energy threshold upper and lower limits are used for motion adaptive rule-regulated stimulation output. The therapeutic window is the lower limit to the upper limit of the stimulation parameter that has therapeutic effect and no side effects. The first parameter / second parameter upper and lower limits are the parameter setting limits for the pulse generator to perform closed-loop stimulation, not the maximum and minimum values ​​that the pulse generator can output. The output range between the maximum and minimum of the pulse generator>the therapeutic window>=the first parameter / second parameter upper and lower limits for the pulse generator to perform closed-loop settings.

[0139] It can be understood that the energy value in the present invention refers to the energy value of a preset frequency band in the physiological signal. In the above steps, the physiological signal in "collecting and calculating the upper limit of the energy threshold of the physiological signal" and "collecting and calculating the lower limit of the energy threshold of the physiological signal" refers to the physiological signal collected within a certain period of time.

[0140] Figure 7 1 is a schematic diagram of the second process flow of configuring the pulse generator parameters in an embodiment of the present invention. The controller configures the parameter range lower limit and the energy threshold upper limit according to the second parameter configuration process (such as: S34 configuring the stimulation parameters), and performs the following steps:

[0141] Step T1, preset parameter range P3-P4, preset step length S4, N=1, N is the number of attempts. Specifically, the parameter range P3-P4, preset step length S4, and value N of the pulse generator can be set through a program control device.

[0142] Step T2, setting stimulation parameters = P3 + S4 (N-1) to perform stimulation output, and collecting physiological signals for a duration of t during the stimulation output.

[0143] Step T3, calculating the energy value of the preset frequency band.

[0144] The characteristic frequency band can be selected according to the physiological signals collected during the patient's MED ON / MED OFF state. If the preset frequency band is the β band, when the β band signal is strong (larger energy value), it indicates that the hypokinetic rigidity symptom is obvious, and when the β band signal is low (smaller energy value), it indicates that the symptom is alleviated.

[0145] Step T4, determining whether the first instruction is received.

[0146] If yes, then execute step T5, if no, then execute step T6. The first instruction can be issued by the doctor according to the patient's symptom judgment. If the symptom improvement occurs for the first time, the first instruction is sent to the pulse generator through the program control device.

[0147] Step T5, using the stimulation parameters and preset frequency band energy value corresponding to the first instruction as the lower limit of the parameter range and the upper limit of the energy threshold for adjusting the stimulation output by the motion adaptive stimulation rule.

[0148] Step T6, N=N+1. If the first instruction is not received, the value of N is increased by 1, and step T2 is executed to continue increasing the stimulation output according to the preset step length S4.

[0149] Figure 8 The controller configures the upper limit of the parameter range and the lower limit of the energy threshold according to the second parameter configuration process (such as: S34 configuration of stimulation parameters), and performs the following steps:

[0150] Step T7, setting stimulation parameter = parameter range lower limit + S4(N-1), and collecting physiological signals for a duration of t.

[0151] Specifically, after receiving the first instruction, the stimulation output is continuously increased according to the preset step length S4, that is, the stimulation parameter is set to be the lower limit of the parameter range + S4*N, where N=1.

[0152] Step T8, calculating the energy value of the preset frequency band.

[0153] Step T9, determine whether the second instruction is received, if yes, execute step T10, otherwise execute step T11. The second instruction can be issued by the doctor according to the patient's symptoms. If the side effect occurs for the first time, the second instruction is sent to the pulse generator through the program control device.

[0154] Step T10, subtracting the preset step length from the stimulation parameter corresponding to the second instruction is configured as the upper limit of the parameter range of the motion adaptive stimulation rule to adjust the stimulation output, and the preset frequency band energy value under the stimulation parameter corresponding to the second instruction is used as the lower limit of the energy threshold of the motion adaptive stimulation rule to adjust the stimulation output.

[0155] Step T11, determine whether the current stimulation parameter + S4 is greater than P4. If yes, execute the third instruction of step T12, otherwise execute step T13.

[0156] Step T12, the third instruction includes configuring the current stimulation parameters and the current preset frequency band energy value as the upper limit of the parameter range and the lower limit of the energy threshold for the motion adaptive stimulation rule to adjust the stimulation.

[0157] Step T13, add 1 to the value of N, and return to step T7, the stimulation parameters are increased by 1 preset step length S4 relative to the previous stimulation parameters.

[0158] The first parameter configuration method is to output stimulation by fixing the stimulation parameter P0, determine the upper and lower limits of the frequency band energy threshold, and finally obtain the upper and lower limits of the parameter range. This method is applicable to a wide range of groups and ensures a good stimulation effect. The second parameter configuration is to adjust the parameters within the preset parameter range, and determine the upper and lower limits of the actual parameter range based on the patient's corresponding status information. Both of the above methods can configure the relevant parameters of the pulse generator and use them as personalized parameters to improve the stimulation effect.

[0159] In summary, the implantable neural stimulation system of the present invention can identify and judge various states according to priority rules around the clock, and execute adaptive stimulation rules corresponding to the states to adjust the stimulation output of the pulse generator. It can also perform personalized settings, upper and lower limits of energy thresholds, and parameter range configurations to make the closed-loop stimulation output more suitable for patients, achieve more accurate and detailed closed-loop regulation, monitor and record events, and take into account convenience and long-term recording.

[0160] In the above, P0, P1, P2, P3, P4, Pup, Plow and S1, S2, S3, S4 in the step size are used to represent a certain value of the stimulation parameter, so as to be called in the execution of closed-loop stimulation output and parameter setting, and the value size can be set by the doctor and / or patient.

[0161] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An implantable neural stimulation system, characterized in that: A controller is included, the controller being configured to perform a closed-loop stimulation output, comprising: S11, obtaining physiological signals; S12, judging a plurality of preset states with priorities according to the physiological signal; S13, if it is determined that the state is in a preset state, adjusting the stimulation output according to the closed-loop stimulation rule corresponding to the state, at least one of the preset states includes multiple categories, and the multiple closed-loop stimulation rules include adaptive parameter adjustment according to the category; S14, if it is determined that the state is not in any of the preset states, adjusting the stimulation output according to the motion adaptive stimulation rule; S15, the motion adaptive stimulation rule or the closed-loop stimulation rule ends and waits for a preset time, and then executes the closed-loop stimulation output again.

2. The implantable neural stimulation system according to claim 1, characterized in that: The preset state includes a sleep state, the sleep state includes a plurality of sleep categories, and the closed-loop stimulation rule corresponding to the sleep state is adaptive parameter adjustment according to the sleep category; The controller is configured to perform adaptive parameter adjustment according to the sleep category by: Determine the sleep category, wherein the sleep categories include wakefulness, sleep stage N1, sleep stage N2, sleep stage N3 and REM stage; Controlling the stimulation amplitude of the wakefulness period to be greater than the stimulation amplitude of the sleep N1 period and the sleep N2 period; The stimulation amplitudes of the sleep stage N1, the sleep stage N2 and the REM stage are controlled to be greater than the stimulation amplitude of the sleep stage N3.

3. The implantable neural stimulation system according to claim 1, characterized in that: The preset state includes gait freezing; The closed-loop stimulation rule corresponding to the gait freezing is to adjust the stimulation output according to the variable frequency stimulation rule.

4. The implantable neural stimulation system according to claim 1, characterized in that: The motion adaptive stimulation rule includes adjusting the stimulation output according to the symptom category, and the controller is configured to adjust the stimulation output according to the symptom category by taking the following steps: identifying a symptom category based on the physiological signal; Stimulation amplitude was adjusted within the parameters associated with the identified symptom category.

5. The implantable neural stimulation system according to claim 1, characterized in that: The motion adaptive stimulation rule includes adaptive parameter adjustment according to the energy value of a preset frequency band in the physiological signal; The controller is configured to perform adaptive parameter adjustments using the following steps: comparing the energy value to an energy threshold range; If the energy value is within the energy threshold range, maintaining the current stimulation; If the energy value is outside the energy threshold range, the stimulation amplitude is adjusted in the same direction or in the opposite direction relative to the energy value.

6. The implantable neural stimulation system according to claim 1, characterized in that: The motion adaptive stimulation rule includes an upper limit of a parameter range; Setting the upper limit of the parameter range includes: Set the upper limit of stimulation parameters and fix stimulation parameter P0; Under the drug on-time and fixed stimulation parameter P0 stimulation output state, the energy threshold lower limit of the physiological signal is collected and calculated; In the drug off period and the fixed stimulation parameter P0 stimulation output state, the stimulation parameter is increased, and the stimulation parameter P1 is recorded when the difference between the energy value and the lower limit of the energy threshold is within the first preset range; The smaller one of the two values ​​of the stimulation parameter upper limit and the stimulation parameter P1 is used as the upper limit of the parameter range for regulating the stimulation output by the motion adaptive stimulation rule.

7. The implantable neural stimulation system according to claim 1, characterized in that: The motion adaptive stimulation rule includes a lower limit of a parameter range; Setting the lower limit of the parameter range includes: Set the lower limit of stimulation parameters and fix the stimulation parameter P0; In the drug-off period and when the stimulation output is turned off, the energy threshold upper limit of the physiological signal is collected and calculated; In the drug on-period and fixed stimulation parameter P0 stimulation output state, reducing the stimulation parameter, and recording the stimulation parameter P2 when the difference between the energy value and the upper limit of the energy threshold is within the second preset range; The larger of the two values ​​of the stimulation parameter lower limit and the stimulation parameter P2 is used as the lower limit of the parameter range for regulating the stimulation output by the motion adaptive stimulation rule.

8. The implantable neural stimulation system according to claim 1, characterized in that: The motion adaptive stimulation rule includes a parameter range lower limit and an energy threshold upper limit; Setting the lower limit of the parameter range and the upper limit of the energy threshold includes: Within the preset parameter range, the stimulation output is gradually increased according to the preset step size; Collect physiological signals during stimulation output and calculate the energy value of the preset frequency band; If a first instruction is received during the stimulation output period, the stimulation parameters and the preset frequency band energy value corresponding to the first instruction are used as the lower limit of the parameter range and the upper limit of the energy threshold for adjusting the stimulation output by the motion adaptive stimulation rule.

9. The implantable neural stimulation system according to claim 8, characterized in that: The motion adaptive stimulation rule includes an upper limit of a parameter range and a lower limit of an energy threshold; Setting the upper limit of the parameter range and the lower limit of the energy threshold includes: After receiving the first instruction, continue to gradually increase the stimulation output according to the preset step length; If a second instruction is received during the stimulation output period, the stimulation parameter corresponding to the second instruction minus the preset step size is used as the upper limit of the parameter range for adjusting the stimulation output by the motion adaptive stimulation rule, and the preset frequency band energy value under the stimulation parameter corresponding to the second instruction is used as the lower limit of the energy threshold for adjusting the stimulation output by the motion adaptive stimulation rule.

10. The implantable neural stimulation system according to claim 9, characterized in that: If the second instruction is not received, and the current stimulation parameter + the preset step length > the stimulation parameter P4, the third instruction is executed; The third instruction includes setting the current stimulation parameter as the upper limit of the adaptive parameter range, and the current preset frequency band energy value as the lower limit of the energy threshold.

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