A neural stimulation system and method for adjusting parameters thereof

Abstract

The application provides a nerve stimulation system, comprising a stimulation device, the stimulation device comprising a signal generating circuit, a control module, a signal collecting circuit and a multiplexed electrode, the stimulation device being configured to be implanted in vivo, to generate a stimulation signal and to apply the stimulation signal to a target nerve through the multiplexed electrode; the control module being configured to perform a closed-loop titration procedure: the signal generating circuit applies a titration stimulation signal to the target nerve according to a preset mode, in which the signal intensity of the titration stimulation signal starts from an initial threshold value, stepwise increases to a peak value, and then gradually decreases to an end threshold value after the peak value is maintained for a period of time or a plurality of stimulation cycles; the signal collecting circuit is capable of collecting an evoked potential corresponding to the application of the titration stimulation signal to the target nerve; and when an evoked potential period meeting a target threshold value is selected, a stimulation parameter with the lowest signal intensity in the evoked potential period is selected as a parameter of a treatment stimulation signal, which is used for the subsequent application of the treatment stimulation signal.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of medical devices, in particular, to a method for stimulating and adjusting parameters of a neural stimulator, which is suitable for deep brain stimulation (DBS), spinal cord stimulation (SCS), vagus nerve stimulation (VNS) and other implantable neural modulation devices. BACKGROUND

[0002] Neural stimulation has gradually become a routine treatment method and is applied in the diagnosis and treatment of various diseases. However, except for neuromuscular stimulation which can produce immediate effects, other types of stimulation (such as vagus nerve stimulation) have slow stimulation effects, and it is difficult to intuitively evaluate whether the expected stimulation effect is achieved. The existing implantable neural stimulator generally adopts an open-loop or semi-closed-loop control strategy, and the stimulation parameters (amplitude, frequency, pulse width) are usually manually adjusted by the doctor during postoperative follow-up. Due to the dynamic changes of neural tissue excitability with factors such as circadian rhythm, drugs, and disease progression, fixed parameters cannot maintain long-term efficacy, and excessive stimulation can easily lead to tissue damage, premature battery depletion, or side effects (such as paresthesia and movement disorders). Although some closed-loop systems attempt to use electrocardiogram, electromyogram or acceleration signals as feedback, there are the following defects: the feedback signal has poor correlation with clinical symptoms and cannot directly reflect the immediate excitability of the neural pathway; the interference of "stimulation artifacts" on the detection of weak evoked potentials has not been solved, the signal-to-noise ratio is low, and the reliability is poor; there is a lack of personalized parameter setting, and how to set stimulation parameters according to individuals still needs to be solved.

[0003] Therefore, in order to solve one or more of the existing problems, the present application proposes a neural stimulator and a method for adjusting parameters thereof. SUMMARY

[0004] In a first aspect, the present application provides a neural stimulation system, which comprises:

[0005] a stimulation device comprising a signal generating circuit, a control module, a signal acquisition circuit and a multiplexed electrode, the stimulation module being configured to be implanted in the body, to generate a stimulation signal and to apply the stimulation signal to a target nerve through the multiplexed electrode;

[0006] the control module is configured to perform a closed-loop titration program:

[0007] the signal generating circuit applies a titration stimulation signal to the target nerve according to a preset mode, in which the signal strength of the titration stimulation signal starts from an initial threshold value, steps up to a peak value, and then gradually decreases to an end threshold value after maintaining the peak value for a period of time or a number of stimulation cycles;

[0008] the signal acquisition circuit can correspondingly acquire an evoked potential when the titration stimulation signal is applied to the target nerve;

[0009] The stimulation parameter with the lowest stimulation signal intensity in the evoked potential period meeting the target threshold is selected as the parameter of the treatment stimulation signal, which is used for subsequent application of the treatment stimulation signal.

[0010] Preferably, in the neural stimulation system of the present application, the signal intensity refers to voltage or current, and does not involve frequency and duty cycle.

[0011] Optionally, in the neural stimulation system of the present application, the control module is configured to perform the closed-loop titration procedure to adjust the parameter of the treatment stimulation signal after applying the treatment stimulation signal for a fixed time.

[0012] Optionally, in the neural stimulation system of the present application, the control module is configured to determine whether to enter the closed-loop titration procedure based on the evoked potential in the closed-loop treatment stimulation process. Further, the determination of whether to enter the closed-loop titration procedure based on the evoked potential in the closed-loop treatment stimulation process is performed by controlling the signal generation circuit to output a stimulation signal using the parameter of the treatment stimulation signal, collecting the evoked potential generated by the stimulation signal on the target nerve through the electrical stimulation, determining whether the evoked potential meets the target threshold, and re-entering the closed-loop titration procedure if the evoked potential does not meet the target threshold.

[0013] Optionally, in the neural stimulation system of the present application, the control module is configured to perform the closed-loop titration procedure to adjust the parameter of the treatment stimulation signal after applying a predetermined number of treatment stimulation signals.

[0014] Optionally, in the neural stimulation system of the present application, the control module is configured to control the positive and negative poles of the multiplexed electrode to be short-circuited before collecting the evoked potential, thereby eliminating accumulated electric charge.

[0015] Optionally, in the neural stimulation system of the present application, the stimulation signal includes a forward signal and a reverse signal, and the integral of the amplitudes of the forward signal and the reverse signal over time is equal. Further, the forward signal and the reverse signal are signals with the same amplitude, opposite directions, and equal time.

[0016] Optionally, in the neural stimulation system of the present application, the control module can selectively perform signal collection, and the ratio of the number of signal collection times to the number of stimulation signal transmission times is not less than a predetermined ratio.

[0017] Optionally, in the neural stimulation system of the present application, a battery and / or an energy unlimited transmission module are further included.

[0018] In a second aspect, the present application provides a parameter adjustment method for a neural stimulation system, which can adjust the parameter of a treatment stimulation signal through a closed-loop titration procedure of stimulation intensity increase-stabilization-decrease using the neural stimulation system.

[0019] In a third aspect, the present application provides a computer readable storage medium, which stores the method instructions described above, and when executed by a processor of an implantable pulse generator, completes adaptive optimization of stimulation parameters.

[0020] The system and method of the present application have at least the following advantages:

[0021] 1. Using evoked potentials as a high-fidelity, low-latency "neural output" indicator, directly reflecting the excitability of the target pathway, avoiding the deviation caused by indirect signals, and ensuring the stimulation effect through closed-loop monitoring;

[0022] 2. By "up-stable-down" stimulation intensity scanning to capture the stimulation-response curve, using evoked potentials (EP) as high-fidelity feedback, using the parameters of the evoked potential amplitude stable stage to automatically lock the "minimum effective stimulation intensity", and realizing individualized adjustment of stimulation parameters, the "just enough" stimulation is realized, and the average energy saving is at least 20%;

[0023] 3. Through the proportion setting of feedback, the energy consumption or the power lower limit of wireless transmission is reduced;

[0024] 4. The discontinuity setting of parameter adjustment realizes the balance of therapeutic effect-energy consumption-individualization. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 Schematic diagram of an implantable neurostimulator system;

[0026] Figure 2 Schematic diagram of the titration stimulation signal and the corresponding evoked signal amplitude curve of the present application;

[0027] Figure 3 Flowchart of steady-state determination and optimal parameter selection;

[0028] Figure 4 Schematic diagram of the stimulation signal output by the signal generation module. DETAILED DESCRIPTION

[0029] Example implementations will now be described more fully with reference to the accompanying drawings. Example implementations may, however, be implemented in many different forms and should not be construed as limited to the implementations set forth herein; rather, these implementations are provided so that this disclosure will be thorough and complete, and will fully convey the inventive aspects of example implementations to those skilled in the art. Like reference numerals refer to like elements throughout the figures, and description of the same will be omitted. In addition, the drawings are only schematic and are not necessarily to scale.

[0030] Although relative terms are used herein, such as "upper", "lower", to describe one component's relationship to another component, these terms are used herein only to facilitate the description of the embodiments of the application, and do not limit the position of the components relative to each other. It is understood that if the device of the icon is turned over, the components described as "upper" will become the components described as "lower". When a structure is "on" another structure, it can mean that the structure is formed integrally on the other structure, or that the structure is "directly" disposed on the other structure, or that the structure is "indirectly" disposed on the other structure through another structure.

[0031] The terms "one", "a", "the", and "at least one" are used to denote the presence of one or more elements / specific parts / etc.; the terms "include" and "have" are used to indicate an open-ended inclusion of elements / specific parts / etc. in the following description; the terms "first", "second", are used only as labels, and do not limit the number of objects.

[0032] Embodiment 1

[0033] Referring to Figure 1 The neural stimulation system provided by the embodiment includes a stimulation device including a signal generation circuit, a control module, a signal acquisition circuit and a multiplexed electrode, the stimulation device being configured to be implanted in the body, to generate a stimulation signal and to apply the stimulation signal to a target nerve through the multiplexed electrode;

[0034] The control module is configured to perform a closed-loop titration procedure:

[0035] The signal generation circuit applies a titration stimulation signal to the target nerve according to a preset mode, in which the signal strength of the titration stimulation signal starts from an initial threshold value, steps up to a peak value, and then gradually decreases to an end threshold value after the peak value is maintained for a period of time or a number of stimulation cycles.

[0036] The signal acquisition circuit is capable of acquiring an evoked potential corresponding to the titration stimulation signal applied to the target nerve.

[0037] The stimulation parameter with the lowest signal strength in the period of the evoked potential satisfying the target threshold value is selected as the parameter of the treatment stimulation signal, which is used for subsequent application of the treatment stimulation signal.

[0038] Specifically, two signal output ends of the signal generation circuit are connected with the multiplexing electrodes respectively, the multiplexing electrodes are in nerve contact with the target nerve, and the whole constitutes a loop for transmitting the stimulation signal to the target nerve. The control module can control whether the signal generation circuit outputs the stimulation signal to the multiplexing electrodes, for example, a switching transistor (such as a bipolar junction transistor or a field effect transistor) is arranged at at least one signal output end of the signal generation circuit, when the stimulation signal needs to be output, the control module adjusts the switching transistor to the on state, and when the stimulation signal does not need to be output, the control module adjusts the switching transistor to the off state, thereby cutting off the loop for transmitting the stimulation signal.

[0039] Two signal input ends of the signal acquisition circuit are connected with the multiplexing electrodes respectively, the multiplexing electrodes are in nerve contact with the target nerve, and the whole constitutes a loop for acquiring the potential signal of the target nerve. The control module can control whether the potential signal of the target nerve is acquired, for example, a switching transistor is arranged at at least one signal input end of the signal acquisition circuit, when the signal needs to be acquired, the control module adjusts the switching transistor to the on state, and when the signal does not need to be acquired, the control module adjusts the switching transistor to the off state, thereby cutting off the loop for acquiring the potential signal.

[0040] Overall, the multiplexing electrodes can not only output the stimulation signal to realize nerve stimulation, but also acquire the potential signal to monitor the stimulation effect.

[0041] In addition, since the evoked potential signal is usually relatively weak, the acquired signal needs to be amplified, however, the power amplifier circuit has relatively high energy consumption, and high-frequency potential signal acquisition can significantly shorten the use time of the battery, therefore, in order to guarantee the use time, the signal acquisition frequency needs to be limited, which reduces the acquisition effect of the evoked potential. Moreover, the evoked potential is also easily disturbed by other noise signals.

[0042] Embodiment 2

[0043] Reference Figure 2 and Figure 3 On the basis of embodiment 1, the application provides a closed-loop parameter optimization system of a nerve stimulator, comprising an implantable pulse generator (IPG) having:

[0044] a constant current source with programmable output amplitude (0.1-25 mA, adjustable step 0.1-1 mA) or a voltage source with programmable output amplitude (0-12 V, adjustable step 0.1-1 V);

[0045] a biphasic rectangular pulse forming circuit with a pulse width of 10-500 µs and a frequency of 1-500 Hz;

[0046] a stimulation direction switching matrix supporting monopolar, bipolar and multipolar field shapes;

[0047] Integrated recording amplifier, common-mode rejection ratio > 110 dB, input-referred noise < 1 µVrms, bandwidth 0.5 Hz–5 kHz;

[0048] High-speed sampling ADC, ≥ 20 kHz, resolution ≥ 12 bit;

[0049] Processor runs:

[0050] Stimulus artifact removal module: restore evoked potential signal within 300 µs by shorting multiplexed electrodes;

[0051] Evoked potential feature extraction module: automatically identify the evoked potential peaks corresponding to the three phases of “rise-steady-fall”, and calculate the peak-to-peak average evoked potential;

[0052] Steady period determination module: exceed threshold and sliding average change amplitude does not exceed 10%;

[0053] Optimal parameter decision module: compare all (stimulus signal, evoked potential) pairs in the steady period, and select the smallest stimulus signal strength;

[0054] Wireless transceiver module for uplink data transmission and downlink physician instructions;

[0055] Rechargeable battery and power management unit.

[0056] Processor can perform closed-loop titration procedure of rise-steady-fall:

[0057] S1. Initialization: set the basic stimulation parameter set P0=(I0, f0, W0), where I0=0.1 mA, f0=10 Hz, W0=50 µs;

[0058] S2. Enter “rise-steady-fall” mode:

[0059] a. Step up current to Imax=5.0 mA with ΔI=0.5 mA / step, interval step time=2 s;

[0060] b. Maintain platform period at Imax for no less than 10 s or at least 5 stimulation cycles;

[0061] c. Reduce current to I0 with the same interval;

[0062] S3. Synchronous evoked potential acquisition: record raw evoked potential within 0.5–10 ms window after each stimulation pulse, and get calibrated evoked potential after artifact removal;

[0063] S4. Steady state determination: When the platform period of Imax is maintained, the latest 5 consecutive super-threshold evoked potentials are taken, and the change amplitude of the moving average of the evoked potentials is not more than 10%, which is marked as steady state;

[0064] S5. Optimal parameter selection: In the steady state interval, all calibrated evoked potentials are traversed, and the minimum intensity value of the stimulation signal corresponding to the threshold evoked potential is taken as the parameter of the treatment stimulation signal.

[0065] Embodiment 3

[0066] Referring to Figure 4 On the basis of any one of the preceding embodiments, the neural stimulation system provided by the application is provided, and the processor is configured to monitor the stimulation effect by collecting evoked potentials during the application of the treatment stimulation; wherein the stimulation signal comprises a positive signal and a reverse signal, and the integral of the amplitudes of the positive signal and the reverse signal in time is equal, and further, the positive signal and the reverse signal are stimulation signals with the same amplitude, opposite directions and equal time; the ratio of the number of evoked potential collection to the number of stimulation signal transmission is not less than a preset ratio, for example, 1:5, 1:10, 1:20, 1:50, etc.

[0067] Embodiment 4

[0068] On the basis of any one of the preceding embodiments, the neural stimulation system provided by the application is provided, and the processor is configured to execute the closed-loop titration program to adjust the parameters of the treatment stimulation signal after applying a fixed time of treatment stimulation signal. The fixed time can be, for example, a set time, for example, 30 minutes, 60 minutes, 4 hours, 24 hours, 7 days, etc.

[0069] Embodiment 5

[0070] On the basis of any one of embodiments 1 to 3, the neural stimulation system provided by the application is provided, and whether to enter the closed-loop titration program is determined based on the evoked potential in the closed-loop treatment stimulation process, and specifically, the signal generation circuit outputs the stimulation signal using the parameters of the treatment stimulation signal, the evoked potential generated by the stimulation signal on the target nerve is collected by the electrical stimulation, it is judged whether the evoked potential meets the target threshold, and if the evoked potential does not meet the target threshold, the closed-loop titration program is re-entered.

[0071] Embodiment 6

[0072] On the basis of any one of embodiments 1 to 3, the neural stimulation system provided by the application is provided, and the processor is configured to execute the closed-loop titration program after applying a predetermined number of treatment stimulation signals, for example, after applying a stimulation of any one of 1000, 2000, or 3000 set periods, the closed-loop titration program is re-executed to determine the subsequent stimulation parameters.

[0073] The present application can realize automatic, low-power and high-robustness stimulation parameter optimization in an implantable nerve stimulator by a "bidirectional ramp scanning + steady-state evoked potential feedback" strategy, and significantly improve long-term efficacy and patient quality of life.

[0074] It should be understood that the general description above and the detailed description below are only exemplary and explanatory, and are not limiting to the present application.

[0075] Other embodiments of the present application will be apparent to those skilled in the art from consideration of the specification and practice of the application disclosed herein. It is intended that the present application cover any and all variations of the application that come within the scope of the present application along with its general principles and including apparent variations of the technology. The specification and examples are intended to be exemplary only and the true scope and spirit of the application should be indicated by the appended claims.

Claims

1. A neural stimulation system, characterized by, The stimulation device comprises a signal generating circuit, a control module, a signal collecting circuit and a multiplexing electrode, and is arranged to be implanted in the body, to generate a stimulation signal and apply it to a target nerve through the multiplexing electrode. The control module is arranged to execute a closed-loop titration procedure. The signal generating circuit applies a titration stimulation signal to the target nerve according to a preset mode, in which the signal strength of the titration stimulation signal starts from an initial threshold value, steps up to a peak value, and then gradually decreases to an end threshold value after the peak value is maintained for a period of time or a number of stimulation cycles. The signal collecting circuit collects evoked potentials corresponding to the titration stimulation signal applied to the target nerve. The stimulation parameter with the lowest signal strength in the evoked potential period meeting the target threshold value is selected as the parameter of the treatment stimulation signal, which is used for subsequent application of the treatment stimulation signal. The stimulation parameter with the lowest signal strength in the evoked potential period meeting the target threshold value is selected as the parameter of the treatment stimulation signal, which is used for subsequent application of the treatment stimulation signal. If at least 5 consecutive evoked potentials exceed the target threshold value and the change amplitude of the sliding average of these evoked potentials does not exceed 10%, these evoked potentials are marked as steady state, and the time period corresponding to these evoked potentials is the steady state interval. In the steady state interval, the minimum intensity value in the stimulation signal corresponding to the evoked potential exceeding the target threshold value is selected as the parameter of the treatment stimulation signal. The control module is arranged to execute the closed-loop titration procedure to adjust the parameter of the treatment stimulation signal after applying the treatment stimulation signal for a fixed time.

2. The neural stimulation system of claim 1, wherein, The control module is arranged to determine whether to enter the closed-loop titration procedure based on the evoked potential in the closed-loop treatment stimulation process.

3. The neural stimulation system of claim 1, wherein, The determination of whether to enter the closed-loop titration procedure based on the evoked potential in the closed-loop treatment stimulation process is performed as follows: the signal generating circuit outputs a stimulation signal using the parameter of the treatment stimulation signal, the evoked potential generated by the stimulation signal on the target nerve is collected through the electrical stimulation, it is judged whether the evoked potential meets the target threshold value, and if the evoked potential does not meet the target threshold value, the closed-loop titration procedure is re-entered.

4. The neural stimulation system of claim 1, wherein The control module is arranged to execute the closed-loop titration procedure to adjust the parameter of the treatment stimulation signal after applying the treatment stimulation signal for a fixed time.

5. The neural stimulation system of claim 1, wherein, The control module is arranged to control the positive and negative electrodes of the multiplexing electrode to short circuit before collecting the evoked potential, to eliminate accumulated charges.

6. The neural stimulation system of claim 1, wherein, The stimulation signal comprises a forward signal and a reverse signal, and the integral of the amplitudes of the forward signal and the reverse signal over time is equal.

7. The neural stimulation system of claim 1, wherein, The forward signal and the reverse signal are signals with the same amplitude, opposite directions and equal time.

8. The neurostimulation system of claim 7, wherein, The control module can selectively execute signal collection, and the ratio of the number of signal collection times to the number of stimulation signal transmission times is not less than a preset ratio.

9. The neural stimulation system of claim 1, wherein, It also comprises a battery and / or an energy unlimited transmission module.

10. The neural stimulation system of claim 1, wherein, ​

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