Systems, devices, and computer-readable storage media for neural stimulation

Abstract

The application discloses a system, device and computer readable storage medium for nerve stimulation. The system comprises a nerve stimulator, which comprises a stimulation module configured to: determine a first energy value of a frequency band of interest in a received local field potential signal; determine a threshold range to which the first energy value belongs; and output a corresponding stimulation signal according to a stimulation scheme corresponding to the threshold range. According to the technical scheme of the embodiment of the application, a closed-loop nerve stimulation mode can be realized.

Description

Technical Field

[0001] This invention generally relates to the field of medical device technology. More specifically, this invention relates to a system, device, and computer-readable storage medium for nerve stimulation. Background Technology

[0002] Traditional deep brain stimulation (DBS) treatment for functional disorders such as Parkinson's disease often employs an open-loop stimulation approach. This open-loop approach provides a fixed, continuous stimulation output, which cannot be precisely adjusted in real-time according to the patient's clinical symptoms or disease changes. Physicians typically adjust the stimulation parameters based on the patient's clinical symptoms and clinical experience. Therefore, when patients experience changes in their clinical symptoms or disease, hospitalization is still necessary for parameter adjustment by a clinician.

[0003] Therefore, there is an urgent need to provide a stimulation system that can achieve closed-loop regulation of stimulation schemes. Summary of the Invention

[0004] In order to at least address one or more of the technical problems mentioned above, the present invention provides a system, device, and computer-readable storage medium for neural stimulation in several aspects.

[0005] In a first aspect, the present invention provides a system for neural stimulation, including a neural stimulator comprising a stimulation module configured to: determine a first energy value of a frequency band of interest in a received local field potential signal; determine a threshold range to which the first energy value belongs; and output a corresponding stimulation signal according to a stimulation scheme corresponding to the threshold range.

[0006] In some embodiments, before determining the threshold range to which the first energy value belongs, the stimulation module is further configured to: determine a second energy value of the frequency band of interest in the local field potential signal of each first state based on the local field potential signal of the patient in at least one first state; the system further includes a control terminal configured to: determine a plurality of threshold ranges according to at least one second energy value corresponding to the received at least one first state; and determine a corresponding stimulation scheme based on each threshold range.

[0007] In other embodiments, the control terminal is further configured to: sort the plurality of second energy values ​​according to their magnitude in response to receiving a plurality of second energy values; and use the sorted second energy values ​​as endpoint values ​​to divide the range into a plurality of threshold ranges.

[0008] In some other embodiments, the at least one first state includes at least one of the following: no medication taken and the neurostimulator not turned on for treatment; no medication taken and the neurostimulator turned on for treatment; medication taken and the neurostimulator not turned on for treatment; medication taken and the neurostimulator turned on for treatment.

[0009] In some embodiments, before determining the first energy value, the stimulation module is further configured to: determine a third energy value for multiple frequency bands in the local field potential signal of each second state based on the local field potential signal of the patient in multiple second states; and the control terminal is further configured to: determine the frequency band of interest in multiple frequency bands based on the amount of change between the third energy values ​​in multiple second states within each frequency band.

[0010] In other embodiments, the multiple second states include at least one of the following: no medication and the neurostimulator not turned on for treatment and medication and the neurostimulator not turned on for treatment; medication and the neurostimulator not turned on for treatment and medication and the neurostimulator turned on for treatment.

[0011] In some other embodiments, the stimulation module is further configured to: determine the first energy value based on the following formula: Among them, S x (k) represents the energy value, x[n] represents a finite-length sequence of length N in the frequency band of interest, X[k] is the discrete Fourier transform pair of the x[n] sequence, 0≤k≤N-1, N represents the sequence length, and the complex exponential signal e jwt =cos(wt)-jsin(), where the angular frequency of the periodic signal is ω = 2π / N, e represents the natural constant, and j represents the imaginary unit.

[0012] In some embodiments, the system further includes electrodes for acquiring local field potential signals in a patient's brain region and outputting stimulation pulses based on received stimulation signals; and the neurostimulator further includes an acquisition module for receiving local field potential signals acquired by the electrodes and sending them to the stimulation module.

[0013] In other embodiments, the neurostimulator further includes: a first communication module configured to transmit the second energy value; and a microcontroller configured to control the stimulation module and the first communication module; the control terminal includes: a second communication module communicatively connected to the first communication module and configured to receive the second energy value; and to transmit the threshold range and its corresponding stimulation scheme.

[0014] In a second aspect, the present invention provides a device for neural stimulation, comprising: a processor for executing program instructions; and a memory storing the program instructions, which, when loaded and executed by the processor, cause the device to perform the following operations: determining a first energy value of a frequency band of interest in a received local field potential signal; determining a threshold range to which the first energy value belongs; and outputting a corresponding stimulation signal according to a stimulation scheme corresponding to the threshold range.

[0015] In some embodiments, when the program instructions are executed by a processor, the device further causes to perform the following operations before determining the threshold range to which the first energy value belongs: determining a second energy value of a frequency band of interest in the local field potential signal of each first state based on the local field potential signal of the patient in at least one first state; determining a plurality of threshold ranges according to at least one second energy value corresponding to at least one first state; and determining a corresponding stimulation scheme based on each threshold range.

[0016] In other embodiments, when the program instructions are run by the processor, the device also performs the following operations in determining a plurality of threshold ranges: in response to receiving a plurality of second energy values, sorting them according to the magnitude of the plurality of second energy values; and using the sorted second energy values ​​as endpoint values ​​to divide the ranges into a plurality of threshold ranges.

[0017] In some other embodiments, the at least one first state includes at least one of the following: no medication taken and the neurostimulator not turned on for treatment; no medication taken and the neurostimulator turned on for treatment; medication taken and the neurostimulator not turned on for treatment; medication taken and the neurostimulator turned on for treatment.

[0018] In some embodiments, when the program instructions are executed by the processor, the device further causes to perform the following operations before determining the first energy value: determining a third energy value for a plurality of frequency bands in the local field potential signal of each second state based on the local field potential signal of the patient in a plurality of second states; and determining the frequency band of interest in the plurality of frequency bands based on the amount of variation between the third energy values ​​in the plurality of second states within each frequency band.

[0019] In other embodiments, the multiple second states include at least one of the following: no medication and the neurostimulator not turned on for treatment and medication and the neurostimulator not turned on for treatment; medication and the neurostimulator not turned on for treatment and medication and the neurostimulator turned on for treatment.

[0020] In some other embodiments, when the program instructions are executed by the processor, the device also performs the following operation in determining a first energy value: determining the first energy value based on the following formula: Among them, S x (k) represents the energy value, x[n] represents a finite-length sequence of length N in the frequency band of interest, X[k] is the discrete Fourier transform pair of the x[n] sequence, 0≤k≤N-1, N represents the sequence length, and the complex exponential signal e jwt = cos(wt)-jsin(), where the angular frequency of the periodic signal is ω=2π / N, e represents the natural constant, and j represents the imaginary unit.

[0021] In a third aspect, the present invention provides a computer-readable storage medium having computer-readable instructions stored thereon, which, when executed by one or more processors, perform operations as described in any of the devices in the second aspect of the invention.

[0022] Using the above-described technical solution for neural stimulation, the system of this invention can determine the first energy value of the frequency band of interest in the local field potential signal through the stimulation module, and output a corresponding stimulation signal according to the threshold range to which the first energy value belongs. This enables a closed-loop neural stimulation method, allowing for timely adjustment of the stimulation protocol based on real-time changes in the energy value of the acquired local field potential signal. Furthermore, in some embodiments, the stimulation module determines the third energy values ​​of multiple frequency bands in the local field potential signal under various second states. This allows for the determination of the frequency band of interest based on the changes in the third energy values ​​of different second states within each frequency band. This helps identify frequency bands of interest with higher disease relevance, thereby improving the accuracy and effectiveness of the stimulation protocol and avoiding blind overstimulation. Attached Figure Description

[0023] The above and other objects, features, and advantages of exemplary embodiments of the present invention will become readily apparent from the following detailed description taken in conjunction with the accompanying drawings. In the drawings, several embodiments of the invention are illustrated by way of example and not limitation, and like or corresponding reference numerals denote like or corresponding parts, wherein:

[0024] Figure 1 A schematic block diagram of a system for nerve stimulation according to an embodiment of the present invention is shown;

[0025] Figure 2 A schematic flowchart illustrating the output of a stimulation signal by a stimulation module according to an embodiment of the present invention is shown.

[0026] Figure 3 A graph showing the first energy value determined in real time according to an embodiment of the present invention is provided.

[0027] Figure 4 A schematic diagram illustrating the adjustment of the stimulation protocol based on a change in a first energy value, according to an embodiment of the present invention, is shown.

[0028] Figure 5 A schematic block diagram of a system including a control terminal according to an embodiment of the present invention is shown;

[0029] Figure 6 A schematic block diagram of a system including electrodes according to an embodiment of the present invention is shown;

[0030] Figure 7 Line graphs of multi-band third energy values ​​under various second states according to embodiments of the present invention are shown; and

[0031] Figure 8 A schematic block diagram of a device for nerve stimulation according to an embodiment of the present invention is shown. Detailed Implementation

[0032] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0033] It should be understood that the terms "comprising" and "including" as used in the specification and claims of this invention indicate the presence of the described features, integrals, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0034] It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention. As used in this specification and claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used in this specification and claims refers to any combination and all possible combinations of one or more of the associated listed items, and includes such combinations.

[0035] As used in this specification and claims, the term "if" may be interpreted, depending on the context, as "when," "once," "in response to determination," or "in response to detection." Similarly, the phrase "if determined" or "if [described condition or event] is detected" may be interpreted, depending on the context, as "once determined," "in response to determination," "once [described condition or event] is detected," or "in response to detection of [described condition or event]."

[0036] The specific embodiments of the present invention will now be described in detail with reference to the accompanying drawings.

[0037] Figure 1 A schematic block diagram of a system for nerve stimulation according to an embodiment of the present invention is shown. Figure 1 As shown, system 100 may include a neurostimulator 110, which may include a stimulation module 111, which may be configured to: determine a first energy value of a frequency band of interest in a local field potential signal based on a received local field potential signal; determine a threshold range to which the first energy value belongs; and output a corresponding stimulation signal according to a stimulation scheme corresponding to the threshold range.

[0038] The neurostimulator 110 can be implanted in a patient's body. In some embodiments, the neurostimulator 110 can be implanted in the patient's skull. Local field potential (LFP) signals are transient electrical signals generated in neural tissue or other tissues by the superposition and synchronization of cellular electrical activity. In some embodiments, the received LFP signal can be filtered, denoised, or processed into multiple frequency bands, with the band of interest being one or more of these bands. In other embodiments, the multiple frequency bands may include, for example, the Delta band (frequency 0-3Hz), the Theta band (frequency 4-7Hz), the Alpha band (frequency 8-12Hz), the Beta band (frequency 13-35Hz), and the Gamma band (frequency 36-200Hz). The frequency band segmentation of the LFP signal is not limited to these and can be more or fewer as needed. In still other embodiments, the band of interest can be set as needed; for example, the band of interest can be a frequency band related to the disease to be treated.

[0039] The first energy value can be obtained through the spectrum, where the spectrum represents the relationship between signal frequency and energy. The first energy value can also be calculated by combining time and frequency, where time and frequency represent the relationship between time and signal frequency. In some embodiments, the method for determining the first energy value can employ classic algorithms such as direct methods (e.g., periodogram methods), indirect methods (e.g., autocorrelation function methods), or improved direct methods (e.g., Barlett's method, Welch's method, and Nuttall's method). In other embodiments, the first energy value can be determined using algorithms such as power spectrum calculation based on parametric modeling or power spectrum calculation based on nonparametric modeling. Parametric modeling power spectrum calculation methods can include methods based on AR models, MA models, ARMA models, etc.; nonparametric modeling power spectrum calculation methods can include power spectrum estimation algorithms based on matrix eigenvalue decomposition, such as power spectrum estimation based on the MUSIC algorithm or power spectrum estimation based on eigenvectors.

[0040] In other embodiments, the stimulation module 111 may be further configured to: perform a discrete Fourier transform on the time-series signal of the frequency band of interest; and determine a first energy value based on the ratio of the square of the discrete Fourier transform result to the number of signal points in the time-series signal. Specifically, in yet another embodiment, the stimulation module 111 may be configured to: determine the first energy value based on the following formula:

[0041]

[0042]

[0043] Among them, S x (k) represents the energy value, x[n] represents a finite-length sequence of length N in the frequency band of interest, X[k] is the discrete Fourier transform pair of the x[n] sequence, 0≤k≤N-1, k can represent the frequency, N represents the sequence length (or the number of signal points), and n can represent the ordinal number of the signal points (i.e., the nth signal point). The complex exponential signal e jwt =cos(wt)-jsin(), where the angular frequency of the periodic signal is ω = 2π / N, e represents the natural constant, and j represents the imaginary unit.

[0044] After determining the first energy value of the frequency band of interest, the stimulation module 111 can determine the threshold range to which the first energy value belongs. In some embodiments, multiple threshold ranges can be preset, and the threshold range to which the first energy value belongs can be determined by comparing the first energy value with each of the multiple threshold ranges. The multiple threshold ranges can each correspond to different stimulation schemes, so that after determining the threshold range to which the first energy value belongs, the stimulation module 111 can directly output the corresponding stimulation signal according to the stimulation scheme corresponding to that threshold range. With this setup, the neurostimulator itself can adjust the stimulation output more appropriately in a timely manner based on the real-time changes in the energy value of the local field potential signal, without relying on a doctor for adjustment, thereby achieving closed-loop control of the stimulation therapy.

[0045] In some embodiments, the stimulation scheme may include a setting scheme for at least one stimulation parameter, such as the amplitude, frequency, and pulse width of the stimulation wave; outputting a corresponding stimulation signal includes outputting at least one stimulation parameter, such as the amplitude, frequency, and pulse width, or a stimulation wave formed by the stimulation parameter. In other embodiments, the stimulation module 111 may be implemented in hardware and / or software, for example, in the form of an integrated circuit. To better understand the operation performed by the stimulation module 111, the following will be combined with... Figure 2 An illustrative example is provided.

[0046] Figure 2 A schematic flowchart illustrating the output of a stimulation signal by a stimulation module according to an embodiment of the present invention is shown. Figure 2 As shown in Figure 2 , in step 210, the stimulation module can receive local field potential signals from brain regions in real time. In some embodiments, the local field potential signals from brain regions can be collected in real time by brain electrodes. Then, in step 220, the stimulation module can determine a first energy value n1 of an interested frequency band in the real-time received local field potential signals. It can be understood that since the local field potential signals are obtained in real time, the first energy value n1 can be obtained in real time. The specific implementation manner of step 220 has been described in detail in the foregoing in conjunction with Figure 1 and will not be elaborated here.

[0047] Then, the process can proceed to step 230, where the threshold range to which the first energy value n1 belongs can be determined. Specifically, it is assumed that the preset multiple threshold ranges include less than a, between a and b, between b and c, and greater than or equal to c, where a, b, and c respectively represent the endpoint values of each threshold range and can increase in sequence. Each threshold range can respectively correspond to at least one stimulation scheme. For example, the threshold range less than a in the figure can correspond to stimulation scheme A, the threshold range between a and b can correspond to stimulation scheme B, the threshold range between b and c can correspond to stimulation scheme C, and the threshold range greater than or equal to c can correspond to stimulation scheme D.

[0048] When the stimulation module executes step 230, the first energy value can be compared with a, b, and c respectively to determine the threshold range to which the first energy value n1 belongs. In response to the first energy value n1 belonging to the threshold range less than a, step 241 can be executed to run stimulation scheme A and output a corresponding stimulation signal according to the stimulation parameters set in stimulation scheme A. In response to the first energy value n1 belonging to the threshold range a ≤ n1 < b, step 242 can be executed to run stimulation scheme B and output a corresponding stimulation signal according to the stimulation parameters set in stimulation scheme B. In response to the first energy value n1 belonging to the threshold range b ≤ n1 < c, step 243 can be executed to run stimulation scheme C and output a corresponding stimulation signal according to the stimulation parameters set in stimulation scheme C. In response to the first energy value n1 belonging to the threshold range ≥ c, step 244 can be executed to run stimulation scheme D and output a corresponding stimulation signal according to the stimulation parameters set in stimulation scheme D.

[0049] According to such a setting, the stimulation module can automatically output a more appropriate stimulation signal in real time based on the locally received field potential signals in real time, rather than continuously stimulating fixedly until the doctor manually adjusts. Further, to more easily understand the specific process of the stimulation module adjusting the stimulation scheme in real time according to the threshold range to which the first energy value determined in real time belongs, the following will be described by way of example in conjunction with Figure 3 and Figure 4 for illustrative purposes.

[0050] Figure 3 A graph showing the first energy value determined in real time according to an embodiment of the present invention is illustrated. By determining the first energy value of the frequency band of interest in the received local field potential signal in real time by the stimulation module, for example, Figure 3 The energy curve shown is illustrated below. Figure 3 As shown in the figure, the horizontal axis T in the graph represents time, the vertical axis represents energy value, a, b, and c represent the endpoint values ​​of each threshold range (their positions are shown by dashed lines in the figure), and t1, t2, t3, t4, t5, t6, t7, t8, t9, t10, t11, t12, and t13 represent different time points (their positions in the curve are shown by dotted lines in the figure). In some embodiments, a can be set to, for example, 1.14 μVp, b can be set to, for example, 1.41 μVp, and c can be set to, for example, 1.67 μVp.

[0051] As further illustrated in the figure, the threshold range less than 'a' corresponds to stimulation scheme A; the threshold range from 'a' to 'b' corresponds to stimulation scheme B; the threshold range from 'b' to 'c' corresponds to stimulation scheme C; and the threshold range exceeding 'c' corresponds to stimulation scheme D. In a specific implementation, different stimulation schemes can be set by using one stimulation parameter as a variable and other stimulation parameters as fixed values. For example, stimulation scheme A may include outputting a stimulation current (i.e., amplitude) of 1.5mA, stimulation scheme B may include outputting a stimulation current of 2.0mA, stimulation scheme C may include outputting a stimulation current of 3.0mA, and stimulation scheme D may include outputting a stimulation current of 3.6mA. Furthermore, the frequency in stimulation schemes A, B, C, and D can all be set to 200Hz and the pulse width to 160μs.

[0052] Figure 4 A schematic diagram is shown illustrating the adjustment of the stimulation scheme according to a change in a first energy value according to an embodiment of the present invention. Figure 4 According to Figure 3 The energy curve shown is a schematic diagram for adjusting the output stimulus scheme. (See diagram for example.) Figure 4 As shown in the figure, the horizontal axis T of the line graph represents time, the vertical axis represents the stimulation current value output by the system according to the embodiment of the present invention, A, B, C, and D respectively represent the stimulation current values ​​set by each stimulation scheme (their positions are shown by dashed lines in the figure), and a, b, and c respectively represent the endpoint values ​​of each threshold range.

[0053] contrast Figure 3 and Figure 4 It can be seen that, Figure 3 In the energy value curve shown, before time point t1, the first energy value is between a and b, corresponding to stimulus scheme B. Therefore, in Figure 4As shown in the schematic diagram of the stimulus protocol, up to time t1, the system output stimulus current is under stimulus protocol B. Further, as... Figure 3 As shown in the figure, the first energy value between t1 and t2 is between b and c, corresponding to stimulus scheme C. Therefore, in... Figure 4 As shown, between t1 and t2, the system output stimulation current gradually increases to the position corresponding to stimulation scheme C and remains stable. After t2, due to the change in the first energy value, the corresponding stimulation scheme changes, and thus the output stimulation current adjusts accordingly. Similarly, the stimulation output at time points t3 to t13 and thereafter changes with the first energy value, which will not be elaborated further here.

[0054] The above combination Figures 1-4 A closed-loop modulation stimulation scheme system according to embodiments of the present invention has been described. It is understood that by adjusting the stimulation output according to changes in the threshold range to which the first energy value belongs in the embodiments of the present invention, the stimulation scheme can be automatically adjusted in real time according to the patient's real-time condition changes, forming a continuous adaptive closed-loop stimulation adjustment, rather than a fixed stimulation output. It is also understood that the above description is exemplary and not limiting; for example, the number of threshold ranges may not be limited to... Figure 2 The four shown can be set to more or fewer as needed. Endpoint values ​​of the threshold range (e.g.) Figures 2-4 The values ​​of a, b, and c) shown can be set as needed. For example, the number of stimulation programs is not limited to the four shown in the figure; more or fewer can be set as needed. The stimulation program is not limited to setting a stimulation current output; a stimulation voltage can also be set as needed. Furthermore, the system according to embodiments of the present invention is not limited to including only a neurostimulator, but may also include other devices. The following will combine... Figure 5 An exemplary description is provided.

[0055] Figure 5 A schematic block diagram of a system including a control terminal according to an embodiment of the present invention is shown. Figure 5 As shown, the system 500 may include a neurostimulator 110 and a control terminal 510. The neurostimulator 110 may include a stimulation module 111, which, before determining the threshold range to which the first energy value belongs, may also be configured to: determine a second energy value of a frequency band of interest in the local field potential signal of each first state based on the local field potential signal of the patient in at least one first state; the control terminal 510 may be configured to: determine a plurality of threshold ranges according to at least one second energy value corresponding to the received at least one first state; and determine a corresponding stimulation scheme based on each threshold range.

[0056] In some embodiments, the first state may include no medication taken and the neurostimulator not activated, no medication taken and the neurostimulator activated, medication taken and the neurostimulator not activated, and medication taken and the neurostimulator activated, etc., and at least one first state may include at least one of these. In some application scenarios, at least one first state may include one first state, such as no medication taken and the neurostimulator activated. In other application scenarios, at least one first state may include multiple first states, such as no medication taken and the neurostimulator not activated, and medication taken and the neurostimulator activated, etc.

[0057] The stimulation module 111 can determine a second energy value of the frequency band of interest in the local field potential signal under each first state based on the local field potential signal under each first state, so as to obtain multiple threshold ranges and their corresponding stimulation schemes determined according to at least one second energy value corresponding to at least one first state. One or more segments of local field potential signal can be acquired under each first state. At least one second energy value can be determined under each first state. In some embodiments, a segment of local field potential signal can be acquired under each first state to determine a corresponding second energy value. In other embodiments, multiple segments of local field potential signal can be acquired under at least one of multiple first states, and correspondingly, multiple second energy values ​​can be obtained under at least one first state. The method for determining the second energy value can be combined with the foregoing description. Figure 1 The methods for determining the first energy value described are the same or similar, and will not be repeated here.

[0058] In some embodiments, the control terminal 510 can be implemented, for example, by a host computer, programmable software / programmable device, etc. In other embodiments, the control terminal 510 can be further configured to: in response to receiving a second energy value, divide two threshold ranges using the second energy value as a dividing point. For example, assuming the control terminal 510 receives a second energy value 'a' corresponding to a first state, it can divide the threshold ranges into two categories: less than a and greater than or equal to a, using a as a dividing point.

[0059] In still other embodiments, the control terminal 510 can be further configured to, upon determining multiple threshold ranges: sort in accordance with the magnitudes of multiple second energy values in response to receiving the multiple second energy values; and use the sorted second energy values as endpoint values for dividing into multiple threshold ranges. For example, assume that the control terminal 510 receives three second energy values a, b, and c corresponding to three first states, and a < b < c. Then, they can be arranged in the order of a, b, and c, and a, b, and c are used as endpoint values to divide the threshold ranges. For example, it can be divided into two threshold ranges between a (including a) and b, and between b (including b) and c, or it can be divided into four threshold ranges less than a, between a (including a) and b, between b (including b) and c, and greater than or equal to c.

[0060] After obtaining multiple threshold ranges, corresponding stimulation schemes can be set according to the high and low levels between the threshold ranges. The setting of the stimulation scheme can be achieved by a doctor operating on the control terminal 510, or can be achieved through technologies such as preset logic or machine learning. The stimulation schemes corresponding to different threshold ranges can be different or the same. The types of stimulation parameters adjusted in different stimulation schemes can be the same or different. For example, the adjustment amplitude is set in one stimulation scheme, and the adjustment frequency is set in another stimulation scheme, etc.

[0061] The above combination Figure 5 has made an exemplary description of the system including a control terminal and the method for determining multiple threshold ranges according to the embodiments of the present invention. It can be understood that by using the control terminal to divide the threshold ranges and formulate corresponding stimulation schemes, and then storing the multiple threshold ranges and their corresponding stimulation schemes in the nerve stimulator, it is equivalent to preloading the treatment schemes for different conditions by doctors into the nerve stimulator in advance. Thus, the nerve stimulator can perform closed-loop real-time adjustment of the stimulation output by monitoring the changes in the patient's condition in real time, without the need for the doctor to make manual judgments and adjustments in the hospital. Therefore, while improving the stimulation effect, it can also provide great convenience for doctors and patients, reducing the pain during the disease process that may be brought about by changes in the patient's condition and the doctor's diagnosis and treatment costs. In addition, performing closed-loop stimulation regulation based on the stimulation scheme provided by the doctor is more conducive to improving the accuracy and stimulation effect of the stimulation scheme. It can also be understood that the above description is exemplary rather than restrictive. For example, the system according to the embodiments of the present invention may not be limited to including the nerve stimulator 110 and the control terminal, and may also include, for example, electrodes. The following will be described in combination with Figure 6 for illustration.

[0062] Figure 6 shows a schematic block diagram of a system including an electrode according to an embodiment of the present invention. As Figure 6As shown, the system 600 may include a neurostimulator 110, a control terminal 510, and an electrode 610. The electrode 610 may be used to acquire local field potential signals in the patient's brain region and to output stimulation pulses according to the received stimulation signals. The neurostimulator 110 may include a stimulation module 111 and a acquisition module 621. The acquisition module 621 may be used to receive the local field potential signals acquired by the electrode 610 and send them to the stimulation module 111.

[0063] In some embodiments, electrode 610 may have four contacts, all of which can be used to acquire local field potential signals and output stimulation pulses. Specifically, in some applications, when using electrode 610 for acquisition, any two contacts can be selected as a positive electrode and a negative electrode. When using electrode 610 to output stimulation pulses, four contacts and a stimulator housing can be configured, where each of the four contacts can be set as either a positive or negative electrode, and the housing can be set as a positive electrode. For example, in other applications, unipolar stimulation can be configured, i.e., the housing is set as a positive electrode and any one contact is set as a negative electrode; bipolar stimulation can also be configured, where any two contacts are set as a positive and a negative electrode respectively; multiple negative electrode stimulation can also be configured, i.e., the housing is a positive electrode and all four contacts are negative electrodes, or one contact is a positive electrode and the other three contacts are negative electrodes.

[0064] In some embodiments, the system according to the present invention may include an in vivo implantable device and an external device (i.e., a control terminal 510). The in vivo implantable device may include a neurostimulator 110 and an electrode 610. The electrode 610 may be implanted in a corresponding brain region within the patient's skull. The neurostimulator 110 may be connected to the electrode 610 and implanted in the patient's skull to output stimulating electrical pulses to the corresponding brain region via the electrode 610. In other embodiments, the electrode 610 may be implanted in a brain region related to the disease to be treated, such as common implantation targets for Parkinson's disease treatment, such as the medial part of the globus pallidus (GPi), the subthalamic nucleus (STN), and the ventral intermediate nucleus of the thalamus (Vim). The number of electrodes 610 implanted in the patient may be one or more as needed. For example, two electrodes 610 may be provided to obtain data from a dual-channel electrode 610.

[0065] In some other embodiments, the neurostimulator 110 may also include a acquisition module 621, which can be connected to the electrode 610 to control the electrode 610 to acquire local field potential signals of the corresponding brain region, so as to sense the local field potential signals of the patient's brain region in real time through the electrode 610, and send the received local field potential signals to the stimulation module 111 for processing.

[0066] like Figure 6As further shown in some embodiments, the neurostimulator 110 may also include: a first communication module 622 configured to transmit a second energy value; and a microcontroller unit 623 configured to control the stimulation module 111, the first communication module 622, and the acquisition module 621, and to merge results from multiple channels, i.e., to control the aggregation and switching of instruction signals between the processing modules. The control terminal 510 may include: a second communication module 631 communicatively connected to the first communication module 622 and configured to receive the second energy value; and to transmit a threshold range and its corresponding stimulation scheme.

[0067] In some embodiments, the first communication module 622 and the second communication module 631 can be wirelessly connected. Through the communication link established between the first communication module 622 and the second communication module 631, acquisition commands and programmed stimulation commands from the control terminal 510 can be sent to the neurostimulator 110, and the neurostimulator 110 can also send the real-time acquired LFP signals to the control terminal 510. Further, in other embodiments, the control terminal 510 may also include an interactive interface 632 for human-computer interaction. In some application scenarios, doctors can use the interactive interface 632 on the control terminal 510 to issue acquisition commands for local field potential signals and / or programmed stimulation commands, etc.

[0068] This setup allows doctors to monitor the patient's condition and the dynamic stimulation effect of the neurostimulator 110 in real time. It also enables the analysis and evaluation of the patient's condition progression based on LFP data, allowing for the objective setting of threshold ranges and stimulation protocols to achieve optimal treatment results. In some embodiments, the system 600 may further include a server. The control terminal 510 can connect to the server via 4G, 5G, WIFI, or other methods, and can upload LFP data to the server for storage and / or data processing.

[0069] The above combination Figure 6 A system comprising electrodes, a neurostimulator, and a control terminal according to embodiments of the present invention has been described exemplarily. It is understood that the above description is exemplary and not limiting. For example, the control terminal 510 is not limited to including only a second communication module and / or an interactive interface, but may also include a processor and a memory, etc. Furthermore, the system according to embodiments of the present invention may not be limited to simultaneously including electrodes, a neurostimulator, and a control terminal, but may also include only electrodes and a neurostimulator.

[0070] Furthermore, the stimulation module and / or control terminal may not be limited to performing only the aforementioned operations. For example, in some embodiments, before determining the first energy value, the stimulation module may also be configured to: determine the third energy value of multiple frequency bands in the local field potential signal of each second state based on the local field potential signal of the patient in multiple second states, i.e., determine the third energy value of each frequency band in each second state; and the control terminal may also be configured to: determine the frequency band of interest in multiple frequency bands based on the amount of change between the third energy values ​​of multiple second states within each frequency band. The following will combine... Figure 7 An exemplary description is provided of the method for determining the frequency band of interest.

[0071] Figure 7 Line graphs of multi-band third energy values ​​under various second states according to embodiments of the present invention are shown. Figure 7 As shown in the diagram, the horizontal axis of the line graph represents the LFP frequency, which can be divided into multiple frequency bands based on its magnitude, such as the Delta band (0-3Hz), Theta band (4-7Hz), Alpha band (8-12Hz), Beta band (13-35Hz), and Gamma band (36-200Hz). The vertical axis of the line graph represents the third energy value determined based on the LFP signal.

[0072] In some embodiments, multiple second states may include at least one group of the following: treatment without medication and neurostimulator not activated, treatment with medication and neurostimulator not activated; treatment with medication and neurostimulator not activated, treatment with medication and neurostimulator activated, etc. Taking the group of multiple second states including treatment without medication and neurostimulator not activated as an example, such as... Figure 7 The broken line 701 shown is formed by connecting the third energy values ​​of each frequency band of the local field potential signal detected in the treatment state without medication and with the neurostimulator off. The broken line 702 is formed by connecting the third energy values ​​of each frequency band of the local field potential signal detected in the treatment state with medication administered and the neurostimulator off. The method for determining the third energy value can be combined with the methods described above. Figure 1 The calculation method for the first energy value described is the same or similar, and will not be repeated here.

[0073] After receiving multiple third energy values ​​from various second states, the control unit can process the data to form... Figure 7 The energy comparison line graph shown illustrates the variations in the third energy value across different second states within each frequency band. In some embodiments, by comparing the distances between the lines representing different second states within each frequency band, frequency bands with significant differences in the third energy value can be identified and designated as frequency bands of interest.

[0074] by Figure 7 For example, comparing the differences between line segments 701 and 702 in each frequency band, it can be seen that the variation between line segments 701 and 702 is the largest in the Beta band (frequency 13-35Hz). That is, the variation in the third energy value among the various second states represented by line segments 701 and 702 is the largest. Furthermore, a peak value of the third energy value appears at 703 of line segment 701, with a frequency of 21.65Hz and a third energy value of 1.24μVp. Based on this, it is indicated that the Beta band is more correlated with the patient's condition; therefore, the Beta band can be identified as the band of interest.

[0075] The above combination Figure 7 The method for determining the frequency band of interest according to embodiments of the present invention has been described exemplarily. It is understood that the above description is exemplary and not limiting. For example, the method may not be limited to determining the change in the third energy value between different second states within each frequency band by drawing a line graph, but may also be determined directly by calculating the difference between the third energy values ​​between different second states within each frequency band, thereby determining the frequency band of interest. Furthermore, the operation of determining the frequency band of interest may not be limited to being performed by the control terminal, but may also be implemented by the stimulation module.

[0076] According to the technical solution of the present invention, a device for nerve stimulation is also provided in a second aspect, which will be described below in conjunction with... Figure 8 Please provide an explanation.

[0077] Figure 8 A schematic block diagram of a device for nerve stimulation according to an embodiment of the present invention is shown. Figure 8 As shown, the device 800 may include: a processor 810, which can be used to execute program instructions; and a memory 820, which can store program instructions that, when loaded and executed by the processor 810, enable the device 800 to perform the following operations: determining a first energy value of a frequency band of interest in the received local field potential signal; determining a threshold range to which the first energy value belongs; and outputting a corresponding stimulation signal according to the stimulation scheme corresponding to the threshold range.

[0078] In some embodiments, when the program instructions are executed by the processor 810, the device 800 is also caused to perform the following operations before determining the threshold range to which the first energy value belongs: determining a second energy value of the frequency band of interest in the local field potential signal in each of the multiple first states based on the local field potential signals of the patient in multiple first states; determining multiple threshold ranges according to the multiple second energy values ​​corresponding to the multiple first states; and determining a corresponding stimulation scheme based on each threshold range.

[0079] In other embodiments, when the program instructions are run by the processor 810, the device 800 also performs the following operations in determining a plurality of threshold ranges: sorting according to the magnitude of a plurality of second energy values; and using the sorted second energy values ​​as endpoint values ​​to divide the ranges into a plurality of threshold ranges.

[0080] In some other embodiments, the multiple first states may include at least two of the following: no medication taken; medication taken; medication effect worn off; no medication taken and the neurostimulator not turned on for treatment; no medication taken and the neurostimulator turned on for treatment; medication taken and the neurostimulator not turned on for treatment; medication taken and the neurostimulator turned on for treatment.

[0081] In some embodiments, when the program instructions are executed by the processor 810, the device 800 is also caused to perform the following operations before determining the first energy value: determining a third energy value for a plurality of frequency bands in the local field potential signal of each second state based on the local field potential signal of the patient in a plurality of second states; and determining the frequency band of interest in the plurality of frequency bands based on the amount of change between the third energy values ​​in the plurality of second states within each frequency band.

[0082] In other embodiments, various second states may include before and after taking the medication.

[0083] In some other embodiments, when the program instructions are executed by the processor 810, the device 820 also performs the following operation in determining a first energy value: determining the first energy value based on the following formula: Among them, s x (k) represents the energy value, x[n] represents a finite-length sequence of length N in the frequency band of interest, X[k] is the discrete Fourier transform pair of the x[n] sequence, 0≤k≤N-1, N represents the sequence length, and the complex exponential signal e jwt = cos(wt)-jsin(), where the angular frequency of the periodic signal is ω=2π / N, e represents the natural constant, and j represents the imaginary unit.

[0084] It is understood that the specific implementation of the device according to the embodiments of the present invention has been described in detail above in conjunction with the implementation of the system, and will not be repeated here.

[0085] Furthermore, in the technical solution of the present invention, a computer-readable storage medium is also provided in the third aspect, on which computer-readable instructions are stored, which, when executed by one or more processors, implement the operations performed by the device as described in any of the second aspects of the present invention.

[0086] Computer-readable storage media can be any suitable magnetic or magneto-optical storage medium, such as Resistive Random Access Memory (RRAM), Dynamic Random Access Memory (DRAM), Static Random Access Memory (SRAM), Enhanced Dynamic Random Access Memory (EDRAM), High-Bandwidth Memory (HBM), Hybrid Memory Cube (HMC), etc., or any other medium that can be used to store desired information and can be accessed by an application, module, or both. Any such computer storage medium can be part of a device or accessible to or connected to a device. Any application or module described in this disclosure can be implemented by computer-readable / executable instructions stored or otherwise maintained on such a computer-readable medium.

[0087] The foregoing detailed description of the technical solution for nerve stimulation according to the present invention, in conjunction with multiple embodiments, illustrates that the system according to embodiments of the present invention calculates a first energy value of the frequency band of interest in the local field potential signal through a stimulation module, and outputs a corresponding stimulation signal based on the threshold range to which the first energy value belongs and its corresponding stimulation scheme. This enables the system according to embodiments of the present invention to achieve closed-loop adaptive stimulation control to adapt to real-time changes in the patient's condition. Furthermore, by using the induced local field potential (LFP) signal as the basis for treatment parameter tuning, it possesses objectivity and real-time performance.

[0088] Furthermore, in some embodiments, by comparing the changes in the third energy value to determine the frequency band of interest, a targeted treatment plan for individualized conditions can be established. By identifying signal frequency bands with high relevance to different diseases in different patients, individualized targeted stimulation plans can be set. Compared to formulating stimulation plans based on the entire frequency band, determining the frequency band of interest and determining the threshold range based on the energy value of the frequency band of interest, according to embodiments of the present invention, is beneficial to improving the accuracy of stimulation therapy and to avoiding blind overstimulation.

[0089] While numerous embodiments of the invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Many modifications, alterations, and alternatives will occur to those skilled in the art without departing from the spirit and essence of the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in the practice of the invention. The appended claims are intended to define the scope of protection of the invention and therefore cover equivalents or alternatives within the scope of these claims.

Claims

1. A system for neural stimulation, comprising a neural stimulator including a stimulation module configured to: Based on the received local field potential signal, determine the first energy value of the frequency band of interest in the local field potential signal; Determine the threshold range to which the first energy value belongs; and Based on the stimulation scheme corresponding to the threshold range, output the corresponding stimulation signal; Before determining the threshold range to which the first energy value belongs, the stimulation module is further configured to: Based on the local field potential signal of the patient in at least one first state, determine the second energy value of the frequency band of interest in the local field potential signal in each first state; The system also includes a control terminal, which is configured for: Based on at least one second energy value corresponding to at least one first state received, determine multiple threshold ranges; and based on each threshold range, determine a corresponding stimulation scheme; The at least one first state includes at least one of the following: No medication was taken and the neurostimulator was not activated during treatment; Treatment was initiated without medication and with the neurostimulator activated. Medication has been taken and the neurostimulator has not been activated for treatment; The patient has already taken medication and the neurostimulator has been activated for treatment. Before determining the first energy value, the stimulation module is also configured to: Based on the patient's local field potential signals in various second states, the third energy values ​​of multiple frequency bands in the local field potential signals of each second state are determined; and The control terminal is also configured to: Based on the change in the third energy value under various second states within each frequency band, the frequency band of interest is determined within multiple frequency bands; The plurality of second states includes at least one of the following: Treatment without medication and with neurostimulator not turned on; and treatment with medication but with neurostimulator not turned on. Treatment with medication already taken and neurostimulator not yet activated, and treatment with medication already taken and neurostimulator already activated.

2. The system according to claim 1, wherein the control terminal is further configured to: In response to receiving multiple second energy values, sort them according to the magnitude of the multiple second energy values; and The sorted second energy value is used as the endpoint value to divide the data into multiple threshold ranges.

3. The system of claim 1, wherein the stimulation module is further configured to: The first energy value is determined based on the following formula: ； ； in, Indicates energy value. This represents a finite-length sequence of length N representing the frequency band of interest. yes Discrete Fourier transform pairs of sequences, 0 ≤ k ≤ N-1, where N represents the sequence length, complex exponential signal. The angular frequency of the periodic signal is ω = 2π / N, where e represents the natural constant and j represents the imaginary unit.

4. The system according to any one of claims 1-3 further includes electrodes for acquiring local field potential signals in a patient's brain region and outputting stimulation pulses according to the received stimulation signals; and The neurostimulator also includes a data acquisition module, which receives local field potential signals acquired by the electrodes and sends them to the stimulation module.

5. The system according to claim 1, wherein The neurostimulator also includes: A first communication module, configured to send the second energy value; as well as A microcontroller unit configured to control the stimulation module and the first communication module; The control terminal includes: The second communication module is communicatively connected to the first communication module and configured to receive the second energy value; And send the threshold range and its corresponding stimulation scheme.

6. A device for nerve stimulation, comprising: A processor is used to execute program instructions; as well as A memory storing the program instructions, which, when loaded and executed by the processor, cause the device to perform the following operations: Based on the received local field potential signal, determine the first energy value of the frequency band of interest in the local field potential signal; Determine the threshold range to which the first energy value belongs; and Based on the stimulation scheme corresponding to the threshold range, output the corresponding stimulation signal; When the program instructions are executed by the processor, the device also performs the following operations before determining the threshold range to which the first energy value belongs: Based on the local field potential signal of the patient in at least one first state, determine the second energy value of the frequency band of interest in the local field potential signal in each first state; Obtain multiple threshold ranges determined according to at least one second energy value corresponding to at least one first state, and a corresponding stimulation scheme determined based on each threshold range; Wherein, the at least one first state includes at least one of the following: No medication was taken and the neurostimulator was not activated during treatment; Treatment was initiated without medication and with the neurostimulator activated. Medication has been taken and the neurostimulator has not been activated for treatment; The patient has already taken medication and the neurostimulator has been activated for treatment. When the program instructions are executed by the processor, the device also performs the following operations before determining the first energy value: Based on the patient's local field potential signals in various second states, the third energy values ​​of multiple frequency bands in the local field potential signals of each second state are determined; and Based on the change in the third energy value under various second states within each frequency band, the frequency band of interest is determined within multiple frequency bands; The multiple second states include at least one of the following: Treatment without medication and with neurostimulator not turned on; and treatment with medication but with neurostimulator not turned on. Treatment with medication already taken and neurostimulator not yet activated, and treatment with medication already taken and neurostimulator already activated.

7. The device of claim 6, wherein when the program instructions are executed by the processor, the device further causes to perform the following operations within a plurality of threshold ranges: In response to receiving multiple second energy values, sort them according to the magnitude of the multiple second energy values; and The sorted second energy value is used as the endpoint value to divide the data into multiple threshold ranges.

8. The device of claim 6, wherein when the program instructions are executed by the processor, the device further causes to perform the following operations in determining the first energy value: The first energy value is determined based on the following formula: ； ； in, Indicates energy value. This represents a finite-length sequence of length N representing the frequency band of interest. yes Discrete Fourier transform pairs of sequences, 0 ≤ k ≤ N-1, where N represents the sequence length, complex exponential signal. The angular frequency of the periodic signal is ω = 2π / N, where e represents the natural constant and j represents the imaginary unit.

9. A computer-readable storage medium having stored thereon computer-readable instructions that, when executed by one or more processors, perform the operations performed by the device as described in any one of claims 6-8.

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