Pulse generator and electrical stimulation device

Abstract

A pulse generator and an electrical stimulation device. The pulse generator is used for generating at least one group of stimulation pulse signals for neuromodulation. The stimulation pulse signals include at least one first pulse signal and at least one second pulse signal. The pulse width of the first pulse signal is smaller than that of the second pulse signal, and the pulse amplitude of the first pulse signal is larger than that of the second pulse signal. Pulse signal parameters of the stimulation pulse signals comprise at least one of the following: the pulse amplitude of the stimulation pulse signals ranges from 0 to 10 V or from 0 to 100 mA; the pulse width of the stimulation pulse signals ranges from 0 to 1,000 μs; and the frequency of the stimulation pulse signals ranges from 60 Hz to 20 kHz. Rapid and efficient nervous tissue stimulation can be achieved, and potential damage to nervous tissue can be reduced.

Description

Pulse generator and electrical stimulation device TECHNICAL FIELD

[0001] The present disclosure relates to the technical field of medical instruments, and in particular, the present disclosure relates to a pulse generator and an electrical stimulation device. BACKGROUND

[0002] Neural modulation technology is a technology that stimulates neural tissue with electrical or magnetic signals to change the electrical activity of nerve cells and thus affect the physiological functions of the human body. This technology has been widely used in the medical field, such as deep brain stimulation (DBS) for treating Parkinson's disease, epilepsy, etc., and spinal cord stimulation (SCS) for treating chronic pain, etc.

[0003] In related technologies, a pulse signal generator is usually used to generate a specific pulse signal to stimulate neural tissue. SUMMARY

[0004] The present disclosure aims to solve at least one aspect of the above technical problems.

[0005] The present disclosure provides a pulse generator, comprising:

[0006] for generating at least one set of stimulation pulse signals for neural modulation, the stimulation pulse signals comprising at least one first pulse signal and at least one second pulse signal, the pulse width of the first pulse signal being smaller than the pulse width of the second pulse signal, the pulse amplitude of the first pulse signal being greater than the pulse amplitude of the second pulse signal, the pulse signal parameters of the stimulation pulse signals comprising at least one of the following: the pulse amplitude of the stimulation pulse signals ranges from 0 to 10 volts or 0 to 100 milliamperes, the pulse width of the stimulation pulse signals ranges from 0 to 1000 microseconds, and the frequency of the stimulation pulse signals ranges from 60 hertz to 20 kilohertz.

[0007] In some embodiments, the stimulation pulse signals comprise a first pulse signal sequence and a second pulse signal sequence output alternately; the first pulse signal sequence comprises at least one first pulse signal, and the second pulse signal sequence comprises at least one second pulse signal.

[0008] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected;

[0009] The controller is configured to adjust the inter-pulse interval between the stimulation pulse signals generated by the pulse generation unit according to the amplitude of the desired inverse group peak potential and a first model; the first model comprises a piecewise linear model or a piecewise exponential model, and is used to characterize the correspondence between the amplitude of the normalized inverse group peak potential during the steady state of the stimulation pulse signals and the inter-pulse interval varying within a preset range.

[0010] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected;

[0011] The controller is configured to control the pulse generation unit to output the first pulse signal first and then output the second pulse signal in a subsequent stimulation pulse signal when parameter values of a plurality of parameter items of the real-time neural signal of the subject are within a first threshold range; and control the pulse generation unit to output the second pulse signal first and then output the first pulse signal in a subsequent stimulation pulse signal when parameter values of the plurality of parameter items of the real-time neural signal are within a second threshold range; the parameter items of the stimulation pulse signal include at least one of a pulse amplitude, a pulse width, a first interphase interval, and a pulse interval.

[0012] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected;

[0013] The controller is further configured to determine, based on a first model, whether the real-time neural signal of the subject meets at least one indication or a pre-onset symptom of the indication; if so, adjust a parameter item of a subsequent stimulation pulse signal based on a parameter value of a stimulation pulse signal corresponding to the indication; the first model further comprises a corresponding relationship among at least one indication and / or a pre-onset symptom thereof, a related neural signal, and a parameter value of a parameter item of a related stimulation pulse signal; the parameter items of the stimulation pulse signal include at least one of a pulse amplitude, a pulse width, a first interphase interval, and a pulse interval.

[0014] The present disclosure provides an electrical stimulation device, comprising an electrode and a pulse generator as described above;

[0015] The electrode is electrically connected to the pulse generator and configured to apply the stimulation pulse signal to a neural-related target point of the subject.

[0016] In some embodiments, the electrical stimulation device is configured to block transmission of a pain signal.

[0017] The pulse generator is configured to generate at least one set of stimulation pulse signals, the stimulation pulse signals comprising at least two types of pulse signals, at least one of a pulse amplitude, a pulse width, and a frequency being different between different types of the pulse signals, the pulse amplitude of the stimulation pulse signals ranging from 0 to 10 volts or 0 to 30 milliamperes, the pulse width of the stimulation pulse signals ranging from 0 to 2000 microseconds, and the frequency of the stimulation pulse signals ranging from 0 to 100 kilohertz.

[0018] The electrode comprises a wire electrode disposed at a spinal cord and / or a pain area of the subject and electrically connected to the pulse generator, and configured to output the stimulation pulse signal to stimulate a pain-related nerve at the spinal cord and / or the pain area of the subject.

[0019] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected; the lead electrode is electrically connected to the pulse generation unit;

[0020] The electrical stimulation device further comprises a recording electrode, which is arranged near the spinal cord and / or the pain area of the subject and is spaced apart from the lead electrode by a preset distance, and is electrically connected to the controller, and is used to detect the action potential of the axon at the spinal cord and / or the pain area and send it to the controller after the lead electrode outputs the stimulation pulse signal.

[0021] The controller is used to adjust the parameter item of the stimulation pulse signal subsequently generated by the pulse generation unit based on the action potential; the parameter item of the stimulation pulse signal includes at least one of pulse amplitude, pulse width, first phase interval, and pulse interval.

[0022] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected;

[0023] The controller is used to control the pulse generation unit to output the first pulse signal first and then output the second pulse signal in the stimulation pulse signal subsequently generated by the pulse generation unit when the parameter value of the parameter item of the real-time neural signal of the subject is in the first threshold range, and control the pulse generation unit to output the second pulse signal first and then output the first pulse signal in the stimulation pulse signal subsequently generated by the pulse generation unit when the parameter value of the parameter item of the real-time neural signal is in the second threshold range; the parameter item of the stimulation pulse signal includes at least one of pulse amplitude, pulse width, first phase interval, and pulse interval.

[0024] In some embodiments, the stimulation pulse signal comprises a first pulse signal sequence and a second pulse signal sequence; the frequency of the first pulse signal sequence is higher than the frequency of the second pulse signal sequence.

[0025] The first pulse signal sequence comprises a plurality of first pulse signals, and the amplitudes of the plurality of first pulse signals are different, and is used to stimulate the neural glia at the spinal cord and / or the pain area of the subject.

[0026] The second pulse signal sequence comprises a plurality of second pulse signals; the amplitudes of the plurality of second pulse signals are equal, and is used to stimulate the neuron at the spinal cord and / or the pain area of the subject.

[0027] In some embodiments, the electrical stimulation device is used to adjust the brain nerve related to epilepsy, comprising:

[0028] The pulse generator is configured to generate at least one set of stimulation pulse signals, the pulse amplitude of the stimulation pulse signals ranges from 0.01 volt to 10 volt or 0.5 milliampere to 25.5 milliampere, the pulse width of the stimulation pulse signals ranges from 20 microseconds to 450 microseconds, and the frequency of the stimulation pulse signals ranges from 2 hertz to 333 hertz; the stimulation pulse signals include at least one first pulse signal and at least one second pulse signal, the pulse width of the first pulse signal is smaller than the pulse width of the second pulse signal, and the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal.

[0029] The electrodes include a first electrode and a second electrode, both of which are electrically connected to the pulse generator, the first electrode is configured to be implanted into the deep brain of the epileptic focus area of the subject, and the second electrode is configured to be implanted into the cerebral cortex of the subject.

[0030] In some embodiments, the pulse generator includes a controller and a pulse generation unit.

[0031] The second electrode and the first electrode are both electrically connected to the controller and are further configured to simultaneously collect real-time electroencephalogram signals of the full frequency band of the epileptic focus area and send the real-time electroencephalogram signals to the controller.

[0032] The controller is configured to extract real-time first features from the real-time electroencephalogram signals, determine whether the premonitory symptom of the epilepsy of the subject is met according to the real-time first features, and if so, control the pulse generation unit to output the stimulation pulse signals according to the real-time first features and pre-stored parameter items and parameter values of the stimulation pulse signals corresponding to the epilepsy; the parameter items of the stimulation pulse signals include at least one of pulse amplitude, pulse width, first interphase interval, and pulse interval.

[0033] The second electrode and the first electrode are both electrically connected to the pulse generation unit.

[0034] In some embodiments, the electrical stimulation device further includes a memory electrically connected to the controller and configured to store a subject epilepsy stimulation pulse database refined based on historical treatment results of the epilepsy of the subject, the subject epilepsy stimulation pulse database includes a plurality of sample first features, and sample parameter items and sample parameter values of the stimulation pulse signals corresponding to each sample first feature. ；

[0035] The controller is configured to determine a sample first feature consistent with or closest to the real-time first feature from the subject epilepsy stimulation pulse database when it is determined that the premonitory symptom of the epilepsy of the subject is met, acquire sample parameter items and sample parameter values of the stimulation pulse signals corresponding to the consistent or closest sample first feature, and control the output of the stimulation pulse signals with the sample parameter items and the sample parameter values.

[0036] In some embodiments, the first electrode comprises at least one ring-shaped detection contact and at least one set of output contacts; each set of the output contacts comprises at least two output contacts arranged along a circumferential direction of the first electrode, the detection contact and the output contacts are arranged in an interval along an extension direction of the first electrode, the detection contact is used to collect real-time electroencephalogram signals of full frequency bands at the epileptic focus area, and at least one set of the output contacts is used to output the stimulation pulse signals.

[0037] In some embodiments, the electrical stimulation device is used to adjust Parkinson-related brain nerves, comprising:

[0038] The electrode is arranged at a target region of a brain of a subject, and the electrode comprises a plurality of first conductive contacts.

[0039] The pulse generator is used to generate at least one set of stimulation pulse signals, the stimulation pulse signals comprise at least two kinds of pulse signals, and at least one of pulse amplitude, pulse width, and first conductive contact combination is different between different kinds of pulse signals; the first conductive contact combination comprises at least one first conductive contact; the pulse amplitude of the stimulation pulse signals ranges from 1 volt to 4 volts or 0 to 25.5 milliamperes, the pulse width of the stimulation pulse signals ranges from 60 microseconds to 3.7 milliseconds, and the frequency of the stimulation pulse signals ranges from 17 hertz to 330 hertz.

[0040] In some embodiments, the pulse generator comprises a controller and a pulse generation unit electrically connected, the controller is used to adjust the stimulation pulse signals, comprising controlling the pulse generation unit to output different pulse signals with pulse amplitude greater than a first preset threshold to different first conductive contact combinations at different time nodes.

[0041] In some embodiments, the pulse generator comprises:

[0042] A detection unit electrically connected with the second conductive contacts of the electrode, used to detect electroencephalogram signals of a target brain region of the subject and output to a controller;

[0043] The controller is electrically connected with the detection unit, used to determine a characteristic value of a beta frequency band according to the electroencephalogram signals; determine whether a real-time characteristic value of the beta frequency band is out of a preset characteristic value range; when the real-time characteristic value of the beta frequency band is out of the preset characteristic value range, adjust the stimulation pulse signals; and the preset characteristic value range is a characteristic value range of the subject in the beta frequency band.

[0044] In some embodiments, the controller is configured to determine the expected real-time pulse amplitude for adjustment according to the minimum pulse amplitude causing the detectable clinical effect of the subject and a real-time pulse variation amount when the real-time power of the beta frequency band exceeds a preset characteristic value range.

[0045] The real-time characteristic value of the beta frequency band includes a real-time power of the brain electrical signal in the beta frequency band; the real-time pulse variation amount includes a real-time proportion of a difference between the maximum pulse amplitude before causing the side effect of the subject and the minimum pulse amplitude causing the detectable clinical effect of the subject; and the real-time proportion includes a ratio of a difference between the real-time power and the minimum power of the beta frequency band of the subject in a medication state, and a difference between the maximum power of the beta frequency band of the subject in a non-medication state and the minimum power of the beta frequency band of the subject in the medication state.

[0046] The technical scheme provided by the embodiments of the present disclosure has the following beneficial technical effects:

[0047] In the embodiments of the present disclosure, the pulse amplitude, pulse width, frequency and other parameter items of the stimulation pulse signal generated by the pulse generator are all within the respective appropriate ranges matched with the neuromodulation, and because the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal, a stronger stimulation effect on the neural tissue can be generated in a short time, and because the pulse width of the first pulse signal is less than the pulse width of the second pulse signal, the stimulation is ensured to be short, fully covered and low in damage, that is, the neural tissue is stimulated by the combination of the first pulse signal and the second pulse signal, which can not only realize fast and effective stimulation of the neural tissue, but also reduce the potential damage to the neural tissue.

[0048] Additional aspects and advantages of the present disclosure will be described in part in the description that follows, and will become apparent to those skilled in the art from the description, or can be learned by the practice of the present disclosure. BRIEF DESCRIPTION OF DRAWINGS

[0049] The above and / or additional aspects and advantages of the present disclosure will become apparent and be readily appreciated from the following description, taken in conjunction with the accompanying drawings, in which:

[0050] FIG. 1 is a structural schematic diagram of an electrical stimulation system according to an embodiment of the present disclosure;

[0051] FIG. 2 is a waveform diagram of a stimulation pulse signal according to an embodiment of the present disclosure;

[0052] FIG. 3 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0053] FIG. 4 is a waveform diagram of still another stimulation pulse signal according to an embodiment of the present disclosure;

[0054] Fig. 5 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0055] Fig. 6 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0056] Fig. 7 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0057] Fig. 8 is a structural diagram of an electrical stimulation device according to an embodiment of the present disclosure;

[0058] Fig. 9 is a structural diagram of an electrical stimulation device for blocking transmission of pain signals according to an embodiment of the present disclosure;

[0059] Fig. 10 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0060] Fig. 11 is a structural diagram of an electrical stimulation system for blocking transmission of pain signals according to an embodiment of the present disclosure;

[0061] Fig. 12 is a structural diagram of an electrical stimulation device for adjusting brain nerves related to epilepsy according to an embodiment of the present disclosure;

[0062] Fig. 13 is a structural diagram of a first electrode according to an embodiment of the present disclosure;

[0063] Fig. 14 is a structural diagram of a second electrode according to an embodiment of the present disclosure;

[0064] Fig. 15 is a structural diagram of another first electrode according to an embodiment of the present disclosure;

[0065] Fig. 16 is a structural diagram of an electrical stimulation system for adjusting brain nerves related to epilepsy according to an embodiment of the present disclosure;

[0066] Fig. 17 is a structural diagram of another electrical stimulation system for adjusting brain nerves related to epilepsy according to an embodiment of the present disclosure;

[0067] Fig. 18 is a structural diagram of an electrical stimulation device for adjusting brain nerves related to Parkinson according to an embodiment of the present disclosure;

[0068] Fig. 19 is a waveform diagram of another stimulation pulse signal according to an embodiment of the present disclosure;

[0069] Fig. 20 is a structural diagram of an electrical stimulation system for adjusting brain nerves related to Parkinson according to an embodiment of the present disclosure;

[0070] Fig. 21 is a structural diagram of another electrical stimulation system for adjusting brain nerves related to Parkinson according to an embodiment of the present disclosure.

[0071] Explanation of reference signs: 10 - stimulation pulse signal; 101 - first pulse signal sequence; 1 - first pulse signal; 102 - second pulse signal sequence; 2 - second pulse signal; 11 - pulse generator; 111 - controller; 112 - pulse generation unit; 113 - detection unit; 114 - wireless communication unit; 115 - memory; 12 - electrode; 121 - lead electrode; 122 - recording electrode; 123 - first electrode; 1230 - electrode body; 1231 - first contact; 1232 - detection contact; 1233 - output contact; 124 - second electrode; 1241 - second contact; 100 - electrical stimulation device; 200 - treatment disc; 300 - remote control terminal; 400 - user control terminal; 500 - object programmer; 600 - cloud. DETAILED DESCRIPTION

[0072] Embodiments of the present disclosure will be described below with reference to the accompanying drawings. It should be understood that the embodiments described below with reference to the accompanying drawings are exemplary descriptions of the technical solutions of the embodiments of the present disclosure, and do not constitute a limitation on the technical solutions of the embodiments of the present disclosure.

[0073] Those skilled in the art can understand that, unless specifically stated otherwise, "said" and "the" used herein can also include plural forms. It should be further understood that the phrase "comprising" used in the specification of the present disclosure means that the features, integers, operations, elements and / or components exist, but does not exclude other features, information, data, steps, operations, elements, components and / or combinations thereof supported by the present technology. It should be understood that when we say that an element is "connected" or "coupled" to another element, the element can be directly connected or coupled to the other element, or can mean that the element and the other element are connected through an intermediate element. In addition, "connected" or "coupled" used herein can include wireless connection or wireless coupling. The term "and / or" used herein means at least one of the items defined by the term, for example, "A and / or B" can be implemented as "A", or as "B", or as "A and B".

[0074] In order to make the purposes, technical solutions and advantages of the present disclosure clearer, the embodiments of the present disclosure will be described in further detail below with reference to the accompanying drawings.

[0075] The inventors have found that in the field of neuromodulation, neurons at different distances from the stimulation electrode can produce different responses to different types of pulse waveforms, thereby producing a diversified modulation effect on the neuron population.

[0076] Therefore, how to design the stimulation pulse signal to produce appropriate nerve response and avoid tissue damage caused by stimulation to the greatest extent becomes a problem to be solved.

[0077] The technical solutions of the present disclosure and how the technical solutions of the present disclosure solve the above technical problems will be described in detail below with specific embodiments. It should be pointed out that the following embodiments can be mutually referenced, borrowed or combined. For the same terms, similar features and similar implementation steps in different embodiments, they will not be described repeatedly.

[0078] The present disclosure provides a pulse generator, see Figure 1.

[0079] The pulse generator 11 is used to generate at least one set of stimulation pulse signals 10 for neuromodulation, the stimulation pulse signals 10 including at least one first pulse signal 1 and at least one second pulse signal 2, the pulse width of the first pulse signal 1 being smaller than the pulse width of the second pulse signal 2, the pulse signal parameters of the stimulation pulse signals including at least one of the following: the pulse amplitude of the first pulse signal 1 being greater than the pulse amplitude of the second pulse signal 2, the pulse amplitude of the stimulation pulse signals 10 ranging from 0 to 10 volts or 0 to 100 milliamperes, the pulse width of the stimulation pulse signals 10 ranging from 0 to 1000 microseconds, and the frequency of the stimulation pulse signals 10 ranging from 60 hertz to 20 kilohertz.

[0080] Among them, the pulse amplitude and the pulse width determine the stimulation range and the activation amount, and the frequency affects the neuron membrane activity and the nerve.

[0081] Since the higher the pulse amplitude, the stronger the stimulation, therefore, the first pulse signal 1 can be used to achieve short-time and timely stimulation, so that the disease is quickly inhibited; the second pulse signal 2 can be used to stimulate for a long time while avoiding overstimulation.

[0082] In the present disclosure, since the pulse amplitude, pulse width, frequency and other parameter items of the stimulation pulse signals generated by the pulse generator are within their respective appropriate ranges matched with neuromodulation, and since the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2, a strong stimulation effect on the neural tissue can be produced in a short time, and since the pulse width of the first pulse signal 1 is smaller than the pulse width of the second pulse signal 2, the shortness, full coverage and low damage of the stimulation can be ensured, that is, the neural tissue is stimulated by the combination of the first pulse signal 1 and the second pulse signal 2, which can not only achieve rapid and effective stimulation of the neural tissue, but also reduce potential damage to the neural tissue.

[0083] Optionally, in the embodiments of the present disclosure, the range of the parameter of the stimulation pulse signal 10 refers to the range of the parameter of each pulse signal in the stimulation pulse signal 10. For example, the range of the pulse width of the stimulation pulse signal 10 is 0 to 1000 microseconds, which means that the range of the pulse width of each pulse signal in the stimulation pulse signal 10 is 0 to 1000 microseconds. The ranges of other parameters such as pulse amplitude and frequency are the same, and details are not repeated here.

[0084] Optionally, in the embodiments of the present disclosure, most numerical ranges include upper and lower limit values; for example, the frequency range of the stimulation pulse signal 10 is 60 Hz to 20 kHz, which includes 60 Hz and 20 kHz. However, the numerical range does not include the upper limit value or the lower limit value of zero; for example, the numerical range of 0 to 100 mA does not include the lower limit value of 0, and in fact is greater than 0 mA and not greater than 100 mA.

[0085] For example, the pulse amplitude of the stimulation pulse signal can be 0.01 volts, 1 volt, 2 volts, 4 volts, 8 volts, 10 volts, etc., or the pulse amplitude of the stimulation pulse signal can be 0.5 mA, 1.3 mA, 5 mA, 10 mA, 25.5 mA, 100 mA, etc. The pulse width of the stimulation pulse signal can be 0.01 microseconds, 1 microsecond, 100 microseconds, 500 microseconds, 1000 microseconds, etc. The frequency of the stimulation pulse signal can be 60 Hz, 100 Hz, 500 Hz, 1 kHz, 10 kHz, 20 kHz, etc.

[0086] Optionally, the subject in the embodiments of the present disclosure includes patients suffering from Parkinson's disease, epilepsy, physical pain, consciousness disorders (coma), etc.

[0087] In practical applications, for the local nerve tissue around the contact, the pulse amplitude of the stimulation pulse signal 10 can be determined according to the size of the tissue and the range that needs to be activated; the pulse width of the stimulation pulse signal 10 can be determined according to the signal transmission characteristics corresponding to the disease.

[0088] Referring to FIGS. 2 to 7, in some embodiments, the stimulation pulse signal 10 includes a first pulse signal sequence and a second pulse signal sequence output alternately; the first pulse signal sequence includes at least one first pulse signal 1, and the second pulse signal sequence includes at least one second pulse signal 2.

[0089] By alternately outputting the first pulse signal sequence and the second pulse signal sequence, switching between short-time strong stimulation and long-time strong stimulation can be realized, so that rapid and effective nerve stimulation can be better achieved while reducing potential damage to nerve tissue.

[0090] It should be noted that the number of stimulation pulse signals 10, the number of first pulse signals 1 in each stimulation pulse signal 10, and the number of second pulse signals 2 in FIGS. 2-7 are only examples, and in actual applications, they can be set arbitrarily as needed.

[0091] It should be noted that the pulse amplitude in the present disclosure refers to the absolute value of the maximum numerical change of the pulse waveform from the bottom to the top. Therefore, the pulse signal can be a cathodic pulse or an anodic pulse or both anodic pulses.

[0092] With reference back to FIG. 2, in some embodiments, the first pulse signal sequence includes at least one first anodic pulse, and the second pulse signal sequence includes at least one second anodic pulse, wherein the pulse width of the first anodic pulse is smaller than the pulse width of the second anodic pulse, and the pulse amplitude of the first anodic pulse is higher than the pulse amplitude of the second anodic pulse.

[0093] Further, the inventors have found that in addition to the activation effect of the cathodic pulse, the anodic pulse itself also has an activation effect, and compared with the cathodic pulse, the anodic pulse can promote the depolarization of the neuron group, thereby enhancing the activation efficiency and avoiding the hyperpolarization block condition caused by the cathodic pulse on the neuron, such as the axon.

[0094] Finally, the anodic phase of the double anodic pulse as shown in FIG. 2 shows a rapid activation effect on the neuron in the neural regulation. Since the pulse amplitude of the first anodic pulse is higher, the stimulation intensity it brings is stronger, and the activation efficiency is higher. Therefore, the use of the first anodic pulse can achieve short-time and timely stimulation, so that the condition is quickly inhibited; and the use of the second anodic pulse in cooperation can maintain a certain stimulation intensity for a long time while avoiding overstimulation. This stimulation waveform is particularly suitable for situations where the neuron needs to be inhibited and / or activated all the time.

[0095] Referring to FIG. 5, in some embodiments, the first pulse signal sequence includes a first cathodic pulse and a first anodic pulse, the first cathodic pulse is used to activate the neuron, and the first anodic pulse is used to balance the charge.

[0096] By setting the first anodic pulse immediately after the first cathodic pulse, the first cathodic pulse is mainly used to activate the neuron, and the first anodic pulse is mainly used to balance the charge, i.e., the first anodic pulse transmits opposite charges to neutralize the charges of the first cathodic pulse, thereby preventing damage caused by charge accumulation.

[0097] In some embodiments, the first cathodic pulse is a rectangular cathodic pulse, and the first anodic pulse is a pulse with a smaller amplitude and a longer pulse width in a rectangular or non-rectangular waveform, thereby reducing the reverse effect of the first anodic pulse and improving the activation efficiency.

[0098] Continuing to refer to FIG. 5, in some embodiments, a first phase interval is provided between the first cathodic pulse and the first anodic pulse.

[0099] The first phase interval is a time interval from the end of the previous first cathodic pulse to the start of the next first anodic pulse.

[0100] Optionally, in some embodiments, the first phase interval ranges from 0 microsecond to 120 microseconds. For example, the first phase interval can be 0 microsecond, 50 microseconds, 80 microseconds, 100 microseconds, 120 microseconds, etc.

[0101] By inserting a short interval (e.g., about 100 microseconds) of the phase interval between the first cathodic pulse and the first anodic pulse, the effect of the first anodic pulse is reduced, thereby eliminating the reverse effect of the first anodic pulse without weakening its function of eliminating charge accumulation.

[0102] Referring to FIG. 6, in other embodiments, the first phase interval can also not be provided between the first cathodic pulse and the first anodic pulse, i.e., the first anodic pulse is output immediately after the end of the first cathodic pulse.

[0103] It should be noted that the second pulse signal sequence can be similarly configured as the first pulse signal sequence, i.e., the second pulse signal sequence includes a second cathodic pulse and a second anodic pulse, the second cathodic pulse is used to activate the neuron, and the second anodic pulse is used to balance the charge. Optionally, a second phase interval is provided between the second cathodic pulse and the second anodic pulse, and the second phase interval ranges from 80 microseconds to 120 microseconds.

[0104] Referring to FIG. 7, in some embodiments, the pulse interval between the two adjacent groups of stimulation pulse signals 10 randomly varies in the range from 5 milliseconds to 15 milliseconds.

[0105] By randomly varying the pulse interval between the two adjacent groups of stimulation pulse signals 10 in the range from 5 milliseconds to 15 milliseconds, the antidromic population spike (APS) can be induced to vary in a larger range, thereby producing diversified stimulation to the neuron and improving the treatment effect.

[0106] Referring to FIG. 7, t1 represents the pulse interval between the first group of stimulation pulse signals 10 and the second group of stimulation pulse signals 10, t2 represents the pulse interval between the second group of stimulation pulse signals 10 and the third group of stimulation pulse signals 10, and t3 represents the pulse interval between the third group of stimulation pulse signals 10 and the fourth group of stimulation pulse signals 10.

[0107] Referring to FIG. 1, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generation unit 112 electrically connected.

[0108] The controller 111 is configured to adjust the pulse intervals between the stimulation pulse signals 10 generated by the pulse generation unit 112 according to the amplitude of the desired reverse population spike potential and a first model; the first model includes a piecewise linear model or a piecewise exponential model, and is configured to represent a correspondence between the amplitude of the normalized reverse population spike potential during a steady state of the stimulation pulse signals 10 and the pulse intervals varying in a preset range.

[0109] The pulse intervals varying in the preset range can be randomly or gradually varied in a range of 5 ms to 15 ms.

[0110] The steady state of the stimulation pulse signals 10 can be understood as a state in which the reverse population spike potential tends to be stable, or a state in which the stimulation pulse signals 10 have a fixed frequency and a stimulation time range of 100 seconds to 180 seconds.

[0111] The linear mathematical model and the exponential model can be used to predict the amplitude of the reverse population spike potential during the steady state of the stimulation pulse signals 10 with the pulse intervals varying in a range of 5 ms to 15 ms, so that the controller 111 can accurately adjust the pulse intervals between the stimulation pulse signals 10 according to the amplitude of the desired reverse population spike potential and the first model, thereby applying a desired stimulation intensity to the neurons.

[0112] Since the neurons will enter a refractory period after transmitting a signal, stimulating the neurons in the refractory period will have no effect. Therefore, by setting appropriate pulse intervals, the stimulation effect can be achieved, energy can be saved, and unnecessary side effects can be avoided.

[0113] Referring to FIG. 1, in some embodiments, the pulse generator 11 includes the controller 111 and the pulse generation unit 112 electrically connected.

[0114] The controller 111 is further configured to determine whether a real-time neural signal of the subject conforms to at least one indication or a premonition of an onset of the indication based on the first model; if so, the parameter values of the stimulation pulse signals 10 corresponding to the indication are used to adjust the parameter items of the subsequent stimulation pulse signals 10; the first model further includes a correspondence between at least one indication and / or a premonition of an onset of the indication, a related neural signal, and a parameter value of a parameter item of a related stimulation pulse signal 10; the parameter item of the stimulation pulse signal 10 includes at least one of a pulse amplitude, a pulse width, a first interphase distance, and a pulse interval.

[0115] Based on the machine learning algorithm, a mathematical model (i.e., the first model) between the pulse signal parameters and the treatment effect is established by learning and analyzing a large amount of treatment data of patients, that is, the first model is obtained by training a large amount of treatment data of patients, and the controller 111 automatically adjusts the parameter items of the subsequent stimulation pulse signal 10 based on the first model according to the indication or the prodrome of the indication, so that the electric stimulation system can automatically output corresponding stimulation for different indications.

[0116] Referring to FIG. 1, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generation unit 112 electrically connected.

[0117] The controller 111 is configured to control the pulse generation unit 112 to output the first pulse signal 1 first and then output the second pulse signal 2 in the stimulation pulse signal 10 generated subsequently when the parameter values of the parameter items of the real-time neural signal of the subject are within the first threshold range, and control the pulse generation unit 112 to output the second pulse signal 2 first and then output the first pulse signal 1 in the stimulation pulse signal 10 generated subsequently when the parameter values of the parameter items of the real-time neural signal are within the second threshold range; and the parameter items of the stimulation pulse signal 10 include at least one of a pulse amplitude, a pulse width, a first phase interval, and a pulse interval.

[0118] For example, the controller 111 is further configured to determine whether the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 or the second pulse signal 2 according to a difference between the real-time neural signal and the threshold when the real-time neural signal exceeds the threshold (voltage threshold or current threshold).

[0119] Specifically, when the difference between the real-time neural signal and the threshold is large (for example, the difference is greater than the first threshold), the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 first and then outputs the second pulse signal 2, so as to enhance the stimulation intensity of the neurons; when the difference between the real-time neural signal and the threshold is small (for example, the difference is less than the first threshold), the subsequent stimulation pulse signal 10 outputs the second pulse signal 2 first and then outputs the first pulse signal 1, so as to reduce the potential damage to the neural tissue on the premise of ensuring that the neurons have a strong response.

[0120] In some embodiments, the controller 111 is further configured to analyze the stimulation effect according to the real-time neural signal, and to adjust the parameter items of the pulse signal adaptively according to the stimulation effect; and the parameter items of the stimulation pulse signal 10 include at least one of a pulse amplitude, a pulse width, a first phase interval, and a pulse interval.

[0121] Referring to FIG. 1, in some embodiments, the pulse generator 11 further includes a detection unit 113 electrically connected to the controller 111, configured to detect the real-time neural signal of the neural tissue of the subject and output to the controller 111.

[0122] In some embodiments, the first pulse signal 1 is any one of an exponential rising stimulation waveform, a central triangle waveform, a Gaussian waveform, a trapezoidal wave, a sinusoidal wave; and / or, the second pulse signal 2 is any one of an exponential rising stimulation waveform, a central triangle waveform, a Gaussian waveform, a trapezoidal wave, a sinusoidal wave.

[0123] In this embodiment, by using non-square waves such as exponential rising stimulation waveform, central triangle waveform, Gaussian waveform, trapezoidal wave, sinusoidal wave, etc., there is an energy saving advantage.

[0124] Using the analysis model of nerve membrane or genetic algorithm, it can be known that the activation effect of the exponential rising stimulation waveform is better, and it is more suitable for peripheral nerve stimulation.

[0125] Since the greater the waveform slope of the stimulation pulse signal 10, the more rapid the neuron response, but for local nerve clusters, it can make the response situation very complex, therefore, the stimulation pulse signal 10 can contain a variety of different waveforms, thereby improving the effect of activating / inhibiting neurons.

[0126] In some embodiments, the pulse width of the stimulation pulse signal 10 ranges from 100 microseconds to 500 microseconds; the pulse generator 11 is configured to generate at least one set of stimulation pulse signals 10 to stimulate a nerve-related target point at the median nerve of the wrist of the subject.

[0127] For example, the pulse width of the stimulation pulse signal 10 can be 100 microseconds, 150 microseconds, 250 microseconds, 350 microseconds, 500 microseconds, etc.

[0128] Since the pulse width of the stimulation pulse signal 10 ranges from 100 microseconds to 500 microseconds, the excitability of neurons is improved, and the wake-promoting effect on patients with consciousness disorders is improved.

[0129] In some embodiments, the pulse amplitude of the stimulation pulse signal ranges from 1 volt to 4 volts, the pulse width of the stimulation pulse signal ranges from 60 microseconds to 1000 microseconds, and the frequency of the stimulation pulse signal ranges from 100 hertz to 330 hertz.

[0130] For example, the pulse amplitude of the stimulation pulse signal can be 1 volt, 2 volts, 3 volts, 4 volts, etc., the pulse width of the stimulation pulse signal can be 60 microseconds, 100 microseconds, 300 microseconds, 500 microseconds, 1000 microseconds, etc., and the frequency of the stimulation pulse signal can be 100 hertz, 150 hertz, 200 hertz, 300 hertz, 330 hertz, etc.

[0131] Since the frequency range is determined according to the refractory period of the neuron electric signal transmission, the refractory period is about 3 ms, theoretically, the stimulation of the stimulus pulse signal 10 with a frequency higher than 330 Hz has little effect on the neuron, and therefore, the frequency of the stimulus pulse signal 10 needs to be less than 330 Hz.

[0132] Optionally, the frequency range of the stimulus pulse signal 10 is 100 Hz to 200 Hz.

[0133] In some embodiments, the pulse width of the stimulus pulse signal 10 ranges from 250 microseconds to 350 microseconds.

[0134] Since the pulse width of the stimulus pulse signal 10 ranges from 250 microseconds to 350 microseconds, and the pulse width of the stimulus pulse signal 10 is optionally 300 microseconds, the neuron excitability is more significant, and the consciousness disorder patient can be better promoted to wake up.

[0135] In some embodiments, the pulse width of the stimulus pulse signal 10 ranges from 100 microseconds to 3.5 milliseconds.

[0136] Experiments show that when the pulse width of the stimulus pulse signal 10 is greater than 100 microseconds, the action potential peak is higher than 0, and the neuron is more likely to be excited. Therefore, by setting the pulse width of the stimulus pulse signal 10 to range from 100 microseconds to 3.5 milliseconds, the neuron can be more easily excited.

[0137] The technical scheme provided by the embodiments of the present disclosure has the following beneficial technical effects:

[0138] In the embodiments of the present disclosure, since the pulse amplitude, pulse width, frequency and other parameter items of the stimulus pulse signal generated by the pulse generator are within the respective appropriate ranges matched with the neuromodulation, and since the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2, a strong stimulation effect on the neural tissue can be generated in a short time, and since the pulse width of the first pulse signal 1 is less than the pulse width of the second pulse signal 2, the shortness, full coverage and low damage of the stimulation can be ensured, that is, the neural tissue is stimulated by the combination of the first pulse signal 1 and the second pulse signal 2, which can not only realize fast and effective stimulation of the neural tissue, but also reduce the potential damage to the neural tissue.

[0139] Based on the same inventive concept, the present disclosure provides an electrical stimulation device, as shown in FIG. 8, which comprises an electrode 12 and a pulse generator 11 as described above.

[0140] The electrode 12 is electrically connected to the pulse generator 11, and is used to apply the stimulus pulse signal to the neural related target point of the subject or the vicinity thereof.

[0141] Referring to FIG. 7, in some embodiments, the pulse generator 11 comprises a controller 111 and a pulse generation unit 112 electrically connected, and the electrode 12 is electrically connected with the pulse generation unit 112.

[0142] In some embodiments, the electrode 12 is also used to collect real-time neural signals and transmit to the pulse generator 11.

[0143] Continuing to refer to FIG. 7, in some embodiments, the pulse generator 11 further comprises a detection unit 113 electrically connected with the controller 111, and the electrode 12 is electrically connected with the detection unit 113 for collecting real-time neural signals and transmitting to the detection unit 113.

[0144] In some embodiments, the electrode 12 comprises at least two contacts, at least one contact is used to collect real-time neural signals at or near the neural related target point of the subject, and at least one contact is used to output the stimulation pulse signal.

[0145] In some embodiments, the electrode 12 further comprises an electrode body, and the contacts are exposed outside the electrode body.

[0146] At this time, at least one contact of the electrode 12 can perform the collection function (i.e., collect real-time neural signals at or near the neural related target point of the subject), and at least one contact of the other contacts is selected to be set as the output source of the stimulation pulse signal 10, so as to realize the synchronous performance of the stimulation function and the collection function.

[0147] In other embodiments, the electrode 12 comprises at least one contact, and the contact is used to collect real-time neural signals at or near the neural related target point of the subject in a first time period, and is used as an output source of the stimulation pulse signal 10 in a second time period.

[0148] The first time period is a time period before the onset of the subject's indication is detected, and the second time period is a time period after the onset of the subject's indication is detected.

[0149] In other words, the contact of the electrode 12 will stop the collection function (i.e., collect real-time neural signals at or near the neural related target point of the subject) when realizing the stimulation function (i.e., output the stimulation pulse signal), and the collection function can be restored after the output of the stimulation pulse signal ends.

[0150] Optionally, the pulse generator 11 further comprises at least one switching unit (not shown in the figure), and the pulse generation unit 112 and the detection unit 113 are respectively electrically connected with at least one contact of the electrode 12 through a transmission channel of the at least one switching unit; and the controller 111 is electrically connected with a control end of each switching unit.

[0151] Optionally, the pulse generation unit 112 is electrically connected to a first end of the switching unit, the detection unit 113 is electrically connected to a second end of the switching unit, and the contacts on the electrode are electrically connected to a third end of the switching unit; the transmission channel is either the first end and the third end of the switching unit being conductive (at this time, the second end and the third end are disconnected), or the second end and the third end of the switching unit being conductive (at this time, the first end and the third end are disconnected). The controller 111 is electrically connected to a control end of the switching unit. The controller 111 is configured to control the first end and the third end of the switching unit to be conductive, so that the pulse generation unit 112 and one of the contacts on the electrode are conductive, and output the stimulation pulse signal; or control the second end and the third end of the switching unit to be conductive, so that one of the contacts on the electrode and the detection unit 113 are conductive, and collect the real-time neural signal.

[0152] In some other embodiments, the electrode 12 includes at least three contacts, at least one of which is configured to collect a real-time neural signal at or near a neural-related target point of the subject, and at least two of which are configured to be a positive electrode and a negative electrode, respectively, to output the stimulation pulse signal.

[0153] That is, the electrode 12 adopts a stimulation mode of bipolar stimulation. Specifically, at least one of the contacts can be configured to collect a real-time neural signal, and at least two of the other contacts can be configured to be a positive electrode and a negative electrode, respectively, to output the stimulation pulse signal, so that the stimulation function and the collection function are performed synchronously.

[0154] It should be noted that the current function (role) of a contact on the electrode 12 can be set by the pulse generator 11, so as to control whether the contact is currently configured to collect a real-time neural signal or output a stimulation pulse signal. In some embodiments, the electrical stimulation device 100 is flexible (for example, the pulse generator 11 and / or the electrode 12 are flexible), and is implanted in the body of the subject.

[0155] By implanting the electrical stimulation device 100 in the body of the subject, the convenience of carrying the electrical stimulation device 100 can be improved, and the situation that the working state is unstable due to the partial exposure of the electrical stimulation device 100 can be avoided.

[0156] Optionally, the electrode 12 is implanted at a neural tissue of the subject, and the pulse generator 11 can be implanted at a head, lower abdomen, back waist, or below the clavicle of the subject.

[0157] For example, part or all of the pulse generator 11 can be made of a flexible circuit board packaged with a silicone material. At this time, the pulse generator 11 is flexible, and can be attached to and limited by the hard parts such as the bones of the subject when implanted in the body of the subject.

[0158] In some other embodiments, the pulse generator 11 is rigid, and the shape of the pulse generator 11 matches the shape of the bones (for example, the skull) of the subject, so as to be attached to the bones of the subject when implanted in the body of the subject.

[0159] Optionally, the electrode 12 can be a flexible wire electrode, so as to be more closely implanted in the body of the subject, reduce the discomfort of the patient caused by the implanted electrode 12, and avoid the problem that the rigid electrode 12 is exposed outside the patient's body due to the daily activities of the patient.

[0160] In some embodiments, the electrical stimulation device 100 includes an electrically connected battery (not shown in the figure) and a wireless charging unit (not shown in the figure), and the battery is electrically connected with the controller 111 and the pulse generating unit 112.

[0161] The wireless charging unit can charge the battery without damaging the skin, thereby improving the endurance of the electrical stimulation device 100.

[0162] As an example, the electrical stimulation device and the electrical stimulation system provided by the first embodiment of the present application can be used to block the transmission of pain signals, which will be described in detail below.

[0163] Referring to FIG. 9, the electrical stimulation device 100 in the embodiment includes a pulse generator 11 and a wire electrode 121. That is, the electrode 12 includes the wire electrode 121.

[0164] The pulse generator 11 is configured to generate at least one set of stimulation pulse signals 10, and the stimulation pulse signals 10 include at least two kinds of pulse signals, at least one of the pulse amplitude, the pulse width, and the frequency of the different kinds of pulse signals is different, the pulse amplitude of the stimulation pulse signals 10 ranges from 0 to 10 volts or 0 to 30 milliamperes, the pulse width of the stimulation pulse signals 10 ranges from 0 to 2000 microseconds, and the frequency of the stimulation pulse signals 10 ranges from 0 to 100 kilohertz.

[0165] The wire electrode 121 is disposed at the spinal cord and / or the pain area of the subject, and is electrically connected with the pulse generator 11, and is configured to output the stimulation pulse signals 10 to stimulate the pain-related nerves of the spinal cord and / or the pain area of the subject.

[0166] Since the stimulation pulse signals 10 generated by the pulse generator 11 include at least two kinds of pulse signals, the pulse amplitude, the pulse width, and the frequency of each kind of pulse signal are within their respective suitable ranges matched with pain, and at least one of the pulse amplitude, the pulse width, and the frequency of the different kinds of pulse signals is different, the tissues of the spinal cord and / or the pain area involved in pain are stimulated by the different kinds of pulse signals, and the characteristics of the different kinds of pulse signals are combined, so as to not only achieve rapid and effective stimulation of the tissues of the spinal cord and / or the pain area to block the transmission of pain signals, but also reduce the potential damage to the tissues of the spinal cord and / or the pain area.

[0167] Optionally, in the embodiments of the present disclosure, the range of the parameter of the stimulation pulse signal 10 refers to the range of the parameter of each pulse signal in the stimulation pulse signal 10. For example, the range of the pulse width of the stimulation pulse signal 10 is 0 to 2000 microseconds, which means that the range of the pulse width of each pulse signal in the stimulation pulse signal 10 is 0 to 2000 microseconds. The ranges of other parameters such as pulse amplitude and frequency are the same, and details are not repeated here.

[0168] Optionally, in the embodiments of the present disclosure, most of the numerical ranges include the upper limit value and the lower limit value. However, the numerical range does not include the upper limit value or the upper limit value of zero. For example, the numerical range of 0 to 30 milliamperes does not include the lower limit value of 0, but includes the upper limit value of 30 milliamperes, that is, actually greater than 0 milliamperes and not greater than 30 milliamperes.

[0169] For example, the range of the pulse amplitude of the stimulation pulse signal is 0 volt to 10 volt, which does not include 0 volt, but includes 10 volt. For example, the pulse amplitude of the stimulation pulse signal can be 0.01 volt, 1 volt, 2 volt, 3 volt, 5 volt, 8 volt, 10 volt, etc.

[0170] For example, the range of the pulse amplitude of the stimulation pulse signal is 0 milliamperes to 30 milliamperes, which does not include 0 milliamperes, but includes 30 milliamperes. For example, the pulse amplitude of the stimulation pulse signal can be 0.5 milliamperes, 1 milliamperes, 1.3 milliamperes, 2 milliamperes, 5 milliamperes, 8 milliamperes, 10 milliamperes, 25.5 milliamperes, 30 milliamperes, etc.

[0171] For example, the range of the pulse width of the stimulation pulse signal is 0 microsecond to 2000 microseconds, which does not include 0 microsecond, but includes 2000 microseconds. For example, the pulse width of the stimulation pulse signal can be 1 microsecond, 50 microseconds, 100 microseconds, 200 microseconds, 500 microseconds, 1000 microseconds, 1500 microseconds, 2000 microseconds, etc.

[0172] For example, the range of the frequency of the stimulation pulse signal is 0 hertz to 100 kilohertz, which does not include 0 hertz, but includes 100 kilohertz. For example, the frequency of the stimulation pulse signal can be 2 hertz, 100 hertz, 500 hertz, 1 kilohertz, 10 kilohertz, 50 kilohertz, 80 kilohertz, 100 kilohertz, etc.

[0173] In some embodiments, the lead electrode 121 is flexible, so as to better fit the spinal cord and / or the pain area, reduce the discomfort of the patient caused by the implanted lead electrode 121, and avoid the problem that the rigid lead electrode 121 is exposed outside the patient's body due to the patient's daily activities.

[0174] Optionally, the subject in the embodiments of the present disclosure includes a patient suffering from body pain.

[0175] Referring to FIG. 9, in some embodiments, the pulse generator 11 comprises a controller 111 and a pulse generation unit 112 electrically connected; the lead electrode 121 is electrically connected with the pulse generation unit 112.

[0176] The electrical stimulation device 100 further comprises a recording electrode 122, which is arranged near the spinal cord and / or the pain area of the subject at a preset distance from the lead electrode 121, and is electrically connected with the controller 111, for detecting the action potential of the axon at the spinal cord and / or the pain area and sending to the controller 111 after the lead electrode 121 outputs the stimulation pulse signal 10. That is, the electrode 12 further comprises the recording electrode 122.

[0177] The controller 111 is configured to adjust a parameter item of the stimulation pulse signal 10 subsequently generated by the pulse generation unit 112 based on the action potential; the parameter item of the stimulation pulse signal 10 comprises at least one of a pulse amplitude, a pulse width, a first phase interval, and a pulse interval.

[0178] By arranging the recording electrode 122 at a distance from the lead electrode 121, the recording electrode 122 is used to record the action potential of the axon, and the controller 111 adjusts the subsequent stimulation pulse signal 10 based on the action potential of the axon, so as to maintain the stability of the treatment energy and avoid or reduce the degree of stimulation discomfort of the patient.

[0179] In some embodiments, the number of recording electrodes 122 is multiple, and each is electrically connected with the controller 111; the multiple recording electrodes 122 surround the lead electrode 121.

[0180] The controller 111 is configured to adjust the parameter item of the stimulation pulse signal 10 subsequently generated by the pulse generation unit 112 based on the average value of the action potential detected by the multiple recording electrodes 122.

[0181] Adjusting the parameter item of the stimulation pulse signal 10 subsequently generated by the pulse generation unit 112 based on the average value of the action potential detected by the multiple recording electrodes 122 can more accurately adjust the stimulation pulse signal 10 and better maintain the stability of the treatment energy.

[0182] In some embodiments, the pulse generator 11 can further comprise a wireless communication unit 114; an external device sends pulse adjustment information to the controller 111 via the wireless communication unit 114; the controller 111 adjusts the parameter item of the stimulation pulse signal 10 subsequently generated by the pulse generator 11 based on the pulse adjustment information, so as to better relieve the pain of the subject.

[0183] In some embodiments, the lead electrode 121 comprises an electrode body and at least two contacts exposed outside the electrode body.

[0184] At least one contact is used to detect the action potential of the axon at the spinal cord and / or the pain area, and at least one of the contacts is used to output the stimulation pulse signal.

[0185] That is, at least one contact of the lead electrode 121 is selected to detect the action potential of the axon at the spinal cord and / or the pain area (i.e., to implement the acquisition function), and at least one of the other contacts is selected to be a negative electrode, or at least one of the other contacts is selected to be a positive electrode, and at least one is a negative electrode to output the stimulation pulse signal (i.e., to implement the stimulation function), so that the lead electrode 121 can simultaneously implement the stimulation function and the acquisition function.

[0186] It should be noted that the current function (acquisition function or stimulation function) of a contact of the lead electrode 121 can be set by the pulse generator 11 to control whether the contact is currently used to acquire the action potential of the axon at the spinal cord and / or the pain area or to output the stimulation pulse signal.

[0187] In some embodiments, the lead electrode includes at least three contacts, at least one of the contacts is used to detect the action potential of the axon at the spinal cord and / or the pain area, and at least two of the contacts are used as a positive electrode and a negative electrode, respectively, to output the stimulation pulse signal.

[0188] That is, at least one contact of the lead electrode 121 is selected to detect the action potential of the axon at the spinal cord and / or the pain area (i.e., to implement the acquisition function), and at least one of the other contacts is selected to be a negative electrode, or at least one of the other contacts is selected to be a positive electrode, and at least one is a negative electrode to output the stimulation pulse signal (i.e., to implement the stimulation function), so that the lead electrode 121 can simultaneously implement the stimulation function and the acquisition function.

[0189] Referring to FIGS. 2-5 and 10, in some embodiments, the stimulation pulse signal 10 includes at least one first pulse signal 1 and at least one second pulse signal 2, the pulse width of the first pulse signal 1 is smaller than the pulse width of the second pulse signal 2, and the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2.

[0190] It should be noted that the number of stimulation pulse signals 10, the number of first pulse signals 1 in each stimulation pulse signal 10, and the number of second pulse signals 2 in FIGS. 2-5 and 10 are only examples, and can be set arbitrarily according to actual needs in actual applications.

[0191] Wherein, the pulse amplitude and the pulse width determine the stimulation range and the activation amount, and the frequency affects the neuron membrane activity and the nerve.

[0192] Since the higher the pulse amplitude, the stronger the stimulation, the first pulse signal 1 can achieve short-time and timely stimulation, so that the disease is quickly suppressed; the second pulse signal 2 can stimulate for a longer period of time while avoiding overstimulation.

[0193] In the embodiment, the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2, so that a stronger stimulation effect can be generated in a short time. In addition, the pulse width of the first pulse signal 1 is less than the pulse width of the second pulse signal 2, so that the shortness, full coverage and low damage of the stimulation can be ensured. That is, the nerve-related target is stimulated by combining the first pulse signal 1 and the second pulse signal 2, so that the rapid and effective nerve stimulation can be achieved, and the potential damage to the nerve tissue can be reduced.

[0194] Optionally, the stimulation pulse signal 10 comprises a first pulse signal sequence 101 and a second pulse signal sequence 102 output alternately; the first pulse signal sequence 101 comprises at least one first pulse signal 1, and the second pulse signal sequence 102 comprises at least one second pulse signal 2.

[0195] By alternately outputting the first pulse signal sequence 101 and the second pulse signal sequence 102, the switching between the short-time strong stimulation and the long-time strong stimulation can be realized, so that the rapid and effective nerve stimulation can be achieved, and the potential damage to the nerve tissue can be reduced.

[0196] In actual application, for the local nerve tissue around the contact, the pulse amplitude of the stimulation pulse signal 10 can be determined according to the size of the tissue and the range to be activated, and the pulse width of the stimulation pulse signal 10 can be determined according to the signal transmission characteristics corresponding to the disease.

[0197] Referring to FIG. 9, in some embodiments, the pulse generator 11 comprises a controller 111 and a pulse generation unit 112 connected electrically.

[0198] The controller 111 is configured to control the pulse generation unit 112 to output the first pulse signal 1 first and then output the second pulse signal 2 in the stimulation pulse signal 10 generated subsequently when the parameter values of the several parameter items of the real-time nerve signal of the object are in the first threshold range, and control the pulse generation unit 112 to output the second pulse signal 2 first and then output the first pulse signal 1 in the stimulation pulse signal 10 generated subsequently when the parameter values of the several parameter items of the real-time nerve signal are in the second threshold range; the parameter items of the stimulation pulse signal 10 comprise at least one of the pulse amplitude, the pulse width, the first inter-phase distance and the pulse interval.

[0199] For example, the controller 111 is further configured to determine whether the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 or the second pulse signal 2 according to a difference between the real-time neural signal and the threshold value when the real-time neural signal exceeds the threshold value (voltage threshold value or current threshold value). Specifically, when the difference between the real-time neural signal and the threshold value is large (e.g., the difference is greater than a first threshold value), the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 first and then outputs the second pulse signal 2, so as to enhance the stimulation intensity of the neurons; when the difference between the real-time neural signal and the threshold value is small (e.g., the difference is less than the first threshold value), the subsequent stimulation pulse signal 10 outputs the second pulse signal 2 first and then outputs the first pulse signal 1, so as to reduce the potential damage to the neural tissue while ensuring that the neurons have a strong response.

[0200] Referring to FIGS. 2-5 and 10, in some embodiments, the first pulse signal sequence includes at least one first anodal pulse, and the second pulse signal sequence includes at least one second anodal pulse, wherein the pulse width of the first anodal pulse is less than the pulse width of the second anodal pulse, and the pulse amplitude of the first anodal pulse is higher than the pulse amplitude of the second anodal pulse.

[0201] Further, the inventors have found that, in addition to the activation effect of the cathodal pulse, the anodal pulse itself also has an activation effect, and compared with the cathodal pulse, the anodal pulse can promote the depolarization of the neuron group, thereby enhancing the activation efficiency and avoiding the hyperpolarization block condition caused by the cathodal pulse on the neurons, such as axons.

[0202] Finally, as shown in FIG. 2, the anodes of the double anodal pulses all exhibit the effect of rapidly activating neurons in neural regulation. Since the first anodal pulse has a higher pulse amplitude, the stimulation intensity brought by the first anodal pulse is stronger, and the activation efficiency is higher, and therefore, the first anodal pulse can be used to achieve short-time and timely stimulation, so that the disease condition is quickly inhibited; in combination with the second anodal pulse, a certain stimulation intensity can be maintained for a long time while avoiding overstimulation. This stimulation waveform is particularly suitable for situations where the neurons need to be inhibited and / or activated all the time.

[0203] Referring to FIG. 10, in some embodiments, the stimulation pulse signal 10 includes a first pulse signal sequence 101 and a second pulse signal sequence 102; the frequency of the first pulse signal sequence 101 is higher than the frequency of the second pulse signal sequence 102.

[0204] The first pulse signal sequence 101 includes a plurality of first pulse signals 1, and the amplitudes of the plurality of first pulse signals 1 are different, for stimulating the neural glia of the spinal cord of the subject and / or the pain area.

[0205] The second pulse signal sequence 102 comprises a plurality of second pulse signals 2; the amplitudes of the plurality of second pulse signals 2 are equal, and are used to stimulate neurons at the spinal cord of the subject and / or the pain area.

[0206] The variable amplitude and high frequency signal is used to stimulate the neuroglia, and the fixed amplitude and low frequency signal is used to stimulate the neurons, so as to modulate the action expression of the neuroglia and the neurons, thereby achieving the effect of relieving pain.

[0207] Optionally, the first pulse signal sequence 101 comprises a plurality of first pulse signals 1 of different stimulation pulse signals 10; and the second pulse signal sequence 102 comprises a plurality of second pulse signals 2 of different stimulation pulse signals 10.

[0208] In some embodiments, the pulse amplitude of the stimulation pulse signal 10 ranges from 2 mA to 8 mA, and the pulse width of the stimulation pulse signal 10 ranges from 100 microseconds to 500 microseconds.

[0209] The frequency of the first pulse signal sequence 101 ranges from 1 Hz to 10 kHz, and the frequency of the second pulse signal sequence 102 ranges from 0 to 100 Hz.

[0210] Experiments show that when the pulse width of the stimulation pulse signal 10 is greater than 100 microseconds, the action potential peak is higher than 0, and the neurons are more easily excited. Therefore, by setting the pulse width of the stimulation pulse signal 10 to be greater than 100 microseconds, the neurons can be more easily excited.

[0211] For example, the pulse amplitude of the stimulation pulse signal can be 2 mA, 3 mA, 5 mA, 6 mA, 8 mA, etc., and the pulse width of the stimulation pulse signal can be 100 microseconds, 200 microseconds, 300 microseconds, 400 microseconds, 500 microseconds, etc.

[0212] For example, the frequency of the first pulse signal sequence 101 can be 1 Hz, 100 Hz, 500 Hz, 1 kHz, 10 kHz, etc., and the frequency of the second pulse signal sequence 102 can be 0.1 Hz, 10 Hz, 30 Hz, 50 Hz, 80 Hz, 100 Hz, etc.

[0213] In some embodiments, the lead electrode 121 is flexible, so as to better fit the spinal cord and / or the pain area, reduce the discomfort of the patient caused by the implanted lead electrode 121, and avoid the problem that the rigid lead electrode 121 is exposed outside the patient's body due to the patient's daily activities.

[0214] In some embodiments, the frequency or pulse width of the stimulation pulse signal 10 can be increased to enhance the stimulation energy, provide higher electric charge to the spinal tissue in a unit of time, generate more heat energy in the spinal tissue, improve the electric sensitivity, and optimize the configuration, thereby providing more effective pain relief.

[0215] In some embodiments, the pulse interval between the two adjacent groups of stimulation pulse signals 10 is randomly varied in a range of 5-15 milliseconds.

[0216] By randomly varying the pulse interval between the two adjacent groups of stimulation pulse signals 10 in a range of 5-15 milliseconds, antidromic population spike (APS) can be induced to vary in a larger range, thereby diversifying the stimulation of neurons and improving the treatment effect.

[0217] In some embodiments, the first pulse signal 1 can be any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave.

[0218] And / or, the second pulse signal 2 can be any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave.

[0219] In this embodiment, by using non-square waves such as exponential rising stimulation waveform, central triangular waveform, Gaussian waveform, trapezoidal wave, and sinusoidal wave, the advantage of energy saving is achieved.

[0220] Using the analysis model of nerve membrane or genetic algorithm, it can be known that the activation effect of the exponential rising stimulation waveform is better, and it is more suitable for peripheral nerve stimulation.

[0221] Since the greater the slope of the stimulation pulse signal 10, the more rapid the response of the neuron, but for local nerve clusters, it can make the response situation very complex, therefore, the stimulation pulse signal 10 can contain a variety of different waveforms, thereby improving the effect of activating / inhibiting neurons.

[0222] Optionally, in some embodiments, the lead electrode 121 is used to apply the stimulation pulse signal 10 to the Aβ fiber at the spinal cord and / or the pain area of the subject, so as to activate the Aβ fiber at the spinal cord and / or the pain area, thereby blocking the transmission of the pain signal.

[0223] The spinal cord can be regarded as a similar gate circuit when transmitting pain signals, the small-diameter A-delta fiber (or C fiber) and the A beta fiber constitute the input of the equivalent gate circuit; when the A beta fiber is activated, the equivalent gate circuit is closed, and the pain signal input by the small-diameter A-delta fiber (or C fiber) cannot be transmitted to the brain; when the A beta fiber is not activated, the equivalent gate circuit can be regarded as open, and the pain signal input by the small-diameter A-delta fiber (or C fiber) can be output to the brain. Since the small-diameter A-delta or C fiber can be activated by harmful stimulation, and the A beta fiber can be activated by harmless stimulation, by applying the stimulation pulse signal 10 to the A beta fiber, the A beta fiber can be activated, the gate for transmitting pain can be closed, and the signal of the small-diameter A-delta or C fiber cannot be transmitted, that is, the pain signal cannot be transmitted, so that the effect of relieving the pain felt by the patient can be achieved.

[0224] In some embodiments, the electrical stimulation device 100 is flexible and implanted in the body of the subject.

[0225] By implanting the electrical stimulation device 100 in the body of the subject, the convenience of carrying the electrical stimulation device 100 can be improved, and the situation that the working state is unstable due to the partial exposure of the electrical stimulation device 100 can be avoided.

[0226] Optionally, the lead electrode 121 is implanted on the epidural space of the spinal cord or the pain area, and the pulse generator 11 can be implanted in the lower abdomen, the back waist or below the clavicle of the subject.

[0227] In some embodiments, the electrical stimulation device 100 includes a battery (not shown in the figure) and a wireless charging unit (not shown in the figure) electrically connected, and the battery is electrically connected with the controller 111 and the pulse generating unit 112.

[0228] By the wireless charging unit, the battery can be charged under the non-invasive premise, and the endurance of the electrical stimulation device 100 can be improved.

[0229] The technical scheme provided by the embodiments of the present disclosure has the following beneficial technical effects:

[0230] In the electrical stimulation device 100 in the embodiments of the present disclosure, the stimulation pulse signal 10 generated by the pulse generator 11 includes at least two kinds of pulse signals, the pulse amplitude, the pulse width, the frequency and other parameter items of each pulse signal are within the respective suitable range matched with the pain, at least one of the pulse amplitude, the pulse width and the frequency of the different kinds of pulse signals is different, the tissues at the spinal cord and / or the pain area involved in the pain are stimulated by the different kinds of pulse signals, and the characteristics of the different kinds of pulse signals are combined, so that the tissues at the spinal cord and / or the pain area can be quickly and effectively stimulated to block the transmission of the pain signal, and the potential damage to the tissues at the spinal cord and / or the pain area can be reduced.

[0231] The embodiments of the present disclosure also provide an electrical stimulation system, as shown in FIG. 11, which comprises the electrical stimulation device 100 shown in FIG. 9.

[0232] The electrical stimulation device 100 comprises the wire electrode 121 and the pulse generator 11 electrically connected, and the wire electrode 121 is arranged at the spinal cord of the subject and / or the pain area.

[0233] Since the stimulation pulse signal 10 generated by the pulse generator 11 in the electrical stimulation device 100 comprises at least two kinds of pulse signals, the pulse amplitude, pulse width, frequency and other parameter items of each pulse signal are within the respective suitable range matched with the pain, and at least one of the pulse amplitude, pulse width and frequency of the different kinds of pulse signals is different, the tissues at the spinal cord and / or the pain area involved in the pain are stimulated by the different kinds of pulse signals, and the characteristics of the different kinds of pulse signals are combined, so that the tissues at the spinal cord and / or the pain area can be quickly and effectively stimulated to block the transmission of the pain signal, and the potential damage to the tissues at the spinal cord and / or the pain area can be reduced.

[0234] In some embodiments, the pulse generator 11 is arranged in the body of the subject; the pulse generator 11 comprises the controller 111 and the wireless communication unit 114 electrically connected.

[0235] The electrical stimulation system further comprises a treatment disc 200 and a remote control terminal 300; the treatment disc 200 is arranged outside the body of the subject and is in communication connection with the wireless communication unit 114; the remote control terminal 300 is in communication connection with the treatment disc 200 through the Internet.

[0236] The treatment disc 200 is used to receive the action potential of the axon at the spinal cord and / or the pain area, and transmit it to the remote control terminal 300 through the Internet.

[0237] The remote control terminal 300 is used to display the action potential of the axon at the spinal cord and / or the pain area; when receiving the pulse adjustment information inputted externally, it is transmitted to the treatment disc 200.

[0238] The treatment disc 200 is also used to receive the pulse adjustment information, and transmit it to the controller 111 through the wireless communication unit 114, so that the controller 111 adjusts the parameter items of the stimulation pulse signal 10 subsequently generated by the pulse generator 11 based on the pulse adjustment information; the parameter items of the stimulation pulse signal 10 comprise at least one of the pulse amplitude, pulse width, first interphase distance and pulse interval.

[0239] After the lead electrode 121 applies the stimulation pulse signal 10 to the subject's spinal cord and / or the pain area, the axon will travel from the stimulation site in an anterograde or retrograde direction, generating an action potential, and the doctor can understand the action potential of the axon of the subject's spinal cord and / or the pain area through the remote control terminal 300, so as to determine whether the current stimulation pulse signal 10 is suitable for the current pain degree of the subject according to the action potential.

[0240] When the doctor determines that the current stimulation pulse signal 10 is not suitable for the current pain degree of the subject, the pulse adjustment information can be input through the remote control terminal 300, so as to adjust the parameter item of the stimulation pulse signal 10 output by the pulse generator 11 subsequently, so that the subsequent stimulation pulse signal 10 is more suitable for the pain degree of the subject.

[0241] The remote control terminal 300 can be a computer, a tablet, a mobile phone, etc., which is not limited here.

[0242] Optionally, the wireless communication connection between the wireless communication unit 114 and the treatment tray 200 can include at least one of a wireless near field communication connection, a wireless local area network connection, a Bluetooth connection, a 4G / 5G connection, and an Internet connection.

[0243] In some embodiments, the treatment tray 200 can be arranged outside the subject (patient) by using a fixing clamp or a waistband and the like accessories, and the pulse generator 11 can be implanted into the lower abdomen, the back waist or below the clavicle of the subject.

[0244] In some embodiments, the electrical stimulation system further comprises a user control terminal 400, which is in wireless communication connection with the treatment tray 200 and is in communication connection with the remote control terminal 300 through the Internet, is used for receiving the pulse adjustment reference information sent by the remote control terminal 300 and displaying the pulse adjustment reference information, and sends the pulse adjustment information to the treatment tray 200 when receiving the externally input pulse adjustment information.

[0245] The treatment tray 200 is further used for receiving the pulse adjustment information and sending the pulse adjustment information to the controller 111 through the wireless communication unit 114, so that the controller 111 adjusts the parameter item of the stimulation pulse signal 10 generated by the pulse generator 11 subsequently based on the pulse adjustment information; the parameter item of the stimulation pulse signal 10 includes at least one of a pulse amplitude, a pulse width, a first phase interval, and a pulse interval.

[0246] The doctor can obtain the pulse adjustment reference information based on the user feedback, the diagnosis and treatment results and the like, the pulse adjustment reference information is used for guiding the subject to adjust the subsequent stimulation pulse signal 10, and the pulse adjustment reference information is sent to the user control terminal 400 through the remote control terminal 300.

[0247] The patient or the family member can understand the pulse adjustment reference information through the user control terminal 400, and input the pulse adjustment information through the user control terminal 400 according to the pulse adjustment reference information and the pain of the patient, so as to adjust the parameter of the subsequent stimulation pulse signal 10 output by the pulse generator 11, so that the subsequent stimulation pulse signal 10 can better relieve the pain of the patient, and avoid the over-adjustment of the stimulation pulse signal 10 by the patient or the family member without medical knowledge, which can cause the damage of the tissue at the spinal cord and / or the pain area.

[0248] The user control terminal 400 can be a computer, a tablet computer, a mobile phone, etc., which is not limited here.

[0249] Optionally, the wireless communication connection between the user control terminal 400 and the treatment disc 200 can include at least one of wireless near field communication connection, wireless local area network connection, Bluetooth connection, 4G / 5G connection, and Internet connection.

[0250] Referring to FIG. 11, in some embodiments, the pulse generator 11 further includes a pulse generation unit 112 electrically connected to the controller 111, and the lead electrode 121 is electrically connected to the pulse generation unit 112. The electrical stimulation device 100 further includes a recording electrode 122 electrically connected to the controller 111, which is used to detect the action potential of the axon at the spinal cord and / or the pain area and send it to the controller 111 after the lead electrode 121 outputs the stimulation pulse signal 10.

[0251] The embodiment is an embodiment of the electrical stimulation system corresponding to the foregoing electrical stimulation device, and the specific technical details and technical effects can be referred to the foregoing, which will not be described here again.

[0252] As an example, the electrical stimulation device and the electrical stimulation system provided by the second embodiment of the present application can be used to adjust the brain nerves related to epilepsy, which will be specifically introduced as follows.

[0253] Referring to FIG. 12, the electrical stimulation device 100 includes a pulse generator 11, a first electrode 123, and a second electrode 124. That is, the electrode 12 includes the first electrode 123 and the second electrode 124.

[0254] The pulse generator 11 is used to generate at least one group of stimulation pulse signals, the pulse amplitude of the stimulation pulse signal ranges from 0.01 volt to 10 volt or 0.5 milliampere to 25.5 milliampere, the pulse width of the stimulation pulse signal ranges from 20 microseconds to 450 microseconds, and the frequency of the stimulation pulse signal ranges from 2 hertz to 333 hertz; the stimulation pulse signal includes at least one first pulse signal and at least one second pulse signal, the pulse width of the first pulse signal is smaller than the pulse width of the second pulse signal, and the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal;

[0255] The first electrode 123 and the second electrode 124 are both electrically connected with the pulse generator 11, the first electrode 123 is configured to be implanted into the deep brain of the subject in the epilepsy lesion area, and the second electrode 124 is configured to be implanted into the cerebral cortex of the subject.

[0256] Since the higher the pulse amplitude, the stronger the stimulation, the first pulse signal can achieve short-time and timely stimulation, so that the disease is quickly inhibited; the second pulse signal can stimulate for a long time while avoiding overstimulation. Optionally, the pulse amplitude includes the voltage amplitude, current amplitude, or power amplitude of the pulse.

[0257] Since the pulse amplitude, pulse width, frequency, and other parameter items of the stimulation pulse signal generated by the pulse generator 11 are all within their respective appropriate ranges matching epilepsy, and since the pulse amplitude of the first pulse signal is greater than that of the second pulse signal, a strong stimulation effect on the epilepsy-related brain nerve tissue can be achieved in a short time. At the same time, since the pulse width of the first pulse signal is smaller than that of the second pulse signal, the shortness, full coverage, and low damage of the stimulation on the epilepsy-related brain nerve tissue can be ensured, and the stimulation on the epilepsy-related brain nerve tissue is maintained through the second pulse signal with a smaller pulse amplitude and a larger pulse width. That is, the epilepsy-related brain nerve tissue is stimulated by combining the first pulse signal and the second pulse signal, which can not only achieve rapid and effective stimulation of the epilepsy-related brain nerve tissue and have a certain effect on relieving seizures, but also reduce potential damage to the nerve tissue.

[0258] Optionally, in the embodiments of the present disclosure, the range of the parameter items of the stimulation pulse signal refers to the range of each parameter item of each pulse signal in the stimulation pulse signal. For example, the range of the pulse width of the stimulation pulse signal is 20 microseconds to 450 microseconds, which means that the pulse width of each pulse signal in the stimulation pulse signal is 20 microseconds to 450 microseconds. The ranges of the pulse amplitude and the frequency and other parameter items are the same, and are not described here.

[0259] Optionally, in the embodiments of the present disclosure, the numerical range includes the upper limit value and the lower limit value.

[0260] For example, the range of the pulse amplitude of the stimulation pulse signal is 0.01 volt to 10 volts, which includes 0.01 volt and 10 volts. For example, the pulse amplitude of the stimulation pulse signal can be 0.01 volt, 1 volt, 2 volt, 3 volt, 5 volt, 8 volt, 10 volt, etc.

[0261] For example, the pulse amplitude of the stimulation pulse signal ranges from 0.5 mA to 25.5 mA, and is inclusive of 0.5 mA and 25.5 mA. For example, the pulse amplitude of the stimulation pulse signal can be 0.5 mA, 1 mA, 1.3 mA, 2 mA, 5 mA, 10 mA, 25.5 mA, etc.

[0262] For example, the pulse width of the stimulation pulse signal ranges from 20 microseconds to 450 microseconds, and is inclusive of 20 microseconds and 450 microseconds. For example, the pulse width of the stimulation pulse signal can be 20 microseconds, 40 microseconds, 100 microseconds, 200 microseconds, 300 microseconds, 400 microseconds, 450 microseconds, etc.

[0263] For example, the frequency of the stimulation pulse signal ranges from 2 Hz to 333 Hz, and is inclusive of 2 Hz and 333 Hz. For example, the frequency of the stimulation pulse signal can be 2 Hz, 10 Hz, 40 Hz, 60 Hz, 100 Hz, 150 Hz, 200 Hz, 250 Hz, 300 Hz, 333 Hz, etc.

[0264] Optionally, the subject in the embodiments of the present disclosure includes a patient with epilepsy.

[0265] In some embodiments, the waveform of the stimulation pulse signal is shown in FIGS. 2-5. It should be noted that the number of stimulation pulse signals, the number of first pulse signals in each stimulation pulse signal, and the number of second pulse signals in FIGS. 2-5 are only examples, and can be set arbitrarily according to needs in actual applications.

[0266] The pulse amplitude and the pulse width determine the stimulation range and the activation amount, and the frequency affects the neuron membrane activity and the nerve.

[0267] In actual applications, for the local nerve tissue around the contact, the pulse amplitude of the stimulation pulse signal can be determined according to the size of the tissue and the range to be activated, and the pulse width of the stimulation pulse signal can be determined according to the signal transmission characteristics corresponding to the disease.

[0268] Optionally, the stimulation pulse signal includes a first pulse signal sequence and a second pulse signal sequence output alternately; the first pulse signal sequence includes at least one first pulse signal, and the second pulse signal sequence includes at least one second pulse signal.

[0269] By alternately outputting the first pulse signal sequence and the second pulse signal sequence, switching between short-time strong stimulation and long-time weak stimulation can be realized, so that rapid and effective nerve stimulation can be achieved while reducing potential damage to the nerve tissue.

[0270] Referring to FIG. 12, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generation unit 112.

[0271] The second electrode 124 and the first electrode 123 are both electrically connected with the controller 111, and are further configured to simultaneously collect real-time electroencephalogram signals of full frequency bands of the epileptic focus area and send the real-time electroencephalogram signals to the controller 111.

[0272] The controller 111 is configured to extract real-time first features from the real-time electroencephalogram signals, determine whether the real-time first features meet the pre-ictal signs of epilepsy of the subject, and if so, control the pulse generating unit 112 to output a stimulation pulse signal according to the real-time first features and pre-stored parameter items and parameter values of the stimulation pulse signal corresponding to epilepsy.

[0273] The second electrode 124 and the first electrode 123 are both electrically connected with the pulse generating unit 112.

[0274] In some embodiments, if the real-time first features do not meet the pre-ictal signs of epilepsy of the subject, the second electrode 124 and the first electrode 123 continue to simultaneously collect real-time electroencephalogram signals of full frequency bands of the epileptic focus area and send the real-time electroencephalogram signals to the controller 111, and the controller 111 continues to extract real-time first features from the real-time electroencephalogram signals and determine whether the real-time first features meet the pre-ictal signs of epilepsy of the subject.

[0275] The brain tissue of the subject can be the deep brain or the cerebral cortex of the epileptic focus area.

[0276] That is, the electric stimulation device in the embodiments of the present disclosure adopts a closed-loop control mode, simultaneously collects real-time electroencephalogram signals of full frequency bands of the epileptic focus area through the second electrode 124 and the first electrode 123, and sends the real-time electroencephalogram signals to the controller 111. The controller 111 determines whether the real-time electroencephalogram signals meet the pre-ictal signs of epilepsy, and outputs a stimulation pulse signal only when the real-time electroencephalogram signals meet the pre-ictal signs of epilepsy, thereby inhibiting abnormal discharge in the brain of the subject and inhibiting the onset of epilepsy, achieving on-demand treatment, and avoiding excessive stimulation in the case where the pre-ictal signs of epilepsy do not occur, thereby affecting the normal life of the subject.

[0277] In actual applications, the controller 111 can be further configured to determine whether the subsequent stimulation pulse signal is the first pulse signal or the second pulse signal according to a difference between the real-time electroencephalogram signals and a threshold value.

[0278] Specifically, when the difference between the real-time electroencephalogram signals and the threshold value is large (for example, the difference is greater than a first threshold value), the subsequent stimulation pulse signal is controlled to output the first pulse signal, thereby enhancing the stimulation intensity of neurons; when the difference between the real-time electroencephalogram signals and the threshold value is small (for example, the difference is less than the first threshold value), the subsequent stimulation pulse signal is controlled to output the second pulse signal, thereby reducing potential damage to neural tissue on the premise of ensuring that neurons have strong responses.

[0279] In some embodiments, the pulse interval between the two adjacent groups of stimulation pulse signals randomly varies in a range of 5 milliseconds to 15 milliseconds. For example, the pulse interval between the two adjacent groups of stimulation pulse signals can be 5 milliseconds, 6 milliseconds, 7 milliseconds, 10 milliseconds, 15 milliseconds, etc.

[0280] By randomly varying the pulse interval between the two adjacent groups of stimulation pulse signals in a range of 5 milliseconds to 15 milliseconds, the antidromic population spike (APS) can be induced to change in a larger range, thereby diversifying the stimulation of neurons and improving the treatment effect.

[0281] Experiments show that when the pulse width of the stimulation pulse signal is greater than 100 microseconds, the action potential peak is higher than 0, and the neuron is more likely to be excited. Therefore, by setting the pulse width of the stimulation pulse signal to be greater than 100 microseconds, the neuron can be more easily excited.

[0282] In some embodiments, the real-time first feature includes a time domain feature and / or a frequency domain feature.

[0283] In other words, whether the real-time electroencephalogram signal conforms to the premonitory symptom of epilepsy is determined by a detection algorithm built in the controller 111, wherein the detection algorithm includes a time domain analysis method, a frequency domain analysis method, and a time-frequency domain analysis method.

[0284] In some embodiments, the time domain analysis method can include that the first feature can be a waveform parameter (e.g., amplitude, period, intercept, approximate entropy, etc.). By extracting the waveform parameter in the real-time electroencephalogram signal (e.g., decomposing the real-time electroencephalogram signal into half waves, and extracting the amplitude, period, intercept, approximate entropy, etc. waveform features), it is determined whether the waveform parameter reaches a preset threshold. When the waveform parameter reaches the preset threshold, it is determined that it conforms to the premonitory symptom of epilepsy.

[0285] In some embodiments, the frequency domain analysis method can include that the first feature can be a signal envelope of a specific frequency band in the real-time electroencephalogram signal. Since the electroencephalogram signal is a time domain random infinite signal, by Fourier transform and Hilbert transform, the signal envelope of the specific frequency band in the real-time electroencephalogram signal can be extracted, i.e., the frequency domain feature is extracted. It is determined whether the frequency domain feature reaches a preset threshold. When the frequency domain feature reaches the preset threshold, it is determined that it conforms to the premonitory symptom of epilepsy.

[0286] In some embodiments, the time-frequency domain analysis method can include: simultaneously analyzing the localized features in the time domain and the frequency domain, performing signal extraction in the frequency domain first, and then using the time domain analysis method to perform feature extraction and threshold discrimination. For example, the line length algorithm, the area algorithm, the band-pass algorithm, the low-frequency algorithm, and the high-frequency algorithm can be used. Since the line length feature reflects the dimension change of the waveform and is sensitive to the amplitude and frequency change of the signal, the line length and area time domain feature detection algorithm has a very high accuracy rate and a high improvement rate in the Bayesian error rate evaluation. While ensuring high recognition accuracy, the recognition algorithm based on the time domain feature has a low calculation cost and a high efficient linear time complexity, and can quickly and accurately detect the pre-seizure of epilepsy.

[0287] Referring to FIG. 12, in some embodiments, the electrical stimulation device further includes a memory 115 electrically connected to the controller 111, configured to store a first feature range of the subject when the subject does not have a seizure.

[0288] The controller 111 is configured to determine that the subject meets the pre-seizure of epilepsy when the real-time first feature exceeds the first feature range by a certain amplitude and / or for a certain duration.

[0289] By pre-storing the first feature range of the subject when the subject does not have a seizure, the first feature range of the subject when the subject does not have a seizure is used as a reference for determining whether the subject currently meets the pre-seizure of epilepsy, and individualization is embodied in the process of determining whether the subject meets the pre-seizure of epilepsy, so that the subject can be more accurately determined whether the subject currently meets the pre-seizure of epilepsy.

[0290] Continuing to refer to FIG. 12, in some embodiments, the electrical stimulation device further includes a memory 115 electrically connected to the controller 111, configured to store a subject's epilepsy stimulation pulse database refined based on the subject's historical treatment results of epilepsy, the subject's epilepsy stimulation pulse database including a plurality of sample first features, and a sample parameter item and a sample parameter value of a stimulation pulse signal corresponding to each sample first feature.

[0291] The controller 111 is configured to determine, when it is determined that the subject meets the pre-seizure of epilepsy, a sample first feature consistent with or closest to the real-time first feature from the subject's epilepsy stimulation pulse database, acquire a sample parameter item and a sample parameter value of a stimulation pulse signal corresponding to the consistent or closest sample first feature, and control the pulse generating unit 112 to output the stimulation pulse signal with the sample parameter item and the sample parameter value.

[0292] In other words, when the real-time first feature is consistent with or closest to the sample first feature, the sample parameter item and the sample parameter value corresponding to the sample first feature value can achieve the best or higher (recognized by the doctor or the patient) treatment effect.

[0293] By extracting the epilepsy stimulation pulse database of the subject from the treatment results of the epilepsy history of the subject, the epilepsy stimulation pulse database of the subject includes a plurality of sample first features, and sample parameter items and sample parameter values of the stimulation pulse signal corresponding to each sample first feature, which can achieve the best or higher (recognized by the doctor or patient) treatment effect. When the onset of epilepsy is determined to be consistent with the premonitory symptom, the sample parameter items and sample parameter values corresponding to the current real-time first feature are obtained from the epilepsy stimulation pulse database of the subject, and the stimulation pulse signal is output according to the sample parameter items and sample parameter values, so as to achieve personalized automatic parameter adjustment, thereby achieving the best or higher (recognized by the doctor or patient) treatment effect.

[0294] With reference to FIGS. 2-5, in some embodiments, the first pulse signal sequence includes at least one first anodal pulse, and the second pulse signal sequence includes at least one second anodal pulse, wherein the pulse width of the first anodal pulse is smaller than the pulse width of the second anodal pulse, and the pulse amplitude of the first anodal pulse is higher than the pulse amplitude of the second anodal pulse.

[0295] Further, the inventor found that, in addition to the activation effect of the cathodal pulse, the anodal pulse itself also has an activation effect, and compared with the cathodal pulse, the anodal pulse can promote the depolarization of the neuron group and thus enhance the activation efficiency, avoiding the hyperpolarization block condition caused by the cathodal pulse on the neuron, such as the axon.

[0296] Finally, the anode phase of the double anodal pulse shown in FIG. 2 exhibits a rapid activation effect on the neuron in the neural regulation. Since the pulse amplitude of the first anodal pulse is higher, the stimulation intensity brought by the first anodal pulse is stronger, and the activation efficiency is higher. Therefore, the first anodal pulse can be used to achieve short-time and timely stimulation, so that the disease condition is quickly inhibited; and the second anodal pulse can be used to maintain a certain stimulation intensity for a long time while avoiding overstimulation. This stimulation waveform is particularly suitable for the case of needing to inhibit and / or activate the neuron all the time.

[0297] Referring to FIG. 13, in some embodiments, the first electrode 123 includes an electrode body 1230 and at least one first contact 1231 exposed outside the electrode body 1230.

[0298] The first contact 1231 is used to collect real-time brain electrical signals of the full frequency band at the deep brain of the epilepsy lesion area in the first time period, and is used as one of the positive electrode or the negative electrode in the second time period to output the stimulation pulse signal 10 in cooperation with the first contact as the other of the positive electrode or the negative electrode.

[0299] The first time period is a time period when no premonitory symptom of epilepsy of the subject is detected, and the second time period is a time period after the premonitory symptom of epilepsy of the subject is detected.

[0300] At this time, the first electrode 123 can adopt a stimulation mode of monopolar stimulation. Specifically, the first contact 1231 collects real-time brain electrical signals of full frequency bands at the deep brain of the epileptic focus area and sends them to the controller 111; the controller 111 determines the premonitory of the onset of epilepsy of the subject according to the real-time brain electrical signals, sets the first contact 1231 as a negative electrode, or sets at least another two first contacts 1231 as positive and negative electrodes respectively, to output a stimulation pulse signal.

[0301] In other words, the first contact 1231 of the first electrode 123 will stop the collection function (i.e., collect real-time brain electrical signals of full frequency bands at the deep brain of the epileptic focus area and send them to the controller 111) when it realizes the stimulation function (i.e., output a stimulation pulse signal), and the collection function can be restored after the output of the stimulation pulse signal ends.

[0302] Similarly, the second electrode 124 can also include at least one second contact 1241 to realize similar functions, which will not be described here.

[0303] Referring to FIG. 13, in some embodiments, the first electrode 123 includes an electrode body 1230 and at least two first contacts 1231 exposed outside the electrode body 1230, at least one first contact 1231 for collecting real-time brain electrical signals of full frequency bands at the deep brain of the epileptic focus area, and at least one first contact 1231 for outputting a stimulation pulse signal.

[0304] At this time, at least one first contact 1231 can perform the collection function, and at least one first contact 1231 is selected from the other first contacts 1231 to output a stimulation pulse signal, so as to realize the synchronous performance of the stimulation function and the collection function.

[0305] Similarly, the second electrode 124 can also include at least one second contact 1241 to realize similar functions, which will not be described here.

[0306] It should be noted that the current function (collection function or stimulation function) of a certain first contact 1231 of the first electrode 123 can be set by the pulse generator 11 to control whether the first contact 1231 is currently used to collect real-time brain electrical signals of full frequency bands or to output a stimulation pulse signal. Similarly, the current function (action) of a certain second contact 1241 of the second electrode 124 can also be set by the pulse generator 11, which will not be described here. In some embodiments, the first electrode 123 includes at least three first contacts 1231, at least one first contact 1231 for collecting real-time brain electrical signals of full frequency bands at the deep brain of the epileptic focus area, and at least two first contacts 1231 for being used as positive and negative electrodes respectively to output the stimulation pulse signal.

[0307] At this time, the first electrode 123 can adopt a stimulation mode of bipolar stimulation. Specifically, at least one first contact 1231 can perform the acquisition function, and at least two first contacts 1231 selected from the other first contacts 1231 are respectively used as the positive electrode and the negative electrode to output the stimulation pulse signal, so as to realize the synchronous performance of the stimulation function and the acquisition function.

[0308] In other embodiments, the second electrode 124 includes at least three second contacts 1241, at least one second contact 1241 is used to collect the real-time brain electrical signals of the full frequency band at the cerebral cortex of the epilepsy lesion area, and at least two second contacts 1241 are used as the positive electrode and the negative electrode respectively to output the stimulation pulse signal.

[0309] In some embodiments, the first electrode 123 includes a plurality of first contacts 1231 arranged at intervals along the extension direction of the first electrode 123. The first contacts 1231 with even arrangement numbers are used to collect the real-time brain electrical signals of the full frequency band at multiple depths of the epilepsy lesion area; and the first contacts 1231 with odd arrangement numbers are used to output the stimulation pulse signal.

[0310] Since the first electrode 123 includes a plurality of first contacts 1231 arranged at intervals along the extension direction (axial direction) of the first electrode 123, the first contacts 1231 for detecting the real-time brain electrical signals (i.e., the detection contacts 1232) and the first contacts 1231 for outputting the pulse signal (i.e., the output contacts 1233) are alternately arranged in the axial direction of the first electrode 123, so that not only the brain electrical signals at different depths can be detected, but also the neural stimulation can be performed on the epilepsy lesion area at different depths.

[0311] In other embodiments, the first contacts 1231 with odd arrangement numbers are used to collect the real-time brain electrical signals of the full frequency band at multiple depths of the epilepsy lesion area; and a first part of the first contacts 1231 with even arrangement numbers are used to output the stimulation pulse signal. It can be understood that this embodiment can also achieve similar technical effects, which will not be described here.

[0312] Referring to FIG. 15, in some embodiments, the first electrode 123 includes at least one annular detection contact 1232 and at least one group of output contacts 1233.

[0313] Each group of output contacts 1233 includes at least two output contacts 1233 arranged at intervals along the circumferential direction of the first electrode 123. The detection contact 1232 and the output contact 1233 are arranged at intervals along the extension direction of the first electrode 123, the detection contact 1232 is used to collect the real-time brain electrical signals of the full frequency band at the epilepsy lesion area, and the at least two output contacts 1233 are used to output the stimulation signal.

[0314] Since the detection contact 1232 is annular, the brain electrical signals in different directions can be detected, and the full-band real-time brain electrical signals at the epileptic focus area can be comprehensively collected.

[0315] Since the at least two output contacts 1233 are arranged along the circumference of the first electrode 123, the stimulation pulse signals can be output in different directions, so that the nerve tissue at the epileptic focus area can be more targetedly stimulated, and the damage to the brain tissue can be reduced.

[0316] Optionally, referring to FIG. 13, in some embodiments, the first electrode 123 includes at least two first contacts 1231, at least one first contact 1231 is used to collect the full-band real-time brain electrical signals at the deep brain of the epileptic focus area, and at least one first contact 1231 is used to output the second pulse signal.

[0317] Referring to FIG. 14, the second electrode 124 includes at least two second contacts 1241, at least one second contact 1241 is used to collect the full-band real-time brain electrical signals at the cerebral cortex, and at least one second contact 1241 is used to output the first pulse signal.

[0318] It should be noted that the current function (role) of a certain first contact 1231 of the first electrode 123 can be set by the pulse generator 11, so as to control whether the first contact 1231 is currently used to collect the full-band real-time brain electrical signals or output the pulse signal. Similarly, the current function (role) of a certain second contact 1241 of the second electrode 124 can also be set by the pulse generator 11, which will not be described here.

[0319] In other embodiments, at least one first contact 1231 is used to output the first pulse signal, and at least one second contact 1241 is used to output the second pulse signal.

[0320] In some embodiments, the first electrode 123 includes at least three first contacts 1231, at least one first contact 1231 is used to collect the full-band real-time brain electrical signals at the deep brain of the epileptic focus area, at least one first contact 1231 is used to output the first pulse signal, and at least one first contact 1231 is used to output the second pulse signal.

[0321] In other embodiments, the second electrode 124 includes at least three second contacts 1241, at least one second contact 1241 is used to collect the full-band real-time brain electrical signals at the cerebral cortex of the epileptic focus area, at least one second contact 1241 outputs the first pulse signal, and at least one second contact 1241 outputs the second pulse signal.

[0322] In some embodiments, the first electrode 123 comprises a plurality of first contacts 1231 arranged at intervals along the extension direction of the first electrode 123. The first contacts 1231 with even arrangement numbers are used to collect real-time brain electrical signals of full frequency bands at multiple depths of the epileptic lesion area; the first part of the first contacts 1231 with odd arrangement numbers are used to output the first pulse signal, and the second part is used to output the second pulse signal.

[0323] Since the first electrode 123 comprises a plurality of first contacts 1231 arranged at intervals along the extension direction (axial direction) of the first electrode 123, the first contacts 1231 for detecting (i.e., the detection contacts 1232) and the first contacts 1231 for outputting pulse signals (i.e., the output contacts 1233) are arranged alternately in the axial direction of the first electrode 123, so that not only the brain electrical signals at different depths can be detected, but also the neural stimulation of the epileptic lesion area at different depths can be performed.

[0324] In other embodiments, the first contacts 1231 with odd arrangement numbers are used to collect real-time brain electrical signals of full frequency bands at multiple depths of the epileptic lesion area; the first part of the first contacts 1231 with even arrangement numbers are used to output the first pulse signal, and the second part is used to output the second pulse signal. It can be understood that this embodiment can also achieve similar technical effects, which will not be described here.

[0325] Referring to FIG. 15, in some embodiments, the first electrode 123 comprises at least one annular detection contact 1232 and at least one group of output contacts 1233.

[0326] Each group of output contacts 1233 comprises at least two output contacts 1233 arranged at intervals along the circumferential direction of the first electrode 123. The detection contacts 1232 and the output contacts 1233 are arranged at intervals along the extension direction of the first electrode 123, the detection contacts 1232 are used to collect real-time brain electrical signals of full frequency bands at the epileptic lesion area, and the at least two output contacts 1233 are used to output the first pulse signal and the second pulse signal.

[0327] Since the detection contacts 1232 are annular, brain electrical signals in different directions can be detected, and comprehensive collection of real-time brain electrical signals of full frequency bands at the epileptic lesion area can be achieved.

[0328] Since the at least two output contacts 1233 are arranged at intervals along the circumferential direction of the first electrode 123, the pulse signals (the first pulse signal and / or the second pulse signal) can be output in different directions, so that the stimulation on the neural tissue at the epileptic lesion area can be more targeted, and the damage to the brain tissue can be reduced.

[0329] Optionally, the at least two groups of output contacts 1233 are arranged in an interval along the extension direction of the first electrode.

[0330] Optionally, in the different groups of output contacts 1233, at least one group of output contacts 1233 is used for outputting the first pulse signal, and at least one group of output contacts 1233 in the remaining groups is used for outputting the second pulse signal.

[0331] Optionally, in the same group of output contacts 1233, a part of the output contacts 1233 are used for outputting the first pulse signal, and another part of the output contacts 1233 are used for outputting the second pulse signal.

[0332] Optionally, the number of detection contacts 1232 can be multiple, and the multiple detection contacts 1232 are arranged in an interval along the extension direction (axial direction) of the first electrode 123; the multiple detection contacts 1232 are used for collecting real-time brain electrical signals of different depths in the epileptic lesion area.

[0333] Optionally, in some embodiments, the edges of the output contacts 1233 can be rounded, so as to avoid charge concentration and reduce damage to the brain tissue.

[0334] Referring to FIGS. 2-5, in some embodiments, the stimulation pulse signal includes a first pulse signal sequence and a second pulse signal sequence output alternately; the first pulse signal sequence includes at least one first pulse signal, and the second pulse signal sequence includes at least one second pulse signal.

[0335] The first pulse signal sequence is a pulse sequence with pulse intervals changing in a Poisson distribution, and / or the second pulse signal sequence is a pulse sequence with pulse intervals changing in a Poisson distribution.

[0336] Using the pulse sequence with pulse intervals changing in a Poisson distribution to stimulate the brain tissue can more effectively reduce seizures.

[0337] In some embodiments, the first pulse signal sequence can also be a pulse sequence with uniformly distributed pulse intervals, and / or the second pulse signal sequence can also be a pulse sequence with uniformly distributed pulse intervals.

[0338] In some embodiments, the first pulse signal can be any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave;

[0339] And / or, the second pulse signal can be any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave.

[0340] In the embodiment, the non-square wave such as the exponential rising stimulation waveform, the central triangular waveform, the Gaussian waveform, the trapezoidal waveform, and the sinusoidal wave has the advantage of energy saving.

[0341] According to the analysis model of the nerve membrane or the genetic algorithm, it can be known that the exponential rising stimulation waveform has better activation effect and is more suitable for peripheral nerve stimulation.

[0342] Since the greater the slope of the stimulation pulse signal is, the more rapid the neuron response is, but for the local nerve cluster, the response condition is very complex, therefore, the stimulation pulse signal can include a plurality of different waveforms, so as to improve the effect of activating / inhibiting the neuron.

[0343] In some embodiments, the pulse generator 11 is flexible and in the form of a sheet and is implanted in the skull of the subject.

[0344] In other words, the electric stimulation device is implanted in the whole skull. In this way, the convenience of carrying the electric stimulation device can be improved, and the situation that the working state is unstable due to the partial exposure of the electric stimulation device can be avoided.

[0345] For example, the pulse generator 11 can be made of a flexible circuit board packaged by silicone. At this time, the pulse generator 11 is flexible and can be attached to the skull of the subject and limited by the skull when implanted in the skull of the subject.

[0346] In other embodiments, the pulse generator 11 is rigid, and the shape of the pulse generator 11 matches the shape of the skull of the subject, so that the pulse generator 11 can be attached to the skull of the subject when implanted in the skull of the subject.

[0347] In some embodiments, the electric stimulation device can include an electrically connected battery (not shown in the figure) and a wireless charging unit (not shown in the figure).

[0348] The battery can be charged by the wireless charging unit under the non-invasive premise, and the endurance of the electric stimulation device can be improved.

[0349] The technical scheme provided by the embodiments of the present disclosure has the following beneficial technical effects:

[0350] The electric stimulation device in the embodiments of the present disclosure can produce a strong stimulation effect on the brain nerve tissue related to epilepsy in a short time, because the pulse amplitude, pulse width, frequency and other parameter items of the stimulation pulse signal generated by the pulse generator 11 are within the respective appropriate ranges matched with epilepsy, and because the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal. At the same time, the shortness, full coverage and low damage of the stimulation on the brain nerve tissue related to epilepsy can be ensured, because the pulse width of the first pulse signal is less than the pulse width of the second pulse signal. That is, the brain nerve tissue related to epilepsy is stimulated by the combination of the first pulse signal and the second pulse signal, which can not only realize fast and effective stimulation of the brain nerve tissue related to epilepsy and play a certain relieving effect on the seizure, but also can reduce the potential damage to the nerve tissue.

[0351] The embodiments of the present disclosure also provide an electric stimulation system, as shown in FIGS. 16 and 17, which includes the electric stimulation device 100 shown in FIG. 12.

[0352] The electric stimulation device 100 includes the pulse generator 11, and the first electrode 123 and the second electrode 124 electrically connected with the pulse generator 11 respectively. The first electrode 123 is arranged at the deep brain of the epilepsy lesion area of the subject, and the second electrode 124 is arranged at the cerebral cortex of the subject.

[0353] In some embodiments, the pulse generator 11 includes the controller 111 and the wireless communication unit 114 electrically connected.

[0354] The electric stimulation system further includes a subject programmer 500 in wireless communication connection with the wireless communication unit 114, configured to acquire an externally input parameter adjustment control signal, and transmit the parameter adjustment control signal to the pulse generator 11 via the wireless communication unit 114 to adjust the parameter items of the subsequent stimulation pulse signal. The parameter items of the stimulation pulse signal include at least one of the pulse amplitude, the pulse width, the first interphase distance and the pulse interval.

[0355] The subject programmer 500 is usually arranged near the subject (patient). The medical workers such as doctors or nurses, or the subject can input the parameter adjustment control signal through the subject programmer 500 under the guidance of the medical workers, so as to adjust the parameter items of the stimulation pulse signal output by the pulse generator subsequently, and realize the self-adjustment of the parameter items of the stimulation pulse signal by the user according to his own feeling.

[0356] Optionally, the object program control instrument 500 is configured to display at least one of the following: information indicating whether the pulse generator 11 is in communication connection, remaining power information of a battery of the pulse generator 11, remaining storage space information of a memory of the pulse generator 11, and whether the data has been read completely. Optionally, the read data includes at least one of the following: a parameter item of the stimulation pulse signal and a parameter value thereof, and physiological data of the object. The physiological data of the object includes an electroencephalogram signal.

[0357] With continued reference to FIGS. 16 and 17, in some embodiments, the electrical stimulation device 100 includes the pulse generator 11, the first electrode 123, and the second electrode 124. The pulse generator 11 includes the controller 111, the pulse generation unit 112, the memory 115, and the wireless communication unit 114, which are electrically connected to the controller 111.

[0358] With continued reference to FIG. 16, in some embodiments, the pulse generator 11 includes the controller 111 and the wireless communication unit 114 that are electrically connected; and the electrical stimulation system further includes an electroencephalogram data management system including the cloud 600 and the remote control terminal 300 that are in communication connection.

[0359] The wireless communication unit 114 is in wireless communication connection with the cloud 600, and is configured to upload the electroencephalogram signal of the target brain region of the object detected by the pulse generator 11 to the cloud 600.

[0360] The remote control terminal 300 is configured to obtain the electroencephalogram signal of the target brain region of the object from the cloud 600, generate and display an electroencephalogram waveform based on the electroencephalogram signal, obtain externally input pulse adjustment information based on the electroencephalogram waveform, and transmit the pulse adjustment information to the pulse generator 11 via the wireless communication unit 114, so that the controller 111 adjusts a parameter item of a subsequent stimulation pulse signal based on the pulse adjustment information. The parameter item of the stimulation pulse signal includes at least one of a pulse amplitude, a pulse width, a first interphase interval, and a pulse interval.

[0361] By uploading the electroencephalogram signal of the target brain region of the object to the cloud 600, a doctor can obtain the electroencephalogram signal from the cloud 600 using the remote control terminal 300, generate and display an electroencephalogram waveform based on the electroencephalogram signal, which can facilitate the doctor to diagnose and analyze the electroencephalogram waveform of the object (patient), and further adjust a parameter item of a stimulation pulse signal output by the pulse generator subsequently using the remote control terminal 300, so as to realize real-time adjustment of the parameter item of the stimulation pulse signal by the doctor based on the electroencephalogram waveform of the user.

[0362] Optionally, referring to FIG. 17, in some embodiments, the wireless communication unit 114 is wirelessly connected with the subject program control instrument 500, and the subject program control instrument 500 is connected with the cloud 600. The wireless communication unit 114 is configured to upload the brain electrical signals of the target brain region of the subject detected by the pulse generator 11 to the cloud 600 through the relay of the subject program control instrument 500. Optionally, the subject program control instrument 500 amplifies and / or modulates the received brain electrical signals of the target brain region of the subject, and then uploads the brain electrical signals to the cloud 600. This is advantageous for reducing the strength requirement of the brain electrical signals transmitted by the wireless communication unit 114, saving energy, improving the endurance of the pulse generator 11, and avoiding or reducing the influence on the brain of the subject.

[0363] The embodiment is an embodiment of the foregoing electric stimulation device corresponding to the electric stimulation system, and specific technical details and technical effects can be referred to the foregoing, which will not be described here again.

[0364] For example, the electric stimulation device and the electric stimulation system provided by the third embodiment of the present application can be used to adjust the Parkinson-related brain nerves, which will be described in detail below.

[0365] Referring to FIG. 18, the electric stimulation device 100 includes a pulse generator 11 and an electrode 12.

[0366] The electrode 12 is arranged at the target brain region of the subject, and the electrode 12 includes a plurality of first conductive contacts.

[0367] The pulse generator 11 is electrically connected with the electrode 12, and is configured to generate at least one group of stimulation pulse signals 10. The stimulation pulse signals 10 include at least two kinds of pulse signals, and at least one of the pulse amplitude, the pulse width, and the first conductive contact combination is different between different kinds of pulse signals. The first conductive contact combination includes at least one first conductive contact. The pulse amplitude of the stimulation pulse signals 10 ranges from 1 to 4 volts or 0 to 25.5 milliamperes, the pulse width of the stimulation pulse signals 10 ranges from 60 microseconds to 3.7 milliseconds, and the frequency of the stimulation pulse signals 10 ranges from 17 hertz to 330 hertz.

[0368] The stimulation pulse signal 10 generated by the pulse generator 11 includes at least two kinds of pulse signals, and each kind of pulse signal has pulse amplitude, pulse width, frequency and other parameter items within a respective suitable range matched with Parkinson's disease. At least one of the pulse amplitude, the pulse width and the first conductive contact combination is different between different kinds of pulse signals. The cross pulse is formed by different kinds of pulse signals, and the nerve tissue of the brain target region related to Parkinson's disease is stimulated alternately. In combination with the characteristics of different kinds of pulse signals, the brain nerve tissue related to Parkinson's disease can be stimulated quickly and effectively, and the onset of Parkinson's disease can be relieved to a certain extent. The potential damage to the nerve tissue is reduced. Optionally, the brain target region includes the brain nerve tissue target point related to Parkinson's disease.

[0369] Optionally, in the embodiments of the present disclosure, the range of the parameter items of the stimulation pulse signal 10 refers to the range of the parameter items of each kind of pulse signal in the stimulation pulse signal 10. For example, the range of the pulse width of the stimulation pulse signal 10 is 60 microseconds to 3.7 milliseconds, which means that the pulse width of each kind of pulse signal in the stimulation pulse signal 10 is 60 microseconds to 3.7 milliseconds. The ranges of the pulse amplitude and the frequency and other parameter items are the same, and details are not repeated here.

[0370] Optionally, in the embodiments of the present disclosure, most of the numerical ranges include the upper limit value and the lower limit value. For example, the range of the pulse amplitude of the stimulation pulse signal 10 is 1 to 4 volts, which includes 1 volt and 4 volts. However, the numerical range does not include the upper limit value or the upper limit value of zero. For example, the numerical range of 0 to 25.5 milliamperes does not include the lower limit value 0, and actually is greater than 0 milliamperes and not greater than 25.5 milliamperes.

[0371] For example, the pulse amplitude of the stimulation pulse signal can be 1 volt, 2 volts, 3 volts, 4 volts, etc. Alternatively, the pulse amplitude of the stimulation pulse signal can be 0.01 milliamperes, 1 milliamperes, 1.3 milliamperes, 2 milliamperes, 5 milliamperes, 10 milliamperes, 25.5 milliamperes, etc. The pulse width of the stimulation pulse signal can be 60 microseconds, 100 microseconds, 300 microseconds, 1000 microseconds, 2000 microseconds, 3700 microseconds, etc. The frequency of the stimulation pulse signal can be 17 hertz, 40 hertz, 60 hertz, 100 hertz, 150 hertz, 200 hertz, 260 hertz, 330 hertz, etc.

[0372] Optionally, in the embodiments of the present disclosure, the subject includes a patient with Parkinson's disease.

[0373] Referring to FIGS. 2 to 5 and 19, in some embodiments, the stimulation pulse signal 10 includes at least one first pulse signal 1 and at least one second pulse signal 2. The pulse width of the first pulse signal 1 is smaller than the pulse width of the second pulse signal 2, and the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2.

[0374] It should be noted that the number of stimulation pulse signals 10, the number of first pulse signals 1 in each stimulation pulse signal 10, and the number of second pulse signals 2 in FIGS. 2-5, FIG. 19 are only examples, and in actual application, they can be set arbitrarily according to needs.

[0375] Among them, the pulse amplitude and pulse width determine the stimulation range and activation amount, and the frequency affects the neuron membrane activity and nerves.

[0376] Because the higher the pulse amplitude, the stronger the stimulation, therefore, the first pulse signal 1 can achieve short-time and timely stimulation, so that the disease is quickly inhibited; the second pulse signal 2 can stimulate for a long time while avoiding overstimulation.

[0377] In this embodiment, because the pulse amplitude of the first pulse signal 1 is greater than the pulse amplitude of the second pulse signal 2, a strong stimulation effect can be achieved in a short time, and because the pulse width of the first pulse signal 1 is less than the pulse width of the second pulse signal 2, the shortness, full coverage and low damage of the stimulation can be ensured, that is, by combining the first pulse signal 1 and the second pulse signal 2 to stimulate the neuron-related target point, both rapid and effective nerve stimulation and reduction of potential damage to nerve tissue can be achieved.

[0378] Optionally, the stimulation pulse signal 10 includes an alternating output of a first pulse signal sequence and a second pulse signal sequence; the first pulse signal sequence includes at least one first pulse signal 1, and the second pulse signal sequence includes at least one second pulse signal 2.

[0379] By alternatingly outputting the first pulse signal sequence and the second pulse signal sequence, switching between short-time strong stimulation and long-time strong intensity stimulation can be achieved, so that rapid and effective nerve stimulation can be better achieved while reducing potential damage to nerve tissue.

[0380] In actual application, for the local nerve tissue around the contact, the size of the tissue and the range to be activated can be used to determine the size of the pulse amplitude of the stimulation pulse signal 10; and the signal transmission characteristics corresponding to the disease can be used to determine the size of the pulse width of the stimulation pulse signal 10.

[0381] Optionally, the pulse width of the stimulation pulse signal 10 ranges from 20 to 450 microseconds.

[0382] Because the frequency range is determined according to the refractory period of the neuron electrical signal transmission of the nerve tissue, the refractory period is about 3ms, and theoretically, the effect of stimulation above 330Hz on neurons will not be too large, therefore, the frequency of the stimulation pulse signal 10 can be less than 330Hz.

[0383] Optionally, the frequency range of the stimulation pulse signal 10 is 17 Hz to 260 Hz.

[0384] In some embodiments, the stimulation pulse signal 10 comprises at least one first pulse signal 1 and at least one second pulse signal 2, i.e., the electrical stimulation device 100 adopts a cross pulse in a cross mode, and the frequency range of the stimulation pulse signal 10 can be 17 Hz to 130 Hz.

[0385] In other words, the cross pulse is that two groups of stimulation programs can be set on the same electrode 12, each group of stimulation programs can use different contact combinations, pulse amplitudes and pulse widths, and the two groups of stimulation programs are alternately stimulated.

[0386] In other embodiments, the stimulation pulse signal 10 comprises at least one first pulse signal 1, at least one second pulse signal 2 and at least one third pulse (not shown in the figure), i.e., the electrical stimulation device 100 adopts a three-cross pulse in a cross mode, and the frequency range of the stimulation pulse signal 10 can be 17 Hz to 85 Hz.

[0387] Referring to FIGS. 2-5 and 19, in some embodiments, a first phase interval is provided between the first pulse signal 1 and the first pulse signal 1, and the first phase interval ranges from 10 microseconds to 120 microseconds.

[0388] For example, the first phase interval can be 10 microseconds, 50 microseconds, 80 microseconds, 100 microseconds, 120 microseconds, etc.

[0389] The first phase interval is the time interval from the end of the first pulse signal 1 to the beginning of the adjacent second pulse signal 2.

[0390] Optionally, the first pulse signal 1 can be a first cathode pulse, and the second pulse signal 2 can be a first anode pulse, the first cathode pulse being used to activate neurons, and the first anode pulse being used to balance the charge.

[0391] By setting the first anode pulse immediately after the first cathode pulse, the first cathode pulse is mainly used to activate neurons, and the first anode pulse is mainly used to balance the charge, i.e., the first anode pulse transmits opposite charges to neutralize the charges of the first cathode pulse, thereby preventing damage caused by charge accumulation.

[0392] In some embodiments, the first cathode pulse is a rectangular cathode pulse, and the first anode pulse is a pulse with a smaller amplitude and a longer pulse width in a rectangular or non-rectangular waveform, thereby reducing the reversing effect of the first anode pulse and improving the activation efficiency.

[0393] The first phase interval is the time interval from the end of the first pulse signal 1 (first cathode pulse) to the beginning of the adjacent second pulse signal 2 (first anode pulse).

[0394] Optionally, the first phase interval is 100 microseconds.

[0395] Optionally, the first phase interval T1 between the first pulse signal 1 and the adjacent second pulse signal 2 is variable. For example, referring to FIG. 19, T11 represents the first phase interval between the first pulse signal 1 and the second pulse signal 2 of the first group of pulse stimulation signals, T12 represents the first phase interval between the first pulse signal 1 and the second pulse signal 2 of the second group of pulse stimulation signals, and T13 represents the first phase interval between the first pulse signal 1 and the second pulse signal 2 of the third group of pulse stimulation signals; T11, T12, and T13 increase in turn.

[0396] By inserting a short time interval of the first phase interval between the first cathode pulse and the first anode pulse, the adverse effect of the first anode pulse is reduced, thereby eliminating the reverse effect of the first anode pulse without weakening its function of eliminating charge accumulation.

[0397] In other embodiments, the first pulse before the second pulse can also be an anode pulse and a cathode pulse.

[0398] In actual applications, the subsequent stimulation pulse signal 10 can be determined to output the first pulse signal 1 or the second pulse signal 2 according to the difference between the real-time brain electrical signal and the threshold value.

[0399] Specifically, when the difference between the real-time brain electrical signal and the threshold value is large (for example, the difference is greater than the first threshold value), the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 first, thereby enhancing the stimulation intensity of the neurons; when the difference between the real-time brain electrical signal and the threshold value is small (for example, the difference is less than the first threshold value), the subsequent stimulation pulse signal 10 outputs the second pulse signal 2 first, thereby reducing the potential damage to the neural tissue on the premise of ensuring that the neurons have a strong response.

[0400] Referring to FIG. 18, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generation unit 112 electrically connected, and the controller 111 is configured to adjust the stimulation pulse signal 10, including controlling the pulse generation unit 112 to output different pulse signals with a pulse amplitude greater than a first preset threshold value to different first conductive contact combinations at different time nodes.

[0401] For example, the pulse generation unit 112 outputs, at a first time node t1, first pulse signals with pulse amplitudes all greater than a first preset threshold to odd-numbered first conductive contacts (i.e., the 1st, 3rd, 5th, etc. first conductive contacts); and the pulse generation unit 112 outputs, at a second time node t2 (the second time node t2 is a time node after the first time node t1, for example, 1 second later), second pulse signals with pulse amplitudes all greater than the first preset threshold to even-numbered first conductive contacts (i.e., the 2nd, 4th, 6th, etc. first conductive contacts).

[0402] In other words, the pulse generator 11 adopts a coordinated reset stimulation mode, in which multiple burst stimulation trains are applied to different first conductive contacts, and the multiple burst stimulation trains are distributed at different time nodes and different locations to disrupt the synchronous oscillatory neural activity. Disrupting the pathological synchronous burst activity can produce persistent changes in interconnected brain circuits, thereby producing persistent symptom improvement. Compared with conventional constant frequency stimulation, the coordinated reset stimulation mode has a longer duration of symptom improvement, and can maintain a more persistent effect improvement after the stimulation is turned off.

[0403] Referring to FIGS. 2-5 and 18-19, in some embodiments, the pulse generator 11 includes an electrically connected controller 111 and a pulse generation unit 112, and the controller 111 is configured to adjust the stimulation pulse signals 10, including controlling the pulse generation unit 112 to output at least one pulse signal with a set pattern of varying frequencies.

[0404] Through the variable frequency stimulation mode with multiple frequencies alternately changed, significant improvement of symptoms such as gait freezing and language impairment of Parkinson's disease patients can be achieved.

[0405] In other embodiments, the controller 111 is configured to adjust the stimulation pulse signals 10, including controlling the pulse generation unit 112 to output at least one pulse signal with a constant frequency.

[0406] In some embodiments, the pulse interval between adjacent two groups of stimulation pulse signals 10 is randomly changed in a range of 5 milliseconds to 15 milliseconds.

[0407] Through the pulse interval between adjacent two groups of stimulation pulse signals 10 being randomly changed in a range of 5 milliseconds to 15 milliseconds, antidromic population spikes (APS) can be induced to change in a larger range, thereby producing diversified stimulation to neurons and improving the treatment effect.

[0408] Experiments show that when the pulse width of the stimulation pulse signal 10 is greater than 100 microseconds, the action potential peak is higher than 0, and the neuron is more likely to be excited. Therefore, by setting the pulse width of the stimulation pulse signal 10 to be greater than 100 microseconds, the neuron can be made more likely to be excited.

[0409] Referring to FIGS. 2-5 and 19, in some embodiments, the first pulse signal sequence includes at least one first anodal pulse, and the second pulse signal sequence includes at least one second anodal pulse, wherein the pulse width of the first anodal pulse is less than the pulse width of the second anodal pulse, and the pulse amplitude of the first anodal pulse is higher than the pulse amplitude of the second anodal pulse.

[0410] Further, the inventors have found that, in addition to the activation effect of the cathodal pulse, the anodal pulse itself also has an activation effect, and compared with the cathodal pulse, the anodal pulse can promote the depolarization of the neuron group and thus enhance the activation efficiency, avoiding the hyperpolarization block condition caused by the cathodal pulse on the neuron, such as the axon.

[0411] Finally, the anode phase of the double anodal pulse shown in FIG. 2 exhibits a rapid activation effect on the neuron in the neural regulation. Since the first anodal pulse has a higher pulse amplitude, the stimulation intensity brought by the first anodal pulse is stronger, and the activation efficiency is higher. Therefore, the first anodal pulse can be used to achieve short-time and timely stimulation, so that the disease condition is quickly inhibited; and the second anodal pulse can be used in cooperation to maintain a certain stimulation intensity for a long time while avoiding overstimulation. This stimulation waveform is particularly suitable for situations where the neuron needs to be inhibited and / or activated all the time.

[0412] Referring to FIG. 18, in some embodiments, the pulse generator 11 includes a detection unit 113 and a controller 111.

[0413] The detection unit 113 is electrically connected with the second conductive contact of the electrode 12, and is configured to detect the electroencephalogram of the target brain region of the subject and output to the controller 111.

[0414] The controller 111 is electrically connected with the detection unit 113, and is configured to determine the characteristic value of the beta frequency band according to the electroencephalogram; determine whether the real-time characteristic value of the beta frequency band is out of a preset characteristic value range; adjust the stimulation pulse signal 10 when the real-time characteristic value of the beta frequency band is out of the preset characteristic value range; and the preset characteristic value range is the characteristic value range of the beta frequency band of the subject.

[0415] Since the electroencephalogram of the beta frequency band is obviously abnormal when the subject is in the Parkinson attack state, the characteristic value of the beta frequency band can be determined by detecting the electroencephalogram to determine whether the subject is in the Parkinson attack state.

[0416] In some embodiments, the real-time characteristic value of the beta band signal in the brain electrical signal can be obtained by sequentially performing Hilbert transform and sliding window integration on the beta band signal. The real-time characteristic value of the beta band used for judging the brain state contains the time domain characteristics and frequency domain characteristics of the brain electrical signal by converting the collected brain electrical signal in the time domain and frequency domain, and thus the brain state can be more accurately judged.

[0417] The preset characteristic value range can be obtained by training personalized treatment data of a certain subject (e.g., a patient). Since the characteristic value of the beta band of the subject in the medication state can represent that the subject is in a normal state (Parkinson's non-onset state), the preset characteristic value range can be the characteristic value range of the beta band of the subject in the medication state. When the real-time characteristic value of the beta band is outside the preset characteristic value range, it represents that the subject is in a Parkinson's onset state.

[0418] Referring back to FIG. 18, in some embodiments, the controller 111 is configured to determine the expected real-time pulse amplitude for adjustment according to the minimum pulse amplitude causing a detectable clinical effect of the subject and the real-time pulse change amount when the real-time power of the beta band is outside the preset characteristic value range.

[0419] The real-time characteristic value of the beta band includes the real-time power of the brain electrical signal in the beta band. The real-time pulse change amount includes the real-time proportion of the difference between the maximum pulse amplitude before causing side effects of the subject and the minimum pulse amplitude causing a detectable clinical effect of the subject. The real-time proportion includes the ratio of the difference between the real-time power and the minimum power of the beta band of the subject in the medication state to the difference between the maximum power of the beta band of the subject in the non-medication state and the minimum power of the beta band of the subject in the medication state. The beta band includes 14 to 36 Hz.

[0420] In this way, a real-time pulse amplitude of the stimulation pulse signal 10 more suitable for the subject can be obtained, and abnormal discharge of the beta band of the brain of the subject can be better inhibited with smaller side effects, thereby relieving the onset of Parkinson's of the subject.

[0421] In some embodiments, the pulse generator 11 further includes a wireless communication unit 114 electrically connected to the controller 111, configured to upload the brain electrical signal of the target brain region of the subject detected by the pulse generator 11 to the cloud.

[0422] In some embodiments, the first pulse signal 1 is any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave.

[0423] And / or, the second pulse signal 2 is any one of an exponential rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal wave, and a sinusoidal wave.

[0424] In this embodiment, by using non-square waves such as an exponentially rising stimulation waveform, a central triangular waveform, a Gaussian waveform, a trapezoidal waveform, and a sinusoidal waveform, energy saving is achieved.

[0425] Using an analysis model of a nerve membrane or a genetic algorithm, it is known that an exponentially rising stimulation waveform has a better activation effect and is more suitable for peripheral nerve stimulation.

[0426] Since the greater the slope of the waveform of the stimulation pulse signal 10, the more rapidly the neuron responds, but for local nerve clusters, it can make the response situation very complex, therefore, the stimulation pulse signal 10 can contain a plurality of different waveforms, thereby improving the effect of activating / inhibiting neurons.

[0427] In some embodiments, the pulse generator 11 is flexible and in the form of a sheet and is implanted in the skull of the subject.

[0428] In other words, the electrical stimulation device 100 is implanted in the whole skull. In this way, the convenience of carrying the electrical stimulation device 100 can be improved, and the situation of unstable working state caused by partial exposure of the electrical stimulation device 100 can be avoided.

[0429] For example, the pulse generator 11 can be made of a flexible circuit board packaged with silicone. At this time, the pulse generator 11 is flexible and can be attached to the skull of the subject and limited by the skull when implanted in the skull of the subject.

[0430] In other embodiments, the pulse generator 11 is rigid, and the shape of the pulse generator 11 matches the shape of the skull of the subject, so that the pulse generator 11 can be attached to the skull of the subject when implanted in the skull of the subject.

[0431] In some embodiments, the electrical stimulation device 100 includes a battery (not shown) and a wireless charging unit (not shown) electrically connected.

[0432] In some embodiments, the battery is electrically connected to the controller 111, the pulse generation unit 112, and the detection unit 113.

[0433] The wireless charging unit can charge the battery without damaging the skin, thereby improving the endurance of the electrical stimulation device 100.

[0434] In some embodiments, the number of electrodes 12 includes at least two, and the target brain region includes at least one of the deep brain and the cerebral cortex.

[0435] In some embodiments, for the treatment of Parkinson's disease, only one or more deep electrodes located in the deep brain are used.

[0436] In other embodiments, for the treatment of Parkinson's disease, a combination of deep electrodes located in the deep brain and cortical electrodes located in the cerebral cortex can also be used.

[0437] The technical scheme provided by the embodiments of the present disclosure has the following beneficial technical effects:

[0438] The electric stimulation device 100 in the embodiments of the present disclosure, since the stimulation pulse signal 10 generated by the pulse generator 11 includes at least two kinds of pulse signals, at least one of the pulse amplitude, the pulse width, and the first conductive contact combination is different between different kinds of pulse signals, cross pulses are formed by different kinds of pulse signals, and the nerve-related target points are alternately stimulated, and the characteristics of different kinds of pulse signals are combined, so that rapid and effective nerve stimulation can be achieved, and the onset of Parkinson's disease can be relieved to a certain extent, and potential damage to the nerve tissue can be reduced.

[0439] Based on the same inventive concept, the embodiments of the present disclosure provide an electric stimulation system, as shown in FIG. 20, which includes the electric stimulation device 100 shown in FIG. 18.

[0440] The electric stimulation device 100 includes the electrode 12 and the pulse generator 11 electrically connected. The electrode 12 is arranged at the target region of the brain of the subject, and the electrode 12 includes a plurality of first conductive contacts.

[0441] Since the stimulation pulse signal generated by the pulse generator in the electric stimulation device 100 includes at least two kinds of pulse signals, at least one of the pulse amplitude, the pulse width, and the first conductive contact combination is different between different kinds of pulse signals, cross pulses are formed by different kinds of pulse signals, and the nerve-related target points are alternately stimulated, and the characteristics of different kinds of pulse signals are combined, so that rapid and effective nerve stimulation can be achieved, and the onset of Parkinson's disease can be relieved to a certain extent, and potential damage to the nerve tissue can be reduced.

[0442] In some embodiments, the pulse generator 11 includes the controller 111 and the wireless communication unit 114 electrically connected.

[0443] The electric stimulation system further includes: a subject programmer 500, which is wirelessly connected with the wireless communication unit 114, and is configured to acquire an externally input parameter adjustment control signal, and transmit the parameter adjustment control signal to the pulse generator 11 via the wireless communication unit 114 to adjust the parameter items of the subsequent stimulation pulse signal; the parameter items of the stimulation pulse signal include at least one of the pulse amplitude, the pulse width, the first phase interval, and the pulse interval.

[0444] The subject programmer 500 is usually arranged near the subject (patient), and a medical worker such as a doctor or a nurse, or the subject can input the parameter adjustment control signal through the subject programmer 500 under the guidance of the medical worker, so as to adjust the parameter items of the stimulation pulse signal output by the pulse generator subsequently, and realize self-adjustment of the parameter items of the stimulation pulse signal by the user according to his / her own feeling.

[0445] Optionally, the object program control instrument 500 is configured to display at least one of the following: information indicating whether the pulse generator 11 is in communication, remaining battery level information of the pulse generator 11, remaining storage space information of the memory of the pulse generator 11, and whether the data has been read. Optionally, the read data includes at least one of the following: a parameter item of the stimulation pulse signal and a parameter value thereof, and physiological data of the object. The physiological data of the object includes an electroencephalogram signal.

[0446] Referring to FIG. 20, in some embodiments, the electrical stimulation device 100 includes the pulse generator 11 and the electrode 12. The pulse generator 11 includes a detection unit 113, a controller 111, a pulse generation unit 112, and a wireless communication unit 114, the wireless communication unit 114 being electrically connected to the controller 111, and the detection unit 113 and the pulse generation unit 112 each being electrically connected to the electrode 12.

[0447] In some embodiments, the pulse generator 11 includes the controller 111 and the wireless communication unit 114 that are electrically connected; and the electrical stimulation system further includes an electroencephalogram data management system including a cloud 300 and a remote control terminal 300 that are in communication.

[0448] The wireless communication unit 114 is in wireless communication with the cloud 300, and is configured to upload an electroencephalogram signal of a target brain region of the object detected by the pulse generator 11 to the cloud 300.

[0449] The remote control terminal 300 is configured to obtain the electroencephalogram signal of the target brain region of the object from the cloud 300, generate and display an electroencephalogram waveform based on the electroencephalogram signal, obtain externally input pulse adjustment information based on the electroencephalogram waveform, and transmit the pulse adjustment information to the pulse generator 11 via the wireless communication unit 114, so that the controller 111 adjusts a parameter item of a subsequent stimulation pulse signal based on the pulse adjustment information. The parameter item of the stimulation pulse signal includes at least one of a pulse amplitude, a pulse width, a first interphase interval, and a pulse interval.

[0450] By uploading the electroencephalogram signal of the target brain region of the object to the cloud 300, a doctor can obtain the electroencephalogram signal from the cloud 300 using the remote control terminal 300, generate and display an electroencephalogram waveform based on the electroencephalogram signal, which can facilitate the doctor to diagnose and analyze the electroencephalogram waveform of the object (patient), and further adjust the parameter item of the stimulation pulse signal output by the pulse generator subsequently using the remote control terminal 300, so as to realize real-time adjustment of the parameter item of the stimulation pulse signal by the doctor according to the electroencephalogram waveform of the user.

[0451] Optionally, referring to FIG. 21, in some embodiments, the pulse generator 11 comprises an electrically connected controller 111 and a wireless communication unit 114. The electric stimulation system further comprises: a subject programmer 500 and an electroencephalogram data management system. The electroencephalogram data management system comprises a cloud 300 and a remote control terminal 300 in communication connection.

[0452] The wireless communication unit 114 is in wireless communication connection with the subject programmer 500, and the subject programmer 500 is in communication connection with the cloud 300. The wireless communication unit 114 is configured to upload the electroencephalogram signal of the target brain region of the subject detected by the pulse generator 11 to the cloud 300 through the relay of the subject programmer 500. Optionally, the subject programmer 500 amplifies and / or modulates the received electroencephalogram signal of the target brain region of the subject and then uploads the signal to the cloud 300. This is advantageous for reducing the strength requirement of the electroencephalogram signal transmitted by the wireless communication unit 114, saving energy, improving the endurance of the pulse generator 11, and avoiding or reducing the impact on the brain of the subject.

[0453] The embodiment of the electric stimulation system corresponding to the electric stimulation device for adjusting the Parkinson-related brain nerves described above has specific technical details and technical effects, which can be referred to above.

[0454] The embodiment of the electric stimulation device corresponding to the pulse generator described above has specific technical details and technical effects, which can be referred to above.

[0455] Those skilled in the art can understand that the steps, measures and schemes in various operations, methods and processes discussed in the disclosure can be alternated, changed, combined or deleted. Further, other steps, measures and schemes in various operations, methods and processes discussed in the disclosure can also be alternated, changed, rearranged, decomposed, combined or deleted. Further, the steps, measures and schemes in various operations, methods and processes in the related art can also be alternated, changed, rearranged, decomposed, combined or deleted.

[0456] The terms "first", "second" are only used for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined with "first", "second" can explicitly or implicitly include one or more of the features. In the description of the disclosure, the meaning of "a plurality of" is two or more, unless otherwise specified.

[0457] In the description of the present specification, specific features, structures, materials or characteristics can be combined in any one or more embodiments or examples in a suitable manner.

[0458] The above merely describes some embodiments of the present disclosure, and it should be noted that, for those skilled in the art, other similar implementation manners based on the technical concept of the present disclosure can be adopted without departing from the technical concept of the present disclosure, and these also belong to the protection scope of the present disclosure.

Claims

1. A pulse generator, wherein, include: This device is used to generate at least one set of stimulation pulse signals for neural modulation. The stimulation pulse signals include at least one first pulse signal and at least one second pulse signal. The pulse width of the first pulse signal is smaller than the pulse width of the second pulse signal, and the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal. The pulse signal parameters of the stimulation pulse signals include at least one of the following: the pulse amplitude of the stimulation pulse signal is in the range of 0 to 10 volts or 0 to 100 mA; the pulse width of the stimulation pulse signal is in the range of 0 to 1000 microseconds; and the frequency range of the stimulation pulse signal is 60 Hz to 20 kHz.

2. The pulse generator according to claim 1, wherein, The stimulation pulse signal includes an alternating sequence of first pulse signals and a sequence of second pulse signals; the first pulse signal sequence includes at least one first pulse signal, and the second pulse signal sequence includes at least one second pulse signal.

3. The pulse generator according to claim 1, wherein, Includes a controller and a pulse generation unit with electrical connections; The controller is used to adjust the pulse interval between the stimulation pulse signals generated by the pulse generation unit according to the expected amplitude of the reverse peak potential and the first model; the first model includes a piecewise linear model or a piecewise exponential model, which is used to characterize the correspondence between the amplitude of the normalized reverse peak potential during the steady state of the stimulation pulse signal and the pulse interval that varies within a preset range.

4. The pulse generator according to claim 1, wherein, Includes a controller and a pulse generation unit with electrical connections; The controller is used to control the pulse generation unit to output the first pulse signal first and then the second pulse signal in the subsequent stimulation pulse signals when the parameter values ​​of several parameters of the real-time neural signal of the object are within a first threshold range. When the parameter values ​​of several parameters of the real-time neural signal are within the second threshold range, the pulse generation unit is controlled to output the second pulse signal first and then the first pulse signal in the subsequent stimulation pulse signals generated. The parameters of the stimulation pulse signal include at least one of the following: pulse amplitude, pulse width, first phase spacing, and pulse interval.

5. The pulse generator according to claim 1, wherein, Includes a controller and a pulse generation unit with electrical connections; The controller is further configured to determine, based on the first model, whether the real-time neural signals of the object conform to at least one indication or the pre-ictal aura of the indication; if so, to adjust the parameter items of the subsequent stimulation pulse signals by calling the parameter values ​​of the stimulation pulse signals corresponding to the indication; the first model also includes the correspondence between the parameter values ​​of at least one indication and / or its pre-ictal aura, related neural signals, and related stimulation pulse signals; the parameter items of the stimulation pulse signals include at least one of pulse amplitude, pulse width, first phase interval, and pulse interval.

6. An electrical stimulation device, wherein, Includes electrodes and a pulse generator as described in any one of claims 1-5 above; The electrode is electrically connected to the pulse generator and is used to apply stimulation pulse signals to or near the neural target of the object.

7. The electrical stimulation device according to claim 6, wherein, The electrical stimulation device is used to block the transmission of pain signals; The pulse generator is used to generate at least one set of stimulation pulse signals, which include at least two types of pulse signals. The pulse amplitude, pulse width, and frequency of the different types of pulse signals are different. The pulse amplitude of the stimulation pulse signal ranges from 0 to 10 volts or from 0 to 30 mA. The pulse width of the stimulation pulse signal ranges from 0 to 2000 microseconds. The frequency of the stimulation pulse signal ranges from 0 to 100 kHz. The electrode includes a wire electrode, which is disposed in the spinal cord and / or pain area of ​​the subject and electrically connected to the pulse generator for outputting the stimulation pulse signal to stimulate the pain-related nerves in the spinal cord and / or pain area of ​​the subject.

8. The electrical stimulation device according to claim 7, wherein, The pulse generator includes an electrically connected controller and a pulse generation unit; The wire electrode is electrically connected to the pulse generating unit; The electrical stimulation device further includes: a recording electrode, disposed near the spinal cord and / or pain area of ​​the subject and spaced at a preset distance from the lead electrode, electrically connected to the controller, for detecting the action potential of the axons in the spinal cord and / or pain area and sending it to the controller after the lead electrode outputs the stimulation pulse signal; The controller is used to adjust the parameters of the stimulation pulse signal subsequently generated by the pulse generation unit based on the action potential; the parameters of the stimulation pulse signal include at least one of pulse amplitude, pulse width, first phase spacing, and pulse interval.

9. The electrical stimulation device according to claim 7, wherein, The pulse generator includes an electrically connected controller and a pulse generation unit; The controller is used to control the pulse generation unit to output the first pulse signal first and then the second pulse signal in the subsequent stimulation pulse signals when the parameter values ​​of several parameters of the real-time neural signal of the object are within a first threshold range. When the parameter values ​​of several parameters of the real-time neural signal are within the second threshold range, the pulse generation unit is controlled to output the second pulse signal first and then the first pulse signal in the subsequent stimulation pulse signals generated. The parameters of the stimulation pulse signal include at least one of the following: pulse amplitude, pulse width, first phase spacing, and pulse interval.

10. The electrical stimulation device according to claim 7, wherein, The stimulation pulse signal includes a first pulse signal sequence and a second pulse signal sequence; the frequency of the first pulse signal sequence is higher than the frequency of the second pulse signal sequence. The first pulse signal sequence includes multiple first pulse signals with varying amplitudes, used to stimulate the glial cells in the spinal cord and / or the painful area of ​​the object; The second pulse signal sequence includes multiple second pulse signals; Multiple second pulse signals have equal amplitudes and are used to stimulate neurons in the spinal cord and / or the painful area of ​​the subject.

11. The electrical stimulation device according to claim 6, wherein, The electrical stimulation device is used to modulate brain nerves associated with epilepsy, including: The pulse generator is used to generate at least one set of stimulation pulse signals, wherein the pulse amplitude of the stimulation pulse signals ranges from 0.01 volts to 10 volts or from 0.5 mA to 25.5 mA, the pulse width of the stimulation pulse signals ranges from 20 microseconds to 450 microseconds, and the frequency range of the stimulation pulse signals ranges from 2 Hz to 333 Hz; the stimulation pulse signals include at least one first pulse signal and at least one second pulse signal, wherein the pulse width of the first pulse signal is smaller than the pulse width of the second pulse signal, and the pulse amplitude of the first pulse signal is greater than the pulse amplitude of the second pulse signal; The electrode includes a first electrode and a second electrode, both of which are electrically connected to the pulse generator. The first electrode is configured to be implanted deep into the brain of the epileptic focus area of ​​the subject, and the second electrode is configured to be implanted into the cerebral cortex of the subject.

12. The electrical stimulation device according to claim 11, wherein, The pulse generator includes a controller and a pulse generation unit; Both the second electrode and the first electrode are electrically connected to the controller and are also used to simultaneously acquire real-time EEG signals of the full frequency band of the epileptic lesion area and send them to the controller; The controller is used to extract a real-time first feature from the real-time EEG signal, and determine whether the real-time first feature matches the premonitory signs of epilepsy in the subject. If so, the controller controls the pulse generation unit to output the stimulation pulse signal according to the real-time first feature and the parameter items and parameter values ​​of the pre-stored stimulation pulse signal corresponding to the epilepsy. The parameter items of the stimulation pulse signal include at least one of pulse amplitude, pulse width, first phase interval, and pulse interval. Both the second electrode and the first electrode are electrically connected to the pulse generating unit.

13. The electrical stimulation device according to claim 12, wherein, It also includes a memory, electrically connected to the controller, for storing a database of epilepsy stimulation pulses extracted from the subject's historical epilepsy treatment results. The database of epilepsy stimulation pulses includes multiple sample first features, and sample parameter items and sample parameter values ​​of the stimulation pulse signal corresponding to each sample first feature. ； The controller is configured to, when determining a premonitory symptom consistent with the subject's epilepsy, determine a sample first feature from the subject's epilepsy stimulation pulse database that is consistent with or closest to the real-time first feature, obtain the sample parameter items and sample parameter values ​​of the stimulation pulse signal corresponding to the consistent or closest sample first feature, and control the output of a stimulation pulse signal having the sample parameter items and the sample parameter values.

14. The electrical stimulation device according to claim 11, wherein, The first electrode includes at least one annular detection contact and at least one set of output contacts; each set of output contacts includes at least two output contacts arranged circumferentially along the first electrode, the detection contact and the output contacts are arranged at intervals along the extension direction of the first electrode, the detection contact is used to acquire real-time EEG signals of the full frequency band at the epileptic lesion area, and at least one set of output contacts is used to output the stimulation pulse signal.

15. The electrical stimulation device according to claim 6, wherein, Used to modulate brain neurons associated with Parkinson's disease, including: The electrode is disposed in a target area of ​​the brain of the object, and the electrode includes a plurality of first conductive contacts; The pulse generator is used to generate at least one set of stimulation pulse signals, the stimulation pulse signals including at least two types of pulse signals, the pulse amplitude, pulse width, and first conductive contact combination being different among the different types of pulse signals; the first conductive contact combination includes at least one first conductive contact; the pulse amplitude of the stimulation pulse signal ranges from 1 volt to 4 volts or from 0 to 25.5 mA, the pulse width of the stimulation pulse signal ranges from 60 microseconds to 3.7 milliseconds, and the frequency range of the stimulation pulse signal ranges from 17 Hz to 330 Hz.

16. The electrical stimulation device according to claim 15, wherein, The pulse generator includes an electrically connected controller and a pulse generation unit. The controller is used to adjust the stimulation pulse signal, including controlling the pulse generation unit to output different pulse signals with pulse amplitudes greater than a first preset threshold at different time nodes and to different combinations of the first conductive contacts.

17. The electrical stimulation device according to claim 15, wherein, The pulse generator includes: The detection unit is electrically connected to the second conductive contact of the electrode and is used to detect the electroencephalogram (EEG) signal of the target brain region of the object and output it to the controller. The controller, electrically connected to the detection unit, is used to determine the characteristic value of the β band based on the EEG signal; determine whether the real-time characteristic value of the β band exceeds a preset characteristic value range; and adjust the stimulation pulse signal when the real-time characteristic value of the β band exceeds the preset characteristic value range; the preset characteristic value range is the characteristic value range of the object in the β band.

18. The electrical stimulation device according to claim 17, wherein, The controller is used to determine the desired real-time pulse amplitude for adjustment based on the minimum pulse amplitude that causes a detectable clinical effect on the object and the amount of real-time pulse change when the real-time power of the β band exceeds the preset characteristic value range. The real-time characteristic value of the β band includes the real-time power of the EEG signal in the β band; the real-time pulse change includes the real-time percentage of the difference between the maximum pulse amplitude before causing side effects in the subject and the minimum pulse amplitude that causes detectable clinical effects in the subject; the real-time percentage includes the ratio of the difference between the real-time power and the minimum power of the β band in the subject under medication conditions to the difference between the maximum power of the β band in the subject under medication-free conditions and the minimum power of the β band in the subject under medication conditions.

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