CN118649358A - Neuromodulator and electrical stimulation system for modulating parkinsonism-associated brain nerves - Google Patents

Abstract

The present application provides a neuromodulator and electrical stimulation system for modulating parkinsonism-associated brain nerves. The neuromodulator includes a pulse generator and an electrode; the electrode is arranged in a brain target area of the object and comprises a plurality of first conductive contacts; the pulse generator is electrically connected with the electrode and is used for generating at least one group 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 combinations among different kinds of pulse signals is different; the first conductive contact assembly includes at least one first conductive contact; the parameters of pulse amplitude, pulse width, frequency and the like of the stimulation pulse signals are all in the respective proper ranges matched with the Parkinson. The application combines the characteristics of different types of pulse signals, not only can realize rapid and effective stimulation of brain nerve tissues related to the Parkinson disease, but also can reduce potential damage to the nerve tissues.

Description

Neuromodulator and electrical stimulation system for modulating parkinsonism-associated brain nerves

Technical Field

The application relates to the technical field of medical instruments, in particular to a nerve regulator for regulating parkinsonism-related brain nerves and an electrical stimulation system.

Background

The nerve control technique is a technique for stimulating nerve tissue by an electric or magnetic signal to change the electric activity of nerve cells, thereby affecting physiological functions of the human body. This technique has been widely used in the medical field, such as Deep Brain Stimulation (DBS) for the treatment of parkinson's disease and the like.

In the related art, a pulse signal generator is generally used to generate a specific pulse signal to stimulate the related nerve tissue of parkinson's disease.

Disclosure of Invention

The application provides a nerve regulator and an electrical stimulation system for regulating parkinsonism-related brain nerves, which can not only realize rapid and effective stimulation of parkinsonism-related nerve tissues, but also reduce potential damage to parkinsonism-related nerve tissues.

Embodiments of the present application provide a neuromodulator for modulating parkinsonism-associated brain nerves, comprising:

an electrode disposed at a target region of a brain of a subject, the electrode comprising a plurality of first conductive contacts;

The pulse generator is electrically connected with the electrodes and is used for generating at least one group of stimulation pulse signals, the stimulation pulse signals comprise at least two pulse signals, and at least one of pulse amplitude, pulse width and first conductive contact combinations among different types of pulse signals is different; the first conductive contact assembly includes at least one first conductive contact; the pulse amplitude of the stimulation pulse signal ranges from 1 to 4 volts or from 0 to 25.5 milliamps, the pulse width of the stimulation pulse signal ranges from 60 microseconds to 3.7 milliseconds, and the frequency of the stimulation pulse signal ranges from 17 hertz to 330 hertz.

In some embodiments, the stimulation pulse signal comprises at least one first pulse signal and at least one second pulse signal, the first pulse signal having a pulse width that is smaller than a pulse width of the second pulse signal, and the first pulse signal having a pulse amplitude that is greater than a pulse amplitude of the second pulse signal.

In some embodiments, a first phase distance is provided between the first pulse signal and the second pulse signal, and the first phase distance ranges from 10 microseconds to 120 microseconds.

In some embodiments, the pulse generator includes a controller and a pulse generating unit electrically connected, the controller being configured to regulate the stimulation pulse signal, including controlling the pulse generating unit to output different pulse signals having pulse amplitudes each greater than a first preset threshold to different combinations of the first conductive contacts at different time nodes.

In some embodiments, the pulse generator comprises a controller and a pulse generating unit electrically connected, the controller being configured to regulate the stimulation pulse signals, including controlling the pulse generating unit to output at least one of the pulse signals whose frequency varies in a set manner.

In some embodiments, the pulse generator comprises:

the detection unit is electrically connected with the second conductive contact of the electrode, and is used for detecting an electroencephalogram signal of a target brain region of the object and outputting the electroencephalogram signal to the controller;

The controller is electrically connected with the detection unit and is used for determining a characteristic value of a beta frequency band according to the electroencephalogram signal; determining whether the real-time characteristic value of the beta frequency band exceeds a preset characteristic value range; when the real-time characteristic value of the beta frequency band exceeds a preset characteristic value range, the stimulation pulse signal is regulated; the preset characteristic value range is the characteristic value range of the object in the beta frequency band.

In some embodiments, the controller is configured to determine a desired real-time pulse amplitude for adjustment based on a minimum pulse amplitude that causes a detectable clinical effect of the subject and a real-time pulse variation when the real-time power of the β -band exceeds a preset characteristic range;

the real-time characteristic value of the beta frequency band comprises the real-time power of the electroencephalogram signal in the beta frequency band; the real-time pulse variation comprises a real-time duty cycle of a difference between a maximum pulse amplitude before causing a side effect in the subject and a minimum pulse amplitude causing a detectable clinical effect in the subject; the real-time duty ratio comprises the ratio of the difference value between the real-time power and the minimum power of the beta frequency band of the object in the medication state to the difference value between the maximum power of the beta frequency band of the object in the medication state and the minimum power of the beta frequency band of the object in the medication state.

In some embodiments, the first pulse signal is any one of an exponentially rising stimulus waveform, a center triangle waveform, a gaussian waveform, a trapezoidal waveform, a sine wave;

and/or the second pulse signal is any one of an exponentially rising stimulation waveform, a central triangle waveform, a gaussian waveform, a trapezoidal waveform and a sine wave.

In some embodiments, the pulse generator is flexible, sheet-like, and is built into the skull bone of the subject.

In some embodiments, the neuromodulator includes an electrically connected battery and a wireless charging unit.

In some embodiments, the number of electrodes comprises at least two, and the target brain region comprises at least one of deep brain, cortex.

The embodiment of the application provides an electrical stimulation system, which comprises the neural regulator for regulating parkinsonism-related brain nerves; the neuromodulator includes an electrode and a pulse generator electrically connected, the electrode disposed at a target region of the brain of the subject, the electrode including a plurality of first conductive contacts.

In some embodiments, the pulse generator comprises a controller and a wireless communication unit electrically connected;

The electrical stimulation system further comprises: the object program control instrument is in communication connection with the wireless communication unit and is used for acquiring an externally input parameter adjustment control signal, transmitting the parameter adjustment control signal to the pulse generator through the wireless communication unit and adjusting a parameter item of a subsequent stimulation pulse signal; the parameter items of the stimulation pulse signals comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.

In some embodiments, the pulse generator comprises a controller and a wireless communication unit electrically connected; the electrical stimulation system further comprises: the brain electricity data management system comprises a cloud end and a remote control terminal which are in communication connection;

the wireless communication unit is in wireless communication connection with the cloud end and is used for uploading the brain electrical signals of the target brain region of the object detected by the pulse generator to the cloud end;

The remote control terminal is used for acquiring the electroencephalogram signals from the cloud, generating and displaying electroencephalogram waveforms according to the electroencephalogram signals, acquiring externally input pulse adjustment information based on the electroencephalogram waveforms, and transmitting the pulse adjustment information to the pulse generator through the wireless communication unit so that the controller adjusts parameter items of subsequent stimulation pulse signals based on the pulse adjustment information; the parameter items of the stimulation pulse signals comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.

The technical scheme provided by the embodiment of the application has the beneficial technical effects that:

According to the nerve regulator for regulating the parkinsonism-related brain nerves, the stimulation pulse signals generated by the pulse generator comprise at least two pulse signals, the pulse amplitude, the pulse width, the frequency and other parameter items of each pulse signal are in the respective proper ranges matched with the parkinsonism, at least one of the pulse amplitude, the pulse width and the first conductive contact combination among the pulse signals of different types is different, cross pulses are formed through the pulse signals of different types, the nerve tissue of the brain target area related to the parkinsonism is alternately stimulated, and the characteristics of the pulse signals of different types are combined, so that the parkinsonism-related brain nerves can be stimulated rapidly and effectively, a certain alleviating effect on parkinsonism attacks can be achieved, and potential damage to the nerve tissue can be reduced.

Additional aspects and advantages of the application will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the application.

Drawings

The foregoing and/or additional aspects and advantages of the application will become apparent and readily appreciated from the following description of the embodiments, taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a schematic diagram of a neuromodulator for modulating parkinsonism-associated brain nerves, in accordance with one embodiment of the present application;

fig. 2 is a waveform diagram of a stimulus pulse signal according to an embodiment of the present application;

fig. 3 is a waveform diagram of another stimulus pulse signal according to an embodiment of the present application;

fig. 4 is a waveform diagram of yet another stimulus pulse signal according to an embodiment of the present application;

fig. 5 is a waveform diagram of a stimulus pulse signal according to another embodiment of the present application;

fig. 6 is a waveform diagram of yet another stimulus pulse signal according to an embodiment of the present application;

Fig. 7 is a schematic structural diagram of an electrical stimulation system according to an embodiment of the present application;

Fig. 8 is a schematic structural diagram of another electrical stimulation system according to an embodiment of the present application.

Description of the reference numerals:

100-neuromodulator;

10-a stimulation pulse signal;

1-a first pulse signal; 2-a second pulse signal;

11-a pulse generator;

111-a controller; 112-a pulse generation unit; 113-a detection unit; 114-a wireless communication unit;

12-electrode;

200-an object program control instrument;

300-cloud end;

400-remote control terminal.

Detailed Description

Embodiments of the present application are described below with reference to the drawings in the present application. It should be understood that the embodiments described below with reference to the drawings are exemplary descriptions for explaining the technical solutions of the embodiments of the present application, and the technical solutions of the embodiments of the present application are not limited.

As used herein, "said" and "the" may also include plural forms, unless specifically stated otherwise, as will be understood by those skilled in the art. It should be further understood that the terms "comprises" and/or "comprising," when used in this specification of the present application, specify the presence of stated features, integers, operations, elements, and/or components, but do not preclude the presence or addition of other features, information, data, steps, operations, elements, components, and/or groups thereof, etc. that may be implemented as desired in the art. It will be understood that when an element is referred to as being "connected" or "coupled" to another element, it can be directly connected or coupled to the other element or intervening elements may be present. Further, "connected" or "coupled" as used herein may include wirelessly connected or wirelessly coupled. The term "and/or" as used herein refers to at least one of the items defined by the term, e.g., "a and/or B" may be implemented as "a", or as "B", or as "a and B".

For the purpose of making the objects, technical solutions and advantages of the present application more apparent, the embodiments of the present application will be described in further detail with reference to the accompanying drawings.

The inventor finds that in the field of nerve regulation, neurons at different distances from a stimulating electrode can generate different responses to different types of pulse waveforms, so that diversified regulation effects on neuron groups are generated.

Therefore, how to design the stimulation pulse signal to generate appropriate neural response and avoid tissue damage caused by stimulation to the greatest extent is a urgent problem to be solved.

The following describes the technical scheme of the present application and how the technical scheme of the present application solves the above technical problems in detail with specific embodiments. It should be noted that the following embodiments may be referred to, or combined with each other, and the description will not be repeated for the same terms, similar features, similar implementation steps, and the like in different embodiments.

Embodiments of the present application provide a neuromodulator for modulating parkinsonism-associated brain nerves, see fig. 1, the neuromodulator 100 comprising a pulse generator 11 and an electrode 12.

Electrode 12 is disposed at a target region of the brain of a subject, and electrode 12 includes a plurality of first conductive contacts.

The pulse generator 11 is electrically connected with the electrode 12 and is used for generating at least one group of stimulation pulse signals 10, the stimulation pulse signals 10 comprise at least two pulse signals, and at least one of pulse amplitude, pulse width and first conductive contact combinations among different pulse signals is different; the first conductive contact assembly includes at least one first conductive contact; the pulse amplitude of the stimulation pulse signal 10 ranges from 1 to 4 volts or 0 to 25.5 milliamps, the pulse width of the stimulation pulse signal 10 ranges from 60 microseconds to 3.7 milliseconds, and the frequency of the stimulation pulse signal 10 ranges from 17 hertz to 330 hertz.

Because the stimulating pulse signal 10 generated by the pulse generator 11 comprises at least two pulse signals, the pulse amplitude, the pulse width, the frequency and other parameter items of each pulse signal are in the respective proper ranges matched with the parkinsonism, at least one of the pulse amplitude, the pulse width and the first conductive contact combination is different among different types of pulse signals, the different types of pulse signals form cross pulses, the nerve tissue of the brain target area related to the parkinsonism is alternately stimulated, and the characteristics of the different types of pulse signals are combined, so that the brain nerve tissue related to the parkinsonism can be stimulated rapidly and effectively, a certain relieving effect is achieved on parkinsonism attacks, and potential damage to the nerve tissue can be reduced. Alternatively, the target region of the brain includes a target of brain neural tissue associated with parkinson's disease.

Optionally, in the embodiment of the present application, the range of the parameter term of the stimulation pulse signal 10 refers to the range of the parameter term of each pulse signal in the stimulation pulse signal 10. For example, the pulse width of the stimulation pulse signal 10 ranges from 60 microseconds to 3.7 milliseconds, meaning that the pulse width of each pulse signal in the stimulation pulse signal 10 ranges from 60 microseconds to 3.7 milliseconds; the ranges of other parameters such as pulse amplitude and frequency are the same, and are not repeated here.

Optionally, in an embodiment of the present application, most of the numerical ranges include an upper limit value and a lower limit value; for example, the pulse amplitude of the stimulation pulse signal 10 ranges from 1 to 4 volts, including 1 volt and 4 volts. But the numerical range does not include an upper limit value or upper limit value of zero; for example, the range of values from 0 to 25.5 milliamps, excluding the lower limit value of 0, is actually greater than 0 milliamps and no greater than 25.5 milliamps.

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

Alternatively, the subject in embodiments of the application includes a patient suffering from parkinson's disease.

Referring to fig. 2-6, 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 being smaller than the pulse width of the second pulse signal 2, the pulse amplitude of the first pulse signal 1 being greater than the pulse amplitude of the second pulse signal 2.

It should be noted that, the number of the stimulation pulse signals 10, the number of the first pulse signals 1 and the number of the second pulse signals 2 in each stimulation pulse signal 10 in fig. 2 to 6 are only examples, and may be arbitrarily set according to the needs in practical applications.

The pulse amplitude and pulse width determine the stimulation range and activation amount, and the frequency affects the neuron membrane activity and nerves.

The higher the pulse amplitude is, the stronger the stimulation is, so that the first pulse signal 1 can realize the short-time and timely stimulation, and the disease is quickly inhibited; the second pulse signal 2 can stimulate for a longer period of time and avoid overstimulation.

In this embodiment, since the pulse amplitude of the first pulse signal 1 is greater than that of the second pulse signal 2, a stronger stimulation effect can be generated in a short time, and meanwhile, since the pulse width of the first pulse signal 1 is smaller than that of the second pulse signal 2, the transience, full coverage and low damage of stimulation can be ensured, that is, the relevant target points of neurons are stimulated by combining the first pulse signal 1 and the second pulse signal 2, so that the rapid and effective nerve stimulation can be realized, and the potential damage to nerve tissues can be reduced.

Optionally, the stimulation pulse signal 10 includes a first pulse signal sequence and a second pulse signal sequence that are alternately output; the first pulse signal sequence comprises at least one first pulse signal 1 and the second pulse signal sequence comprises at least one second pulse signal 2.

By alternately outputting the first pulse signal sequence and the second pulse signal sequence, the short-time strong stimulation and the long-time strong stimulation are switched, so that the rapid and effective nerve stimulation can be better realized, and the potential damage to the nerve tissue is reduced.

In practical applications, for 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; the pulse width of the stimulation pulse signal 10 is sized according to the disease-corresponding signal transmission characteristics.

Alternatively, the pulse width of the stimulation pulse signal 10 ranges from 20 to 450 microseconds.

Since the frequency range is determined according to the refractory period of neuron electrical signal transmission of the neural tissue, the refractory period is about 3ms, and the influence of stimulation exceeding 330 hz on neurons is not too great theoretically, the frequency of the stimulation pulse signal 10 may be less than 330 hz.

Optionally, the frequency of the stimulation pulse signal 10 ranges from 17 hz to 260 hz.

In some embodiments, the stimulation pulse signal 10 includes at least one first pulse signal 1 and at least one second pulse signal 2, i.e., the neuromodulator 100 employs cross-mode cross-pulsing, where the stimulation pulse signal 10 may have a frequency in the range of 17 hz to 130 hz.

In other words, the cross pulses are on the same electrode 12, and two groups of stimulation programs can be set, each group of stimulation programs can use different contact combinations, pulse amplitudes and pulse widths, and the two groups of stimulation programs alternately perform the stimulation.

In other embodiments, the stimulation pulse signal 10 includes at least one first pulse signal 1, at least one second pulse signal 2, and at least one third pulse (not shown), i.e., the neuromodulator 100 employs a tri-cross pulse in a cross mode, where the frequency of the stimulation pulse signal 10 may range from 17 hz to 85 hz.

Referring to fig. 2 to 6, 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.

For example, the first phase spacing may be 10 microseconds, 50 microseconds, 80 microseconds, 100 microseconds, 120 microseconds, or the like.

Wherein the first phase interval is a time interval from the end of the first pulse signal 1 to the start of an adjacent one of the second pulse signals 2.

Alternatively, the first pulse signal 1 may be a first cathodic pulse, and the second pulse signal 2 may be a first anodic pulse, the first cathodic pulse being used to activate neurons, the first anodic pulse being used to balance charges.

By setting the first anodic pulse immediately after the first cathodic pulse, the first cathodic pulse is mainly used for activating neurons, and the first anodic pulse is mainly used for balancing charges, 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.

In some embodiments, the first cathodic pulse is a rectangular cathodic pulse, and the first anodic pulse is a pulse with a rectangular or non-rectangular waveform, smaller in amplitude and longer in pulse width, so that the reversing effect of the first anodic pulse is reduced, and the activation efficiency is improved.

Wherein the first phase interval is a time interval from the end of the first pulse signal 1 (first cathodic pulse) to the start of an adjacent one of the second pulse signals 2 (first anodic pulse).

Optionally, the first phase distance is 100 microseconds.

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. 6, T11 represents a 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 a 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 a 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 sequence.

By inserting a first phase interval of a shorter time interval between the first cathodic pulse and the first anodic pulse, the reaction of the first anodic pulse is reduced, thereby eliminating the reversal effect of the first anodic pulse without impairing its function of eliminating charge accumulation.

In other embodiments, the first pulse may be an anodic pulse and the second pulse may be a cathodic pulse.

In practical application, it may also be determined whether the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 or the second pulse signal 2 according to the difference between the real-time electroencephalogram signal and the threshold value.

Specifically, when the difference between the real-time electroencephalogram signal and the threshold value is larger (for example, the difference is larger than the first threshold value), the subsequent stimulation pulse signal 10 outputs the first pulse signal 1 first, so as to enhance the stimulation intensity of the neuron; when the difference between the real-time electroencephalogram signal and the threshold value is smaller (for example, the difference is smaller than the first threshold value), the subsequent stimulation pulse signal 10 outputs the second pulse signal 2 first, so that potential damage to the nerve tissue is reduced on the premise of ensuring that the neuron has stronger response.

Referring to fig. 1, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generating unit 112 electrically connected, where the controller 111 is configured to regulate the stimulation pulse signal 10, and includes controlling the pulse generating unit 112 to output different pulse signals having pulse amplitudes greater than a first preset threshold to different combinations of first conductive contacts at different time nodes.

For example, the pulse generation unit 112 outputs first pulse signals each having a pulse amplitude greater than a first preset threshold value to the odd-numbered first conductive contacts (i.e., the 1 st first conductive contact, the 3 rd first conductive contact, the 5 th first conductive contact) at the first time node t 1; the pulse generating unit 112 outputs the second pulse signals each having the pulse amplitude greater than the first preset threshold value to the even number of first conductive contacts (i.e., the 2 nd first conductive contact, the 4 th first conductive contact, the 6 th first conductive contact.) at the second time node t2 (the second time node t2 is a certain time node after the first time node t1, for example, after 1 second).

In other words, the pulse generator 11 adopts a set-up coordinated reset stimulation mode by applying a plurality of bursts of stimulation to different first electrically conductive contacts, the plurality of bursts of stimulation being distributed at different time nodes and at different locations to disrupt the neural activity of the synchronous oscillation. Disrupting pathologically synchronized explosive events may produce persistent changes in the interconnected brain circuits, resulting in persistent symptomatic improvement. The coordinated reset stimulation mode has a longer duration for symptomatic improvement than traditional constant frequency stimulation, and can maintain a longer lasting effect improvement after stimulation is turned off.

Referring to fig. 1 and 6, in some embodiments, the pulse generator 11 includes a controller 111 and a pulse generating unit 112 electrically connected, the controller 111 being configured to regulate the stimulation pulse signal 10, including controlling the pulse generating unit 112 to output at least one pulse signal whose frequency varies in a set manner.

Through the variable frequency stimulation mode with a plurality of frequencies being alternately changed, the method can realize the obvious improvement of symptoms such as gait freezing, language disorder and the like of patients suffering from the Parkinson's disease.

In other embodiments, the controller 111 is configured to regulate the stimulation pulse signal 10, and includes controlling the pulse generating unit 112 to output at least one pulse signal with a constant frequency.

In some embodiments, the pulse interval between adjacent two sets of stimulation pulse signals 10 varies randomly in the range of 5 milliseconds to 15 milliseconds.

The pulse interval between two adjacent groups of stimulation pulse signals 10 is randomly changed within the range of 5 milliseconds to 15 milliseconds, so that the reverse group peak potential (antidromic population spike, APS) can be induced to change within a larger range, thereby generating diversified stimulation to neurons and improving the treatment effect.

Experiments show that when the pulse width of the stimulation pulse signal 10 is greater than 100 microseconds, the action potential peak value is higher than 0, and neurons are more excitable. Therefore, by setting the pulse width of the stimulation pulse signal 10 to be greater than 100 μs, it is possible to enhance the excitation of neurons.

Referring to fig. 2-6, in some embodiments, the first pulse signal sequence comprises at least one first anodic pulse and the second pulse signal sequence comprises at least one second anodic pulse, wherein the first anodic pulse has a pulse width that is less than a pulse width of the second anodic pulse and the first anodic pulse has a pulse amplitude that is higher than a pulse amplitude of the second anodic pulse.

Further, the inventors have found that in addition to the activation of the cathodic pulse, the anodic pulse itself also has an activation effect, and that the anodic pulse promotes depolarization of the population of neurons to enhance activation efficiency, as compared to the cathodic pulse, avoiding hyperpolarization retardation of the neurons, such as axons, by the cathodic pulse.

Finally, the anodal phase of the bi-anodic pulse as shown in fig. 2 shows the effect of rapid activation of neurons in neuromodulation. The higher the pulse amplitude of the first anodic pulse is, the stronger the stimulus intensity brought by the first anodic pulse is, and the higher the activation efficiency is, so that the first anodic pulse can be used for realizing short-time and timely stimulus, and the disease is quickly inhibited; the second anodic pulse is cooperatively utilized, so that the overstimulation can be avoided while the certain stimulation intensity is maintained for a long time. Such a stimulus waveform is particularly useful where it is desired to inhibit and/or activate neurons at all times.

Referring to fig. 1, in some embodiments, the pulse generator 11 includes a detection unit 113 and a controller 111.

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

The controller 111 is electrically connected with the detection unit 113, and is used for determining a characteristic value of the beta frequency band according to the brain electrical signal; determining whether the real-time characteristic value of the beta frequency band exceeds a preset characteristic value range; when the real-time characteristic value of the beta frequency band exceeds the preset characteristic value range, the stimulation pulse signal 10 is regulated; the preset characteristic value range is the characteristic value range of the object in the beta frequency band.

Since the brain electrical signal of the beta frequency band is obviously abnormal when the subject is in the Parkinson's attack state, the characteristic value of the beta frequency band can be determined by detecting the brain electrical signal, and whether the subject is in the Parkinson's attack state is determined.

In some embodiments, hilbert transformation and sliding window integration can be sequentially performed on the beta-band signal in the electroencephalogram signal to obtain the real-time characteristic value of the beta-band. The acquired brain electrical signals are subjected to time domain and frequency domain conversion, so that the real-time characteristic value of the beta frequency band for judging the brain state comprises the time domain characteristic and the frequency domain characteristic of the brain electrical signals, and further whether the brain state is normal or not can be judged more accurately.

The preset feature value range may be trained for personalized treatment data of a certain object (e.g., a patient). The characteristic value of the beta frequency band of the subject in the medication state can represent that the subject is in a normal state (Parkinson's disease state), so the preset characteristic value range can be the characteristic value range of the beta frequency band of the subject in the medication state, and when the real-time characteristic value of the beta frequency band exceeds the preset characteristic value range, the subject is represented to be in the Parkinson's disease state.

With continued reference to fig. 1, in some embodiments, the controller 111 is configured to determine a desired real-time pulse amplitude for adjustment based on a minimum pulse amplitude that causes a detectable clinical effect of the subject and a real-time pulse variation when the real-time power of the β -band exceeds a preset characteristic range;

the real-time characteristic value of the beta frequency band comprises the real-time power of the brain electrical signal in the beta frequency band; the real-time pulse variation includes a real-time duty cycle of a difference between a maximum pulse amplitude before causing a side effect in the subject and a minimum pulse amplitude causing a detectable clinical effect in the subject; the real-time duty ratio comprises the ratio of the difference value between the real-time power and the minimum power of the beta frequency band of the subject in the medication state and the difference value between the maximum power of the beta frequency band of the subject in the medication state and the minimum power of the beta frequency band of the subject in the medication state. The beta band comprises 14 to 36 hertz.

By the arrangement, the real-time pulse amplitude of the stimulation pulse signal 10 which is more suitable for the subject can be obtained, and the abnormal discharge of the beta frequency band of the brain of the subject can be well restrained under the condition of smaller side effect, so that the onset of Parkinson's disease of the subject is relieved.

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

In some embodiments, the first pulse signal 1 is any one of an exponentially rising stimulus waveform, a center triangle waveform, a gaussian waveform, a trapezoidal waveform, a sine wave;

And/or the second pulse signal 2 is any one of an exponentially rising stimulus waveform, a center triangle waveform, a gaussian waveform, a trapezoidal waveform, and a sine wave.

In this embodiment, by adopting non-square waves such as an exponentially rising stimulus waveform, a center triangle waveform, a gaussian waveform, a trapezoidal waveform, a sine wave, and the like, there is an advantage of energy saving.

By using an analysis model of the neural membrane or a genetic algorithm, the activation effect of the stimulation waveform with the increased index is better, and the stimulation waveform is more suitable for peripheral nerve stimulation.

Since the larger the slope of the waveform of the stimulation pulse signal 10, the more rapid the neuron response, but the more complex the situation in which it can respond to local nerve clusters, the stimulation pulse signal 10 can contain a variety of different waveforms, thereby enhancing the effect of activating/inhibiting neurons.

In some embodiments, the pulse generator 11 is flexible, sheet-like, and built into the skull of the subject.

In other words, the neuromodulator 100 employs a full skull implant. By such arrangement, the convenience of carrying the neuromodulator 100 can be improved, and the unstable operation state caused by the partial exposure of the neuromodulator 100 can be avoided.

For example, the pulse generator 11 may be manufactured by encapsulating a flexible circuit board with a silicone material. At this time, the pulser 11 has flexibility, and can be attached to the skull of the subject and restrained by the skull when the skull of the subject is implanted.

In other embodiments, the pulser 11 is rigid, and the shape of the pulser 11 matches the shape of the subject's skull so as to conform to the subject's skull when implanted.

In some embodiments, the neuromodulator 100 includes a battery (not shown) and a wireless charging unit (not shown) that are electrically connected.

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

The wireless charging unit can be used for charging the battery on the non-invasive premise, so that the cruising ability of the neuromodulator 100 can be improved.

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

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

In other embodiments, for the treatment of Parkinson's disease, a combination of deep electrodes located deep in the brain and cortical electrodes located in the cortex of the brain may be used.

The technical scheme provided by the embodiment of the application has the beneficial technical effects that:

In the neural regulator 100 according to the embodiment of the present application, since the stimulation pulse signal 10 generated by the pulse generator 11 includes at least two pulse signals, at least one of the pulse amplitude, the pulse width and the first conductive contact combination between the pulse signals of different types is different, and the pulse signals of different types form cross pulses, the number of the thorns of the neural related target spots is alternately performed, and the characteristics of the pulse signals of different types are combined, so that the rapid and effective neural stimulation can be realized, a certain effect of alleviating the parkinson attack can be achieved, and the potential damage to the neural tissue can be reduced.

Based on the same inventive concept, an embodiment of the present application provides an electrical stimulation system, as shown in fig. 7, including a neuromodulator 100 as described above.

The neuromodulator 100 includes an electrode 12 and a pulse generator 11 electrically connected. Electrode 12 is disposed at a target region of the brain of a subject, and electrode 12 includes a plurality of first conductive contacts.

Because the stimulating pulse signals generated by the pulse generator in the nerve regulator 100 comprise at least two pulse signals, at least one of pulse amplitude, pulse width and first conductive contact combinations among the pulse signals of different types is different, cross pulses are formed through the pulse signals of different types, the stimulation is alternately performed on nerve related targets, and the characteristics of the pulse signals of different types are combined, so that the rapid and effective nerve stimulation can be realized, a certain relieving effect on parkinsonism is achieved, and potential damage to nerve tissues can be reduced.

In some embodiments, the pulse generator 11 includes a controller 111 and a wireless communication unit 114 that are electrically connected.

The electrical stimulation system further comprises: the object program control apparatus 200 is connected with the wireless communication unit 114 in a wireless communication manner, and is used for acquiring an externally input parameter adjustment control signal, transmitting the parameter adjustment control signal to the pulse generator 11 through the wireless communication unit 114, so as to adjust the parameter item of the subsequent stimulation pulse signal; the parameter items of the stimulation pulse signal comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.

The object program control apparatus 200 is usually disposed near the object (patient), and medical workers such as doctors or nurses, or the object can input parameter adjustment control signals through the object program control apparatus 200 under the guidance of the medical workers, so as to adjust the parameter items of the stimulation pulse signals output by the pulse generator subsequently, and realize the self-adjustment of the parameter items of the stimulation pulse signals according to the self feeling of the user.

Optionally, object programmer 200 is used for at least one of: information showing whether the communication connection with the pulse generator 11 has been made, information on the remaining power of the battery of the pulse generator 11, information on the remaining storage space of the memory of the pulse generator 11, and whether the data has been read. Optionally, the read data includes at least one of: parameters of the stimulation pulse signal, parameter values of the stimulation pulse signal and physiological data of the subject. The physiological data of the subject includes brain electrical signals.

Referring to fig. 7, in some embodiments, the neuromodulator 100 includes a pulse generator 11 and an 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, the detection unit 113 and the pulse generation unit 112 being electrically connected to the electrode 12.

In some embodiments, the pulse generator 11 includes a controller 111 and a wireless communication unit 114 that are electrically connected; the electrical stimulation system further comprises an electroencephalogram data management system, and the electroencephalogram data management system comprises a cloud end 300 and a remote control terminal 400 which are in communication connection.

The wireless communication unit 114 is in wireless communication connection with the cloud 300, and is configured to upload the brain electrical signal of the target brain region of the subject detected by the pulse generator 11 to the cloud 300.

The remote control terminal 400 is configured to obtain an electroencephalogram signal of a target brain region of the subject from the cloud 300, generate and display an electroencephalogram waveform according to 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 parameter items of a subsequent stimulation pulse signal based on the pulse adjustment information; the parameter items of the stimulation pulse signal comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.

By uploading the brain electrical signal of the target brain region of the subject to the cloud 300, a doctor obtains the brain electrical signal from the cloud 300 by using the remote control terminal 400, generates brain electrical waveforms according to the brain electrical signal and displays the brain electrical waveforms, so that the doctor can conveniently perform diagnosis and analysis according to the brain electrical signal of the subject (patient), and further adjust parameter items of the stimulation pulse signals output by the pulse generator by using the remote control terminal 400, and the doctor can adjust the parameter items of the stimulation pulse signals according to the brain electrical signal of the user in real time.

Optionally, referring to fig. 8, in some embodiments, the pulse generator 11 includes a controller 111 and a wireless communication unit 114 that are electrically connected. The electrical stimulation system further comprises: an object program control instrument 200 and an electroencephalogram data management system. The electroencephalogram data management system comprises a cloud end 300 and a remote control terminal 400 which are in communication connection.

The wireless communication unit 114 is in wireless communication connection with the object program control instrument 200, and the object program control instrument 200 is in communication connection with the cloud 300. The wireless communication unit 114 is configured to upload the brain electrical signal of the target brain region of the subject detected by the pulse generator 11 to the cloud 300 after passing through the relay of the subject programmer 200. Optionally, the object programmer 200 amplifies and/or modulates the received brain electrical signal of the target brain region of the object, and then uploads the brain electrical signal to the cloud 300. The strength requirement on the brain electrical signal sent by the wireless communication unit 114 is reduced, energy conservation is facilitated, the cruising ability of the pulse generator 11 is improved, and the influence on the brain of the subject can be avoided, or the influence probability or degree is reduced.

The present embodiment is an embodiment of the aforementioned electrical stimulation system corresponding to the neuromodulator for modulating parkinsonism-related brain nerves, and specific technical details and technical effects may be referred to the foregoing, and will not be repeated here.

Those of skill in the art will appreciate that the various operations, methods, steps in the flow, acts, schemes, and alternatives discussed in the present application may be alternated, altered, combined, or eliminated. Further, other steps, means, or steps in a process having various operations, methods, or procedures discussed herein may be alternated, altered, rearranged, disassembled, combined, or eliminated. Further, steps, measures, schemes in the related art having various operations, methods, flows disclosed in the present application may also be alternated, altered, rearranged, decomposed, combined, or deleted.

The terms "first," "second," and the like, are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, a feature defining "a first" or "a second" may explicitly or implicitly include one or more such feature. In the description of the present application, unless otherwise indicated, the meaning of "a plurality" is two or more.

In the description of the present specification, a particular feature, structure, material, or characteristic may be combined in any suitable manner in one or more embodiments or examples.

The foregoing is only a part of the embodiments of the present application, and it should be noted that, for those skilled in the art, other similar implementation means based on the technical idea of the present application may be adopted without departing from the technical idea of the solution of the present application, which is also within the protection scope of the embodiments of the present application.

Claims (14)

1. A neuromodulator for modulating parkinsonism-associated brain nerves, comprising:

an electrode disposed at a target region of a brain of a subject, the electrode comprising a plurality of first conductive contacts;

the pulse generator is electrically connected with the electrodes and is used for generating at least one group of stimulation pulse signals, the stimulation pulse signals comprise at least two pulse signals, and at least one of pulse amplitude, pulse width and first conductive contact combinations among different types of pulse signals is different; the first conductive contact assembly 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 milliamps, the pulse width of the stimulation pulse signal ranges from 60 microseconds to 3.7 milliseconds, and the frequency of the stimulation pulse signal ranges from 17 hertz to 330 hertz.

2. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the stimulation pulse signal comprises at least one first pulse signal and at least one second pulse signal, the first pulse signal having a pulse width that is less than a pulse width of the second pulse signal, the first pulse signal having a pulse amplitude that is greater than a pulse amplitude of the second pulse signal.

3. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 2, wherein a first phase distance is provided between the first pulse signal and the second pulse signal, the first phase distance being in the range of 10 microseconds to 120 microseconds.

4. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the pulse generator comprises an electrically connected controller and pulse generating unit, the controller for modulating the stimulation pulse signal comprising controlling the pulse generating unit to output different pulse signals having pulse amplitudes each greater than a first preset threshold to different ones of the first conductive contact combinations at different time nodes.

5. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the pulse generator comprises an electrically connected controller and pulse generating unit, the controller for modulating the stimulation pulse signal comprising controlling the pulse generating unit to output at least one of the pulse signals having a frequency that varies in a set manner.

6. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the pulse generator comprises:

the detection unit is electrically connected with the second conductive contact of the electrode, and is used for detecting an electroencephalogram signal of a target brain region of the object and outputting the electroencephalogram signal to the controller;

The controller is electrically connected with the detection unit and is used for determining a characteristic value of a beta frequency band according to the electroencephalogram signal; determining whether the real-time characteristic value of the beta frequency band exceeds a preset characteristic value range; when the real-time characteristic value of the beta frequency band exceeds a preset characteristic value range, the stimulation pulse signal is regulated; the preset characteristic value range is the characteristic value range of the object in the beta frequency band.

7. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 6,

The controller is used for determining an expected real-time pulse amplitude value for adjustment according to the minimum pulse amplitude value and the real-time pulse variation which cause the clinical effect detectable by the object when the real-time power of the beta frequency band exceeds a preset characteristic value range;

the real-time characteristic value of the beta frequency band comprises the real-time power of the electroencephalogram signal in the beta frequency band; the real-time pulse variation comprises a real-time duty cycle of a difference between a maximum pulse amplitude before causing a side effect in the subject and a minimum pulse amplitude causing a detectable clinical effect in the subject; the real-time duty ratio comprises the ratio of the difference value between the real-time power and the minimum power of the beta frequency band of the object in the medication state to the difference value between the maximum power of the beta frequency band of the object in the medication state and the minimum power of the beta frequency band of the object in the medication state.

8. The neuromodulator for modulating a parkinsonism-associated brain nerve of claim 1, wherein the first pulse signal is any one of an exponentially rising stimulation waveform, a center triangular waveform, a gaussian waveform, a trapezoidal waveform, a sine wave;

and/or the second pulse signal is any one of an exponentially rising stimulation waveform, a central triangle waveform, a gaussian waveform, a trapezoidal waveform and a sine wave.

9. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the pulser is flexible, sheet-like, and is embedded in the skull bone of the subject.

10. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 9, wherein the neuromodulator comprises an electrically connected battery and a wireless charging unit.

11. A neuromodulator for modulating a parkinsonism-associated brain nerve as defined in claim 1, wherein the number of electrodes comprises at least two and the target brain region comprises at least one of a deep brain, a cortex.

12. An electro-stimulation system comprising a neuromodulator for modulating parkinsonism-associated brain nerves as claimed in any one of claims 1 to 11; the neuromodulator includes an electrode and a pulse generator electrically connected, the electrode disposed at a target region of the brain of the subject, the electrode including a plurality of first conductive contacts.

13. The electrical stimulation system of claim 12, wherein the pulse generator comprises a controller and a wireless communication unit electrically connected;

the electrical stimulation system further comprises: the object program control instrument is in wireless communication connection with the wireless communication unit and is used for acquiring an externally input parameter adjustment control signal, transmitting the parameter adjustment control signal to the pulse generator through the wireless communication unit and adjusting a parameter item of a subsequent stimulation pulse signal; the parameter items of the stimulation pulse signals comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.

14. The electrical stimulation system of claim 12, wherein the pulse generator comprises a controller and a wireless communication unit electrically connected; the electrical stimulation system further comprises an electroencephalogram data management system, and the electroencephalogram data management system comprises a cloud end and a remote control terminal which are in communication connection;

the wireless communication unit is in wireless communication connection with the cloud end and is used for uploading the brain electrical signals of the target brain region of the object detected by the pulse generator to the cloud end;

The remote control terminal is used for acquiring the electroencephalogram signals from the cloud, generating and displaying electroencephalogram waveforms according to the electroencephalogram signals, acquiring externally input pulse adjustment information based on the electroencephalogram waveforms, and transmitting the pulse adjustment information to the controller through the wireless communication unit, so that the controller adjusts parameter items of subsequent stimulation pulse signals based on the pulse adjustment information; the parameter items of the stimulation pulse signals comprise at least one of pulse amplitude, pulse width, first phase interval and pulse interval.