Noninvasive deep brain electrical stimulation system with adjustable polarity

Abstract

The polarity-adjustable non-invasive deep brain electrical stimulation system comprises a waveform generation module which generates a first frequency waveform by using a first signal generator and generates a second frequency waveform by using a second signal generator; the waveform rectification module is used for performing full-wave rectification on the first frequency waveform and the second frequency waveform by using a first rectification assembly and a second rectification assembly to obtain a first rectification waveform and a second rectification waveform; the first rectification waveform and the second rectification waveform pass through a first current stabilization assembly and a second current stabilization assembly to obtain a first stimulation waveform and a second stimulation waveform; and outputting the stimulation waveform to a stimulation target spot by using the stimulation electrode so as to generate a stimulation waveform with low frequency envelope in the deep brain part. According to the invention, the polarity-adjustable time interference waveform is obtained through the stimulation current rectification, so that the low-frequency envelope current with different polarities is utilized to selectively apply suitable electrical stimulation for different brain abnormal activity characteristics, and the pertinence and effectiveness of the electrical stimulation are improved.

Description

Technical Field

[0001] This application belongs to the field of medical device technology, specifically relating to a polarity-adjustable non-invasive deep brain stimulation system. Background Technology

[0002] Deep brain stimulation (DBS) is a non-invasive technique that modulates nerve signal transduction in the central and peripheral nervous systems, thereby controlling the electrical activity of the brain's neural networks and improving neurological function. Non-invasive DBS involves fixing electrodes to specific areas of the scalp and using a pulse generator connected to the electrodes to produce electrical pulses. This interferes with and modulates abnormal brain signals associated with neurological disorders, aiming to alleviate patients' symptoms and improve their quality of life.

[0003] The paper "Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields" and patent US10173061B2 disclose a noninvasive deep brain stimulation technique based on temporal interference. This technique applies two high-frequency sinusoidal stimulation currents (e.g., frequencies f1 and f2) to the brain via scalp electrodes. While the two high-frequency currents themselves are too high to effectively activate neurons, they can overlap and interfere deep within the brain, generating a low-frequency envelope (Δf = |f1-f2|) amplitude-modulated current that effectively activates neurons located deep within the brain.

[0004] This time-interference-based electrical stimulation method can non-invasively and selectively stimulate the deep brain without affecting the brain surface, achieving non-invasive deep brain electrical stimulation and providing a safer and more effective method for the deep regulation of brain diseases. Based on this technology, patents CN108744273B and US11071862B2 further propose a non-invasive deep brain dual-focus stimulation method. This method uses transcranial current to interfere with the deep brain, generating two stimulation focal points that simultaneously target and activate two deep brain regions within specific neural circuits, thus assisting the brain in achieving certain functional effects.

[0005] In particular, abnormal brain activity associated with brain diseases exhibits characteristics, which can be categorized into abnormally enhanced brain activity and abnormally weakened brain activity, such as abnormal inhibition associated with depression. Therefore, deep brain stimulation (DBS) targeting different diseases, if tailored to the specific abnormal brain activity characteristics (excitation or inhibition) of the brain disease, can achieve more precise symptomatic stimulation based on existing time-interference-based non-invasive DBS, thereby more effectively regulating the corresponding brain diseases. However, the aforementioned non-invasive DBS based on sinusoidal time interference contains both positive and negative waveforms in its stimulation waveform; that is, it does not select specific polarities for stimulation of specific brain regions, and therefore cannot provide stimulation of specific polarities to specific functional areas of the brain.

[0006] Therefore, if a polarity-tunable electrical stimulation model could be constructed based on the non-invasive deep brain stimulation technology disclosed in the aforementioned patents (US10173061B2, CN108744273B, and US11071862B2), for example, if enhancing or inhibiting stimulation could be set and used for electrical stimulation treatment of target patients, brain activity could be more precisely controlled, thereby achieving more precise intervention for diseases in related brain regions. However, due to the relative difficulty in generating and maintaining unipolar stimulation waveforms and the current limitations of researchers in this field in applying and improving time-interference electrical stimulation methods due to technological maturity and safety concerns, no one has yet proposed such a polarity-tunable non-invasive deep brain stimulation technology, nor has any corresponding stimulation control device been developed or produced. Utility Model Content

[0007] To address the problems existing in the prior art, the purpose of this application is to propose a polarity-adjustable non-invasive deep brain stimulation system. By rectifying the stimulation current before generating the time interference waveform of the dual-channel stimulation waveform, an all-positive waveform or an all-negative waveform is obtained. This allows for selective electrical stimulation of target patients with different abnormal brain activity characteristics using amplitude-modulated currents of two low-frequency envelopes.

[0008] Specifically, this application relates to the following aspects:

[0009] 1. A polarity-adjustable non-invasive deep brain stimulation system, comprising: a waveform generation module for generating a first frequency waveform using a first signal generator and a second frequency waveform using a second signal generator; a waveform rectification module connected to the output of the waveform generation module for performing full-wave rectification of the first frequency waveform using a first rectification component to obtain a first rectified waveform, and performing full-wave rectification of the second frequency waveform using a second rectification component to obtain a second rectified waveform; a current stabilization module connected to the output of the waveform rectification module for passing the first rectified waveform through the first current stabilization component to obtain a high-frequency undistorted first stimulation waveform, and passing the second rectified waveform through the second current stabilization component to obtain a high-frequency undistorted second stimulation waveform; and a stimulation output module connected to the output of the current stabilization module for outputting the first stimulation waveform and the second stimulation waveform to target scalp stimulation points using stimulation electrodes to generate a low-frequency envelope stimulation waveform in the deep brain.

[0010] 2. According to the stimulation system of item 1, wherein the first rectifier component and the second rectifier component include: a voltage input unit, a unidirectional conductive unit and a load, wherein the voltage input unit adjusts the voltage amplitude of the first frequency waveform or the second frequency waveform to a preset voltage amplitude; the unidirectional conductive unit adjusts the direction of the current flowing through the load during the positive half-cycle and the negative half-cycle of the first frequency waveform or the second frequency waveform, respectively, so that the direction of the current flowing through the load is consistent during the whole cycle of the first frequency waveform or the second frequency waveform, thereby generating a first rectified waveform or a second rectified waveform with a constant current direction.

[0011] 3. According to the stimulation system of item 2, wherein the unidirectional conductive unit includes a first rectifier diode and a second rectifier diode, wherein the first rectifier diode and the second rectifier diode have a first terminal and a second terminal, respectively; during the positive half-cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is turned on and the second rectifier diode is reversed to cut off the current, and the current flows through the first terminal of the first rectifier diode to the second terminal of the first rectifier diode; during the negative half-cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is reversed to cut off the current and the second rectifier diode is turned on, and the current flows through the first terminal of the second rectifier diode to the second terminal of the second rectifier diode.

[0012] 4. According to the stimulation system of item 2, wherein the unidirectional conductive unit includes a first rectifier diode and a second rectifier diode, wherein the first rectifier diode and the second rectifier diode have a first terminal and a second terminal, respectively; during the positive half-cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is turned on and the second rectifier diode is reverse-biased, and the current flows through the second terminal of the first rectifier diode to the first terminal of the first rectifier diode; during the negative half-cycle of the first frequency waveform or the second frequency waveform, the first rectifier diode is reverse-biased and the second rectifier diode is turned on, and the current flows through the second terminal of the second rectifier diode to the first terminal of the second rectifier diode.

[0013] 5. According to the stimulation system of item 1, wherein the first current stabilizing component and the second current stabilizing component respectively include a primary constant current unit and a secondary constant current unit, wherein the secondary constant current unit adjusts the high-frequency component of the current through the first rectified waveform or the second rectified waveform of the primary constant current unit to keep the high-frequency component of the current constant.

[0014] 6. The stimulation system according to item 1 further includes: a stimulation polarity detection module, used to acquire resting-state functional magnetic resonance data of the target, extract the blood oxygen level dependent signal of the target's brain functional network and / or brain region from the resting-state functional magnetic resonance data through a data preprocessing unit and a data postprocessing unit; determine the scalp stimulation target point of the target, the current direction of the first rectified waveform obtained by the first rectifier component, and the current direction of the second rectified waveform obtained by the second rectifier component based on the abnormal state of the target's blood oxygen level dependent signal.

[0015] 7. According to the stimulation system of item 6, wherein the extraction of blood oxygen level-dependent signals of target brain functional networks and / or brain regions from resting-state functional magnetic resonance imaging (fMRI) data by the data preprocessing unit and the data postprocessing unit includes: the data preprocessing unit performing quality checks, time point removal, slice time correction, head motion correction, image registration, standardization, smoothing, and / or low-frequency bandpass filtering on the resting-state fMRI data; the fMRI data postprocessing unit includes performing time series extraction, functional connectivity matrix calculation, and / or statistical analysis on the resting-state fMRI data processed by the data preprocessing unit.

[0016] 8. The stimulation system according to item 1 further includes: a stimulation assessment module for detecting the electrical stimulation parameters and effects received by the target using a non-invasive deep brain stimulation assessment unit; and adjusting the frequency, amplitude, wave rise, wave fall, or on / off ratio of the first stimulation waveform and / or the second stimulation waveform according to the electrical stimulation effect to improve the electrical stimulation effect.

[0017] Beneficial effects

[0018] 1. The polarity-adjustable non-invasive deep brain stimulation system proposed in this application, compared with the existing sinusoidal time-interference electrical stimulation system, can use a waveform rectification module to adjust the polarity of the electrode stimulation signal as needed, so that the stimulation polarity of the time-interference deep brain stimulation wave is adjustable. This allows for more targeted and personalized stimulation of the target brain region, thereby improving the effectiveness and precision of individual neuromodulation. It provides a more effective application system for regulating the brain and intervening in the progression of brain diseases through time-interference non-invasive deep brain stimulation technology.

[0019] 2. The polarity-adjustable non-invasive deep brain stimulation system proposed in this application utilizes its current-stabilizing module to stably regulate the intensity of the stimulation signal output to the electrodes and control the distortion and attenuation that easily occurs in the high-frequency part of the stimulation signal, thereby ensuring that a high-quality and stable stimulation signal is delivered to the target deep brain to form a more precise low-frequency envelope stimulation current. Based on this stable stimulation signal current-stabilizing function, it is also possible to conveniently adjust the parameters of the stimulation signal based on the treatment effect of the target patient, providing the target patient with a more effective optimization of the electrical stimulation program, and further avoiding discomfort or accidents to the target patient.

[0020] 3. This application can also evaluate the effects of electrical stimulation on the target, and then adjust the frequency, amplitude, and other stimulation parameters of the stimulation signal according to the effect of electrical stimulation, so as to improve the therapeutic effect of stimulation, the comfort of the target patient, and other clinical indicators such as the treatment process. Attached Figure Description

[0021] Figure 1A The figure shows a schematic diagram of the stimulation electrode connection according to an embodiment of this application;

[0022] Figure 1B The figure shows a schematic diagram of a polarity-adjustable non-invasive deep brain stimulation system according to an embodiment of this application;

[0023] Figure 2A The figure shows a time-domain waveform diagram of a first stimulus waveform with full positive amplitude, a second stimulus waveform, and a corresponding time-interference stimulus waveform according to an embodiment of this application.

[0024] Figure 2B The illustration shows the spectrum of the first stimulus waveform, the second stimulus waveform, and the corresponding time-interference stimulus waveform with full positive amplitude according to an embodiment of this application.

[0025] Figure 3A The figure shows a time-domain waveform diagram of a first stimulus waveform with full negative amplitude, a second stimulus waveform, and a corresponding time-interference stimulus waveform according to an embodiment of this application.

[0026] Figure 3B The illustration shows the spectrum of the first stimulus waveform, the second stimulus waveform, and the corresponding time-interference stimulus waveform with full negative amplitude according to an embodiment of this application.

[0027] Figure 4A The figure shows a schematic diagram of a first rectifier assembly and a second rectifier assembly according to an embodiment of the present application;

[0028] Figure 4B The illustration shows another structural schematic diagram of the first rectifier component and the second rectifier component according to an embodiment of this application;

[0029] Figure 5The illustration shows a flowchart of a method of using a polarity-adjustable non-invasive deep brain stimulation system according to an embodiment of this application. Detailed Implementation

[0030] The present application is further illustrated below with reference to embodiments. It should be understood that the embodiments are only used to further illustrate and explain the present application and are not intended to limit the present application.

[0031] Unless otherwise defined, technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. While similar or identical methods and materials may be applied in experimental or practical applications, materials and methods are described herein. In case of conflict, the definitions included herein shall prevail. Furthermore, materials, methods, and examples are for illustrative purposes only and are not intended to be limiting. The present application is further described below with reference to specific embodiments, but is not intended to limit the scope of the application.

[0032] As mentioned above, time-interference non-invasive deep brain stimulation (DBS) techniques based on sinusoidal waveforms have been widely validated to date. However, polarity-tunable time-interference non-invasive DBS techniques have not yet been proposed, due to the following factors:

[0033] (1) The stimulation waveform of the polarity-adjustable time-interference non-invasive deep brain stimulation technology is more complex and has more high-frequency components, which places higher demands on the performance of the constant current source circuit; (2) At present, there is a lack of clinical research on the polarity-adjustable time-interference non-invasive deep brain stimulation technology to verify its stability and feasibility in targeted treatment of specific diseases compared with the polarity-fixed time-interference non-invasive deep brain stimulation technology.

[0034] Nevertheless, this polarity-tunable time-interference non-invasive deep brain stimulation (DBS) technique has unique advantages for regulating specific diseases. Traditional sinusoidal waveform-based DBS techniques can modulate brain activity, but cannot produce stimulation with specific polarities, such as enhancement or inhibition. However, abnormal brain activity associated with brain diseases has specific characteristics, which can be divided into abnormally enhanced brain activity, such as the abnormal excitation in people with Alzheimer's disease, and abnormally weakened brain activity, such as the abnormal inhibition exhibited in people with depression. In these cases, using a polarity-tunable non-invasive DBS device to generate unipolar time-interference electrical stimulation to regulate the abnormal excitation or inhibition in the brains of the above-mentioned diseases can more precisely regulate brain activity, thereby achieving the goal of specific disease intervention.

[0035] Based on this consideration, this application provides a polarity-adjustable non-invasive deep brain stimulation system, which may include: a waveform generation module, a waveform rectification module, a current stabilization module, and a stimulation output module. The waveform generation module generates and outputs two high-frequency stimulation waveforms of different frequencies. The waveform rectification module rectifies the two stimulation waveforms to form a stimulation waveform with the same specified polarity. The current stabilization module regulates the current of the stimulation waveforms, and the two stimulation waveforms are delivered to specified stimulation target points on the scalp of the target subject through two pairs of stimulation electrodes in the stimulation output module. This forms a low-frequency envelope amplitude-modulated stimulation current with a specific polarity in the deep brain region of the target subject. Figure 1A As shown.

[0036] In some implementations, the waveform generation module may include two signal generators, such as a first signal generator and a second signal generator, to generate two high-frequency sinusoidal waveforms with different frequencies, such as a first frequency waveform and a second frequency waveform. The first frequency waveform and the second frequency waveform can overlap and interfere deep within the brain, thereby generating an amplitude-modulated current with a low-frequency envelope whose frequency is the difference between the frequencies of the interference waveforms. This can effectively activate neurons in deep brain functional areas, thereby precisely regulating brain activity.

[0037] However, the low-frequency envelope stimulation current generated by the interference of two high-frequency sinusoidal waveforms contains both positive and negative waveforms. It does not specify the polarity for the stimulation of a specific brain region, nor can the polarity be regulated by adjustment. Therefore, it cannot produce stimulation of a specific polarity for a particular brain region.

[0038] To address this deficiency, this application proposes using a waveform rectification module to adjust the polarity of the stimulation waveform to generate a stimulation current of a specified polarity. Specifically, as shown... Figure 1B As shown, the waveform rectification module may include two waveform rectification components, such as a first rectification component and a second rectification component, to rectify the two high-frequency sine waves output by the waveform generation module, respectively. Each waveform rectification component may include a voltage input unit for receiving the high-frequency sine wave output by the signal generator and adjusting its amplitude to a preset value required for functional electrical stimulation; a unidirectional conductive unit for rectifying the high-frequency sine wave to obtain a DC waveform with a specified polarity; and a load for loading the obtained DC waveform.

[0039] In one embodiment, the voltage input unit may be exemplified as a power transformer. Preferably, the voltage input unit is a power transformer SMW3225S102HTE. The SMW3225S102HTE has high insulation resistance and stable electrical performance, which can ensure that the current and voltage fluctuate within a safe range, reducing the risk of potential harm to the target subject.

[0040] In some implementations, the unidirectional conductive unit can adjust the direction of the current flowing through the load during the negative half-cycle of the alternating high-frequency sinusoidal waveform, such as the first frequency waveform or the second frequency waveform, so that the direction of the current flowing through the load remains unchanged during the full cycle of the alternating first frequency waveform or the second frequency waveform, so as to output a fully positive DC waveform through the load.

[0041] Therefore, the unidirectional conductive unit needs to provide a stable, high-frequency stimulation waveform without polarity changes through rectification. Rectifier bridges, rectifier diodes, and filter circuits can all utilize the voltage signal from a signal generator or transformer to generate a unipolar stimulation waveform. While a rectifier bridge can perform rectification, its structure is relatively complex, consisting of multiple diodes. In systems with complex logic chains and numerous electronic components, the high-frequency DC waveform obtained by the rectifier bridge may exhibit varying degrees of distortion. Filter circuits can further smooth the rectified DC waveform, but they do not have independent rectification capabilities. Therefore, in an advantageous implementation, the unidirectional conductive unit is designed with a rectifier circuit composed of multiple rectifier diodes, such as... Figure 4A As shown. The first rectifier diode (D1) and the second rectifier diode (D2) each have a first terminal 1 and a second terminal 2. The first terminal of D1 and the first terminal of D2 are respectively connected to the two ends of the secondary coil of the power transformer SMW3225S102HTE. The second terminals of D1 and D2 are respectively connected to one end of the load R1. The connection terminals of the load R1 and D1 and D2 are also connected to the center tap of the secondary coil of the power transformer SMW3225S102HTE. D1 and D2 can be turned on from terminal 1 to terminal 2. After the first frequency waveform, converted by the power transformer SMW3225S102HTE, is input to the rectifier circuit, during the positive half-cycle of the first frequency waveform, D1 conducts and D2 reverses direction to cut off the current. The current flows from terminal 1 of D1 to terminal 2, forming a DC waveform with positive on the left and negative on the right across the load R1. During the negative half-cycle of the first frequency waveform, D1 reverses direction to cut off the current and D2 conducts. The current flows from terminal 1 of D2 to terminal 2, forming a DC waveform with positive on the left and negative on the right across the load R1. Thus, within one full cycle of the first frequency waveform, the direction of the DC waveform formed across the load R1 does not change, exhibiting a fixed polarity. This DC waveform with a positive voltage drop across the load R1 can be defined as a positive DC waveform, such as... Figures 2A-2B As shown.

[0042] In this way, under reverse current-cut-off conditions, the relationship of the PN junction inside the rectifier diode effectively prevents and minimizes reverse leakage current. Furthermore, the input voltage typically required for deep brain stimulation is within the maximum reverse operating voltage range of the rectifier diode, preventing the polarity of the rectified waveform from reversing due to adjustments in voltage or current intensity. Compared to a rectifier bridge, this dual-rectifier diode design is more suitable for non-invasive deep brain stimulation systems and is easier to maintain and replace. In addition, the rectifier diode has very low on-resistance when forward biased, allowing for efficient current conduction. This reduces energy loss when rectifying AC waveforms to DC waveforms, resulting in lower power consumption compared to rectifier bridges or filter circuits.

[0043] Furthermore, the unidirectional conductive units of the two rectifier components can be used to generate DC waveforms of different frequencies and the same polarity, such as a first rectifier waveform and a second rectifier waveform. The two DC waveforms, which only have amplitude changes in the positive direction, can be used to interfere in the deep brain to generate a low-frequency envelope stimulation current that only has amplitude changes in the positive direction.

[0044] In another embodiment, the unidirectional conductive unit includes a rectifier circuit composed of multiple rectifier diodes, such as... Figure 4B As shown. The first rectifier diode (D1) and the second rectifier diode (D2) each have a first terminal 1 and a second terminal 2. The first terminal of D1 and the first terminal of D2 are respectively connected to the two ends of the secondary coil of the power transformer SMW3225S102HTE. The second terminals of D1 and D2 are respectively connected to one end of the load R1. The connection terminals of the load R1 and D1 and D2 are also connected to the center tap of the secondary coil of the power transformer SMW3225S102HTE. D1 and D2 can be switched from terminal 2 to terminal 1. After the first frequency waveform, converted by the power transformer SMW3225S102HTE, is input to the rectifier circuit, during the positive half-cycle of the first frequency waveform, D1 conducts and D2 reverses direction, cutting off current. The current flows from terminal 2 of D1 to terminal 1, forming a DC waveform with negative on the left and positive on the right across the load R1. During the negative half-cycle of the first frequency waveform, D1 reverses direction, cutting off current and D2 conducts. The current flows from terminal 2 of D2 to terminal 1, forming a DC waveform with negative on the left and positive on the right across the load R1. Thus, within one full cycle of the first frequency waveform, the direction of the DC waveform formed across the load R1 remains unchanged, exhibiting a fixed polarity. This DC waveform with a negative voltage drop across the load R1 can be defined as a negative DC waveform, such as... Figures 3A-3B As shown.

[0045] Furthermore, the unidirectional conductive units of the two rectifier components can be used to generate DC waveforms of different frequencies and the same polarity, such as the first rectifier waveform and the second rectifier waveform. The two DC waveforms, which only have amplitude changes in the negative direction, can be used to interfere in the deep brain to generate a low-frequency envelope stimulation current that only has amplitude changes in the negative direction.

[0046] It is particularly important to note that the DC waveforms proposed in this application, such as the first rectified waveform and the second rectified waveform, have the characteristic that the direction of the DC signal does not change with time, but they can still have an alternating period in which the amplitude changes with time. That is, the phases of the first rectified waveform and the second rectified waveform change periodically in the same direction with time. Therefore, they still have the characteristics of alternating signals and can interfere with other alternating signals.

[0047] Thus, by rectifying a high-frequency sinusoidal waveform using the non-invasive deep brain stimulation system proposed in this application, two positive or negative DC waveforms of different frequencies can be obtained. The interference of these two positive DC waveforms in the deep brain can produce a low-frequency envelope positive stimulation waveform, such as an enhancing stimulation waveform, which can provide effective unipolar electrical stimulation to target subjects whose deep brain functional network regions are abnormally inhibited. Similarly, the interference of these two negative DC waveforms in the deep brain can produce a low-frequency envelope negative stimulation waveform, such as an inhibitory stimulation waveform, which can provide effective unipolar electrical stimulation to target subjects whose deep brain functional network regions are abnormally excited.

[0048] In some implementations, the current stabilizing module may include two current stabilizing components, such as a first current stabilizing component and a second current stabilizing component, which respectively regulate and stabilize the current of the positive or negative DC waveform output from the load of the waveform rectifier module, thereby controlling the current of the positive or negative DC waveform. Specifically, the current stabilizing component may include adjusting the current intensity of the positive or negative DC waveform, adjusting the current change rate of the positive or negative DC waveform, and stabilizing the high-frequency components of the current in the positive or negative DC waveform.

[0049] To achieve the aforementioned current regulation and stabilization functions, the current stabilization component may include two constant current units connected in series, such as a primary constant current unit and a secondary constant current unit. The primary constant current unit is used to regulate the current of the positive or negative DC waveform, such as current intensity and current change rate. Since the positive or negative DC waveform output by the current stabilization component does not have directional changes, the primary constant current unit can be configured as a current constant current source based on an operational amplifier.

[0050] The secondary constant current unit is used to maintain the high-frequency components of the positive or negative DC waveform. It is known that the high-frequency components of the high-frequency DC waveform obtained after full-wave rectification of a high-frequency sinusoidal waveform by the waveform rectifier module are easily distorted due to the nonlinear characteristics and frequency response of the components. When further considering the influence of system noise, how to avoid high-frequency distortion is a crucial issue. Therefore, the secondary constant current unit can be configured as a transistor-based constant current source to protect the high-frequency components of the DC waveform and ensure the frequency accuracy of the stimulated waveform.

[0051] In other words, the secondary constant current unit may include a constant current circuit based on a transistor constant current source circuit. This gives the secondary constant current unit a higher frequency response, ensuring that the output amplitude of the high-frequency components in the first or second rectified waveform after passing through the primary constant current unit remains highly stable. This is also an important prerequisite for the first or second rectified waveform to be used for target stimulation, thereby avoiding distortion of the high-frequency components in the rectified waveform. In other words, it ensures that the output amplitude of the high-frequency components in the rectified waveform is stable and there will be no amplitude attenuation, so as to avoid reducing the stimulation and treatment effect.

[0052] In some implementations, the non-invasive deep brain stimulation system of this application may further include: a stimulation polarity detection module, which includes a polarity selection switch, which can be used to acquire resting-state functional magnetic resonance imaging (fMRI) data of the target subject, extract the blood oxygen level dependent (BOLD) signal of the target subject's brain functional network and / or brain region from the resting-state fMRI data through a data preprocessing unit and a data postprocessing unit; determine the preset stimulation mode information of the target subject based on the abnormal state of the target blood oxygen level dependent signal, including the scalp stimulation target point, the current direction of the first rectified waveform obtained by the first rectifier component and the current direction of the second rectified waveform obtained by the second rectifier component, and can use the polarity selection switch to control the polarity of the first rectified waveform or the second rectified waveform.

[0053] Specifically, resting-state functional magnetic resonance imaging (fMRI) data is chosen to extract the BOLD signal in order to assess abnormal excitation or inhibition in specific brain regions and thereby determine stimulus polarity and stimulation targets. FMRI can non-invasively detect signals in deep brain regions and has high spatial resolution, meaning it has high spatial accuracy in identifying stimulation targets. Furthermore, the BOLD signal from resting-state fMRI is an effective marker for detecting activity in specific target brain regions, that is, detecting whether the target brain region is abnormally excited or inhibited.

[0054] In other words, the non-invasive deep brain stimulation system according to the embodiments of this application can determine the required stimulation mode of the target subject through a stimulation polarity detection module before applying any type of unipolar time-interference electrical stimulation, and provide targeted enhanced or inhibited stimulation. The purpose of this is to determine or adjust the stimulation protocol based on the target subject's real-time state before treatment. For example, for target subjects receiving long-term enhanced stimulation, the current stimulation protocol may have already interfered with their normal brain function, such as interfering with the transmission of neural signals or affecting the brain's processing and integration of information—issues that require particular attention during long-term unipolar time-interference electrical stimulation treatment.

[0055] Therefore, the non-invasive deep brain stimulation system of this application can determine the stimulation plan based on the resting-state functional magnetic resonance imaging of the target subject before each treatment, based on the stimulation polarity detection module. For example, it can adjust the scalp stimulation target point to ensure that the unipolar electrical stimulation reaches the target brain region directly, so as to reduce adverse interference to other non-target brain regions; or adjust the rectified waveform direction appropriately according to the degree of improvement of the condition to avoid potential safety problems such as brain electrolyte imbalance caused by long-term strong stimulation.

[0056] In some implementations, extracting oxygenation level-dependent signals of target brain functional networks and / or brain regions from resting-state functional magnetic resonance imaging (fMRI) data via a data preprocessing unit and a data postprocessing unit may include:

[0057] The data preprocessing unit performs preprocessing operations on the resting-state functional magnetic resonance data, including quality checks, removal of time points, slice time correction, head motion correction, image registration, normalization, smoothing, and / or low-frequency bandpass filtering, to obtain standard data for functional network state analysis.

[0058] Furthermore, the functional magnetic resonance data post-processing unit can be used to perform functional network state analysis, including time series extraction, functional connectivity matrix calculation, and / or statistical analysis of resting-state functional magnetic resonance data processed by the data preprocessing unit.

[0059] By obtaining the analysis results, for example, if a specific functional network or brain region of the target subject is abnormally inhibited, the stimulation polarity detection module can determine a treatment plan to provide the target subject with enhanced stimulation, which can be achieved by providing the target subject with an enhanced stimulation waveform; conversely, it can determine a treatment plan to provide the target subject with a negative waveform inhibitory stimulation. Thus, the non-invasive deep brain stimulation system of this application can obtain a guiding result for stimulation polarity selection based on magnetic resonance BOLD signals, enhancing the accuracy of time-interventional electrical stimulation for target subjects in different physical states.

[0060] According to some implementation schemes, the non-invasive deep brain stimulation system of this application may further include: a stimulation assessment module for detecting the electrical stimulation parameters and effects received by the target, wherein the electrical stimulation parameters include the frequency, amplitude, rise, fall or on / off ratio of the first stimulation waveform and / or the second stimulation waveform, and the electrical stimulation effects may include the therapeutic efficacy of the target subject and the effects brought about by the stimulation components output by each system, such as the frequency, amplitude, rise and / or fall or on / off ratio of the first stimulation waveform and / or the second stimulation waveform. In addition, the stimulation assessment module may also continuously monitor the current amplitude and frequency of the stimulation waveform output by the stimulation output module to monitor the electrical stimulation status of the target subject in real time.

[0061] Specifically, using the stimulation assessment module to detect the electrical stimulation parameters and effects received by the target can include using the stimulation assessment unit to evaluate the effects of electrical stimulation on the target subject based on the results of neurophysiological examinations such as electroencephalography (EEG), local field potentials, functional magnetic resonance imaging (fMRI), functional ultrasound, and behavioral studies. Based on this, by analyzing the correlation between the electrical stimulation effect and the stimulation parameters, suggested adjustment parameters for the first and / or second stimulation waveforms can be obtained. In this way, through long-term targeted stimulation and real-time modulation, functional intervention of the target subject's brain can be achieved, as well as further effective treatment of brain diseases in the target subject.

[0062] Another advantage of configuring a stimulation assessment module is that it can serve as a supplement or alternative to the stimulation polarity detection module. By evaluating the electrical stimulation effect after each stimulation, the feasibility of the entire system for the target subject can be assessed, and the treatment plan can be strengthened or adjusted accordingly, such as by changing the polarity of the stimulation waveform. In other words, the cooperation between the stimulation polarity detection module and the stimulation assessment module further enhances the applicability of the stimulation plan provided by the entire system to the target subject. When it is difficult to pre-determine the stimulation plan by acquiring the target subject's resting-state functional magnetic resonance imaging data multiple times, the existing stimulation plan can also be adjusted in a timely manner based on the post-treatment effect assessment, thereby reducing the usage cost of the non-invasive deep brain stimulation system according to the embodiments of this application.

[0063] The non-invasive deep brain stimulation system of this application may further include a power supply module and a microprocessor. The power supply module can be connected to and supply power to the waveform generation module, waveform rectification module, current stabilization module, stimulation output module, and microprocessor, respectively. The microprocessor can be electrically connected to the waveform generation module, waveform rectification module, current stabilization module, stimulation output module, polarity detection module, and stimulation evaluation module, respectively, to realize the functional control of each module. In particular, the current stabilization module, after preset current stabilization parameters, such as the current intensity of the rectified waveform, can also independently implement the current stabilization function of the rectified waveform.

[0064] Specifically, the power supply module may include a first power output terminal, a second power output terminal, a third power output terminal, a fourth power output terminal, and a fifth power output terminal, which respectively supply power to the waveform generation module, the waveform rectification module, the current stabilization module, the stimulation output module, and the microprocessor. The current stabilization module receives high-voltage power from the second power output terminal, while the other power output terminals provide low-voltage power to the corresponding modules.

[0065] According to some implementation schemes, the procedure for the non-invasive deep brain stimulation system of this application to perform targeted, predefined polarity non-invasive electrical stimulation on the target subject is as follows: Figure 5 As shown, the steps may include the following:

[0066] The polarity detection module performs data preprocessing and postprocessing based on the collected functional magnetic resonance data of the target subject to obtain preset stimulation pattern information.

[0067] The microprocessor receives the preset stimulation mode information from the stimulation polarity detection module and determines the stimulation polarity required by the target subject, thereby obtaining the first control command;

[0068] The microprocessor sends the first control instruction to the stimulation output module, which controls the stimulation output module to determine the stimulation target position, stimulation duration, current amplitude and frequency of the stimulation waveform of the stimulation electrode;

[0069] The control stimulation output module starts to output the stimulation waveform to the designated area of ​​the target subject's scalp through two pairs of stimulation electrodes. The stimulation assessment module continuously monitors the stimulation current within the preset stimulation duration to ensure that the target subject receives accurate and safe electrical stimulation.

[0070] After the preset stimulation duration, the stimulation output module stops outputting the stimulation waveform, and the stimulation assessment module collects the neurophysiological electroencephalogram, local field potential, functional magnetic resonance imaging, functional ultrasound, and behavioral examination results of the target subject at this time and obtains the electrical stimulation effect.

[0071] The microprocessor receives the electrical stimulation effect from the stimulation assessment module and determines the adjustment scheme of the stimulation waveform required by the target subject, thus obtaining a second control command. The microprocessor sends the second control command to the waveform generation module to adjust the frequency of the next output stimulation waveform; sends the second control command to the waveform rectification module to adjust the voltage amplitude, polarity, and on / off ratio of the next output stimulation waveform; sends the second control command to the current stabilization module to adjust the current intensity and rate of change of the next output stimulation waveform; and sends the second control command to the stimulation output module to adjust the stimulation target position of the next output stimulation waveform.

[0072] The basic principles of this application have been described above with reference to specific embodiments. However, it should be noted that the advantages, benefits, and effects mentioned in this application are merely examples and not limitations, and should not be considered as essential features of each embodiment of this application. Furthermore, the specific details disclosed above are for illustrative and facilitative purposes only, and are not limitations. These details do not limit the application to the necessity of employing the aforementioned specific details for implementation.

[0073] In this application, words such as “including,” “comprising,” and “having” are open-ended terms meaning “including but not limited to” and are used interchangeably. The terms “or” and “and” as used herein refer to the terms “and / or” and are used interchangeably unless the context explicitly indicates otherwise. The term “such as” as used herein refers to the phrase “such as but not limited to” and is used interchangeably.

[0074] It should also be noted that in the methods, systems, and apparatus of this application, each step or module can be decomposed and / or recombined. These decompositions and / or recombinations should be considered as equivalent solutions of this application.

[0075] The above description has been given for purposes of illustration and description. Furthermore, this description is not intended to limit the embodiments of this application to the forms disclosed herein. Although numerous exemplary aspects and embodiments have been discussed above, those skilled in the art will recognize certain variations, modifications, alterations, additions, and sub-combinations thereof.

Claims

1. A polar adjustable non-invasive deep brain stimulation system, characterized in that, The method comprises the following steps: a waveform generating module generates a first frequency waveform by using a first signal generator and generates a second frequency waveform by using a second signal generator; a waveform rectifying module is connected to the output end of the waveform generating module, rectifies the first frequency waveform by using a first rectifying component to obtain a first rectified waveform, and rectifies the second frequency waveform by using a second rectifying component to obtain a second rectified waveform; a current stabilizing module is connected to the output end of the waveform rectifying module, the first rectified waveform passes through a first current stabilizing component to obtain a high-frequency distortion-free first stimulation waveform, and the second rectified waveform passes through a second current stabilizing component to obtain a high-frequency distortion-free second stimulation waveform; a stimulation output module is connected to the output end of the current stabilizing module, and the first stimulation waveform and the second stimulation waveform are respectively output to the scalp stimulation target point of the target by using a stimulation electrode to generate a low-frequency envelope stimulation waveform in the deep brain.

2. The stimulation system of claim 1, wherein, In the method, the first rectifying component and the second rectifying component comprise a voltage input unit, a unidirectional conductive unit and a load, wherein the voltage input unit adjusts the voltage amplitude of the first frequency waveform or the second frequency waveform to a preset voltage amplitude; the unidirectional conductive unit adjusts the current direction flowing through the load in the positive half cycle and the negative half cycle of the first frequency waveform or the second frequency waveform respectively, so that the current direction flowing through the load is consistent in a whole cycle of the first frequency waveform or the second frequency waveform, and the first rectified waveform or the second rectified waveform with constant current direction is generated.

3. The stimulation system of claim 2, wherein, In the method, the unidirectional conductive unit comprises a first rectifying diode and a second rectifying diode, wherein the first rectifying diode and the second rectifying diode respectively have a first end and a second end; in the positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is turned on, and the second rectifying diode is reversely cut off, and the current flows from the first end of the first rectifying diode to the second end of the first rectifying diode; in the negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is reversely cut off, and the second rectifying diode is turned on, and the current flows from the first end of the second rectifying diode to the second end of the second rectifying diode.

4. The stimulation system of claim 2, wherein, In the method, the unidirectional conductive unit comprises a first rectifying diode and a second rectifying diode, wherein the first rectifying diode and the second rectifying diode respectively have a first end and a second end; in the positive half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is turned on, and the second rectifying diode is reversely cut off, and the current flows from the second end of the first rectifying diode to the first end of the first rectifying diode; in the negative half cycle of the first frequency waveform or the second frequency waveform, the first rectifying diode is reversely cut off, and the second rectifying diode is turned on, and the current flows from the second end of the second rectifying diode to the first end of the second rectifying diode.

5. The stimulation system of claim 1, wherein, In the method, The first current stabilizing component and the second current stabilizing component respectively include a first constant current unit and a second constant current unit, wherein, The second constant current unit includes a transistor-based constant current source circuit with higher frequency response to ensure the output amplitude stability of high frequency components in the first rectified waveform or the second rectified waveform.

6. The stimulation system of claim 1, wherein, Further comprising: a stimulation polarity detection module for collecting resting state functional magnetic resonance data of the target, extracting the brain function network of the target and / or the blood oxygen level dependent signal of the brain region in the resting state functional magnetic resonance data through a data preprocessing unit and a data post-processing unit; determining the scalp stimulation target point of the target, the current direction of the first rectified waveform obtained by the first rectifying component and the current direction of the second rectified waveform obtained by the second rectifying component according to the abnormal state of the blood oxygen level dependent signal of the target.

7. The stimulation system of claim 6, wherein, wherein, the extraction of the brain function network of the target and / or the blood oxygen level dependent signal of the brain region in the resting state functional magnetic resonance data through the data preprocessing unit and the data post-processing unit includes: the data preprocessing unit performs quality inspection, time point removal, layer scanning time correction, head motion correction, image registration, standardization processing, smoothing processing and / or low frequency band pass filtering on the resting state functional magnetic resonance data; the functional magnetic resonance data post-processing unit includes time series extraction, functional connection matrix calculation and / or statistical analysis on the resting state functional magnetic resonance data processed by the data preprocessing unit.

8. The stimulation system of claim 1, wherein, Further comprising: a stimulation evaluation module for detecting the electrical stimulation parameters and effects received by the target.

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