A pulse parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device

Abstract

The application discloses a pulse parameter self-adaptive adjusting system for a non-invasive transcranial nanosecond pulse electric field stimulation device, which comprises a parameter input and template calling module, a contact checking module, a legality checking and automatic correcting module, a double-frequency nested pulse string timing generating module, a nanosecond pulse output module, an online monitoring and key electric parameter calculating module, a hierarchical adjusting and out-of-limit locking module and a contact drift judging and self-adaptive processing module. The application can realize the cooperative regulation of abnormal nerve rhythm and A beta related pathological process by applying a nanosecond pulse electric field through the cranium without invading the brain, adopting a double-frequency nested pulse string coding mode, embedding a high-frequency variable f1 (used for corresponding gamma wave band rhythm regulation / entrainment) in a low-frequency variable f2 (used for corresponding theta rhythm modulation), so as to improve the AD disease process through a multi-pathway mechanism.

Description

Technical Field

[0001] This invention relates to the field of brain disease treatment technology, specifically to an adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device. Background Technology

[0002] Alzheimer's disease (AD) is one of the most common types of dementia worldwide, affecting a huge population and imposing a heavy medical and economic burden. One of its typical pathological features is the abnormal deposition and plaque formation of β-amyloid protein (Aβ) in the brain, which further induces neuronal activity imbalance and decreased network synchronicity. Numerous studies have shown that there are significant defects in the neural rhythms closely related to learning and memory in AD-related brain networks, manifested as weakened rapid oscillations (γ band, usually >30 Hz) and disordered slower rhythms (θ band, usually about 4–8 Hz), and even abnormal θ–γ coupling, leading to a decline in the efficiency of information encoding and memory consolidation.

[0003] In the treatment of Alzheimer's disease (AD), targeted clearance of Aβ plaques or inhibition of their formation holds significant transformative potential. However, current drug therapies often provide only limited symptom relief, and some drug trials have failed to effectively halt the ongoing progression of Aβ deposition. Meanwhile, various non-invasive or minimally invasive physical intervention strategies are being developed, such as transcranial focused ultrasound (tFUS), multisensory stimulation, and transcranial magnetic stimulation (TMS). These methods can modulate cortical activity or induce rhythmic entrainment to some extent. However, because key lesions in AD often involve deep structures (such as the hippocampus), these interventions remain limited in terms of depth of action, local stimulation intensity, and controllability over deep networks. This makes it difficult to stably trigger sufficient regulatory effects in deep target areas, thus affecting their intervention efficiency against Aβ pathology.

[0004] Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) for static polarization and transcranial alternating current stimulation (tACS) for rhythm entrainment, typically uses weak currents and low frequencies due to safety requirements. This limits the electric field distribution and deep penetration in complex brain tissues (multilayered media, anisotropic conductivity / dielectric properties). In particular, Alzheimer's disease (AD) patients often experience structural and electrical changes such as brain atrophy, altered brain tissue water content, and changes in dielectric parameters, making it even more difficult for traditional low-amplitude, single-frequency DC or AC electric fields to effectively reach deep target areas and achieve the threshold for biological effects. Therefore, there is an urgent need to develop a novel electric field mechanism that can generate an effective electric field effect on deep brain regions under non-invasive conditions, while also considering both Aβ pathological intervention and neural rhythm remodeling. Summary of the Invention

[0005] The purpose of this invention is to provide an adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulse electric field stimulation device, comprising: a parameter input and template calling module, a contact verification module, a legality check and automatic correction module, a dual-frequency nested pulse train timing generation module, a nanosecond pulse output module, an online monitoring and key electrical parameter calculation module, a graded adjustment and over-limit blocking module, and a contact drift determination and adaptive processing module.

[0006] The parameter input and template calling module is used to obtain pulse parameters and to input the pulse parameter legality check and automatic correction module.

[0007] The contact verification module is used to verify the contact of the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device. If the contact verification fails, the electrodes are reattached and the contact verification is performed again until the contact verification is successful.

[0008] The legality check and automatic correction module is used to perform constraint checks on the input pulse parameters, automatically correct parameters that do not meet the constraint checks, and input the obtained pulse parameters that meet the constraint checks into the dual-frequency nested pulse train timing generation module and the nanosecond pulse output module.

[0009] The dual-frequency nested pulse train timing generation module generates a pulse trigger sequence based on the input pulse parameters.

[0010] The nanosecond pulse output module outputs nanosecond pulses based on the pulse trigger sequence and the input pulse parameters.

[0011] During the nanosecond pulse output process, the online monitoring and key electrical parameter calculation module collects the voltage across the electrodes and the current flowing through the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device, and calculates the key electrical parameters based on the collected voltage and current.

[0012] The graded adjustment and limit-overlocking module determines whether the pulse parameter triggers a limit over-limit based on key electrical parameters. If a limit over-limit is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down and locked. If no limit over-limit is triggered, it determines whether the pulse parameter triggers an early warning. If an early warning is triggered, the pulse parameter is automatically reduced and returned to the dual-frequency nested pulse train timing generation module. If no early warning is triggered, the corresponding pulse parameter is directly output.

[0013] The contact drift determination and adaptive processing module calculates the relative drift based on key electrical parameters and determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger a shutdown condition based on the relative drift. If the shutdown condition is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down, and the system returns to the contact verification module. If the shutdown condition is not triggered, it determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger a drift warning. If a drift warning is triggered, the pulse parameters output by the graded modulation and over-limit locking module are automatically reduced, and the automatically reduced pulse parameters are returned to the dual-frequency nested pulse train timing generation module. If no drift warning is triggered, the pulse parameters for the non-invasive transcranial nanosecond pulse electric field stimulation device are directly output.

[0014] Furthermore, the adjustment system also includes a recording module.

[0015] The recording module is used to record pulse parameters, as well as corresponding key electrical parameters and parameter adjustment logs.

[0016] The parameter adjustment log includes warnings, exceeding limits, and parameter reduction situations.

[0017] Furthermore, the non-invasive transcranial nanosecond pulsed electric field stimulation device includes two pulse generators and two electrodes.

[0018] The pulse generator outputs nanosecond pulses based on the pulse parameters output by the adaptive adjustment system.

[0019] The electrodes and pulse generators are connected in a one-to-one correspondence, and the nanosecond pulses output by the pulse generators are applied to the head of the organism.

[0020] The electrode is attached to one side of the scalp and also has a hydrogel patch.

[0021] Two nanosecond pulses interfere with each other in the deep brain regions of a living organism, generating a low-frequency modulation envelope, which in turn regulates neural network activity.

[0022] The deep brain regions include the hippocampus and the entorhinal cortex.

[0023] The low-frequency modulation envelope signal includes the θ-band electric field envelope and the γ-band electric field envelope.

[0024] The nanosecond-level leading edge of the two nanosecond pulses generates a transient electric field that directly acts on subcellular structures in the deep brain regions of the organism, promoting the clearance of pathological proteins.

[0025] The pathological proteins include β-amyloid oligomers and plaques.

[0026] Furthermore, the pulse parameters include the number of nanosecond pulse trains N, the effective gate window Ton, the peak voltage Vpk of the nanosecond pulse, the pulse width tpw of the nanosecond pulse, the pulse train variable f1 corresponding to γ-related rhythm modulation, and the pulse train variable f2 corresponding to θ-related rhythm modulation.

[0027] The relationship between the number of nanosecond pulse trains N and the effective gate window Ton is as follows:

[0028] Ton=(N-1)·T1+tguard(1)

[0029] T1=1 / f1(2)

[0030] In the formula, tguard is the protection margin. T1 represents the trigger interval within the string.

[0031] Furthermore, the contact verification steps are as follows:

[0032] A1 acquires the test pulse parameters and outputs test pulse signals on the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device based on the test pulse parameters.

[0033] A2 acquires the peak voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. and test peak current .

[0034] A3 is based on the peak voltage of the test. and test peak current Calculate the test impedance As shown below:

[0035] (3)

[0036] A4 Determine the test impedance If the impedance is within the preset window, the contact test is successful; otherwise, the contact test is unsuccessful.

[0037] Furthermore, the constraint conditions for the constraint check are as follows:

[0038] f1>f2(4)

[0039] Ton≤T2(5)

[0040] N≥1(6)

[0041] tpw∈[ , (7)

[0042] +tguard≤Ton(8)

[0043] T2=1 / f2(9)

[0044] In the formula, f1 is the pulse train variable corresponding to γ-related rhythm modulation. f2 is the pulse train variable corresponding to θ-related rhythm modulation. Ton is the effective gating window. T2 is the external period. N is the number of pulse trains of nanosecond pulses. tpw is the pulse width of the nanosecond pulse. , These represent the upper and lower limits of the nanosecond pulse width, respectively. tguard represents the protection margin. This indicates the trigger time within the pulse train numbered N-1.

[0045] The trigger times within the string are as follows:

[0046] = +k·T1(10)

[0047] In the formula, k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1. This indicates the trigger time within the pulse train numbered 0. T1 represents the trigger time within the pulse train numbered k. T1 represents the trigger interval within the pulse train.

[0048] If the input pulse parameters do not meet the constraints of the constraint check, automatic correction is performed first by shortening the effective gating window Ton or reducing the number of nanosecond pulse trains N. If the automatically corrected pulse parameters still do not meet the constraints of the constraint check, the pulse parameters are reacquired.

[0049] Furthermore, the triggering times of the pulse triggering sequence are as follows:

[0050] =m·T2+ (11)

[0051] In the formula, m is the index of the number of external periods. T2 is the external period. k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1. N is the number of pulse trains of the nanosecond pulse. This indicates the trigger time within the pulse train numbered k. This indicates the trigger time corresponding to the m-th external cycle.

[0052] The silent window of the pulse trigger sequence is shown below:

[0053] Toff = T2 - Ton (12)

[0054] In the formula, Toff is the silent window of the pulse trigger sequence. Ton is the gating effective window.

[0055] Furthermore, the key electrical parameters include single-pulse energy Ep, peak voltage Vpk, peak current Ipk, average power Pavg, and peak impedance Zeq.

[0056] The single-pulse energy Ep, average power Pavg, and peak impedance Zeq are shown below:

[0057] (13)

[0058] Pavg = Ep·N·f2 (14)

[0059] Zeq = Vpk / Ipk (15)

[0060] In the formula, Indicates time. This indicates the voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. This represents the current collected flowing through the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. f2 is the pulse train variable corresponding to the θ-related rhythm modulation. N is the number of nanosecond pulse trains.

[0061] Furthermore, the triggering conditions include single pulse energy exceeding the limit, peak voltage exceeding the limit, peak current exceeding the limit, average power exceeding the limit, and peak impedance exceeding the limit.

[0062] The single-pulse energy exceeding the limit is as follows:

[0063] Ep≥Emax(16)

[0064] In the formula, Ep represents the single pulse energy. Emax represents the single pulse energy exceeding the limit threshold.

[0065] The peak voltage exceeding the limit is as follows:

[0066] Vpk≥Vmax(17)

[0067] In the formula, Vpk represents the peak voltage. Vmax represents the peak voltage over-limit threshold.

[0068] The peak current exceeding the limit is as follows:

[0069] Ipk≥Imax(18)

[0070] In the formula, Ipk represents the peak current. Imax represents the peak current over-limit threshold.

[0071] The average power exceeding the limit is as follows:

[0072] Pavg≥Pmax(19)

[0073] In the formula, Pavg represents the average power, and Pmax represents the average power exceeding the limit threshold.

[0074] The peak impedance exceeding the limit is as follows:

[0075] (20)

[0076] In the formula, This indicates the peak impedance. These represent the upper and lower limits of peak impedance, respectively.

[0077] The conditions for triggering the early warning include single-pulse energy warning, peak current warning, and average power warning.

[0078] The single-pulse energy warning is as follows:

[0079] Ep≥0.8Emax(21)

[0080] The peak current warning is as follows:

[0081] Pavg≥0.8Pmax(22)

[0082] The average power warning is as follows:

[0083] Ipk≥0.8Imax(23)

[0084] The shutdown conditions include drift amount shutdown conditions, as shown below:

[0085] DZ = |Zeq - Zref| / Zref (24)

[0086] DZ≥Dstop(25)

[0087] Zref= (26)

[0088] In the formula, DZ represents the relative drift. Zref represents the reference impedance. Dstop represents the upper limit of the drift stop. This indicates the test impedance.

[0089] The conditions for triggering the drift warning include a drift amount warning, as shown below:

[0090] DZ∈[Dwarn,Dstop)(27)

[0091] In the formula, Dwarn represents the lower limit of the drift amount that would stop the machine.

[0092] Furthermore, the priority of the automatic parameter reduction includes four levels.

[0093] The first level of automatic parameter reduction reduces the voltage peak of the nanosecond pulse based on a preset voltage peak parameter reduction step size. .

[0094] The second-level automatic parameter reduction reduces the number of nanosecond pulses N based on a preset pulse train number and step size.

[0095] The third-level automatic parameter reduction is based on a preset step size for reducing the pulse train variable f2 corresponding to the θ-related rhythm modulation.

[0096] The fourth level of automatic parameter reduction is based on the preset gating effective window step size, which reduces the gating effective window Ton.

[0097] The technical effects of this invention are undeniable. This invention proposes a novel intervention strategy—Nanosecond Transcranial Pulsed Field Stimulation (ns-tPFS): without invading the brain, nanosecond-level pulsed electric fields are applied transcranially, and a dual-frequency nested pulse train coding mode is used. The high-frequency variable f1 (used to correspond to γ-band rhythm regulation / entrainment) is nested within the low-frequency variable f2 (used to correspond to θ-rhythm modulation), thereby achieving synergistic regulation of abnormal neural rhythms and Aβ-related pathological processes, and thus is expected to improve the progression of AD through multi-pathway mechanisms.

[0098] The non-invasive transcranial nanosecond pulsed electric field stimulation method (ns-tPFS) proposed in this invention employs nanosecond-level pulses and dual-frequency nested coding (high-frequency f1 + low-frequency f2), which can simultaneously and synergistically regulate AD pathology and function, with beneficial effects including:

[0099] 1. Enhance the effective action capability of deep target areas: Nanosecond-level pulsed electric fields have the advantages of wide spectrum characteristics and the ability to achieve high peak field strength. While maintaining low thermal effects, they are conducive to improving the effective distribution in complex brain tissues, making it more likely that the electric field will cover deep related brain regions and improve the accessibility of regulation of deep structures such as the hippocampus.

[0100] 2. Programmable rhythm entrainment and network reshaping: By nesting high-frequency f1 (corresponding to γ-related rhythm modulation) into a pulse train of low-frequency f2 (corresponding to θ-related rhythm modulation), it is possible to simultaneously act on γ oscillation, θ rhythm and their coupling relationship at the rhythm level, thereby promoting the recovery of abnormal synchronicity and the reconstruction of cross-frequency coupling.

[0101] 3. Potential for intervention in Aβ-related pathological processes: Ultrashort high-field pulses may have a physical modulation effect on the structure of pathological protein aggregates and related microenvironments, and can synergistically work with the rhythmic remodeling of the neuro-glial network to promote the reduction of Aβ load and delay the pathological process.

[0102] 4. Non-invasive, safe and low thermal burden: The electrodes are placed on the scalp surface, eliminating the need for craniotomy for implantation, thus reducing the risk of infection and tissue damage; the nanosecond pulse has a low duty cycle and minimal heat accumulation, allowing stimulation to be achieved within a safe window.

[0103] 5. Frequency and dose parameters are expandable and have a wide coverage: The coding structure is described by variables f1 and f2, which can flexibly set the frequency and pulse train parameters according to the rhythm characteristics and disease stages of different models and individuals, which facilitates individualized optimization and scheme expansion and improves the adaptability of patented technology.

[0104] In summary, this invention provides a non-innovative electric field stimulation scheme that combines "deep accessibility + rhythm remodeling + pathological intervention", offering a new technical approach for non-pharmacological intervention in Alzheimer's disease (AD). Attached Figure Description

[0105] Figure 1 This is a schematic diagram of the system structure of the present invention;

[0106] Figure 2 Flowchart for the generation and controllable application of transcranial nanosecond pulsed electric field stimulation signals;

[0107] Figure 3 This is a schematic diagram of the components of a non-invasive transcranial nanosecond pulsed electric field stimulation device. Figure 3 (a) is a schematic diagram of the overall structure of the non-invasive transcranial nanosecond pulsed electric field stimulation device; Figure 3 (b) is a schematic diagram of the electrode sheet structure; Figure 3 (c) is a physical diagram of the device;

[0108] Figure 4 This is a schematic diagram of the ns-tPFS dual-frequency pulse train waveform structure;

[0109] Figure 5 A finite element model of a mouse head and a simulation diagram of the electric field distribution in the brain. Figure 5 (a) is a schematic diagram of the finite element model of a mouse head; Figure 5 (b) is a top view of the finite element model of the mouse head; Figure 5(c) is a cross-sectional view of the finite element model of the mouse head; Figure 5 (d) is a simulation diagram of the electric field distribution in the mouse brain;

[0110] Figure 6 This is a diagram showing the results of a mouse behavioral experiment. Figure 6 (a) is a flowchart of an animal experiment plan; Figure 6 (b) is a graph showing the change in escape latency over time for the normal sham stimulation group and the normal stimulation group during the water maze learning period; Figure 6 (c) is a graph showing the change in escape latency over time for the AD sham stimulation group and the AD stimulation group during the water maze learning period; Figure 6 (d) shows the typical swimming trajectories of each group in the water maze; Figure 6 (e) is a chart showing the number of times platforms were traversed on day 6 of the water maze; Figure 6 (f) is a statistical chart showing the time taken to reach the platform area for the first time on the 6th day of the water maze; Figure 6 (g) is a statistical chart of the total time spent in the platform quadrant area on the 6th day of the water maze; Figure 6 (h) is a statistical graph showing the total swimming distance of mice on day 6 of the water maze; Figure 6 (i) is a thermal image of the Y-maze experiment; Figure 6 (j) is a thermal image of the open field experiment; Figure 6 (k) is a statistical graph of the alternation rate of the Y maze; Figure 6 (l) is a statistical chart of the total number of transfers in the Y maze; Figure 6 (m) is a statistical graph of the total distance traveled in the open field experiment; Figure 6 (n) is a statistical chart of the time percentage in the central region of the open field experiment;

[0111] Figure 7 Immunofluorescence staining results and quantitative analysis of Aβ deposition in mouse brain tissue; Figure 7 (a) is a representative immunofluorescence image of Aβ42 in the hippocampus; Figure 7 (b) is a representative immunofluorescence image of Aβ42 in the cortical region; Figure 7 (c) is a statistical chart of the number of Aβ42 patches in the hippocampus; Figure 7 (d) is a statistical chart of the number of Aβ42 plaques in the cortex; Figure 7 (e) is a statistical graph of the relative fluorescence intensity of Aβ42 in the hippocampus; Figure 7 (f) is a statistical graph of the relative fluorescence intensity of Aβ42 in the cortical region;

[0112] Figure 8 This is a graph showing the quantitative analysis of the effect of ns-tPFS on the neural rhythm of mice. Figure 8 (a) is a monitoring screen and schematic diagram of the mouse EEG acquisition platform; Figure 8 (b) is a comparison curve of the power spectral density of EEG signals across the entire frequency band; Figure 8 (c) is a statistical comparison of the power spectral density of the delta band EEG; Figure 8 (d) is a comparative statistical chart of the power spectral density of the theta band EEG; Figure 8 (e) is a comparative statistical chart of the power spectral density of the α-band EEG; Figure 8 (f) is a statistical comparison of the power spectral density of the β-band EEG; Figure 8 (g) is a statistical comparison of the power spectral density of the γ-band EEG. Detailed Implementation

[0113] The present invention will be further described below with reference to embodiments, but it should not be construed that the scope of the present invention is limited to the following embodiments. Various substitutions and modifications made based on ordinary technical knowledge and common practices in the art without departing from the above-described technical concept of the present invention should be included within the scope of protection of the present invention.

[0114] Example 1:

[0115] See Figures 1 to 8 An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulse electric field stimulation device includes: a parameter input and template calling module, a contact verification module, a legality check and automatic correction module, a dual-frequency nested pulse train timing generation module, a nanosecond pulse output module, an online monitoring and key electrical parameter calculation module, a graded adjustment and over-limit blocking module, and a contact drift judgment and adaptive processing module.

[0116] The parameter input and template calling module is used to obtain pulse parameters and to input the pulse parameter legality check and automatic correction module.

[0117] The contact verification module is used to verify the contact of the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device. If the contact verification fails, the electrodes are reattached and the contact verification is performed again until the contact verification is successful.

[0118] The legality check and automatic correction module is used to perform constraint checks on the input pulse parameters, automatically correct parameters that do not meet the constraint checks, and input the obtained pulse parameters that meet the constraint checks into the dual-frequency nested pulse train timing generation module and the nanosecond pulse output module.

[0119] The dual-frequency nested pulse train timing generation module generates a pulse trigger sequence based on the input pulse parameters.

[0120] The nanosecond pulse output module outputs nanosecond pulses based on the pulse trigger sequence and the input pulse parameters.

[0121] During the nanosecond pulse output process, the online monitoring and key electrical parameter calculation module collects the voltage across the electrodes and the current flowing through the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device, and calculates the key electrical parameters based on the collected voltage and current.

[0122] The graded adjustment and limit-overlocking module determines whether the pulse parameter triggers a limit over-limit based on key electrical parameters. If a limit over-limit is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down and locked. If no limit over-limit is triggered, it determines whether the pulse parameter triggers an early warning. If an early warning is triggered, the pulse parameter is automatically reduced and returned to the dual-frequency nested pulse train timing generation module. If no early warning is triggered, the corresponding pulse parameter is directly output.

[0123] The contact drift determination and adaptive processing module calculates the relative drift based on key electrical parameters and determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger a shutdown condition based on the relative drift. If the shutdown condition is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down, and the system returns to the contact verification module. If the shutdown condition is not triggered, it determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger a drift warning. If a drift warning is triggered, the pulse parameters output by the graded modulation and over-limit locking module are automatically reduced, and the automatically reduced pulse parameters are returned to the dual-frequency nested pulse train timing generation module. If no drift warning is triggered, the pulse parameters for the non-invasive transcranial nanosecond pulse electric field stimulation device are directly output.

[0124] Example 2:

[0125] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device is described in Embodiment 1. Furthermore, the adjustment system also includes a recording module.

[0126] The recording module is used to record pulse parameters, as well as corresponding key electrical parameters and parameter adjustment logs.

[0127] The parameter adjustment log includes warnings, exceeding limits, and parameter reduction situations.

[0128] Example 3:

[0129] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device is provided. The main technical contents are described in any one of Embodiments 1 to 2. Further, the non-invasive transcranial nanosecond pulsed electric field stimulation device includes two pulse generators and two electrodes.

[0130] The pulse generator outputs nanosecond pulses based on the pulse parameters output by the adaptive adjustment system.

[0131] The electrodes and pulse generators are connected in a one-to-one correspondence, and the nanosecond pulses output by the pulse generators are applied to the head of the organism.

[0132] The electrode is attached to one side of the scalp and also has a hydrogel patch.

[0133] Two nanosecond pulses interfere with each other in the deep brain regions of a living organism, generating a low-frequency modulation envelope, which in turn regulates neural network activity.

[0134] The deep brain regions include the hippocampus and the entorhinal cortex.

[0135] The low-frequency modulation envelope signal includes the θ-band electric field envelope and the γ-band electric field envelope.

[0136] The nanosecond-level leading edge of the two nanosecond pulses generates a transient electric field that directly acts on subcellular structures in the deep brain regions of the organism, promoting the clearance of pathological proteins.

[0137] The pathological proteins include β-amyloid oligomers and plaques.

[0138] Example 4:

[0139] An adaptive adjustment system for pulse parameters in a non-invasive transcranial nanosecond pulsed electric field stimulation device is provided. The main technical contents are described in any one of Embodiments 1 to 3. Further, the pulse parameters include the number of nanosecond pulse trains N, the effective gate window Ton, the peak voltage Vpk of the nanosecond pulse, the pulse width tpw of the nanosecond pulse, the pulse train variable f1 corresponding to γ-related rhythm modulation, and the pulse train variable f2 corresponding to θ-related rhythm modulation.

[0140] The relationship between the number of nanosecond pulse trains N and the effective gate window Ton is as follows:

[0141] Ton=(N-1)·T1+tguard(1)

[0142] T1=1 / f1(2)

[0143] In the formula, tguard is the protection margin. T1 represents the trigger interval within the string.

[0144] Example 5:

[0145] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device, the main technical contents of which are described in any one of Embodiments 1 to 4, further wherein the contact verification steps are as follows:

[0146] A1 acquires the test pulse parameters and outputs test pulse signals on the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device based on the test pulse parameters.

[0147] A2 acquires the peak voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. and test peak current .

[0148] A3 is based on the peak voltage of the test. and test peak current Calculate the test impedance As shown below:

[0149] (3)

[0150] A4 Determine the test impedance If the impedance is within the preset window, the contact test is successful; otherwise, the contact test is unsuccessful.

[0151] Example 6:

[0152] An adaptive adjustment system for pulse parameters in a non-invasive transcranial nanosecond pulsed electric field stimulation device, the main technical contents of which are described in any one of Embodiments 1 to 5, further wherein the constraint conditions of the constraint check are as follows:

[0153] f1>f2(4)

[0154] Ton≤T2(5)

[0155] N≥1(6)

[0156] tpw∈[ , (7)

[0157] +tguard≤Ton(8)

[0158] T2=1 / f2(9)

[0159] In the formula, f1 is the pulse train variable corresponding to γ-related rhythm modulation. f2 is the pulse train variable corresponding to θ-related rhythm modulation. Ton is the effective gating window. T2 is the external period. N is the number of pulse trains of nanosecond pulses. tpw is the pulse width of the nanosecond pulse. , These represent the upper and lower limits of the nanosecond pulse width, respectively. tguard represents the protection margin. This indicates the trigger time within the pulse train numbered N-1.

[0160] The trigger times within the string are as follows:

[0161] = +k·T1(10)

[0162] In the formula, k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1. This indicates the trigger time within the pulse train numbered 0. T1 represents the trigger time within the pulse train numbered k. T1 represents the trigger interval within the pulse train.

[0163] If the input pulse parameters do not meet the constraints of the constraint check, automatic correction is performed first by shortening the effective gating window Ton or reducing the number of nanosecond pulse trains N. If the automatically corrected pulse parameters still do not meet the constraints of the constraint check, the pulse parameters are reacquired.

[0164] Example 7:

[0165] An adaptive pulse parameter adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device, the main technical contents of which are described in any one of Embodiments 1 to 6, further wherein the triggering times of the pulse triggering sequence are as follows:

[0166] =m·T2+ (11)

[0167] In the formula, m is the index of the number of external periods. T2 is the external period. k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1. N is the number of pulse trains of the nanosecond pulse. This indicates the trigger time within the pulse train numbered k. This indicates the trigger time corresponding to the m-th external cycle.

[0168] The silent window of the pulse trigger sequence is shown below:

[0169] Toff = T2 - Ton (12)

[0170] In the formula, Toff is the silent window of the pulse trigger sequence. Ton is the gating effective window.

[0171] Example 8:

[0172] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device is provided. The main technical contents are described in any one of Examples 1 to 7. Further, the key electrical parameters include single pulse energy Ep, peak voltage Vpk, peak current Ipk, average power Pavg, and peak impedance Zeq.

[0173] The single-pulse energy Ep, average power Pavg, and peak impedance Zeq are shown below:

[0174] (13)

[0175] Pavg = Ep·N·f2 (14)

[0176] Zeq = Vpk / Ipk (15)

[0177] In the formula, Indicates time. This indicates the voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. This represents the current collected flowing through the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. f2 is the pulse train variable corresponding to the θ-related rhythm modulation. N is the number of nanosecond pulse trains.

[0178] Example 9:

[0179] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device is provided. The main technical contents are described in any one of Examples 1 to 8. Further, the triggering conditions for exceeding the limit include exceeding the limit of single pulse energy, exceeding the limit of peak voltage, exceeding the limit of peak current, exceeding the limit of average power, and exceeding the limit of peak impedance.

[0180] The single-pulse energy exceeding the limit is as follows:

[0181] Ep≥Emax(16)

[0182] In the formula, Ep represents the single-pulse energy. Emax represents the single-pulse energy exceeding the limit threshold, which can be set from 0.01 mJ to 10 mJ, preferably from 0.05 mJ to 5 mJ. In different application scenarios, Emax can also be adjusted according to the actual detection load, adaptive parameter tuning strategy, and safety boundary.

[0183] The peak voltage exceeding the limit is as follows:

[0184] Vpk≥Vmax(17)

[0185] In the formula, Vpk represents the peak voltage. Vmax represents the peak voltage over-limit threshold.

[0186] The peak current exceeding the limit is as follows:

[0187] Ipk≥Imax(18)

[0188] In the formula, Ipk represents the peak current. Imax represents the peak current over-limit threshold.

[0189] The average power exceeding the limit is as follows:

[0190] Pavg≥Pmax(19)

[0191] In the formula, Pavg represents the average power, and Pmax represents the average power exceeding the limit threshold.

[0192] The peak impedance exceeding the limit is as follows:

[0193] (20)

[0194] In the formula, This indicates the peak impedance. These represent the upper and lower limits of peak impedance, respectively.

[0195] The conditions for triggering the early warning include single-pulse energy warning, peak current warning, and average power warning.

[0196] The single-pulse energy warning is as follows:

[0197] Ep≥0.8Emax(21)

[0198] The peak current warning is as follows:

[0199] Pavg≥0.8Pmax(22)

[0200] The average power warning is as follows:

[0201] Ipk≥0.8Imax(23)

[0202] The shutdown conditions include drift amount shutdown conditions, as shown below:

[0203] DZ = |Zeq - Zref| / Zref (24)

[0204] DZ≥Dstop(25)

[0205] Zref= (26)

[0206] In the formula, DZ represents the relative drift. Zref represents the reference impedance. Dstop represents the upper limit of the drift stop. This indicates the test impedance.

[0207] The conditions for triggering the drift warning include a drift amount warning, as shown below:

[0208] DZ∈[Dwarn,Dstop)(27)

[0209] In the formula, Dwarn represents the lower limit of the drift amount that would stop the machine.

[0210] Vmax can be set from 100 V to 10000 V, preferably from 500 V to 5000 V; Imax can be set from 1 mA to 10 A, preferably from 10 mA to 2 A; Pmax can be set from 1 mW to 50 W, preferably from 10 mW to 10 W; Zmin can be set from 10 Ω to 1000 Ω, preferably from 50 Ω to 500 Ω; Zmax can be set from 1 kΩ to 1 MΩ, preferably from 5 kΩ to 200 kΩ. In practical applications, these settings or adjustments can be made based on the rated output capacity, electrode area, contact impedance, organism type, stimulation site, and safety control requirements of the non-invasive transcranial nanosecond pulsed electric field stimulation device.

[0211] Example 10:

[0212] An adaptive adjustment system for pulse parameters of a non-invasive transcranial nanosecond pulsed electric field stimulation device is provided. The main technical contents are described in any one of Examples 1 to 9. Furthermore, the priority of the automatic parameter reduction includes four levels.

[0213] The first level of automatic parameter reduction reduces the voltage peak of the nanosecond pulse based on a preset voltage peak parameter reduction step size. .

[0214] The second-level automatic parameter reduction reduces the number of nanosecond pulses N based on a preset pulse train number and step size.

[0215] The third-level automatic parameter reduction is based on a preset step size for reducing the pulse train variable f2 corresponding to the θ-related rhythm modulation.

[0216] The fourth level of automatic parameter reduction is based on the preset gating effective window step size, which reduces the gating effective window Ton.

[0217] Automatic parameter reduction is performed according to a preset fixed difference or preset ratio, for example, reducing the voltage peak value of a nanosecond pulse. When reducing the voltage, the voltage is decreased by 1 V to 500 V each time, preferably 10 V to 200 V; when reducing the number of pulse trains N, the voltage is decreased by 1 to 10 each time, preferably 1 to 5; when reducing the corresponding rhythm modulation variable f2, the voltage is decreased by 0.1 Hz to 10 Hz each time, preferably 0.5 Hz to 5 Hz; when reducing the effective gating window Ton, the voltage is decreased by 1 ns to 1000 ns each time, preferably 10 ns to 500 ns. The above parameter reduction step sizes are only examples, and can be set according to the rated output capacity of the equipment, load conditions, contact stability, and safety control requirements.

[0218] Example 11:

[0219] See Figures 1 to 8 An adaptive pulse parameter adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device, the main technical contents of which include:

[0220] This embodiment proposes an implementable and repeatable method for generating and controlling the application of transcranial nanosecond pulsed electric field stimulation signals. A "dual-frequency nested pulse train" trigger sequence is generated using variables f1 and f2, and closed-loop parameter tuning, limit-crossing locking, and contact drift adaptive processing are achieved based on electrical parameter monitoring.

[0221] Parameter input and template invocation: Create parameter group P={f1,f2,tpw,Vpk,Ton,N,Tstim}; support calling a set of parameters from the "template / prescription library" and generating version number and log number for traceability.

[0222] S2 Electrode Attachment and Contact Verification: Attach the two electrodes to the predetermined positions on the scalp and set a conductive dielectric layer at the electrode-skin interface; output a low-energy test signal and collect the peak voltage Vpk,test and peak current Ipk,test, calculate Zeq,test=Vpk,test / Ipk,test, and compare it with the preset window [Zmin,Zmax]; if it fails, prompt for reattachment / addition of adhesive / adjustment and repeat until it passes.

[0223] S3 Dual-Frequency Nested Pulse Train Timing Generation (External Gating + Internal Trigger): Calculate the external period T2 = 1 / f2, set the effective gating window Ton and the silent window Toff = T2 - Ton; calculate the internal trigger interval T1 = 1 / f1. Determine the calculation methods for N and Ton: Method A (N is automatically calculated given Ton): N = max(1, floor((Ton - tguard) / T1) + 1); Method B (Ton is automatically calculated given N): Ton = (N - 1)·T1 + tguard; where tguard is the protection margin. Generate the internal trigger time tk = t0 + k·T1 (k = 0..N-1 and tk ∈ [t0, t0 + Ton)), and concatenate the m-th external period to obtain the full trigger time tm,k = m·T2 + tk, until Tstim is covered.

[0224] S4 Legality Check and Automatic Correction: Perform constraint checks on parameters: f1>f2, Ton≤T2, N≥1, tpw∈[tpw,min,tpw,max], and tN-1+tguard≤Ton; if not satisfied, automatically correct according to preset rules (e.g., prioritize shortening Ton or reducing N) or prompt the user to adjust and regenerate.

[0225] S5 outputs nanosecond pulses according to the trigger sequence: For each trigger time tm,k, outputs a nanosecond pulse with a pulse width of tpw and a target peak value of Vpk; no output is made within the silent window Toff; execution continues until Tstim is reached or the protection logic is triggered.

[0226] S6 Online Monitoring and Key Electrical Parameter Calculation: Acquire output voltage V(t) and current I(t); Calculate single pulse energy Ep=∫V(t)I(t)dt within each pulse window, and extract Vpk and Ipk; Calculate average power Pavg=Ep·N·f2 according to nested structure; Periodically calculate Zeq=Vpk / Ipk.

[0227] S7 Tiered parameter adjustment and over-limit blocking: Set a threshold set {Vmax, Imax, Emax, Pmax, Zmin, Zmax}. When a warning is issued (e.g., Ep > 0.8Emax, Pavg > 0.8Pmax, or Ipk > 0.8Imax), the parameters are automatically reduced, according to priority: reduce Vpk → reduce N → reduce f2 → shorten Ton; Over-limit blocking occurs (Ep ≥ Emax, Pavg ≥ Pmax, Ipk ≥ Imax, or Vpk ≥ Vmax, or...). If the machine is stopped and locked immediately, the lockout must be restored to normal based on the following conditions: "indicators return to normal + delay + reset".

[0228] S8 Contact Drift Detection and Adaptive Handling: Set the reference impedance Zref=Zeq,test, and calculate the relative drift DZ=|Zeq-Zref| / Zref. When DZ∈[Dwarn,Dstop), it is judged as a drift warning and the parameter is automatically reduced; when DZ≥Dstop or The machine stops and prompts for reattaching the electrodes / replenishing the conductive medium before returning to contact calibration.

[0229] S9 End and Record: After reaching Tstim or locking out, the output stops, and the parameter group, trigger sequence summary, V / I / Ep / Pavg / Zeq statistics, and warning / limit overrun / parameter tuning logs are saved to achieve traceability and repeatability.

[0230] Example 12:

[0231] An adaptive pulse parameter adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device, the main technical contents of which are described in Example 11, further include: 1. Electrode arrangement.

[0232] like Figure 3 As shown, the transcranial electrode is made of flexible conductive material and can be in the shape of a circular or elliptical patch. It is adhered to the temporal region on both sides of the mouse scalp or adjacent locations by conductive adhesive and is kept in stable contact by a fixation frame.

[0233] 2. Stimulus waveform design

[0234] like Figure 4 As shown, this embodiment employs a dual-frequency nested ns-tPFS pulse train waveform. Specifically, nanosecond-level pulses are output in a series at a frequency of f1; these pulse groups are modulated into a rhythmic output of f2. Example: For instance, taking f1=40Hz, f2=5Hz, and a 200ms cycle as an example, several high-voltage pulses with a width of 100ns are sequentially emitted at 40Hz intervals within the first 100ms, followed by a 100ms window period for tissue recovery. By adjusting the number of pulses and the duty cycle within each pulse train, the stimulation intensity and neural modulation effect can be precisely controlled.

[0235] 3. Animal experimental protocol (taking f1 as 40Hz and f2 as 5Hz as an example)

[0236] Experimental animals and grouping: Transgenic AD model mice (e.g., 5xFAD) around 10 months old were selected and randomly divided into two groups:

[0237] Group A: ns-tPFS intervention group (n≥6);

[0238] Group B: Sham sham stimulation control group (n≥6), with only electrodes placed but no power applied or extremely low intensity pulses output.

[0239] like Figure 6 As shown, the WT-sham group was the normal sham stimulation group (negative control), the WT-ns-tPFS group was the normal stimulation group, the 5xFAD-sham group was the AD sham stimulation group (positive control), and the 5xFAD-ns-tPFS group was the AD stimulation group.

[0240] 4. Overview of Experimental Results (Confirmatory)

[0241] Confirmatory results from comprehensive behavioral assessment, histological examination, and electroencephalogram (EEG) analysis indicate that when using the non-invasive transcranial nanosecond pulsed electric field stimulation signal described in this embodiment (using nested pulse trains of f1 / f2 as an example parameter) for experimental verification, the experimental group showed a distinguishable trend from the control group in terms of relevant behavioral indicators, histological / molecular marker signals, and neurophysiological characteristics of the target frequency band. Furthermore, no significant abnormalities were observed under the monitoring and protective conditions set in the experimental setup. These results demonstrate that the stimulation signal generation and controllable application method of this embodiment is feasible, repeatable, and parameter-adjustable, providing a reference for further verification and application development under different models and parameter configurations.

Claims

1. A pulse parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device, characterized in that, include: The module includes: parameter input and template calling module, contact verification module, legality check and automatic correction module, dual-frequency nested pulse train timing generation module, nanosecond pulse output module, online monitoring and key electrical parameter calculation module, graded adjustment and over-limit interlocking module, and contact drift judgment and adaptive processing module. The parameter input and template calling module is used to obtain pulse parameters and input the pulse parameter legality check and automatic correction module; The contact verification module is used to verify the contact of the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device. If the contact verification fails, the electrodes are reattached and the contact verification is performed again until the contact verification is successful. The legality check and automatic correction module is used to perform constraint checks on the input pulse parameters, automatically correct parameters that do not meet the constraint checks, and input the obtained pulse parameters that meet the constraint checks into the dual-frequency nested pulse train timing generation module and the nanosecond pulse output module. The dual-frequency nested pulse train timing generation module generates a pulse trigger sequence based on the input pulse parameters; The nanosecond pulse output module outputs nanosecond pulses based on the pulse trigger sequence and the input pulse parameters; During the nanosecond pulse output process, the online monitoring and key electrical parameter calculation module collects the voltage at both ends of the electrodes and the current flowing through the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device, and calculates the key electrical parameters based on the collected voltage and current. The graded adjustment and limit-overlocking module determines whether the pulse parameter triggers a limit over-limit based on key electrical parameters. If a limit over-limit is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down and locked. If no limit over-limit is triggered, it determines whether the pulse parameter triggers an early warning. If an early warning is triggered, the pulse parameter is automatically reduced and returned to the dual-frequency nested pulse train timing generation module. If no early warning is triggered, the corresponding pulse parameter is directly output. The contact drift determination and adaptive processing module calculates the relative drift based on key electrical parameters and determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger the shutdown condition based on the relative drift. If the shutdown condition is triggered, the non-invasive transcranial nanosecond pulse electric field stimulation device is shut down and returned to the contact verification module. If the shutdown condition is not triggered, it determines whether the pulse parameters output by the graded modulation and over-limit locking module trigger a drift warning. If a drift warning is triggered, the pulse parameters output by the graded modulation and over-limit locking module are automatically reduced, and the automatically reduced pulse parameters are returned to the dual-frequency nested pulse train timing generation module. If no drift warning is triggered, the pulse parameters for the non-invasive transcranial nanosecond pulse electric field stimulation device are directly output.

2. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The adjustment system also includes a recording module; The recording module is used to record pulse parameters, as well as corresponding key electrical parameters and parameter adjustment logs; The parameter adjustment log includes warnings, exceeding limits, and parameter reduction situations.

3. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The non-invasive transcranial nanosecond pulsed electric field stimulation device includes two pulse generators and two electrodes; The pulse generator outputs nanosecond pulses based on the pulse parameters output by the adaptive adjustment system. The electrodes and pulse generators are connected in a one-to-one correspondence, and the nanosecond pulses output by the pulse generators are applied to the head of the organism. The electrode is attached to one side of the scalp and is also provided with a hydrogel patch; Two nanosecond pulses interfere with each other in the deep brain regions of a living organism, generating a low-frequency modulated envelope, which in turn regulates neural network activity; The deep brain regions include the hippocampus and the entorhinal cortex; The low-frequency modulation envelope signal includes the θ-band electric field envelope and the γ-band electric field envelope. The nanosecond-level leading edge of the two nanosecond pulses generates a transient electric field that directly acts on subcellular structures in the deep brain regions of organisms, promoting the clearance of pathological proteins; The pathological proteins include β-amyloid oligomers and plaques.

4. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The pulse parameters include the number of nanosecond pulses N, the effective gate window Ton, the peak voltage Vpk of the nanosecond pulse, the pulse width tpw of the nanosecond pulse, the pulse train variable f1 corresponding to γ-related rhythm modulation, and the pulse train variable f2 corresponding to θ-related rhythm modulation. The relationship between the number of nanosecond pulse trains N and the effective gate window Ton is as follows: Ton=(N-1)·T1+tguard(1) T1=1 / f1(2) In the formula, tguard is the protection margin; T1 represents the trigger interval within the string.

5. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The contact verification steps are as follows: A1 acquires the test pulse parameters and outputs the test pulse signal on the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device based on the test pulse parameters; A2 acquires the peak voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. and test peak current ; A3 is based on the peak voltage of the test. and test peak current Calculate the test impedance As shown below: （3） A4 Determine the test impedance If the impedance is within the preset window, the contact test is successful; otherwise, the contact test is unsuccessful.

6. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The constraint conditions for the constraint check are as follows: f1>f2(4) Ton≤T2(5) N≥1（6） tpw∈[ , ](7) +tguard≤Ton(8) T2=1 / f2(9) In the formula, f1 is the pulse train variable corresponding to γ-related rhythm modulation; f2 is the pulse train variable corresponding to θ-related rhythm modulation; Ton is the effective gating window; T2 is the external period; N is the number of pulse trains of nanosecond pulses; tpw is the pulse width of nanosecond pulses; , These represent the upper and lower limits of the nanosecond pulse width, respectively; tguard is the protection margin. This indicates the trigger time within the pulse train numbered N-1; The trigger times within the string are as follows: = +k·T1(10) In the formula, k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1; This indicates the trigger time within the pulse train numbered 0; T1 represents the trigger time within the pulse train numbered k; T1 represents the trigger interval within the pulse train. If the input pulse parameters do not meet the constraints of the constraint check, automatic correction is performed first by shortening the effective gating window Ton or reducing the number of nanosecond pulse trains N. If the automatically corrected pulse parameters still do not meet the constraints of the constraint check, the pulse parameters are reacquired.

7. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The triggering times of the pulse triggering sequence are as follows: =m·T2+ (11) In the formula, m is the index of the number of external periods; T2 is the external period; k represents the pulse train number index of the nanosecond pulse, k=0,1,...,N-1; N is the number of pulse trains of the nanosecond pulse; This indicates the trigger time within the pulse train numbered k; This indicates the trigger time corresponding to the m-th external cycle; The silent window of the pulse trigger sequence is shown below: Toff = T2 - Ton (12) In the formula, Toff is the silent window of the pulse trigger sequence; Ton is the gating effective window.

8. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The key electrical parameters include single-pulse energy Ep, peak voltage Vpk, peak current Ipk, average power Pavg, and peak impedance Zeq. The single-pulse energy Ep, average power Pavg, and peak impedance Zeq are shown below: （13） Pavg = Ep·N·f2 (14) Zeq = Vpk / Ipk (15) In the formula, Indicates time; This indicates the voltage across the electrodes of the non-invasive transcranial nanosecond pulsed electric field stimulation device. f1 represents the current collected flowing through the electrodes of the non-invasive transcranial nanosecond pulse electric field stimulation device; f2 is the pulse train variable corresponding to the θ-related rhythm modulation; N is the number of nanosecond pulse trains.

9. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The triggering conditions include single pulse energy exceeding the limit, peak voltage exceeding the limit, peak current exceeding the limit, average power exceeding the limit, and peak impedance exceeding the limit. The single-pulse energy exceeding the limit is as follows: Ep≥Emax(16) In the formula, Ep represents the single pulse energy; Emax represents the single pulse energy exceeding the limit threshold. The peak voltage exceeding the limit is as follows: Vpk≥Vmax(17) In the formula, Vpk represents the peak voltage; Vmax represents the peak voltage over-limit threshold. The peak current exceeding the limit is as follows: Ipk≥Imax(18) In the formula, Ipk represents the peak current; Imax represents the peak current over-limit threshold. The average power exceeding the limit is as follows: Pavg≥Pmax(19) In the formula, Pavg represents the average power; Pmax represents the average power exceeding the threshold. The peak impedance exceeding the limit is as follows: （20） In the formula, Indicates peak impedance; These represent the upper and lower limits of peak impedance exceeding the limit, respectively. The conditions for triggering the early warning include single-pulse energy warning, peak current warning, and average power warning; The single-pulse energy warning is as follows: Ep≥0.8Emax(21) The peak current warning is as follows: Pavg≥0.8Pmax(22) The average power warning is as follows: Ipk≥0.8Imax(23) The shutdown conditions include drift amount shutdown conditions, as shown below: DZ = |Zeq - Zref| / Zref (24) DZ≥Dstop(25) Zref= (26) In the formula, DZ represents the relative drift; Zref represents the reference impedance; Dstop indicates the maximum stop limit for drift; Indicates the test impedance; The conditions for triggering the drift warning include a drift amount warning, as shown below: DZ∈[Dwarn,Dstop)(27) In the formula, Dwarn represents the lower limit of the drift amount that would stop the machine.

10. The parameter adaptive adjustment system for a non-invasive transcranial nanosecond pulsed electric field stimulation device according to claim 1, characterized in that, The automatic parameter reduction priority includes four levels; The first level of automatic parameter reduction reduces the voltage peak of the nanosecond pulse based on a preset voltage peak parameter reduction step size. ; The second-level automatic parameter reduction reduces the number of nanosecond pulses N based on a preset pulse train number and step size. The third-level automatic parameter reduction is based on the preset pulse train variable parameter reduction step size, which reduces the pulse train variable f2 corresponding to the θ-related rhythm modulation. The fourth level of automatic parameter reduction is based on the preset gating effective window step size, which reduces the gating effective window Ton.

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