Targeted nucleus and cortex paired transcranial electromagnetic combined stimulation system

Abstract

The invention provides a targeted nucleus and cortex paired transcranial electromagnetic combined stimulation system, which comprises a deep layer-cortex paired combined regulation and control module used for obtaining a deep nucleus-cortex paired combined stimulation strategy; the individualized navigation engine module is used for carrying out transcranial electromagnetic stimulation individualized positioning on the deep nuclei and the cortex target spots based on a pairwise combined stimulation strategy and the individual imaging data of the deep nuclei and the cortex target spots to obtain target spot parameters; the deep electrical stimulation synchronous electroencephalogram acquisition module is used for acquiring a cortex evoked potential incubation period; the individualized sequential pairing stimulation technology module is used for obtaining transcranial electromagnetic stimulation time interval parameters; and the multi-device linkage software platform module is used for realizing time sequence synchronous regulation and control of the transcranial electromagnetic stimulation device and other devices and completing paired transcranial electromagnetic combined stimulation of the targeted nuclei and the cortex. According to the method, the time-space parameters are accurately controlled, so that the tTIS and the TMS can act synergistically.

Description

Technical Field

[0001] The present invention belongs to the technical field of non-invasive neuromodulation, and particularly relates to a paired transcranial electromagnetic combined stimulation system targeting nuclei and cortex. Background Art

[0002] Temporal interference transcranial electrical stimulation (tTIS) is an emerging non-invasive brain stimulation technology. In tTIS technology, two high-frequency currents with different but similar frequencies are injected into the brain by electrodes respectively. The direct stimulation effect of high-frequency currents on the superficial brain tissue is weak, which can significantly reduce the discomfort when the current passes through the skin and superficial neurons. When the two high-frequency currents meet in the brain tissue, due to the frequency difference, an interference effect (Temporal Interference) is generated, forming a low-frequency envelope field, whose frequency is equal to the frequency difference between the two currents. The envelope field acts on the deep brain tissue at the frequency difference. Since deep neurons are sensitive to low-frequency electric fields, the envelope field can effectively activate neurons in the deep target area, while high-frequency currents cannot cause neuronal discharge due to their too high frequency, thus avoiding interference with the superficial brain tissue. And tTIS realizes efficient and non-invasive deep electrical stimulation by reasonably designing the electrode placement positions and parameters and using imaging (fMRI) and brain atlas simulation technology to individualize the electrode positioning. This method breaks through the limitation of current attenuation.

[0003] Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technology that uses a rapidly changing magnetic field to induce an electric current in the cerebral cortex, thereby activating neurons or regulating brain function. TMS has high spatio-temporal resolution, can achieve stimulation of specific brain regions, and at the same time does not require craniotomy surgery, so it has high safety. Currently, TMS has been widely used in brain function research and the neuromodulation of various neuropsychiatric diseases, such as depression, anxiety, and motor dysfunction. In addition, TMS can also be combined with other technologies (such as EEG and fMRI) to evaluate the brain function effect of the stimulation in real time, providing a powerful tool for non-invasive neuromodulation.

[0004] Paired associative stimulation methods can be divided into three types. One type is the combination of peripheral electrical stimulation and cortical magnetic stimulation. For example, sequential associative stimulation of the cerebral cortex is performed through the median nerve and transcranial magnetic stimulation (TMS), which is usually used to explore the plasticity mechanism between peripheral input and central cortex. The second type is dual cortical magnetic stimulation, that is, two pairs of transcranial magnetic stimulations act on different cortical regions. By adjusting the stimulation interval and intensity, the excitatory, inhibitory regulation, and functional connection status between cortices are studied. The third type is the combined application of deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), that is, DBS is used to stimulate deep nuclei (such as the basal ganglia) and TMS acts on the cortex to explore the synergistic effect of deep nuclei and cortex in motor function. However, the DBS technology is invasive and requires surgical implantation of electrodes, which has certain surgical risks and technical limitations. Its application is currently mainly limited to the research of single motor function. These three paired associative stimulation methods have important application values in revealing the neural excitatory regulation mechanism, brain plasticity, and its changes in disease states.

[0005] Spike-timing dependent plasticity (STDP) is the neural regulation principle of paired associative stimulation (PAS). Through the stimulation input with a specific timing relationship, long-term potentiation (LTP) or long-term depression (LTD) of neuron synapses is induced. Its core lies in the relative order and time interval of the firing times of presynaptic neurons and postsynaptic neurons. When presynaptic activity precedes postsynaptic activity and the interval is within a specific time window, LTP is usually induced; on the contrary, if postsynaptic activity precedes presynaptic activity, LTD is more likely to be induced. Therefore, the time interval between paired associative stimulations is particularly important, which affects the stimulation effect and has individual differences.

[0006] Currently, the combined application of tTIS and TMS is still in the exploratory stage, and there is no non-invasive spatio-temporal combined stimulation of deep brain nuclei and cortex. tTIS achieves non-invasive deep stimulation through the principle of temporal interference, while TMS mainly acts on the cortex and activates neurons through the principle of electromagnetic induction. The synchronous stimulation of the two is expected to break the existing limitations and form a combined regulation effect across brain regions. By precisely controlling spatio-temporal parameters, tTIS and TMS can act synergistically to regulate the functional connection between deep brain nuclei and cortex, providing a new approach for studying complex brain network dynamics and developing innovative neuromodulation methods. Summary of the Invention

[0007] To solve the problems existing in the prior art, the present invention provides a paired transcranial electromagnetic combined stimulation system targeting the nucleus and the cortex to achieve precise regulation of neural circuits.

[0008] A paired transcranial electromagnetic combined stimulation system targeting the nucleus and the cortex includes:

[0009] A deep-cortex paired joint regulation module for setting parameters for transcranial magnetic stimulation and temporal interference transcranial electrical stimulation through cortical plasticity regulation of the target based on the deep nucleus-cortex target points selected on the target neural circuit, and obtaining a deep nucleus-cortex paired joint stimulation strategy;

[0010] An individualized navigation engine module for performing individualized positioning of transcranial electromagnetic stimulation on the deep nucleus and the cortex target points based on the paired joint stimulation strategy and the individual imaging data of the deep nucleus and the cortex target points, and obtaining target point parameters;

[0011] A deep electrical stimulation synchronous electroencephalogram acquisition module for real-time collecting electroencephalogram signals during the temporal interference transcranial electrical stimulation of the deep nucleus, and removing artifacts from the electroencephalogram signals to obtain the latency of cortical evoked potentials;

[0012] An individualized timing paired stimulation technology module for obtaining transcranial electromagnetic stimulation time interval parameters based on the latency of cortical evoked potentials and the functional requirements of the target neural circuit;

[0013] A multi-device linkage software platform module for realizing the timing synchronous regulation of the transcranial electrical stimulation device, the transcranial magnetic stimulation device, and the deep electrical stimulation synchronous electroencephalogram acquisition module based on the target point parameters and the transcranial electromagnetic stimulation time interval parameters, and completing the paired transcranial electromagnetic combined stimulation targeting the nucleus and the cortex.

[0014] Preferably, the deep-cortex paired joint regulation module includes:

[0015] A target area selection unit for selecting directly or indirectly connected deep nucleus-cortex target points based on the primary motor function and the higher cognitive function of the brain;

[0016] A functional type division unit for dividing the functional types of the deep nucleus-cortex target points according to the preset regulation requirements;

[0017] A parameter setting unit for setting parameters for the transcranial magnetic stimulation and the temporal interference transcranial electrical stimulation based on the deep nucleus-cortex target points of different functional types.

[0018] Preferably, in the parameter setting unit, the parameters of transcranial magnetic stimulation include stimulation frequency and intensity; the parameters of temporal interference transcranial electrical stimulation include current intensity, carrier frequency, Burst frequency, on / off pulse number, on / off time, and total duration; the parameter setting further includes setting the time interval of transcranial electromagnetic stimulation.

[0019] Preferably, the individualized navigation engine module includes:

[0020] A nuclear mass individualized electrode positioning unit, configured to obtain the positions of electrodes for temporal interference transcranial electrical stimulation of deep nuclear masses by using a finite element simulation method based on the acquired individual imaging data and brain atlas;

[0021] A cortical individualized coordinate navigation unit, configured to construct a three-dimensional brain model based on the acquired individual imaging data, and combine navigation technology to real-time track the position and direction of the transcranial magnetic stimulation coil to obtain the transcranial magnetic stimulation coordinates of cortical targets;

[0022] A target parameter acquisition unit, configured to obtain the target parameters based on the positions of electrodes for temporal interference transcranial electrical stimulation of deep nuclear masses and the transcranial magnetic stimulation coordinates of cortical targets.

[0023] Preferably, in the nuclear mass individualized electrode positioning unit, the process of obtaining the positions of electrodes for temporal interference transcranial electrical stimulation of deep nuclear masses includes:

[0024] Based on the individual imaging data, segment multiple layers of brain tissue, and combine the electric field transmission theory to obtain a discrete three-dimensional finite element model;

[0025] Based on the discrete three-dimensional finite element model, preset electrode positions, and combined with individual imaging data, calculate the leadfield matrix of the full-channel electric field configuration;

[0026] Based on the leadfield matrix and the electric field matrix, obtain the quantitative contribution of each electrode channel to the electric field in the brain;

[0027] Based on the quantitative contribution and the brain atlas, obtain the positions of electrodes for temporal interference transcranial electrical stimulation of deep nuclear masses.

[0028] Preferably, the deep brain stimulation synchronous electroencephalogram acquisition module includes:

[0029] An electroencephalogram signal acquisition unit, configured to real-time collect electroencephalogram signals during the process of temporal interference transcranial electrical stimulation of deep nuclear masses;

[0030] An artifact removal unit, configured to remove artifacts from the electroencephalogram signals to obtain pure electroencephalogram signals;

[0031] The cortical evoked potential latency calculation unit is used to calculate the cortical evoked potential latency based on the pure electroencephalogram signal and the individualized synaptic conduction individualized delay time.

[0032] Preferably, the deep brain stimulation synchronous electroencephalogram acquisition module further includes a synaptic conduction time estimation unit, which is used to estimate the individualized synaptic conduction individualized delay time based on the positive and negative evoked potentials induced on the cortex by the time-interfering transcranial electrical stimulation acting on the deep nuclei.

[0033] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0034] 1. The present invention innovatively designs a deep-cortical paired joint regulation module for precisely stimulating and regulating brain functions. This module optimizes the stimulation mode. For the primary motor function or high-level cognitive function of the brain, deep and cortical targets are selected based on neural networks and functional circuits, forming a non-invasive deep and cortical joint regulation experimental paradigm library.

[0035] 2. The present invention realizes the precise positioning of deep nuclei and cortical targets through a high-precision individualized navigation engine module. The nuclear individualized electrode positioning unit combines individual imaging data and brain atlases to accurately determine the stimulation targets of deep nuclei; the cortical individualized coordinate navigation unit is based on a three-dimensional brain model and real-time navigation technology to ensure the precise matching of transcranial magnetic stimulation (TMS) targets. Compared with the prior art, this module significantly improves the accuracy of electromagnetic stimulation positioning and meets the needs of personalized neural circuit regulation.

[0036] 3. The present invention innovatively develops a deep brain stimulation synchronous electroencephalogram acquisition module to collect the cortical signals induced when the tTIS stimulates the deep part, shield the artifact interference of high-frequency electrical stimulation signals on the cortex, and calculate the latency of the evoked potential, providing a feasible scientific basis for measuring the conduction time from deep nuclei to the cortex.

[0037] 3. The present invention uses a multi-device linkage software platform module to achieve the precise timing synchronization of time-interfering transcranial electrical stimulation (tTIS) and transcranial magnetic stimulation (TMS) by setting the output signal parameters of different channels of the transcranial electrical stimulation device. The pulse burst mode is used to replace the continuous oscillation time-interfering transcranial electrical technology, creating the conditions for the spatio-temporal joint regulation of the deep part and the cortex. It provides an advanced technical means for the research of neural circuit regulation. Description of the Drawings

[0038] In order to more clearly illustrate the technical solutions of the present invention, the drawings required for use in the embodiments are briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0039] Figure 1 This is the structural diagram of a paired transcranial electromagnetic combined stimulation system targeting the nucleus and cortex according to an embodiment of the present invention;

[0040] Figure 2 This is the schematic flowchart of nucleus individual electrode positioning, cortical evoked potential latency calculation, multi-device linkage, and deep-cortical paired combined regulation according to an embodiment of the present invention;

[0041] Figure 3 This is the schematic diagram of the principle of the deep-cortical paired combined regulation module according to an embodiment of the present invention;

[0042] Figure 4 This is the schematic diagram of the tTIS-TMS stimulation mode according to an embodiment of the present invention;

[0043] Figure 5 This is the algorithm flowchart of nucleus individual electrode positioning according to an embodiment of the present invention;

[0044] Figure 6 This is the working flowchart of the paired transcranial electromagnetic combined stimulation system targeting the nucleus and cortex according to an embodiment of the present invention. Detailed implementation manners

[0045] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0046] To make the above objects, features, and advantages of the present invention more obvious and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific implementation manners.

[0047] Embodiment 1

[0048] As Figure 1 、 Figure 2 shown, a paired transcranial electromagnetic combined stimulation system targeting the nucleus and cortex includes: a deep-cortical paired combined regulation module, an individual navigation engine module, a deep brain stimulation synchronous electroencephalogram acquisition module, an individual sequential paired stimulation technology module, and a multi-device linkage software platform module.

[0049] As Figure 3As shown, the deep-cortical paired associative regulation module is used to set parameters for transcranial magnetic stimulation (TMS) and temporal interference transcranial electrical stimulation (tTIS) based on the selected deep nucleus-cortical targets on the target neural circuit, and obtain a deep nucleus-cortical paired associative stimulation strategy. In this embodiment, the neural circuit is determined according to the disease type or brain function requirement, and the deep nucleus and cortical target on it are selected. Based on the regulation requirement of the activity state of the neural circuit, the excitability and plasticity of the cortex are precisely enhanced or inhibited to meet the personalized requirements of neural function research.

[0050] A further implementation manner is that the deep-cortical paired associative regulation module includes:

[0051] A target area selection unit for selecting directly or indirectly connected deep nucleus-cortical targets based on the primary motor function and higher cognitive function of the brain;

[0052] A functional type division unit for dividing the deep nucleus-cortical targets into different functional types according to the preset regulation requirements; In this embodiment, the brain function is the result of the coordinated work of multiple regions, and there are close functional and anatomical connections between different brain regions. The regulation of many neurological, mental diseases and cognitive functions involves multiple interacting brain regions. As Figure 3 shown, this module divides the deep-cortical target areas into different functional types such as motor improvement (thalamus-primary motor cortex), emotion regulation (amygdala-dorsolateral prefrontal cortex), memory enhancement (hippocampus-dorsolateral prefrontal cortex), cognitive control (striatum-inferior frontal gyrus) and conflict monitoring (cingulate gyrus-medial prefrontal cortex) according to the regulation requirements.

[0053] A parameter setting unit for setting parameters for transcranial magnetic stimulation (TMS) and temporal interference transcranial electrical stimulation (tTIS) based on deep nucleus-cortical targets of different functional types. A further implementation manner is that in the parameter setting unit, the parameters of transcranial magnetic stimulation include stimulation frequency and intensity; the parameters of temporal interference transcranial electrical stimulation include current intensity, carrier frequency, Burst frequency, on / off pulse number, on / off time and total duration; the parameter setting also includes setting the transcranial electromagnetic stimulation interval (ISI). Through this combined regulation strategy, coordinated regulation of deep and cortical regions for different functional requirements can be achieved, thereby improving the accuracy and effectiveness of research.

[0054] Specifically, as Figure 4As shown, the regulatory exercise improves function. The deep tTIS target area is the thalamus, and the cortical TMS target area is the primary motor cortex; tTIS uses an intermittent theta burst stimulation pattern (iTBS), the paired tTIS-TMS stimulation frequency (TMS stimulation frequency) is 0.1 Hz, the stimulation interval between TMS and tTIS is 25 ms, and the intensity is 120% of the resting motor threshold (rMT); the basic settings of tTIS include a current intensity of 2 mA and a carrier frequency of 2 kHz, and then the pulse trigger parameters are set, the interference frequency is 100 Hz, the burst frequency is 5 Hz, the on / off pulse number is 3 / 17, the on / off time is 2 s / 8 s, and the total duration is 190 s. Among them, the tTIS parameter settings conform to the following formula.

[0055]

[0056] The individualized navigation engine module is used to perform individualized positioning of transcranial electromagnetic stimulation on deep nuclei and cortical targets based on the paired combined stimulation strategy and individual imaging data of deep nuclei and cortical targets, and obtain target parameters.

[0057] A further implementation is that the individualized navigation engine module includes:

[0058] As Figure 5 shown, the nuclear individualized electrode positioning unit is used to obtain the positions of the electrodes for transcranial electrical stimulation with time interference of deep nuclei by using the finite element simulation method based on the obtained individual imaging data and brain atlas.

[0059] A further implementation is that in the nuclear individualized electrode positioning unit, the process of obtaining the positions of the electrodes for transcranial electrical stimulation with time interference of deep nuclei includes:

[0060] Based on individual imaging data, multiple layers of brain tissue are segmented, and combined with the electric field transmission theory, a discrete three-dimensional finite element model is obtained; specifically, based on individual MRI images, fine segmentation of multiple layers of brain tissue such as the scalp, skull, gray matter, and white matter of the brain is completed, and an accurate three-dimensional finite element model is constructed. Subsequently, based on the classical electric field transmission theory, the formula is:

[0061]

[0062] Among them, σ represents the conductivity of each tissue, φ is the electric potential, and ρ is the charge density. The complex head structure is discretized into multiple small units by the finite element method, and its weak form is expressed as

[0063]

[0064] Here, Ω represents the head region, v is the test function, and this discretization process ensures the accuracy and stability of the model calculation.

[0065] Based on a discrete three-dimensional finite element model, preset electrode positions combined with individual imaging data, calculate the leadfield matrix for the full-channel electric field configuration; specifically, after the model is constructed, according to the preset electrode positions in the 10-20 international standard lead system, combined with the individual MRI structural data, further calculate the leadfield matrix for the full-channel electric field configuration. This matrix describes the influence relationship of each electrode on the electric field distribution in various regions of the head, and its calculation can use the following matrix formula:

[0066] L = J -1 E,

[0067] where E is the electric field matrix, reflecting the electric field distribution generated by the external current in the model, and J is the admittance matrix,

[0068] Based on the leadfield matrix and the electric field matrix, obtain the quantitative contribution of each electrode channel to the electric field in the brain; specifically, by multiplying the inverse of the leadfield matrix by the electric field matrix, the quantitative contribution of each electrode channel to the electric field in the brain can be obtained.

[0069] Based on the quantitative contribution and the brain atlas, obtain the electrode positions for deep brain time-interference transcranial electrical stimulation. Specifically, determine the spatial coordinates and radius range of the target nucleus according to the individualized brain atlas to ensure accurate localization of the stimulation target point, which can be achieved by marking the central coordinates of the brain region and defining the radius of the influence range for targeted stimulation. After determining that the target target point is accurately located, based on the grey wolf optimization algorithm, optimize the channel and stimulation parameter configuration for the target target point localization, and finally generate multiple groups of stimulation schemes (electrode arrangements and current parameters). Finally, select the stimulation combination scheme based on the target point electric field.

[0070] X1 = X α -A1·D α

[0071] X2 = X β -A2·D β

[0072] X3 = X δ -A3·D δ ,

[0073]

[0074] where X α , X β , X δ are the positions of the group leaders Alpha, secondary leader Beta, and tertiary leader Delta respectively. X is the position of the current grey wolf. A1, A2, A3 are coefficient vectors used to control the step size of the grey wolf moving towards the leader. D α, D β , D δ is the current distance between the grey wolf and the leader.

[0075] Coefficient vectors A and C

[0076]

[0077] Where a is a linearly decreasing parameter that linearly decreases from 2 to 0 and is used to control the exploration and exploitation phases of the search process. r1 and r2 are random vectors between [0, 1] and are used to increase the randomness and diversity of the search.

[0078] Cortical individualized coordinate navigation unit, which is used to construct a three-dimensional brain model based on the acquired individual imaging data, combine navigation technology to real-time track the position and direction of the transcranial magnetic stimulation coil, and obtain the transcranial magnetic stimulation coordinates of the cortical target point; specifically, construct an individualized three-dimensional brain model based on MRI (magnetic resonance imaging) image data, clarify the anatomical and functional coordinates of the target area and accurately calibrate them. During the TMS navigation process, the system uses infrared tracking to real-time monitor the relative position between the coil and the head, dynamically adjust the spatial coordinates and angles of the coil, ensure that its magnetic field direction best matches the target area, and at the same time provide real-time feedback to optimize the accuracy of coil positioning. Among them, regarding the infrared tracking technology, it has been maturely applied in the existing neurosurgical navigation system Brainsight TMS. Brainsight TMS navigation is a world-leading neurosurgical navigation system that allows users to position their TMS coil based on the MRI images of individual subjects, MRI-generated 3D curve reconstructed brain or MNI average head model brain. The characteristics and functions of Brainsight TMS navigation make this system an ideal choice for rapid, simple, and reliable target selection and coil positioning for single-pulse TMS, double-pulse TMS, repetitive TMS, and quadruple-pulse stimulation (QPS) research. In the system, an optical (infrared) position sensor is adopted, and the tracking tools include a subject tracker, a coil tracker, a coil calibration block, and a pointer tool.

[0079] Target point parameter acquisition unit, which is used to obtain target point parameters based on the position of the transcranial electrical stimulation electrode for deep brain nucleus time interference and the transcranial magnetic stimulation coordinates of the cortical target point.

[0080] Deep brain stimulation synchronous electroencephalogram acquisition module, which is used to real-time collect the electroencephalogram signals during the transcranial electrical stimulation of deep brain nucleus time interference, and remove the artifacts from the electroencephalogram signals to obtain the cortical evoked potential latency, which reflects the conduction time and functional state between the deep brain area and the cortex.

[0081] A further implementation manner lies in that the deep brain stimulation synchronous electroencephalogram acquisition module includes:

[0082] The electroencephalogram (EEG) signal acquisition unit is used to collect EEG signals in real time during transcranial electrical stimulation with temporal interference on deep nuclei.

[0083] The artifact removal unit is used to remove artifacts from the EEG signals to obtain pure EEG signals.

[0084] The cortical evoked potential latency calculation unit is used to calculate the cortical evoked potential latency based on the pure EEG signals and the individualized synaptic conduction individualized delay time.

[0085] A further implementation is that the deep brain stimulation synchronous EEG acquisition module further includes a synaptic conduction time estimation unit, which is used to estimate the individualized synaptic conduction individualized delay time based on the positive and negative evoked potentials induced on the cortex by the temporal interference transcranial electrical stimulation acting on the deep nuclei.

[0086] In the deep brain stimulation synchronous EEG acquisition module, the process of processing the EEG signals includes:

[0087] This module non-invasively stimulates the deep nuclei with a single pulse through electrodes on the cortex. After the nuclei are activated, they are transmitted to the cortical regions on the same loop. Developed based on Qt5, implemented using QML, C++, and JavaScript languages, and integrated with the functional modules of MATLAB, including the MatlabEngine and MatlabScript components. Among them, MatlabEngine is used to connect to the MATLAB shared engine, and MatlabScript is responsible for calling the evoked potential extraction program in the program directory. The signal processing flow includes the following steps:

[0088] 1. Filtering: Perform band-pass filtering (such as 0.1–45 Hz) on the EEG signals to remove low-frequency drift and high-frequency noise;

[0089] 2. Re-referencing: Select the bilateral mastoid electrodes M1 and M2 as reference electrodes;

[0090] 3. Interpolation to replace the stimulation electrode: Interpolate and repair the signal of the stimulation electrode affected by the electrical stimulation artifact.

[0091] 4. Event segmentation: Extract the signal in the time window [-50 ms, 50 ms] according to the stimulation event because of the bandwidth of the single pulse.

[0092] 5. Baseline correction: Use the signal mean before stimulation as the baseline to correct the signal within the time window:

[0093] 6. Artifact Subspace Reconstruction (ASR) artifact processing: Remove interferences such as electrooculogram and electromyogram to restore the real EEG signals. The formula is

[0094]

[0095] where Z clean is the reconstructed clean signal, Z is the input signal, V is the eigenvector of the covariance matrix, and M is the square root of the geometric median of the covariance matrix, represents the Moore-Penrose pseudoinverse.

[0096] 7. Superposition averaging: The signals after M stimulations are superimposed and averaged to extract the evoked potential on the electrodes of the region of interest (ROI):

[0097]

[0098] This module provides reliable support for studying the changes in cortical evoked potentials caused by deep time-interference transcranial electrical stimulation. By analyzing the amplitudes and latencies of the positive and negative cortical potentials, this module can effectively evaluate the nerve conduction efficiency and synaptic activity status between deep nuclei and cortical regions. These data provide a scientific basis for optimizing the intensity of deep electrical stimulation and the inter-stimulus interval (ISI) of paired electromagnetic combined stimulation.

[0099] The individualized sequential paired stimulation technology module is used to obtain the transcranial electromagnetic stimulation inter-stimulus interval parameter (ISI) based on the latency of cortical evoked potentials and the functional requirements of the target neural circuit, so as to achieve precise facilitation and inhibitory responses to neural circuit plasticity. Specifically, the individualized stimulation inter-stimulus interval (transcranial electromagnetic stimulation inter-stimulus interval parameter) is set by precisely measuring the latency of the cortical potential induced by deep stimulation, and the stimulation interval is dynamically set to optimize the neural circuit regulation effect. Specifically, based on the characteristics of the evoked potential, the module uses the latencies of the positive and negative potentials as the inter-stimulus interval (ISI) for tTIS-TMS paired combined stimulation. For example, if the measured latency of the individualized cortical induced negative potential is 10 ms and the latency of the positive potential is 22 ms, the system will use 10 ms and 22 ms as the stimulation intervals to evaluate and optimize the impact of the stimulation on cortical plasticity facilitation or inhibition. This method can more precisely match the conduction characteristics of individual neural circuits, thereby achieving precise regulation and optimization of nerve function.

[0100] The multi-device linkage software platform module is used to achieve the timing synchronization control of transcranial electromagnetic stimulation (TMS) devices, transcranial electrical stimulation (tES) devices, transcranial magnetic stimulation (TMS) devices, and the synchronous electroencephalogram (EEG) acquisition module for deep brain stimulation based on target parameters and transcranial electromagnetic stimulation time interval parameters, and complete paired transcranial electromagnetic combined stimulation of the target nucleus and the cortex. The software platform independently developed based on the Qt program uses a time series control mechanism to control TMS with the trigger level of the tES channel, achieving precise timing coordination between the two. Specifically, a time series trigger mechanism is adopted, and the stimulation channel of the tTIS device outputs a sine wave to achieve deep - tTIS, and the synchronous I / O terminal triggers the TMS device to stimulate the cortical target area. The multi-device linkage software platform module selects the serial port and parallel port as the communication interfaces according to different devices, and can control TMS with the trigger level of the tES channel.

[0101] As Figure 6 shown, compared with the traditional tTIS frequency regulation method, the deep nucleus stimulation adopts a new frequency modulation mode, switching between the modulation and non-modulation states by changing the carrier frequency to generate the theta burst stimulation (TBS) mode. Different from continuous oscillation stimulation, the pulsed stimulation method creates the conditions for the spatio-temporal combined regulation of the deep brain and the cortex. The specific implementation method is that the first channel continuously outputs a 2 kHz current, the second channel switches from 2 kHz to 2.1 kHz every 200 milliseconds, lasts for 30 milliseconds, and then switches back to 2 kHz, forming three pulses with a frequency of 100 Hz, and every three pulses form a cluster. After every 10 pulse clusters are output, the module sends a square wave signal at a high level to trigger the TMS device at a set time interval (ISI) in the third channel, completing a pair of tTIS-TMS combined stimulations, and the interval between each pair of stimulations is 10 seconds.

[0102] Deep nuclei and cortical regions were paired-stimulated according to the above-mentioned inter-stimulus interval (ISI). 90 pairs of tTIS and TMS stimulations were performed at each inter-stimulus interval (ISI). TMS alone stimulating the cortical target area was used as a means to measure cortical excitability to determine the individualized optimal inter-stimulus interval (ISI). And according to different requirements for regulating brain functions, including motor circuit regulation and non-motor circuit regulation, different effect evaluation indexes were selected. In motor circuit regulation, the M1 area was used as the target area for evaluating the regulation effect, and the motor evoked potential (MEP) was used as the evaluation index. TMS was used to stimulate the motor cortex, and the amplitude change of MEP was observed to evaluate the cortical excitability and plasticity state. In non-motor circuit regulation, the cortical stimulation target was used as the target area for evaluation. For example, when regulating cognitive control function, the cortical target area was the inferior frontal gyrus. The transcranial evoked potential (TEP) of TMS stimulation on the inferior frontal gyrus was recorded by using the TMS combined with EEG signal analysis technology. The amplitude and latency changes of TEP components (such as N45 or P180) were used to evaluate the enhancement or inhibition of the middle cortex.

[0103] The embodiments described above are only descriptions of the preferred embodiments of the present invention and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A paired transcranial electromagnetic stimulation system targeting nuclei and cortex, characterized in that: include: The deep-cortical paired joint regulation module is used to set parameters for transcranial magnetic stimulation and time-interference transcranial electrical stimulation based on the deep nucleus-cortical targets selected on the target neural circuit through the cortical plasticity regulation target to obtain the deep nucleus-cortical paired joint stimulation strategy; An individualized navigation engine module is used to perform individualized transcranial electromagnetic stimulation positioning of deep nuclei and cortical targets based on the paired joint stimulation strategy and individual imaging data of deep nuclei and cortical targets to obtain target parameters; A deep electrical stimulation synchronous EEG acquisition module is used to collect EEG signals in real time during the deep nucleus temporal interference transcranial electrical stimulation process, and remove artifacts from the EEG signals to obtain the latency of cortical evoked potentials; An individualized sequential paired stimulation technology module is used to obtain a transcranial electromagnetic stimulation time interval parameter based on the cortical evoked potential latency and the functional requirements of the target neural circuit; The multi-device linkage software platform module is used to realize the timing synchronization control of the transcranial electrical stimulation device, the transcranial magnetic stimulation device and the deep electrical stimulation synchronous EEG acquisition module based on the target parameters and the transcranial electromagnetic stimulation time interval parameters, and complete the paired transcranial electromagnetic combined stimulation of the targeted nuclei and cortex.

2. The system according to claim 1, characterized in that The deep layer-cortex paired joint regulation module includes: A target selection unit is used to select directly or indirectly connected deep nucleus-cortex targets based on the primary motor function and higher cognitive function of the brain; A functional type classification unit, used for classifying the deep nucleus-cortex target into functional types according to preset regulation requirements; A parameter setting unit is used to set parameters for the transcranial magnetic stimulation and the time interference transcranial electrical stimulation based on deep nucleus-cortical targets of different functional types.

3. The system according to claim 2, characterized in that In the parameter setting unit, the parameters of the transcranial magnetic stimulation include stimulation frequency and intensity; the parameters of the time interference transcranial electrical stimulation include current intensity, carrier frequency, Burst frequency, number of on / off pulses, on / off time and total duration; the parameter setting also includes setting the transcranial electromagnetic stimulation time interval.

4. The system according to claim 1, characterized in that The individualized navigation engine module comprises: The nucleus individualized electrode positioning unit is used to obtain the position of the deep nucleus temporal interference transcranial electrical stimulation electrode based on the acquired individual imaging data and brain atlas using the finite element simulation method; Cortical individualized coordinate navigation unit, used to build a three-dimensional brain model based on the acquired individual imaging data, and combined with navigation technology to track the position and direction of the transcranial magnetic stimulation coil in real time to obtain the transcranial magnetic stimulation coordinates of the cortical target; The target parameter acquisition unit is used to obtain the target parameters based on the position of the deep nucleus time interference transcranial electrical stimulation electrode and the transcranial magnetic stimulation coordinates of the cortical target.

5. The system according to claim 1, characterized in that In the nucleus individualized electrode positioning unit, the process of obtaining the position of the deep nucleus temporal interference transcranial electrical stimulation electrode includes: Based on individual imaging data, multiple layers of brain tissue are segmented and combined with electric field transmission theory to obtain a discrete three-dimensional finite element model; Based on the discrete three-dimensional finite element model, the preset electrode positions and the individual imaging data, the leadfield matrix of the full channel electric field configuration is calculated; Based on the leadfield matrix and the electric field matrix, the quantitative contribution of each electrode channel to the electric field in the brain is obtained; Based on the quantitative contribution and the brain atlas, the locations of transcranial electrical stimulation electrodes for temporal interference in deep nuclei were obtained.

6. The system according to claim 1, characterized in that The deep electrical stimulation synchronous EEG acquisition module comprises: An EEG signal acquisition unit, used for real-time acquisition of EEG signals during the time-interference transcranial electrical stimulation of deep nuclei; An artifact removal unit, used for removing artifacts from the EEG signal to obtain a pure EEG signal; The cortical evoked potential latency calculation unit is used to calculate the cortical evoked potential latency based on the pure EEG signal and the individualized synaptic conduction individualized delay time.

7. The system according to claim 6, characterized in that The deep electrical stimulation synchronous EEG acquisition module also includes a synaptic conduction time estimation unit, which is used to estimate the individualized synaptic conduction individualized delay time based on the positive and negative evoked potentials induced on the cortex by time interference transcranial electrical stimulation acting on the deep nuclei.

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