Transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directivity detection

Abstract

The invention discloses a transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directivity detection. The device comprises a magnetic stimulation module, a data acquisition module, a data processing module and an evaluation module, the magnetic stimulation module is connected with the microelectrode and is used for generating magnetic stimulation on a prefrontal lobe brain region and a hippocampal brain region; the data acquisition module is used for acquiring a tested local field potential signal; wherein the local field potential signals comprise local field potential signals of a prefrontal lobe brain region and a hippocampal brain region during transcranial magnetic stimulation and during non-stimulation; the data processing module is connected with the data acquisition module and is used for processing the data acquired by the data acquisition module; and the evaluation module is used for analyzing the processed data based on a phase slope index algorithm to obtain an analysis result. Through the processing scheme disclosed by the invention, the purpose of improving phase amplitude coupling can be stably and continuously achieved, and the transcranial magnetic stimulation effect is evaluated.

Description

Technical Field

[0001] The present invention relates to the technical field of transcranial magnetic stimulation, and particularly to an apparatus for evaluating transcranial magnetic stimulation effects based on phase-amplitude coupling directivity detection. Background Art

[0002] With the aggravation of the problem of population aging, the number of patients with Alzheimer disease (AD) is increasing day by day, seriously threatening human health. At present, the treatment methods for brain diseases such as AD mainly include drug treatment and supportive therapies. However, drug treatment has large side effects, cannot form a long-term treatment effect, and cannot prevent the onset process of AD; while supportive therapies such as rehabilitation therapy and behavioral therapy, although they do not cause side effects, the treatment effects are not obvious, and they also bring great economic and psychological pressures to patients.

[0003] With the continuous progress of science and the improvement of medical conditions, electromagnetic nerve regulation and electrophysiological technologies have gradually been applied to brain science research and the diagnosis and treatment of brain diseases. At present, transcranial magnetic stimulation (TMS), as a non-invasive brain nerve stimulation technology, is receiving more and more attention and recognition. In addition, intermittent Theta-burst Stimulation (iTBS), as a new type of repetitive transcranial magnetic stimulation (rTMS) paradigm, can regulate the activities of potential regions in a shorter time and produce stronger and more lasting post-stimulus effects. iTBS has been widely used in the scientific research and clinical treatment of nervous system diseases. At present, a large number of studies have shown that iTBS can improve cognitive dysfunction in different aspects, thereby alleviating a series of pathological characteristics caused by AD, showing its potential value in the fields of nerve regulation and brain science.

[0004] As one of the important research directions in the field of neuroscience, phase-amplitude coupling reveals the mutual correlation of neural oscillations between different brain regions and its important role in neural information transmission and brain function execution, which is crucial for maintaining stable rhythm activities in the brain. Its coupling directivity is a key factor in brain information processing and cognitive function, which can help determine the dominant direction in signal transmission and contribute to understanding the connection pattern and information transmission mechanism of neural networks. In neurodegenerative diseases such as AD, the abnormality of phase-amplitude coupling may be related to the pathological process. Therefore, finding a method to improve phase-amplitude coupling is of great significance for improving the nerve function of AD patients.

[0005] However, although iTBS has achieved some positive results in the field of treating brain diseases, the prior art has not deeply studied the regulatory effect of the phase-amplitude coupling directionality of neural signals in the theta and low-gamma frequency bands during its stimulation, nor has it deeply explored the dynamic changes and persistent effects of its coupling directionality, which brings difficulties to the treatment of neurodegenerative diseases such as AD. Summary of the Invention

[0006] In view of this, embodiments of the present disclosure provide a transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directionality detection, which at least partially solves the problems existing in the prior art.

[0007] Embodiments of the present disclosure provide a transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directionality detection, the device comprising: a magnetic stimulation module, a data acquisition module, a data processing module, and an evaluation module; The magnetic stimulation module is connected to a microelectrode and is used to generate magnetic stimulation on the prefrontal brain region and the hippocampal brain region; The data acquisition module is used to acquire the local field potential signals of the subject; wherein, the local field potential signals include the local field potential signals of the prefrontal brain region and the hippocampal brain region during and without transcranial magnetic stimulation; The data processing module is connected to the data acquisition module and is used to process the data acquired by the data acquisition module; The evaluation module is used to analyze the processed data based on the phase slope index algorithm to obtain an analysis result.

[0008] According to a specific implementation manner of embodiments of the present disclosure, the device further comprises a feedback module; The feedback module receives the analysis result of the evaluation module and controls the magnetic stimulation module based on the analysis result.

[0009] According to a specific implementation manner of embodiments of the present disclosure, the feedback module includes a switch controller; The switch controller includes a magnetic stimulation gear and a turn-off magnetic stimulation gear; When the feedback module receives that the cross-frequency coupling direction value in the analysis result of the evaluation module is less than the first threshold range, it activates the magnetic stimulation gear; When the feedback module receives that the cross-frequency coupling direction value in the analysis result of the evaluation module is greater than the second threshold range, it turns off the magnetic stimulation gear.

[0010] According to a specific implementation manner of an embodiment of the present disclosure, the stimulation intensity of the magnetic stimulation gear is iTBS stimulation of 0.48 T, the inter-burst frequency is 5 Hz, each burst stimulation contains 3 single pulses with a frequency of 50 Hz, the stimulation lasts for 2 seconds and the interval is 8 seconds, the single stimulation duration is 200 s, a total of 600 pulses, and continuous stimulation is performed for 14 days.

[0011] According to a specific implementation manner of an embodiment of the present disclosure, the data processing module includes a motion artifact removal module, a power frequency interference removal module, and a filtering and extraction module; The motion artifact removal module is used to perform curve fitting on the local field potential signal to obtain the fitting curve of the motion artifact; subtract the fitting curve of the motion artifact from the local field potential signal before fitting to obtain the local field potential signal after removing the motion artifact; The power frequency interference removal module is used to perform multi-taper spectral analysis on the local field potential signal after removing the motion artifact to obtain the fitting curve of the 50 Hz power frequency interference; subtract the fitting curve of the 50 Hz power frequency interference from the local field potential signal after removing the motion artifact to obtain the local field potential signal after removing the power frequency interference; The filtering and extraction module is used to extract the theta band and the low-gamma band from the local field potential signal after removing the power frequency interference.

[0012] The transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection in the embodiments of the present disclosure has the following advantages compared with the prior art: 1. Starting from the directivity of cross-brain region neural rhythm coupling, the neural rhythm coupling value directivity between the prefrontal lobe and the hippocampus is calculated based on PSI, and it is found that the abnormality of phase-amplitude coupling will cause the phenomenon that the low-gamma band guides the theta band across brain regions in the coupling direction, resulting in a reduction in information transmission between related brain regions, while iTBS can reverse this coupling modulation direction, so as to achieve the purpose of improving phase-amplitude coupling, and accordingly evaluate the transcranial magnetic stimulation effect.

[0013] 2. After the stimulation process ends, the persistent effect of iTBS on the phase-amplitude coupling directivity between the theta and low-gamma band neural signals of the target object is explored, providing more support for the stability and persistence of the treatment plan. Description of the Drawings

[0014] The above is only an overview of the technical solution of the present invention. In order to be able to understand the technical means of the present invention more clearly, the following further describes the present invention in detail in conjunction with the drawings and specific embodiments.

[0015] Figure 1Schematic diagram of a transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection provided by an embodiment of the present disclosure; Figure 2 Schematic diagram of the usage process of a transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection provided by an embodiment of the present disclosure; Figure 3 Schematic diagram of the CDF average value of theta-low-gamma of two groups of target objects in the PFC-HPC circuit; among them, (a) is during the stimulation process; (b) is the maintenance period; Figure 4 Schematic diagram of the coupling directivity analysis of theta phase in the prefrontal brain region and low-gamma amplitude in the hippocampal brain region of two groups of target objects; among them, (a) is before stimulation in the stimulation group; (b) is before stimulation in the control group; (c) is after stimulation in the stimulation group; (d) is after stimulation in the control group; Figure 5 Schematic diagram of the curve of the change of the CDF mean value with the number of days during the stimulation process of the target objects in the stimulation group and the control group; Figure 6 Schematic diagram of the curve of the change of the CDF mean value with the number of days during the maintenance period of the target objects in the stimulation group and the control group. Specific implementation manners

[0016] The following describes the embodiments of the present disclosure in detail with reference to the accompanying drawings.

[0017] The following illustrates the implementation manners of the present disclosure through specific specific examples. Those skilled in the art can easily understand other advantages and effects of the present disclosure from the content disclosed in this specification. Obviously, the described embodiments are only a part of the embodiments of the present disclosure, rather than all the embodiments. The present disclosure can also be implemented or applied through other different specific implementation manners. Various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present disclosure. It should be noted that, without conflict, the following embodiments and the features in the embodiments can be combined with each other. All other embodiments obtained by those of ordinary skill in the art based on the embodiments in the present disclosure without making creative efforts belong to the scope of protection of the present disclosure.

[0018] It should be noted that the following describes various aspects of embodiments within the scope of the appended claims. It will be apparent that the aspects described herein can be embodied in a wide variety of forms, and any specific structure and / or function described herein is illustrative only. Based on this disclosure, those skilled in the art should understand that one aspect described herein can be implemented independently of any other aspect, and two or more of these aspects can be combined in various ways. For example, any number of aspects described herein can be used to implement a device and / or practice a method. Additionally, this device can be implemented and this method can be practiced using other structures and / or functionality in addition to one or more of the aspects described herein.

[0019] It should also be noted that the diagrams provided in the following embodiments only illustrate the basic concept of the present disclosure schematically. Only the components related to the present disclosure are shown in the diagrams, rather than being drawn according to the number, shape, and size of the components in actual implementation. The type, quantity, and proportion of each component in actual implementation can be arbitrarily changed, and the component layout type may also be more complex.

[0020] In addition, in the following description, specific details are provided to facilitate a thorough understanding of the examples. However, those skilled in the art will understand that the aspects can be practiced without these specific details.

[0021] An embodiment of the present invention provides a transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection, aiming to improve the cognitive dysfunction of Alzheimer's disease targets. By performing iTBS stimulation on a target subject, local field potential signals in a specific brain region are collected, and the dynamic changes and persistent effects of the phase-amplitude coupling directivity of neural oscillations in the theta and low-gamma frequency bands during iTBS stimulation are explored. Embodiments of the present invention show that by adjusting the phase-amplitude coupling directivity of neurons, the neural information transmission and coordination between the prefrontal lobe and the hippocampus of Alzheimer's disease target subjects can be improved, thereby affecting the related neural network functions, and its persistent effect is still significant within 14 days after the stimulation ends. The present invention is non-invasive and highly safe, providing a theoretical basis for further exploring transcranial magnetic stimulation as a potential means for treating cognitive dysfunction, and at the same time providing a new strategy for the treatment of neurodegenerative diseases such as Alzheimer's disease.

[0022] Figure 1 Schematic diagram of the transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection provided for embodiments of the present disclosure.

[0023] As Figure 1As shown, the transcranial magnetic stimulation effect evaluation device based on phase-amplitude coupling directivity detection disclosed by the present invention includes: a magnetic stimulation module, a data acquisition module, a data processing module, and an evaluation module; The magnetic stimulation module is connected to a microelectrode and is used to generate magnetic stimulation on the prefrontal brain region and the hippocampal brain region; The data acquisition module is used to acquire the local field potential signals of the subject; wherein, the local field potential signals include the local field potential signals of the prefrontal brain region and the hippocampal brain region during transcranial magnetic stimulation and when not stimulated; The data processing module is connected to the data acquisition module and is used to process the data acquired by the data acquisition module; The evaluation module is used to analyze the processed data based on the phase slope index algorithm to obtain an analysis result.

[0024] In an embodiment of the present invention, the device further includes a feedback module; the feedback module receives the analysis result of the evaluation module and controls the magnetic stimulation module based on the analysis result.

[0025] In an embodiment of the present invention, the feedback module includes a switch controller; the switch controller includes a magnetic stimulation gear and a turn-off magnetic stimulation gear; when the feedback module receives that the cross-frequency coupling direction value in the analysis result of the evaluation module is less than the first threshold range, it starts the magnetic stimulation gear; when the feedback module receives that the cross-frequency coupling direction value in the analysis result of the evaluation module is greater than the second threshold range, it turns off the magnetic stimulation gear.

[0026] Furthermore, the data processing module re-acquires the local field potential signals of the subject at preset time intervals and analyzes them through the evaluation module; the feedback module re-adjusts the magnetic stimulation module based on the analysis result.

[0027] In an embodiment of the present invention, the stimulation intensity of the magnetic stimulation gear is iTBS stimulation of 0.48T, the inter-burst frequency is 5 Hz, each burst stimulation contains 3 single pulses with a frequency of 50 Hz, the stimulation lasts for 2 seconds and the interval is 8 seconds, the single stimulation duration is 200 s, a total of 600 pulses, and continuous stimulation is performed for 14 days.

[0028] In an embodiment of the present invention, the data processing module includes a motion artifact removal module, a power frequency interference removal module, and a filtering and extraction module; the motion artifact removal module is configured to perform curve fitting on the local field potential signal to obtain a fitting curve of the motion artifact; subtract the fitting curve of the motion artifact from the local field potential signal before fitting to obtain a local field potential signal after removing the motion artifact; the power frequency interference removal module is configured to perform multi-taper spectral analysis on the local field potential signal after removing the motion artifact to obtain a fitting curve of 50 Hz power frequency interference; subtract the fitting curve of 50 Hz power frequency interference from the local field potential signal after removing the motion artifact to obtain a local field potential signal after removing the power frequency interference; the filtering and extraction module is configured to extract the theta band and the low-gamma band from the local field potential signal after removing the power frequency interference.

[0029] The present invention is verified through the following examples.

[0030] As Figure 2 shown, using the device process of the present invention includes the following steps: First step, implant microelectrodes in the prefrontal brain region and the hippocampal brain region of the target object, and perform transcranial magnetic stimulation on it.

[0031] First, perform a microelectrode implantation surgery on the target object: inject atropine sulfate injection (0.5 mg / ml, 0.2 ml) into the abdominal cavity of the target object before anesthesia, and then use high-concentration isoflurane for anesthesia; after the target object enters the anesthesia state, shave the hair on its head to expose the skull, and fix its head on a stereotaxic apparatus. Under the assistance of a microscope, find the bregma point and locate the prefrontal brain region (2.5 mm - 4.5 mm anterior, 0.2 mm - 1.2 mm right lateral, 2.5 mm - 3 mm deep) and the hippocampal brain region (4.0 mm - 5.3 mm posterior, 4.0 mm - 5.0 mm right lateral, 7.5 mm - 8.5 mm deep); then use an electric cranial drill to open a window, expose and remove the dura mater; use a precision electric pusher to implant the dual-brain region microelectrode array into the above target brain regions. After the implantation is completed, protect the electrode window with agar and tissue repair fluid, and use dental cement for comprehensive encapsulation and fixation to prevent the electrodes from falling off. After the implantation surgery, let the target object recover for 2 days.

[0032] Then, 10 target subjects were randomly divided into the iTBS stimulation group (hereinafter referred to as the stimulation group) and the AD control group (hereinafter referred to as the control group). The two groups received iTBS stimulation and sham stimulation respectively. The target subjects in the stimulation group were given iTBS stimulation with an intensity of 0.48 T, an interburst frequency of 5 Hz. Each burst stimulation contained 3 single pulses with a frequency of 50 Hz. The stimulation lasted for 2 seconds with an 8-second interval, and the single stimulation duration was 200 s, for a total of 600 pulses, and continuous stimulation was performed for 14 days. The target subjects in the control group were given sham iTBS stimulation at the same time period every day, that is, the coil was placed perpendicular to the scalp surface of the vertex of the target subject to ensure that its effective stimulation surface would not produce a stimulation effect on the target subject. The other stimulation parameters were the same as those in the stimulation group. After the stimulation, the mean CDF of the target subjects was recorded continuously for two weeks to explore the persistent effect of iTBS on neural oscillation.

[0033] Step 2: The local field potential signals of the prefrontal lobe and hippocampal brain regions of the target subjects before and after stimulation were collected separately through microelectrodes, and this process lasted for 14 days. After the stimulation ended, the local field potential signals of the prefrontal lobe and hippocampal brain regions of the target subjects were collected again, and this process also lasted for 14 days. The collected local field potential signals were preprocessed to extract the theta and low-gamma frequency bands. The in-vivo multi-channel neuroelectrophysiological recording system was used to simultaneously and synchronously collect and record the local field potential signals (LFPs) of the prefrontal cortex (PFC) and hippocampus (HPC) brain regions of the target subjects to obtain real-time data of the two brain regions, so as to explore the improvement of the phase-amplitude coupling direction between the resting-state neural signals of the target subjects after the action of iTBS. The original neuroelectrical signals of the PFC and HPC were transmitted into the amplifier through wires. The amplifier amplified the original neuroelectrical signals by 5 k times, and then converted them into digital signals through the host computer and transmitted them into the system. The signals were first sampled at a sampling rate of 40 kHz, then filtered through a low-pass filter with a cut-off frequency of 500 Hz, and then downsampled to 1 kHz to obtain the original LFPs signals required for the experiment. The original LFPs signals were passed through a 50 Hz notch filter to remove power frequency interference and through wavelet filtering to eliminate baseline drift, and finally the LFPs signals required for the experiment were obtained.

[0034] Among them, the specific steps of the preprocessing are as follows: 1) Remove motion artifacts: Curve fitting was performed on the local field potential signals to obtain the fitting curve of the motion artifacts. The local field potential signals before fitting were subtracted from the fitting curve of the motion artifacts to obtain the local field potential signals after removing the motion artifacts. 2) Removal of power frequency interference: Perform multi-taper spectral analysis on the local field potential signal after removing motion artifacts to obtain the fitting curve of 50 Hz power frequency interference, and subtract the fitting curve of 50 Hz power frequency interference from the local field potential signal after removing motion artifacts to obtain the local field potential signal after removing power frequency interference; 3) Filtering and extracting specific frequency bands: Extract the theta (4 - 12 Hz) and low-gamma (30 - 48 Hz) frequency bands from the local field potential signal after removing power frequency interference.

[0035] After the above preprocessing, passing the LFPs signal through a Butterworth filter can extract the theta frequency band (4 - 12 Hz) and low-gamma frequency band (30 - 48 Hz) required for the experiment.

[0036] Step 3: Calculate and analyze the phase-amplitude coupling directionality between the neural oscillations of the theta and low-gamma frequency bands during iTBS stimulation based on the phase slope index algorithm, and explore the dynamic changes and persistent effects of its phase-amplitude coupling directionality.

[0037] To explore the directional relationship in phase coupling, the cross-frequency directionality (CFD) index is introduced, which calculates the phase difference between two signals based on the phase slope index (PSI).

[0038] First, divide the signals and into windows, and calculate the complex coherence : (1) Among them, represents the cross-spectrum matrix across windows, represents the frequency, represents the phase component of the low-frequency signal; represents the power envelope of the high-frequency signal; represents the cross-spectrum density; represents the power spectral density of the low-frequency phase signal at frequency f; represents the power spectral density of the high-frequency power signal at frequency f.

[0039] Then the definition of PSI is: (2) Among them, represents the phase slope index; represents the imaginary part, " ” denotes the complex conjugate, is the frequency resolution determined by the window length, is the set of frequencies for slope summation; denotes at frequency the complex coherence.

[0040] Based on this, and are expressed as the time signal of window , denotes at frequency the filtered envelope. Thus, the complex coherence can be rewritten as: (3) where, , , which respectively denote the Fourier transforms of signals , corresponding to the frequency of the current theta phase signal; is the Hanning window; is the number of points of the fast Fourier transform; is the number of segments into which the signal is divided.

[0041] Therefore, based on CFD, PSI can be rewritten as: (4) where, is the bandwidth for measuring the phase slope, fixed at 2 Hz, which is 4 times the resolution ( = 0.5 Hz).

[0042] Thus, this equation can be applied to calculate the phase slope to determine the influence direction of the low-frequency phase on the high-frequency amplitude and analyze their coupling directivity. The sign of PSI indicates the slope direction of the phase difference between the two signals varying with frequency: if the phase gradients are in the same direction, the CFD value is positive, indicating a directional phase coupling; if the phase gradients are in the opposite direction, the CFD value is negative, indicating another directional phase coupling; if the phase gradients are close to zero, it indicates a lack of obvious directivity.

[0043] When the phase of the low-frequency oscillation leads the amplitude of the high-frequency oscillation, it is called positive phase coupling (CFD>0), that is, the theta phase guides the low-gamma amplitude; while when the amplitude of the high-frequency oscillation leads the phase of the low-frequency oscillation, it is called negative phase coupling (CFD<0), that is, the low-gamma amplitude guides the theta phase.

[0044] ​To study the results of the coupling directions of the phase-frequency of the theta band in the PFC and the amplitude-frequency of the low-gamma band in the HPC for two groups of target objects, next, the CFD values will be calculated for the low-frequency theta band and the high-frequency gamma band within different frequency ranges according to different windows and step sizes, and statistical analysis will be performed on their average coupling direction values, as Figure 3 shown. All the data obtained in the present invention are statistically analyzed using the Wilcoxon signed-rank test and the one-way analysis of variance, with P the magnitude of the P value as a reference to determine whether the difference between groups is statistically significant: when

[0045] it can be seen that whether during the stimulation process or during the retention period, the mean CFD of the target objects in the stimulation group is greater than 0, and the mean CFD of the target objects in the control group is less than 0. Moreover, analyzed by the Wilcoxon test method, the difference between the two groups is statistically significant ( P <0.05). This indicates that the coupling direction of the experimental objects in the stimulation group is mainly that the phase of the theta band in the PFC guides the amplitude of the low-gamma band in the HPC, while the coupling direction of the experimental objects in the control group is mainly that the amplitude of the low-gamma band in the HPC guides the amplitude of the theta band in the PFC, that is, an inverse coupling phenomenon is shown, which suggests that the state of cross-regional neural coupling is abnormal under the pathological state of AD.

[0046] Figure 4Taking the PFC-HPC circuit as an example, the x-axis represents the phase frequency of the theta band in the target object's PFC, and the y-axis represents the amplitude frequency of the low-gamma band in the HPC. The color of the boxes in the figure represents the result of the cross-frequency coupling direction value (i.e., the CFD value). The colorbar on the right can quantitatively represent the magnitude of the CFD value. The darker the color, the larger the absolute value of the CFD value. When CFD > 0, the color in the figure is red, indicating that the phase of the theta band in the PFC guides the amplitude of the low-gamma band in the HPC; when CFD < 0, the color is blue, indicating that the amplitude of the low-gamma band in the HPC guides the phase of the theta band in the PFC. It can be seen from the figure that after iTBS stimulation, the coupling directionality between the prefrontal lobe and the hippocampus in the target object has changed significantly. Compared with the control group of target objects, the mean value of CFD in the stimulation group has increased to a certain extent, and it is significantly higher than that of the control group as a whole. That is, the coupling direction of the experimental objects in the stimulation group is mainly that the phase of the theta band in the PFC guides the amplitude of the low-gamma band in the HPC, while the coupling direction of the experimental objects in the control group is mainly that the amplitude of the low-gamma band in the HPC guides the amplitude of the theta band in the PFC. This shows that at rest in the target object, the phase of the low-gamma band in the HPC is regulated by the amplitude of the theta band in the PFC, and iTBS can promote the regulatory effect of this coupling direction; while the control group of target objects showed a reverse coupling phenomenon because in the AD pathological state, cross-regional neural coupling has abnormal changes, and iTBS can reverse this coupling modulation direction.

[0047] Next, explore the phase-amplitude coupling directionality between the neural oscillations of the theta and low-gamma bands during iTBS stimulation, as well as its dynamic changes and persistent effects on the phase-amplitude coupling directionality: Calculate the mean value of CDF of the PFC-HPC circuit during magnetic stimulation for each target object in the stimulation group and the control group respectively, and then average the analysis results. Continuously record for 14 days to obtain the curve of the mean value of CDF of the two groups of target objects changing with the number of days during the stimulation process as Figure 5 shown. It can be seen that after long-term iTBS stimulation in the stimulation group, the trend of its mean CDF value generally shows an upward trend, and in the early stage of stimulation, the change degree of CDF is relatively large. After 9 days of stimulation, the stimulation effect tends to be stable; while in the control group of target objects, after 14 days of sham stimulation, the change of the mean CDF value is relatively gentle, and its value is always negative. It can be seen that iTBS stimulation can promote the coupling direction of the phase of the theta band in the PFC guiding the low-gamma band in the HPC.

[0048] After the stimulation was completed, the mean CDF of the PFC-HPC circuit in the resting state of each target subject in the stimulation group and the control group was calculated, and the analysis results were averaged and recorded for 14 days. The curve of the mean CDF of the two groups of target subjects in the retention period with the number of days was obtained as shown in the figure below: Figure 6 As shown. Figure 6 It can be seen that the change of the mean CDF of the target objects in the stimulation group is relatively stable, and CFD>0 can always be maintained, and it is always higher than the target objects in the control group. This shows that the lasting effect of iTBS stimulation on the target objects is still significant 14 days after the end of stimulation.

[0049] This result shows that the amplitude of the low-gamma frequency band in HPC is regulated by the phase of the theta frequency band of PFC, and iTBS stimulation will enhance this regulatory effect, further affecting the signal transmission between HPC and PFC, and iTBS stimulation can have a more lasting effect on the neural oscillation of the target object. These findings not only help to further understand the functional connection between PFC and HPC and the changes in neural coupling under AD pathological conditions, but also provide important clues for exploring the impact of iTBS on neural activity.

[0050] Through the above steps, the present invention can achieve the regulation of the directionality of the neural rhythm coupling of the target object, thereby improving the cognitive dysfunction caused by AD and the like.

[0051] The results showed that when the target subjects were in a resting state, the theta frequency phase of the prefrontal brain region was regulated by the amplitude of the low-gamma frequency band in the hippocampus, and iTBS stimulation promoted the regulatory effect of this coupling direction; the coupling direction observed in the control group was different from that in other stimulation groups, suggesting that abnormal changes occurred in cross-brain neural coupling under the pathological state of AD, and iTBS can reverse this coupling modulation direction and have a more lasting effect on the neural oscillations of the target subjects.

[0052] Compared with the prior art, the present invention has the following advantages: 1. Starting from the directionality of neural rhythm coupling across brain regions, the directionality of neural rhythm coupling values ​​across the prefrontal cortex and hippocampus was calculated based on PSI, and it was found that abnormal phase-amplitude coupling would cause the low-gamma frequency band to guide the theta frequency band across brain regions in the coupling direction, thereby reducing information transmission between related brain regions. iTBS can reverse this coupling modulation direction, thereby achieving the purpose of improving phase-amplitude coupling.

[0053] 2. After the stimulation process, the persistent effect of iTBS on the phase-amplitude coupling directionality between the target subjects’ theta and low-gamma frequency bands was investigated, providing more support for the stability and sustainability of the treatment program.

[0054] As described above, it is only the specific implementation manner of the present disclosure, but the protection scope of the present disclosure is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present disclosure should be covered within the protection scope of the present disclosure. Therefore, the protection scope of the present disclosure shall be subject to the protection scope of the claims.

Claims

1. A transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directionality detection, characterized in that: The device comprises: a magnetic stimulation module, a data acquisition module, a data processing module and an evaluation module; The magnetic stimulation module is connected to microelectrodes and is used to generate magnetic stimulation to the prefrontal lobe and hippocampus brain regions; The data acquisition module is used to collect local field potential signals of the subject; wherein the local field potential signals include local field potential signals of the prefrontal lobe and hippocampus during transcranial magnetic stimulation and without stimulation; The data processing module is connected to the data acquisition module and is used to process the data collected by the data acquisition module; The evaluation module is used to analyze the processed data based on the phase slope index algorithm to obtain analysis results.

2. The transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directionality detection according to claim 1, characterized in that: The device also includes a feedback module; The feedback module receives the analysis result of the evaluation module and controls the magnetic stimulation module based on the analysis result.

3. The transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directionality detection according to claim 2, characterized in that: The feedback module includes a switch controller; The switch controller includes a magnetic stimulation gear and a magnetic stimulation off gear; The feedback module starts the magnetic stimulation gear when receiving the analysis result of the evaluation module that the cross-frequency coupling direction value is less than the first threshold range; The feedback module turns off the magnetic stimulation gear when receiving the analysis result of the evaluation module that the cross-frequency coupling direction value is greater than the second threshold range.

4. The transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directionality detection according to claim 3, characterized in that: The stimulation intensity of the magnetic stimulation gear is 0.48 T iTBS stimulation, the inter-cluster frequency is 5 Hz, each cluster stimulation contains 3 single pulses with a frequency of 50 Hz, the stimulation is 2 seconds and the rest is 8 seconds, the single stimulation duration is 200 s, a total of 600 pulses, and the continuous stimulation is 14 days.

5. The transcranial magnetic stimulation effect evaluation device based on phase amplitude coupling directionality detection according to claim 1, characterized in that: The data processing module includes a motion artifact removal module, a power frequency interference removal module and a filter extraction module; The motion artifact removal module is used to perform curve fitting on the local field potential signal to obtain a fitting curve of the motion artifact; subtract the local field potential signal before fitting from the fitting curve of the motion artifact to obtain the local field potential signal after the motion artifact is removed; The power frequency interference removal module is used to perform multi-window spectrum analysis on the local field potential signal after the motion artifacts are removed to obtain a fitting curve of the 50 Hz power frequency interference; subtract the fitting curve of the 50 Hz power frequency interference from the local field potential signal after the motion artifacts are removed to obtain the local field potential signal after the power frequency interference is removed; The filtering and extraction module is used to extract theta frequency band and low-gamma frequency band from the local field potential signal after the power frequency interference is removed.

Images