Left basal joint cerebral hemorrhage rat through-ear vagus nerve electrical stimulation fMRI brain region activation map construction method and activation brain map

Abstract

The invention relates to a left basal joint cerebral hemorrhage rat ear vagus nerve electrical stimulation fMRI brain region activation map construction method and an activation brain map. The method comprises the steps of adaptation, grouping, modeling, intervention and evaluation of rats; the brain of the rat is scanned, and image data are collected; carrying out data processing, statistics and analysis on the acquired image data based on an SPM12 algorithm architecture; based on the mixed effect model, analyzing the effectiveness of longitudinal remodeling and VNS regulation of spontaneous brain activity in the brain region of the rat, and establishing a VNS brain activity map database; and based on the mixed effect model, analyzing the effectiveness of longitudinal remodeling and VNS regulation of the core nodes in the rat brain region, and establishing a VNS brain core node database. According to the present invention, the current rat brain function change condition is detected, the VNS stimulation brain region activation map is established according to the active state of the current brain region of interest, the comparison reference data is provided for the VNS regulation brain function experiment, and the reference is provided for the experiment process of the optimization of other rat brain function pathological models.

Description

Technical Field

[0001] The present invention belongs to the field of animal nervous system, and in particular, relates to a method for constructing a brain region activation map of rats with left basal ganglia cerebral hemorrhage via transauricular vagus nerve electrical stimulation fMRI and an activated brain map. Background Art

[0002] The brain is the most complex organ in the human body. Its huge neurons, glial cells, and tiny blood vessels crisscross each other, creating a complex electrical signal transmission network and blood supply network. Different brain regional networks cooperate, coordinate, and antagonize each other, creating the interactive realization of brain functions. The emergence of functional magnetic resonance imaging (fMRI) has brought new hope and dawn for a clearer understanding of brain networks and their functions. The blood oxygen level dependent effect (BOLD) was discovered by S. Ogawa et al., and the activity of neurons is closely related to hemodynamics, which is the basis of brain functional magnetic resonance imaging. When neurons are excited, energy consumption and oxygen consumption increase, blood flow increases significantly, and the amount of deoxyhemoglobin in the relative area decreases, which leads to the enhancement of the nuclear magnetic T2 phase. In other words, the nuclear magnetic T2 phase can reflect local neuronal activity, which is also the basic principle and physiological basis of the BOLD effect. This also made BOLD-fMRI quickly become an important method in the field of brain science research in subsequent studies.

[0003] Functional connectivity (FC) refers to the correlation between brain regions that are far apart in space during activity. It is generally calculated using the Pearson correlation coefficient. If the value is positive, it means that the activity between the two brain regions is in a synergistic relationship. If it is a negative value, it means that the activity between the two brain regions is in an antagonistic relationship. The region of interest (ROI) is the area of ​​focus of the task. Voxel is the smallest unit corresponding to a pixel.

[0004] Vagus nerve stimulation (VNS) has been found to be effective in accelerating brain function remodeling and improving neurological deficits in stroke patients, and has clear efficacy beyond the time window. A large number of preclinical studies have demonstrated the application prospects of VNS in the field of stroke, that is, it can effectively improve the sensorimotor function of stroke rats, and deeply reveal the possible biomolecular mechanisms. Specifically, VNS may play a role by regulating synaptic plasticity, inhibiting inflammatory response, promoting angiogenesis, and protecting the blood-brain barrier. Following the evidence from animal studies, a series of clinical studies have been carried out to explore the efficacy of VNS in improving the sensorimotor function of stroke patients from different levels.

[0005] Transauricular vagus nerve stimulation is an advanced non-invasive neuromodulatory method. It has been found in clinical applications to have clear therapeutic effects in many diseases (such as stroke, cluster headache, and epilepsy). However, there are still many blind spots about its brain network regulation mechanism, which requires a large number of animal studies to reveal. At present, no fMRI normative brain map of rats with left basal ganglia intracerebral hemorrhage after transauricular vagus nerve stimulation has been established. Summary of the invention

[0006] The embodiments of the present application provide a method for constructing a brain region activation map of rats with left-sided basal ganglia hemorrhage by transauricular vagus nerve electrical stimulation fMRI and an activated brain map. Based on the revelation of the transauricular vagus nerve mechanism in animal studies, a stable and reliable functional magnetic resonance imaging (fMRI) norm for brain activation in rats with left-sided basal ganglia hemorrhage by transauricular vagus nerve electrical stimulation, i.e., an activated brain map, is established.

[0007] In a first aspect, the present application provides a method for constructing a brain region activation map of rats with left basal ganglia intracerebral hemorrhage subjected to transauricular vagus nerve electrical stimulation fMRI, comprising:

[0008] Acclimation, grouping, modeling, intervention, and evaluation of rats;

[0009] Scan the rats' brains and collect imaging data;

[0010] Based on the SPM12 algorithm framework, the collected image data is processed, counted and analyzed;

[0011] Based on the mixed effects model, the longitudinal remodeling of spontaneous brain activity in rat brain regions and the effectiveness of VNS regulation were analyzed, and a VNS brain activity atlas database was established;

[0012] Based on the mixed effects model, the longitudinal remodeling of core nodes in the rat brain and the effectiveness of VNS regulation were analyzed, and a VNS brain core node database was established.

[0013] In some embodiments, the rat adaptation, grouping, modeling, intervention and assessment include:

[0014] The purchased rats were kept in the animal house for 1 week to allow the rats to adapt to the new environment;

[0015] The rats were randomly divided into a control group and a modeling-regulation group after blind numbering. The control group was a modeling-sham stimulation group.

[0016] After 3 days of rest, the rats were randomly divided into 7-day, 14-day, and 28-day groups;

[0017] The control group was given transaural VNS + conventional running wheel, and the control group was given only conventional running wheel;

[0018] Neurological deficit scoring, functional imaging acquisition and sampling were performed at 1, 2 and 4 weeks after modeling.

[0019] In some embodiments, the intervention regimen comprises:

[0020] The control group was given left transauricular VNS control and conventional wheel running, while the control group was only given conventional wheel running training. All interventions were applied until the fourth week after modeling. The parameters were as follows:

[0021] Conventional running wheel: Passive running wheel was performed, 10 m / min, twice a day, 30 minutes each time;

[0022] Transauricular VNS regulation: transauricular VNS was administered in combination with conventional running wheel, with VNS parameters of 0.8 mA, 100 μs pulse width, and 30 / 60 Hz frequency. The operation process included: cleaning the left concha area of ​​the rat with alcohol, attaching the magnetic positive and negative electrodes to both sides of the left concha of the rat after the alcohol evaporated, and energizing the stimulation after checking that they were firmly fixed. After 1 minute of pre-adaptation, the running wheel mode was turned on, and the running wheel parameters were the same as above. If the electrode became loose or fell off, the intervention would continue after correction.

[0023] In some embodiments, a brain scan is performed on a rat to collect imaging data, including:

[0024] The rats were scanned in the brain using a Bruker 11.7T MRI system. After inducing anesthesia with 5% isoflurane, the rats were fixed in the scanning head circle and continued to be anesthetized with 1.5% isoflurane combined with 0.05 mg / kg dexmedetomidine. The body temperature was maintained at 37.5°C, and vital signs were monitored throughout the scanning process.

[0025] In some embodiments, data processing, statistics and analysis are performed on the collected image data, including:

[0026] Manually strip non-brain tissue; manually make whole-brain mask; voxel magnification 10 times; exclude the first 10 time points; use the 50th layer as reference for time correction; head motion correction; spatial normalization to the rat brain template; remove linear drift; filter; use Gaussian kernel for spatial smoothing; when calculating spontaneous brain activity indicators, smoothing will be performed first, and then filtering will be performed after obtaining the data; when calculating core node indicators, filtering will be performed first, and then smoothing will be performed after obtaining the indicators; Rest 1.8 is used to remove the superimposed hematoma area and then calculate the fractional low-frequency amplitude, capture spontaneous brain activity and calculate degree centrality to evaluate the spatial distribution of core nodes, aiming to establish a brain area activation map from a macroscopic functional scale;

[0027] A mixed effects model was used to compare the fractional low-frequency amplitude and DC properties of the whole brain of rats horizontally and longitudinally from the following perspectives: in the control group and the control group of the 28-day group, the interaction effect compared the differences between the 1st week and the 4th week study samples from the time dimension; the differences between the control group and the control group were compared between the groups; and the interaction effects of time and between groups were analyzed; the most representative brain areas in the sensorimotor area were selected as ROIs from the above two indicators, and the corresponding signals were extracted, and the Pearlman model was used for correlation analysis with the mNSS score.

[0028] In some embodiments, based on a mixed effects model, the longitudinal remodeling of spontaneous brain activity in rat brain regions and the effectiveness of VNS regulation are analyzed, and a VNS brain activity atlas database is established, including:

[0029] The results showed that compared with the control group, the degree of longitudinal remodeling in the brainstem, right basal forebrain, right basal ganglia, right thalamus, right primary sensory cortex, right secondary sensory cortex, right primary auditory cortex and right secondary auditory cortex, left secondary motor cortex, right primary motor cortex, right primary sensory cortex, left primary motor cortex, and left secondary motor cortex in the control group was more significant, as manifested by a significant increase in the fractional low-frequency amplitude: AlphaSim correction_P<0.001, Cluster>19.

[0030] In some embodiments, based on a mixed effects model, the longitudinal remodeling of core nodes in rat brain regions and the effectiveness of VNS regulation are analyzed, and a VNS brain core node database is established, including:

[0031] The results revealed that compared with the control group, the degree of longitudinal remodeling in the sensorimotor area of ​​the right secondary sensory cortex, right primary sensory cortex, right primary motor cortex, right secondary motor cortex, left primary sensory cortex, left primary motor cortex, and left secondary motor cortex in the control group was more significant, as manifested by a significant increase in DC levels: AlphaSim correction_P<0.001, Cluster>19.

[0032] In a second aspect, the present application provides an activated brain map, which is constructed according to the method for constructing fMRI brain region activation map of rats with left basal ganglia hemorrhage via transauricular vagus nerve electrical stimulation as described in any of the above items.

[0033] The method for constructing the fMRI brain region activation map and the activated brain map of rats with left basal ganglia hemorrhage via transauricular vagus nerve electrical stimulation in the present application embodiment have the following beneficial effects:

[0034] This application detects the current changes in rat brain function by electrically stimulating the rat's vagus nerve through the ear, collecting and analyzing brain functional magnetic resonance images, and establishing a VNS-stimulated brain area activation map based on the current activity status of the brain's area of ​​interest, providing comparative reference data for VNS-modulated brain function experiments, and also providing a reference for optimizing the experimental process of other rat brain function pathology models. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 It is a schematic diagram of the rat's adaptation, recuperation, and regulation;

[0036] Figure 2a Comprehensive evidence of longitudinal remodeling of spontaneous brain activity and the effectiveness of VNS regulation revealed by mixed-effects analysis;

[0037] Figure 2b Schematic diagram of the difference in spontaneous brain activity in the right secondary motor cortex between the control group and the control group at week 4;

[0038] Figure 2c This is a schematic diagram of the negative correlation between spontaneous brain activity in the right secondary motor cortex and neurological deficit score;

[0039] Figure 3a Comprehensive evidence for the longitudinal remodeling of the core node (DC) and the effectiveness of VNS regulation based on the functional attribute scale revealed by mixed effects analysis;

[0040] Figure 3b Schematic diagram of the DC value after z-transformation of the extracted typical remodeled brain area (left primary motor cortex);

[0041] Figure 3c Schematic diagram of the negative correlation between the zDC value of the left primary motor cortex and the neurological deficit score. DETAILED DESCRIPTION

[0042] The present application is further described below in conjunction with the accompanying drawings and embodiments.

[0043] In the following introduction, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance. The following introduction provides multiple embodiments of the present invention, and different embodiments can be replaced or combined, so this application can also be considered to include all possible combinations of the same and / or different embodiments recorded. Therefore, if one embodiment includes features A, B, and C, and another embodiment includes features B and D, then this application should also be considered to include embodiments containing one or more of all other possible combinations of features A, B, C, and D, even though the embodiment may not be clearly recorded in the following text.

[0044] like Figure 1As shown, the method for constructing the fMRI brain region activation map of rats with left basal ganglia cerebral hemorrhage via transauricular vagus nerve electrical stimulation in this application includes:

[0045] (1) The purchased rats were kept in the animal room for 1 week to allow them to adapt to the new environment;

[0046] (2) The rats were randomly divided into a control group (modeling-sham stimulation) and a modeling-control group after blind numbering;

[0047] (3) After 3 days of rest, the rats were randomly divided into 7-day, 14-day, and 28-day groups;

[0048] (4) The control group was given transaural VNS + conventional running wheel, and the control group was only given conventional running wheel.

[0049] The intervention program specifically included: the control group was given left transauricular VNS control + conventional wheel running; while the control group was only given conventional wheel running training; all intervention programs were applied to the fourth week after modeling. The specific parameters are as follows: Conventional wheel running: passive wheel running was performed, 10m / min, twice a day, 30 minutes each time.

[0050] Transauricular VNS regulation: Combined transauricular VNS with conventional running wheel, VNS parameters: current 0.8mA, pulse width 100μs, frequency 30 / 60Hz (stimulator from Shanghai Jiesheng Biotechnology Co., Ltd.). For specific operation, clean the left concha area of ​​the rat with alcohol, and after the alcohol evaporates, accurately adsorb the magnetic positive and negative electrodes on both sides of the left concha of the rat. After checking that it is firmly fixed, turn on the power to stimulate, and start the running wheel mode after 1 minute of pre-adaptation (running wheel parameters are the same as above). If the electrode is loose or falls off, continue the intervention after correction.

[0051] (5) Outcome assessment:

[0052] At 1, 2, and 4 weeks after modeling, neurological deficits were scored, functional images were collected (collected in rats of the 28-day group and matched before and after, only images of the 1st and 4th weeks were collected), and samples were collected. Specifically, for the 7-day and 14-day groups, scores were scored first and samples were collected at the corresponding time points; for the 28-day group, scores were scored first and images were collected.

[0053] (6) Image data collection

[0054] The rats were scanned using a German Bruker 11.7T MRI system (Bruker Medizintechnik), provided by the Fudan University Brain Research Institute. The MRI is equipped with a synchronized inhalation anesthesia machine, a synchronized vital signs monitor, and a constant temperature system. Specifically, this study used 5% isoflurane to induce anesthesia, fixed the rats in the scanning head circle, and continued to be anesthetized with 1.5% isoflurane combined with 0.05mg / kg dexmedetomidine, and maintained the body temperature at around 37.5°C, and monitored vital signs throughout the scan.

[0055] In addition, longitudinal functional imaging data (rs-fMRI, T2 and DWI) were collected from the 1st and 4th weeks of the control group and the control group on the 28th day, in order to explore the longitudinal remodeling characteristics of the sensorimotor area and the effectiveness of transauricular VNS regulation from a macroscopic scale.

[0056] SWI sequence parameters: repetition time (TR) = 400 ms, echo time (TE) = 12 ms, field of view (FOV) = 30×30 mm, flip angle (FA') = 40 degrees, slice thickness = 0.5 mm, number of slices = 17.

[0057] Echo planar imaging (EPI) rs-fMRI parameters: TR = 2000 ms, TE = 12.8 ms, FOV = 30 × 30 mm, FA' = 90 degrees, Slice thickness = 0.5 mm, Slices = 50, 300 volumes in total.

[0058] Structural image T2 parameters: TR=4200ms, TE=25ms, FOV=30×30mm, FA'=40 degrees, Slicethickness=0.5mm, Slices=50.

[0059] Echo planar imaging (EPI) DWI parameters: TR = 3000 ms, TE = 22 ms, FOV = 30 × 30 mm, FA' = 90 degrees, Slice thickness = 0.5 mm, Slices = 35, and 30 diffusion gradients were given in the non-collinear direction after 5 b0 fields.

[0060] (7) rs-fMRI data processing

[0061] Based on the SPM12 algorithm architecture, the code was used to call each step for rs-fMRI data preprocessing. The main process included: manual stripping of non-brain tissue; manual production of whole-brain mask; voxel magnification 10 times; exclusion of the first 10 time points; time correction with the 50th layer as the reference; head motion correction; spatial normalization to the rat brain template; removal of linear drift; filtering (0.01-0.1Hz); and spatial smoothing using a 4×4×4mm3 Gaussian kernel. It is worth noting that smoothing will be performed first when calculating spontaneous brain activity indicators, and filtering will be performed after obtaining the data; when calculating the degree centrality (DC) indicator, filtering will be performed first, and smoothing will be performed after obtaining the indicator. Rest 1.8 (https: / / rfmri.org / REST) ​​was used to capture the spontaneous brain activity of the sensorimotor area and calculate the degree centrality (DC) to evaluate the spatial distribution of the core nodes in the sensorimotor area after removing the superimposed hematoma area, aiming to establish a brain area activation map from a macroscopic functional scale.

[0062] rs-fMRI data: A mixed effects model was used to compare the fractional low-frequency amplitude and DC properties of the whole brain of rats from the following perspectives, both horizontally and longitudinally. Specifically, in the control and control groups of the 28-day group, the interaction effect compared the differences between the study samples in the first and fourth weeks in terms of time; the differences between the control and control groups were compared between groups; and the interaction effects between time and between groups were analyzed. This section focuses on the interaction effects of sensorimotor areas (AlphaSim correction_P<0.01, Cluster>19), aiming to capture the longitudinal remodeling characteristics and the regulatory efficacy of transaural VNS from a functional scale. Subsequently, the study selected the most representative brain areas in the sensorimotor areas as ROIs from the above two indicators, extracted the corresponding signals, and performed correlation analysis with the mNSS scores using the Pierman model.

[0063] (8) Spontaneous brain activity

[0064] This study investigated the longitudinal remodeling of a functional attribute scale - spontaneous brain activity (fractional low-frequency amplitude) and the effectiveness of VNS modulation based on a mixed-effects model. Figure 2aAs shown in the results, compared with the control group, the brainstem (MNI-8, -95.05, -32.8, T value 14.60), right basal forebrain, right basal ganglia, right thalamus, right primary sensory cortex, right secondary sensory cortex, right primary auditory cortex and right secondary auditory cortex (MNI 19, -35.05, -17.8, T value 74.23), left secondary motor cortex (MNI-2, 36.95, 36.2, T value 31.16), right primary motor cortex, right primary sensory cortex (MNI The longitudinal remodeling was more significant in the left primary motor cortex and left secondary motor cortex (MNI-20, -35.05, 54.2, T value 44.01), as shown by a significant increase in the fractional low-frequency amplitude (AlphaSim correction_P<0.001, Cluster>19). In addition, we extracted the z-transformed fractional low-frequency amplitude values ​​of the typical remodeling brain area (right secondary motor cortex), and post hoc analysis found that at week 4, compared with the control group, Figure 2b As shown, the fractional low-frequency amplitude of the control group was significantly increased.

[0065] Figure 2a Comprehensive evidence of longitudinal remodeling of spontaneous brain activity and the effectiveness of VNS regulation revealed by mixed-effects analysis; Figure 2b The difference in spontaneous brain activity in the right secondary motor cortex between the control group and the control group at week 4 revealed the effectiveness of VNS control; Figure 2c The spontaneous brain activity in the right secondary motor cortex was negatively correlated with the neurological deficit score; ROI: right secondary motor cortex; zfALFF: z-transformed fractional low-frequency amplitude; tVNS: transaural VNS modulation; mNSS: modified rat neurological deficit score.

[0066] (9) Core Node Distribution

[0067] The study explored the longitudinal remodeling of the functional attribute scale-core node (DC) and the effectiveness of VNS regulation based on a mixed effects model. The results revealed that Figure 3aAs shown, compared with the control group, the degree of longitudinal remodeling in the right secondary sensory cortex (MNI73, -14.05, 6.2, T value 16.77), right primary sensory cortex, right primary motor cortex (MNI 58, 24.95, 18.2, T value 61.57), right secondary motor cortex (MNI 16, 51.95, 30.2, T value 13.64), left primary sensory cortex (MNI-62, -26.05, 39.2, T value 14.01), left primary motor cortex, left secondary motor cortex (MNI-23, 12.95, 45.2, T value 13.36) of the control group was more significant, as shown by a significant increase in DC levels (AlphaSim correction_P<0.001, Cluster>19). In addition, we extracted the z-transformed DC values ​​of the typical remodeling brain area (left primary motor cortex), and post hoc analysis showed that at week 4, compared with the control group, Figure 3b As shown, the zDC value of the control group was significantly increased.

[0068] Figure 3a Comprehensive evidence of longitudinal remodeling of core nodes and effectiveness of VNS regulation revealed by mixed effects analysis; Figure 3b The difference in zDC in the left primary motor cortex between the control group and the control group at week 4 revealed the effectiveness of VNS control; Figure 3c The zDC value of the left primary motor cortex was negatively correlated with the neurological deficit score; ROI: left primary motor cortex; zDC: z-converted DC; tVNS: transaural VNS modulation; mNSS: modified rat neurological deficit score.

[0069] The present application provides an activated brain atlas, which is constructed according to any of the above-mentioned methods for constructing fMRI brain region activation atlases in rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation.

[0070] This application detects the current changes in brain function in rats by electrical stimulation of the vagus nerve via the ear, and collects and analyzes brain functional magnetic resonance images in rats with left basal ganglia cerebral hemorrhage. It also establishes a VNS-stimulated brain area activation map based on the current activity of the brain's area of ​​interest, providing comparative reference data for VNS-modulated brain function experiments, and also providing a reference for optimizing the experimental process of other rat brain function pathology models.

[0071] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for constructing a brain region activation map of rats with left basal ganglia hemorrhage subjected to transauricular vagus nerve electrical stimulation fMRI, characterized in that: include: Acclimation, grouping, modeling, intervention, and evaluation of rats; Scan the rats' brains and collect imaging data; Based on the SPM12 algorithm framework, the collected image data is processed, counted and analyzed; Based on the mixed effects model, the longitudinal remodeling of spontaneous brain activity in rat brain regions and the effectiveness of VNS regulation were analyzed, and a VNS brain activity atlas database was established; Based on the mixed effects model, the longitudinal remodeling of core nodes in the rat brain and the effectiveness of VNS regulation were analyzed, and a VNS brain core node database was established.

2. The method for constructing fMRI brain region activation atlas of rats with left basal ganglia hemorrhage via transauricular vagus nerve electrical stimulation according to claim 1, characterized in that: Rat acclimation, grouping, modeling, interventions, and assessments included: The purchased rats were kept in the animal house for 1 week to allow the rats to adapt to the new environment; The rats were randomly divided into a control group and a modeling-regulation group after blind numbering. The control group was a modeling-sham stimulation group. After 3 days of rest, the rats were randomly divided into 7-day, 14-day, and 28-day groups; The control group was given transaural VNS + conventional running wheel, and the control group was given only conventional running wheel; Neurological deficit scoring, functional imaging acquisition and sampling were performed at 1, 2 and 4 weeks after modeling.

3. The method for constructing fMRI brain region activation atlas of rats with left basal ganglia hemorrhage via transauricular vagus nerve electrical stimulation according to claim 2, characterized in that: Intervention options include: The control group was given left transauricular VNS control and conventional wheel running, while the control group was only given conventional wheel running training. All interventions were applied until the fourth week after modeling. The parameters were as follows: Conventional running wheel: Passive running wheel was performed, 10 m / min, twice a day, 30 minutes each time; Transauricular VNS regulation: transauricular VNS was administered in combination with conventional running wheel, with VNS parameters of 0.8 mA, 100 μs pulse width, and 30 / 60 Hz frequency. The operation process included: cleaning the left concha area of ​​the rat with alcohol, attaching the magnetic positive and negative electrodes to both sides of the left concha of the rat after the alcohol evaporated, and energizing the stimulation after checking that they were firmly fixed. After 1 minute of pre-adaptation, the running wheel mode was turned on, and the running wheel parameters were the same as above. If the electrode became loose or fell off, the intervention would continue after correction.

4. The method for constructing fMRI brain region activation atlas of rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation according to any one of claims 1 to 3, characterized in that: The rats were scanned in the brain to collect imaging data, including: The rats were scanned in the brain using a Bruker 11.7T MRI system. After inducing anesthesia with 5% isoflurane, the rats were fixed in the scanning head circle and continued to be anesthetized with 1.5% isoflurane combined with 0.05 mg / kg dexmedetomidine. The body temperature was maintained at 37.5°C, and vital signs were monitored throughout the scanning process.

5. The method for constructing fMRI brain region activation maps of rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation according to any one of claims 1 to 3, characterized in that: Perform data processing, statistics and analysis on the collected image data, including: Manually strip non-brain tissue; manually make whole-brain mask; voxel magnification 10 times; exclude the first 10 time points; use the 50th layer as reference for time correction; head motion correction; spatial normalization to the rat brain template; remove linear drift; filter; use Gaussian kernel for spatial smoothing; when calculating spontaneous brain activity indicators, smoothing will be performed first, and then filtering will be performed after obtaining the data; when calculating core node indicators, filtering will be performed first, and then smoothing will be performed after obtaining the indicators; Rest 1.8 is used to remove the superimposed hematoma area and then calculate the fractional low-frequency amplitude, capture spontaneous brain activity and calculate degree centrality to evaluate the spatial distribution of core nodes, aiming to establish a brain area activation map from a macroscopic functional scale; A mixed effects model was used to compare the fractional low-frequency amplitude and DC properties of the whole brain of rats horizontally and longitudinally from the following perspectives: in the control group and the control group of the 28-day group, the interaction effect compared the differences between the 1st week and the 4th week study samples from the time dimension; the differences between the control group and the control group were compared between the groups; and the interaction effects of time and between groups were analyzed; the most representative brain areas in the sensorimotor area were selected as ROIs from the above two indicators, and the corresponding signals were extracted, and the Pearlman model was used for correlation analysis with the mNSS score.

6. The method for constructing fMRI brain region activation maps of rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation according to any one of claims 1 to 3, characterized in that: Based on the mixed effects model, the longitudinal remodeling of spontaneous brain activity in rat brain regions and the effectiveness of VNS regulation were analyzed, and a VNS brain activity atlas database was established, including: The results showed that compared with the control group, the degree of longitudinal remodeling in the brainstem, right basal forebrain, right basal ganglia, right thalamus, right primary sensory cortex, right secondary sensory cortex, right primary auditory cortex and right secondary auditory cortex, left secondary motor cortex, right primary motor cortex, right primary sensory cortex, left primary motor cortex, and left secondary motor cortex in the control group was more significant, as manifested by a significant increase in the fractional low-frequency amplitude: AlphaSim correction_P<0.001, Cluster>19.

7. The method for constructing fMRI brain region activation maps of rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation according to any one of claims 1 to 3, characterized in that: Based on the mixed effects model, the longitudinal remodeling of core nodes in the rat brain and the effectiveness of VNS regulation were analyzed, and a VNS brain core node database was established, including: The results revealed that compared with the control group, the degree of longitudinal remodeling in the sensorimotor area of ​​the right secondary sensory cortex, right primary sensory cortex, right primary motor cortex, right secondary motor cortex, left primary sensory cortex, left primary motor cortex, and left secondary motor cortex in the control group was more significant, as manifested by a significant increase in DC levels: AlphaSim correction_P<0.001, Cluster>19.

8. An activated brain map, characterized in that: The method for constructing fMRI brain region activation atlas of rats with left basal ganglia intracerebral hemorrhage via transauricular vagus nerve electrical stimulation according to any one of claims 1 to 7.

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