Mental disease assessment method based on visual evoked potential abnormality

Abstract

The invention discloses a mental disease assessment method based on visual evoked potential abnormity, which comprises the following steps of: taking chessboard overturning as a stimulation graph, acquiring graphic visual evoked potential by utilizing electrophysiology visual acquisition equipment, and analyzing visual evoked potential waveform by utilizing an assessment module; and finally comparing whether the difference between the latency parameter and the amplitude parameter in the graphic visual evoked potential has significance or not, and providing a statistical index for a doctor and the patient to indicate the illness degree of the patient or whether the illness state is controlled or not. The method changes the traditional influence of clinical experience of doctors, subjective factors of patients and the like on objectivity of diagnosis results, is repeatable and low in cost, is a non-invasive and rapid evaluation method, and is expected to become a biomarker for mental disease patients and a potential tool for psychiatric diagnosis in the future.

Description

Technical Field

[0001] The present invention relates to the technical field of visual evoked potential analysis, and particularly relates to a method for evaluating mental diseases based on abnormal visual evoked potentials. Background Art

[0002] Schizophrenia is a chronic and severe mental disorder, including abnormalities in an individual's perception, emotion, and behavior. Because patients have main symptoms such as hallucinations and delusions with unknown causes, and are accompanied by various cognitive function disorders in aspects such as thinking, sensation, emotion, and behavior. Depression is mainly clinically characterized by a significant and persistent low mood. Typical symptoms include that patients with depression are prone to self-blame and a sense of helplessness, slow speech speed, and loss of interest in life, etc.

[0003] Researchers have long realized the connection between schizophrenia and visual function. Schizophrenia patients are accompanied by various structural and functional disorders, and the retina may be particularly affected because the retina is part of the central nervous system and has similar structures and functions to the brain and spinal cord in some aspects, and has similar responses to injury and immunity. In addition, from an embryonic perspective, the retina and optic nerve originate from the neuroectoderm and emerge from the diencephalon. The visual processing ability of schizophrenia patients is impaired, and these changes in the visual system include dopaminergic abnormalities, output abnormalities, retinal lesions such as macular, cataracts, and thinning of the retinal nerve fiber layer, resulting in low vision.

[0004] Radiomics has broken through the subjective limitations of traditional imaging that rely on diagnosticians in the diagnosis of schizophrenia, and has made certain progress in enhancing the objectivity of clinical diagnosis of schizophrenia, guiding individualized treatment, and prognosis evaluation, but it still cannot meet the clinical needs. At present, the application of this method still needs to be further improved. For example, the automatic and semi-automatic methods used in the image segmentation process are not clearly standardized, which may affect the research results, and the cost of this method is relatively high.

[0005] In recent years, various omics technologies, including genomics, epigenomics, transcriptomics, and gut microbiomics, etc., have been applied to the study of schizophrenia. However, the omics methods mainly focus on the study of the pathogenesis of schizophrenia. Currently, the omics research on schizophrenia mainly focuses on European populations. Considering factors such as eating habits and genetic backgrounds, there may be differences in the pathogenesis of schizophrenia among different populations. Therefore, more omics research needs to be carried out in the future. However, omics research requires a large sample size, and in addition, because chips need to be used during the examination, the examination cost is expensive.

[0006] In existing evaluation methods, factors such as doctors' clinical experience and patients' subjective factors often have a relatively large impact on the objectivity of the diagnosis results. In summary, it is particularly important to develop a reliable, repeatable and low-cost evaluation method for mental diseases. Summary of the Invention

[0007] In view of the deficiencies of the prior art, the present invention provides an evaluation method for mental diseases based on abnormal visual evoked potentials to overcome the defects in the prior art.

[0008] The technical solution of the present invention is realized as follows: An evaluation method for mental diseases based on abnormal visual evoked potentials uses a checkerboard flip as the stimulation pattern, uses an electrophysiological visual acquisition device to collect the graphic visual evoked potentials, and uses an evaluation module to analyze the waveform of the visual evoked potentials. Finally, it compares whether the difference in the latency parameter and amplitude parameter in the graphic visual evoked potentials is significant, providing statistical indicators for doctors and patients to indicate the degree of illness or whether the condition is under control.

[0009] Further, when using the checkerboard flip as the stimulation pattern, the visual evoked potentials are stimulated by a 1° and 15′ checkerboard flip, the stimulation distance is 1 meter, and the viewing angle is 17°.

[0010] Further, when using the electrophysiological visual acquisition device to collect the graphic visual evoked potentials, before collection, first connect the line from the bridge of the nose through the vertex to the external occipital protuberance. The active electrode is located at the 10% point forward from the external occipital protuberance end of this line, the reference electrode is located at the 30% point backward from the bridge of the nose of this line, and the ground electrode is located on the forehead, the vertex of this line, behind the ear mastoid or the earlobe.

[0011] Further, the use of the electrophysiological visual acquisition device to collect the graphic visual evoked potentials includes the following steps:

[0012] S1, Clean the skin: Use a special skin cleaning paste to clean the skin at the site where the electrodes are to be placed to remove the grease on the skin surface;

[0013] S2, Connect the electrodes to the amplifier: Connect the three electrodes to the corresponding color ports of the external amplifier;

[0014] S3, Place the electrodes: First dip the electrodes in the electrode conductive paste filled, and then place the three electrodes in the corresponding positions in sequence and fix them with adhesive tape;

[0015] S4, Monocular occlusion examination: First check the right eye, then check the left eye. When performing monocular examination, cover the contralateral eye with a black eye mask or a black sheet inserted into the trial frame;

[0016] S5, Refractive correction: Place the corresponding corrective lens for the eye to be examined according to the best corrected visual acuity examination result at 1 meter.

[0017] Further, the evaluation module is a software program embedded in the electrophysiological vision acquisition device.

[0018] Further, when comparing whether there is a significant difference in the latency parameter and amplitude parameter in the pattern visual evoked potential, the diseased group and the normal group are distinguished and compared. The parameters are expressed as mean ± SEM, and the non-parametric Mann-Whitney test is used to determine the difference between the diseased group and the normal group. All significance levels are set at p = 0.05, and statistical significance is expressed as *p < 0.05, **p < 0.01, and ***p < 0.001.

[0019] Further, during the monocular occlusion examination in S4, first cover the left eye, click the start button in the evaluation module to perform the examination, and sequentially examine the right eye at 1° spatial frequency twice and the right eye at 15′ spatial frequency twice. The electrophysiological vision acquisition device acquires at least 50 times, and then change to cover the right eye, click the start button in the evaluation module to perform the examination, and sequentially examine the left eye at 1° spatial frequency twice and the left eye at 15′ spatial frequency twice.

[0020] Further, the evaluation module selects the program P-VEP×2(M) to provide VEP examination options.

[0021] Further, the ages of the people in the diseased group and the normal group are matched with each other.

[0022] The present invention has the following positive effects:

[0023] Different from the existing evaluation methods, the present invention adopts the judgment of abnormal visual evoked potential to evaluate the significance of parameter differences in mental diseases. By comparing whether there is a significant difference in the latency parameter and amplitude parameter in the pattern visual evoked potential, it provides statistical indicators for doctors and patients to indicate the degree of illness or whether the condition of the patient is under control. It changes the influence of traditional factors such as the clinical experience of doctors and the subjective factors of patients on the objectivity of the diagnosis results. The present invention uses the Roland electrophysiological diagnosis system RETI Scan 21 device, which adopts a standardized flash stimulator, an ophthalmology-specific DC amplifier, and has the normal electrophysiological values of the Chinese human eye built-in. It customizes the examination parameters individually and fully complies with the international ISCEV visual electrophysiology standard. Because this method can provide quantitative data, it can provide a relatively accurate basis for judging the curative effect before and after treatment and during the treatment process of the same patient, and has high reference value. This method is repeatable and the evaluation cost is low. It is a non-invasive and rapid evaluation method, and is expected to become a biomarker for patients with mental diseases and a potential tool for psychiatric diagnosis in the future. Description of the Drawings

[0024] Figure 1This is a schematic flowchart of the method for evaluating mental diseases based on abnormal visual evoked potentials of the present invention.

[0025] Figure 2 This is a schematic diagram of the electrode placement positions of the present invention. Detailed implementation manners

[0026] 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.

[0027] In the following description of the present invention, it should be noted that the orientation or positional relationship indicated by the terms "upper", "lower", "left", "right", "inner", "outer", etc. is based on the orientation or positional relationship shown in the accompanying drawings. It is only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation or be constructed and operated in a specific orientation. The term "connection" only represents the connection between devices and has no special meaning.

[0028] The specific embodiment refers to Figure 1 、 2 As shown, a method for evaluating mental diseases based on abnormal visual evoked potentials uses a checkerboard flip as the stimulus pattern, collects the graphic visual evoked potentials using an electrophysiological visual acquisition device, and analyzes the visual evoked potential waveforms using an evaluation module. Finally, it compares whether the differences in the latency parameters and amplitude parameters in the graphic visual evoked potentials are significant, providing statistical indicators for doctors and patients to indicate the degree of illness or whether the condition is under control of the patient.

[0029] Specifically, the checkerboard flip is used as the stimulus pattern, and the visual evoked potentials are stimulated by the 1° and 15′ checkerboard flips. The stimulation distance is 1 meter, and the viewing angle is 17°. When collecting the graphic visual evoked potentials using the electrophysiological visual acquisition device, before collection, first connect the line from the bridge of the nose through the vertex to the external occipital protuberance. The active electrode is located at the 10% point from the external occipital protuberance end of this line forward, the reference electrode is located at the 30% point from the bridge of the nose end of this line backward, and the ground electrode is located on the forehead, the vertex of this line, behind the ear mastoid or the earlobe.

[0030] Specifically, the collection of the graphic visual evoked potentials using the electrophysiological visual acquisition device includes the following steps:

[0031] S1, Clean the skin: Use a special skin cleaning paste to clean the skin at the site where the electrodes are to be placed to remove the grease on the skin surface;

[0032] S2. Connect the electrodes to the amplifier: Connect the three electrodes to the ports of the external amplifier with corresponding colors respectively;

[0033] S3. Place the electrodes: First, dip the electrodes into the electrode conductive paste filled, and then place the three electrodes at the corresponding positions in sequence and fix them with adhesive tape;

[0034] S4. Monocular occlusion examination: Examine the right eye first, and then the left eye. When performing monocular examination, cover the contralateral eye with a black eye mask or a black sheet inserted into the trial frame;

[0035] S5. Refractive correction: Place the corresponding corrective lens for the eye to be examined according to the best corrected visual acuity examination result at a distance of 1 meter.

[0036] Specifically, during the monocular occlusion examination in S4, first cover the left eye, click the start button in the evaluation module to perform the examination, and sequentially examine the right eye at 1° spatial frequency twice and the right eye at 15′ spatial frequency twice. The electrophysiological visual acquisition device acquires at least 50 times. Then change to cover the right eye, click the start button in the evaluation module to perform the examination, and sequentially examine the left eye at 1° spatial frequency twice and the left eye at 15′ spatial frequency twice. The evaluation module selects the program P-VEP×2(M) and provides VEP examination options.

[0037] Specifically, the evaluation module is a software program embedded in the electrophysiological visual acquisition device. When comparing whether there is a significant difference in the latency parameter and amplitude parameter in the pattern visual evoked potential, the diseased group and the normal group are distinguished and compared. The parameters are expressed as mean ± SEM, and the non-parametric Mann-Whitney test is used to determine the difference between the diseased group and the normal group. All significance levels are set to p = 0.05, and statistical significance is expressed as *p < 0.05, **p < 0.01, and ***p < 0.001. The ages of the people in the diseased group and the normal group are matched with each other.

[0038] When the present invention is specifically operated, the model of the electrophysiological visual acquisition device is: RETI-Port / Scan21. The Roland electrophysiological diagnosis system RETI Scan 21 device adopts a standardized flash stimulator, an ophthalmology dedicated DC amplifier, with the electrophysiological normal values of the Chinese eyes built-in, and customized examination parameters, which fully comply with the international ISCEV visual electrophysiological standards and can perform non-invasive and objective functional examinations.

[0039] The specific steps of the evaluation method of the present invention are as follows:

[0040] During the collection of pattern visual evoked potential (PVEP), mydriasis or miosis is not allowed, and the pupil should be kept in its natural state. Refraction should be performed before the collection. When examining PVEP, the user should wear glasses to obtain the best corrected visual acuity at a distance of 1 meter. The stimulating pattern is checkerboard reversal, with 1° and 15′ pattern reversal VEP. The stimulating distance is 1 meter, and the visual angle is 17°.

[0041] The collection of pattern visual evoked potential using the electrophysiological visual acquisition device includes the following five specific steps:

[0042] Step 1, Clean the skin: Use a special skin cleansing cream to clean the skin at the site where the electrodes are to be placed to remove the grease on the skin surface.

[0043] Step 2, Connect the electrodes to the amplifier: Connect the three electrodes to the corresponding color ports of the external amplifier respectively.

[0044] Step 3, Place the electrodes: First, dip the electrodes into the electrode conductive paste filled. Then place the three electrodes at the corresponding positions in turn and fix them with adhesive tape. According to the international 10 / 20 system, the scalp electrodes should be placed relative to the bone landmarks and are proportional to the head size. To accurately set the electrode positions, connect the line between the nasion, vertex, and inion. At the 10% site forward from the inion end of the line, place the active electrode, which is the visual cortex area; at the 30% site backward from the nasion, place the reference electrode. The position of the ground electrode can be selected from the forehead, vertex, mastoid, or earlobe. All three electrodes for PVEP use eeg skin electrodes.

[0045] Step 4, Monocular occlusion: The right eye should be examined first, and then the left eye. When performing monocular examination, the contralateral eye needs to be occluded. Generally, a black eye mask or a black sheet inserted into the trial frame is used for occlusion.

[0046] Step 5, Refractive correction: Place the corresponding corrective lens on the eye to be examined according to the result of the best corrected visual acuity at a distance of 1m.

[0047] During the monocular detection process of the above steps, the evaluation module runs synchronously to collect data. The evaluation module is a software program embedded in the electrophysiological visual acquisition device, and software synchronization operation is adopted. Select the program VEP. Select the program P-VEP×2(M). Enter the information and click Store Patient to save the information. Click Impedance in the lower right corner to detect the impedance. The international standard requires that the impedance should be less than 5kΩ, and the impedance difference between the active electrode and the reference electrode should be less than 1kΩ, otherwise there will be greater interference.

[0048] Specifically, first perform the right-eye PVEP examination: cover the left eye with an eye patch, and click (Start) in the lower right corner to start the examination. Examine the right eye at 1° spatial frequency twice and at 15' spatial frequency twice in sequence. The minimum number of PVEP acquisitions is 50 times. Artifacts are caused by blinking or poor fixation, and the fewer the number of artifacts, the better. For the left-eye PVEP examination: after the right-eye examination is completed, change to covering the right eye. Use the same procedure to perform the left-eye examination, examining at 1° and 15' spatial frequencies twice in sequence. After the examination is completed, click (Analysis) in the upper menu to view the waveform.

[0049] As another implementation manner of the present invention, during the monocular detection process, if the two results differ greatly, repeat the operation for the third time, and take the two results that are close as the final result.

[0050] Normal PVEP: At 1° spatial frequency, the P100 peak time is approximately 90 - 110 ms, and at 15' stimulation, the P100 peak time is 5 - 10 ms later than that at 1°. The P100 amplitude > 10 μV (generally, for children under 15 years old, the P100 amplitude should > 20 μV, and for adults, the P100 amplitude is 7 - 20 μV). The PVEP examinations at both 1° and 15' spatial frequencies are repeated twice according to the international standard requirements, and the amplitude and peak time consistency of the two examination results are both good, confirming that the result has high reliability.

[0051] During specific operation, use the visual evoked potential in visual electrophysiology as the detection means, establish a controlled group and an uncontrolled group, and compare whether there is a significant difference in two parameters in the VEP between the controlled group, the uncontrolled group, and the normal corresponding age population. The specific parameters are: latency (1° and 15' P100 ms) and amplitude (1° and 15' N75 - P100 (μV)).

[0052] When grouping the controlled group, the uncontrolled group, and the normal group, for the controlled group, there are 2 cases over 40 years old and 3 cases under 40 years old; for the uncontrolled group, there are 8 cases over 40 years old and 9 cases under 40 years old; for the normal group, there are 12 cases over 40 years old and 7 cases under 40 years old. Binocular data are selected for all, and outliers are excluded.

[0053] The data are expressed as mean ± SEM. The non-parametric Mann-Whitney test is used to determine the differences between the controlled group, the uncontrolled group, and the normal group. All significance levels are set to p = 0.05, and statistical significance is expressed as *p < 0.05, **p < 0.01, ***p < 0.001.

[0054] The results obtained by implementing the evaluation method of the present invention are as follows:

[0055] 1. There was no statistically significant difference in latency and amplitude between the controlled group of people aged 40 and above or below and the age-matched normal group.

[0056] 2. When comparing the latency of the uncontrolled group of people aged 40 and above with that of the age-matched normal group, the latency of the uncontrolled group was prolonged compared to the normal group, showing statistical significance. When comparing the amplitudes, the amplitude of the uncontrolled group was smaller than that of the normal group, showing statistical significance.

[0057] 3. When comparing the latency of the uncontrolled group of people aged 40 and below with that of the age-matched normal group, the latency of the uncontrolled group was prolonged compared to the normal group, and the difference in 1°P100ms was statistically significant. The latency of the uncontrolled group at 15′P100ms was also prolonged compared to the normal group, but the difference was not significant. When comparing the amplitudes, the amplitude of the uncontrolled group was smaller than that of the normal group, showing statistical significance.

[0058] The specific comparative analysis results are shown in the following table:

[0059]

[0060]

[0061] As can be seen from the above table, the present invention is repeatable and has a relatively low evaluation cost. It is a non-invasive and rapid evaluation method, and is expected to become a biomarker for patients with mental diseases and a potential tool for psychiatric diagnosis in the future.

[0062] Although the embodiments of the present invention have been shown and described, for those of ordinary skill in the art, it can be understood that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for evaluating mental diseases based on abnormal visual evoked potentials, characterized in that, Using the checkerboard reversal as the stimulus pattern, the electrophysiological visual acquisition device is used to collect the pattern visual evoked potential, and the evaluation module is used to analyze the waveform of the visual evoked potential. Finally, it is determined whether there is a significant difference in the latency parameter and amplitude parameter in the pattern visual evoked potential, providing statistical indicators for doctors and patients to indicate the degree of the patient's illness or whether the condition is under control.

2. The method for evaluating mental disorders based on abnormal visual evoked potentials according to claim 1, wherein Regarding using the checkerboard reversal as the stimulus pattern, the visual evoked potential is stimulated by the checkerboard reversal of 1° and 15′, the stimulation distance is 1 meter, and the viewing angle is 17°.

3. The method for evaluating mental diseases based on abnormal visual evoked potentials according to claim 1, characterized in that, Regarding using the electrophysiological visual acquisition device to collect the pattern visual evoked potential, before collection, first connect the line between the nasion, vertex, and inion. The active electrode is located at the 10% site forward from the inion end of this line, the reference electrode is located at the 30% site backward from the nasion of this line, and the ground electrode is located on the forehead, the vertex of this line, behind the ear mastoid, or the earlobe.

4. The method for evaluating mental disorders based on abnormal visual evoked potentials according to claim 1, wherein The use of the electrophysiological visual acquisition device to collect the pattern visual evoked potential includes the following steps: S1, Clean the skin: Use a special skin cleansing cream to clean the skin at the site where the electrodes are to be placed to remove the grease on the skin surface. S2, Connect the electrodes to the amplifier: Connect the three electrodes to the corresponding color ports of the external amplifier respectively. S3, Place the electrodes: First dip the electrodes in the electrode conductive paste filled, and then place the three electrodes at the corresponding positions in turn and fix them with adhesive tape. S4, Monocular occlusion examination: First examine the right eye, and then the left eye. When performing the monocular examination, cover the contralateral eye with a black eye mask or a trial frame with a black piece inserted. S5, Refractive correction: Place the corresponding corrective lens for the eye to be examined according to the best corrected visual acuity examination result at 1 meter.

5. The method for evaluating mental diseases based on abnormal visual evoked potentials according to claim 1, wherein The evaluation module is a software program embedded in the electrophysiological visual acquisition device.

6. The method for evaluating mental diseases based on abnormal visual evoked potentials according to claim 1, wherein, When determining whether there is a significant difference in the latency parameter and amplitude parameter in the pattern visual evoked potential, the diseased group and the normal group are distinguished and compared. The parameters are expressed as mean ± SEM, and the non-parametric Mann-Whitney test is used to determine the difference between the diseased group and the normal group. All significance levels are set at p = 0.05, and statistical significance is expressed as *p < 0.05, **p < 0.01, and ***p < 0.

001.

7. The method for evaluating mental diseases based on abnormal visual evoked potentials according to claim 4, characterized in that, During the monocular occlusion examination in S4, first cover the left eye, click the start button in the evaluation module to perform the examination, and sequentially examine the right eye at 1° spatial frequency twice and the right eye at 15′ spatial frequency twice. The electrophysiological visual acquisition device collects at least 50 times, and then change to cover the right eye, click the start button in the evaluation module to perform the examination, and sequentially examine the left eye at 1° spatial frequency twice and the left eye at 15′ spatial frequency twice.

8. The method for evaluating mental disorders based on abnormal visual evoked potentials according to claim 5, characterized in that, The evaluation module selects the program P-VEP×2(M) to provide VEP examination options.

9. The method for evaluating mental diseases based on abnormal visual evoked potentials according to claim 6, characterized in that, The ages of the people in the diseased group and the normal group match each other.

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