技术领域technical field
本发明涉及神经交互的技术领域，具体地，涉及脑区神经交互作用的测试分析度量程序方法及系统。The present invention relates to the technical field of neural interaction, in particular, to a test, analysis and measurement program method and system for neural interaction in brain regions.
背景技术Background technique
帕金森病(Parkinson’s disease，PD)是一种神经系统退行性疾病，临床表现主要分运动症状，和非运动症状，运动症状包括；静止性震颤、肌强直、远动迟缓及姿势步态不稳等，非运动症状临床表现包括自主神经症状、认知障碍及感觉症状等等。非运动症状中认知功能障碍及幻视(visual hallucination，VH)是最常见的精神症状，伴有幻视的PD患者有进一步增加及发生认知功能障碍风险。PD患者的幻视表现形式多种多样，主要包括幻视、听幻、嗅幻、触幻及味幻觉等，其中幻视是最常见的表现形式，较大比例中晚期PD患者自述有VH症状。帕金森病幻视已成为一种常见临床表现，可引致患者进一步增加功能障碍、抑郁和焦虑等。引起PD患者幻视VH存在着复杂的各脑区神经信息传输、相互影响及交互作用，以致使脑功能障碍愈加严重。Parkinson's disease (PD) is a degenerative disease of the nervous system. The clinical manifestations are mainly divided into motor symptoms and non-motor symptoms. Motor symptoms include; resting tremor, muscle rigidity, telekinesis and gait instability etc. The clinical manifestations of non-motor symptoms include autonomic symptoms, cognitive impairment and sensory symptoms, etc. Cognitive dysfunction and visual hallucinations (VH) are the most common psychiatric symptoms among non-motor symptoms, and PD patients with visual hallucinations have a further increased risk of developing cognitive dysfunction. There are various forms of visual hallucinations in PD patients, mainly including visual hallucinations, auditory hallucinations, olfactory hallucinations, tactile hallucinations, and gustatory hallucinations, among which visual hallucinations are the most common form of manifestation, and a large proportion of mid-to-advanced PD patients report having VH symptoms . Visual hallucinations in Parkinson's disease have become a common clinical manifestation, which can lead to further increased functional impairment, depression and anxiety in patients. There are complex neural information transmissions, mutual influences and interactions in various brain regions that cause phantom VH in PD patients, resulting in more serious brain dysfunction.
已有研究基于磁共振成像技术(Magnetic Resonance Imaging，MRI)对帕金森疾病诊断及其运动症状具有相应相应MRI研究结果和诊断方法。相应的脑区、特别是运动皮层等的主要脑区的神经萎缩、缺失及交互作用做了较多的研究和已经具有相对成熟的测试方法。Existing studies based on magnetic resonance imaging (Magnetic Resonance Imaging, MRI) have corresponding MRI research results and diagnostic methods for the diagnosis of Parkinson's disease and its motor symptoms. Corresponding brain regions, especially the main brain regions such as the motor cortex, have done a lot of research on neural atrophy, loss and interaction, and have relatively mature testing methods.
目前亦有报道采用功能磁共振技术(functional MRI，fMRI)的测量分析方式检测帕金森神经病病(Parkinson′s di sease psychosis，PDP)方法，该方法基于多元/多体素VBM的分析方式，通过多元模式分析技术(multivariate pattern analys is，MVPA)，以监督学习的方式等机器学习算法识别人脑磁共振图像中的空间模式,实现大脑状态的解码,及对健康和患病脑的区分分析。亦有报道，阐述“静息态”fMRI帕金森幻视患者的脑区活动及脑区损伤情况和脑网络连接情况。At present, it is also reported that the measurement and analysis method of functional MRI (functional MRI, fMRI) is used to detect Parkinson's di seaase psychology (PDP). Multivariate pattern analysis (MVPA) uses machine learning algorithms such as supervised learning to identify spatial patterns in human brain magnetic resonance images, realize the decoding of brain states, and distinguish between healthy and diseased brains. It has also been reported that the brain activity, brain region damage and brain network connection of patients with "resting state" fMRI Parkinson's hallucinations have been described.
以上还没有形成单一针对非运动症状的基于fMRI大脑检测、并采用MVPA方式，通过对大脑体素VBM的分析方式，在“任务态”状态下，度量帕金森幻视(PDVH)脑区域神经功能、效应连接及功能性连接方法；缺少多组别“静息态”及“任务态”同时测量分析PDVH的成套程序方法；较少的看到采用“国际国内及行业认可的模式”形成一套PDVH的测量分析程序方法。The above has not yet formed a single fMRI-based brain detection for non-motor symptoms, and adopts the MVPA method to measure the neurological function of Parkinson's visual hallucinations (PDVH) brain regions in the "task state" by analyzing the brain voxel VBM , effect connection and functional connection methods; lack of multi-group "resting state" and "task state" simultaneous measurement and analysis of a complete set of procedures for PDVH; few see the use of "international, domestic and industry-approved models" to form a set PDVH measurement analysis procedure method.
因此，需要提出一种新的技术方案以改善上述技术问题。Therefore, a new technical solution needs to be proposed to improve the above technical problems.
发明内容Contents of the invention
针对现有技术中的缺陷，本发明的目的是提供一种脑区神经交互作用的测试分析度量程序方法及系统。Aiming at the defects in the prior art, the object of the present invention is to provide a method and system for testing, analyzing and measuring the neural interaction of brain regions.
根据本发明提供的一种脑区神经交互作用的测试分析度量程序方法，所述方法包括如下步骤：According to a method for testing, analyzing and measuring program of brain region neural interaction provided by the present invention, the method comprises the following steps:
步骤S1：将PDVH患者组、PD患者组与对照组确立筛选，经过测试达到标准要求，得到组群；Step S1: Establish and screen the PDVH patient group, PD patient group and control group, and after testing meet the standard requirements, obtain the group;
步骤S2：组群共同排除筛选方法与标准，排除干扰因素；Step S2: The group jointly excludes screening methods and standards, and eliminates interference factors;
步骤S3：组群认知评测方法与工具，采用测量工具与方法进行认知评测；Step S3: Group cognitive evaluation methods and tools, using measurement tools and methods for cognitive evaluation;
步骤S4：组群进行期待与视觉感知任务方法；Step S4: the method of performing anticipation and visual perception tasks in groups;
步骤S5：核磁共振检测条件及测试过程、设置；Step S5: NMR testing conditions, testing process, and settings;
步骤S6：组群进行视觉想象任务实施方法；Step S6: a method for implementing visual imagination tasks in groups;
步骤S7：基于体素的形态计量学VBM分析，采用相关工具箱软件对灰质进行全脑基于体素的形态计量学VBM分析，分析与VH程度相关的特异脑区，通过VBM全脑分析和ROI脑区PCS与VH相关度分析，寻找用以鉴别对真实世界和想象出的世界分辨的对应脑区；Step S7: voxel-based morphometric VBM analysis, using relevant toolbox software to perform whole-brain voxel-based morphometric VBM analysis on gray matter, and analyze specific brain regions related to the degree of VH, through VBM whole-brain analysis and ROI Correlation analysis between PCS and VH in the brain area, to find the corresponding brain area for distinguishing between the real world and the imagined world;
步骤S8：功能性连接FC分析，基于具有独立认知功能的感兴趣区域ROI脑区进行功能性连接FC分析，比较VH+、VH-以及健康对照组在基于已感知物体的记忆产生的视觉想象过程中脑区功能连接的区别；Step S8: Functional connection FC analysis, perform functional connection FC analysis based on ROI brain regions with independent cognitive functions, and compare the visual imagination process of VH+, VH- and healthy control groups based on the memory of perceived objects Differences in functional connectivity of midbrain regions;
步骤S9：分析结果图表，通过体素的形态计量学VBM分析及功能性连接FC分析，得出PD和PDVH患者脑区功能图及相关数据图表，得出PDVH关联脑区交互作用图。Step S9: Analyze the result chart, obtain the functional map of the brain regions and related data charts of PD and PDVH patients through voxel-based morphometric VBM analysis and functional connection FC analysis, and obtain the interaction map of PDVH-related brain regions.
优选地，所述步骤S1中的标准包括伴有VH症状的PD患者组VH+选择及标准、未伴有VH症状的PD患者组VH-选择及标准、健康控制组选择及标准。Preferably, the criteria in step S1 include VH+ selection and criteria for the PD patient group with VH symptoms, VH- selection and criteria for the PD patient group without VH symptoms, and healthy control group selection and criteria.
优选地，所述步骤S2中的干扰因素包括视觉受损矫正后仍无法完成测试者、患有严重内科疾病者、患有中枢神经系统疾病者、患有严重抑郁症、精神分裂症及长期服用精神类药物的患者、患有血管性痴呆者、有酒精依赖及其他精神活性物质滥用史的患者、磁共振扫描禁忌症患者、不能耐受MRI扫描环境者。Preferably, the interfering factors in step S2 include those who cannot complete the test after the visual impairment is corrected, those with serious medical diseases, those with central nervous system diseases, those with severe depression, schizophrenia, and long-term medication Patients with psychotropic drugs, patients with vascular dementia, patients with history of alcohol dependence and other psychoactive substance abuse, patients with MRI scan contraindications, and those who cannot tolerate MRI scan environment.
优选地，所述步骤S3中的测量工具与方法包括IQ测试、视觉想象丰富度测试、空间工作记忆测试、客体工作记忆测试及帕金森统一评分量表。Preferably, the measurement tools and methods in step S3 include IQ test, visual imagery richness test, spatial working memory test, object working memory test and Parkinson's Unified Rating Scale.
优选地，所述步骤S5中的磁共振检测条件分为结构相、静息态和任务态；数据由3.0T以上磁共振扫描仪采集完成，包括T1w、T2w和静息态。Preferably, the magnetic resonance detection conditions in step S5 are divided into structural phase, resting state and task state; the data is collected by a magnetic resonance scanner above 3.0T, including T1w, T2w and resting state.
本发明还提供一种脑区神经交互作用的测试分析度量程序系统，所述系统包括如下模块：The present invention also provides a test, analysis and measurement program system for neural interaction in brain regions, and the system includes the following modules:
模块M1：将PDVH患者组、PD患者组与对照组确立筛选，经过测试达到标准要求，得到组群；Module M1: Establish and screen the PDVH patient group, PD patient group and control group, and get the group after testing to meet the standard requirements;
模块M2：组群共同排除筛选系统与标准，排除干扰因素；Module M2: Group common elimination screening system and criteria, eliminating interference factors;
模块M3：组群认知评测系统与工具，采用测量工具与系统进行认知评测；Module M3: Group cognitive evaluation system and tools, using measurement tools and systems for cognitive evaluation;
模块M4：组群进行期待与视觉感知任务系统；Module M4: Group performance anticipation and visual perception task system;
模块M5：核磁共振检测条件及测试过程、设置；Module M5: NMR testing conditions, testing process and settings;
模块M6：组群进行视觉想象任务实施系统；Module M6: Group visual imagination task implementation system;
模块M7：基于体素的形态计量学VBM分析，采用相关工具箱软件对灰质进行全脑基于体素的形态计量学VBM分析，分析与VH程度相关的特异脑区，通过VBM全脑分析和ROI脑区PCS与VH相关度分析，寻找用以鉴别对真实世界和想象出的世界分辨的对应脑区；Module M7: voxel-based morphometric VBM analysis, using relevant toolbox software to perform whole-brain voxel-based morphometric VBM analysis on gray matter, and analyze specific brain regions related to the degree of VH, through VBM whole-brain analysis and ROI Correlation analysis between PCS and VH in the brain area, to find the corresponding brain area for distinguishing between the real world and the imagined world;
模块M8：功能性连接FC分析，基于具有独立认知功能的感兴趣区域ROI脑区进行功能性连接FC分析，比较VH+、VH-以及健康对照组在基于已感知物体的记忆产生的视觉想象过程中脑区功能连接的区别；Module M8: Functional connection FC analysis, based on the functional connection FC analysis of ROI brain regions with independent cognitive functions, comparing the visual imagination process of VH+, VH- and healthy control groups based on the memory of perceived objects Differences in functional connectivity of midbrain regions;
模块M9：分析结果图表，通过体素的形态计量学VBM分析及功能性连接FC分析，得出PD和PDVH患者脑区功能图及相关数据图表，得出PDVH关联脑区交互作用图。Module M9: Analyze the result charts. Through voxel-based morphometric VBM analysis and functional connectivity FC analysis, the functional map of the brain regions and related data charts of PD and PDVH patients are obtained, and the interaction map of the brain regions associated with PDVH is obtained.
优选地，所述模块M1中的标准包括伴有VH症状的PD患者组VH+选择及标准、未伴有VH症状的PD患者组VH-选择及标准、健康控制组选择及标准。Preferably, the criteria in the module M1 include VH+ selection and criteria for the PD patient group with VH symptoms, VH- selection and criteria for the PD patient group without VH symptoms, and healthy control group selection and criteria.
优选地，所述模块M2中的干扰因素包括视觉受损矫正后仍无法完成测试者、患有严重内科疾病者、患有中枢神经系统疾病者、患有严重抑郁症、精神分裂症及长期服用精神类药物的患者、患有血管性痴呆者、有酒精依赖及其他精神活性物质滥用史的患者、磁共振扫描禁忌症患者、不能耐受MRI扫描环境者。Preferably, the interfering factors in the module M2 include those who cannot complete the test after the visual impairment is corrected, those with serious medical diseases, those with central nervous system diseases, those with severe depression, schizophrenia, and long-term medication Patients with psychotropic drugs, patients with vascular dementia, patients with history of alcohol dependence and other psychoactive substance abuse, patients with MRI scan contraindications, and those who cannot tolerate MRI scan environment.
优选地，所述模块M3中的测量工具与系统包括IQ测试、视觉想象丰富度测试、空间工作记忆测试、客体工作记忆测试及帕金森统一评分量表。Preferably, the measurement tools and systems in the module M3 include IQ test, visual imagery richness test, spatial working memory test, object working memory test and Parkinson's Unified Rating Scale.
优选地，所述模块M5中的磁共振检测条件分为结构相、静息态和任务态；数据由3.0T以上磁共振扫描仪采集完成，包括T1w、T2w和静息态。Preferably, the magnetic resonance detection conditions in the module M5 are divided into structural phase, rest state and task state; the data is collected by a magnetic resonance scanner above 3.0T, including T1w, T2w and rest state.
与现有技术相比，本发明具有如下的有益效果：Compared with the prior art, the present invention has the following beneficial effects:
1、本发明可以伴幻视、未伴幻视的PD患者或其它干扰混淆PDVH组群以及健康人群等多为基础，同时进行测试比较分析，区别出非PD患者VH的脑区影响；1. The present invention can be based on PD patients with or without visual hallucinations or other interferences that confuse PDVH groups and healthy people, etc., and perform test comparison and analysis at the same time to distinguish the influence of brain regions of VH in non-PD patients;
2、本发明通过视觉想象与视觉感知的认知关系、记忆的视觉想象手法测试分析PDVH；2. The present invention tests and analyzes PDVH through the cognitive relationship between visual imagination and visual perception, and the visual imagination technique of memory;
3、本发明通过磁共振成像技术及体素计量学(VBM)、脑功能性连接(FC)分析等先进技术，形成一种对帕金森幻视脑结构、脑功能连接及交互作用情况进行测试分析度量方法；3. The present invention forms a method for testing Parkinson's visual hallucinations brain structure, brain functional connection and interaction through advanced technologies such as magnetic resonance imaging technology, voxel metrology (VBM), and brain functional connectivity (FC) analysis. Analytical measurement methods;
4、本发明通过此种方法可以寻找与PD患者中产生VH相关的脑结构、脑功能连接情况及交互作用，并根据脑状态情况推演PD发生、甚至度量PD发病程度；4. The present invention can find out the brain structure, brain function connection and interaction related to the generation of VH in PD patients through this method, and deduce the occurrence of PD according to the state of the brain, and even measure the incidence of PD;
5、本发明根据脑区PDVH脑区的相互影响，亦可能确认主要影响脑区及PD幻视的治疗靶点。5. According to the mutual influence of brain regions PDVH and brain regions, the present invention may also identify therapeutic targets that mainly affect brain regions and PD phantoms.
附图说明Description of drawings
通过阅读参照以下附图对非限制性实施例所作的详细描述，本发明的其它特征、目的和优点将会变得更明显：Other characteristics, objects and advantages of the present invention will become more apparent by reading the detailed description of non-limiting embodiments made with reference to the following drawings:
图1为本发明的方法流程框图；Fig. 1 is a method block diagram of the present invention;
图2为本发明的期待与视觉感知的实验范式图；Fig. 2 is the experimental paradigm diagram of expectation and visual perception of the present invention;
图3为本发明的视觉想象实验范式图；Fig. 3 is a visual imagination experiment paradigm figure of the present invention;
图4为本发明的基于的12个用于功能性连接分析的感兴趣区域ROI图；Fig. 4 is based on 12 regions of interest ROI diagrams for functional connectivity analysis based on the present invention;
图5为本发明的神经功能图；Fig. 5 is the nerve function figure of the present invention;
图6为本发明的交互作用图；Fig. 6 is an interaction diagram of the present invention;
图7为本发明的PDVH静息态脑区关联图；Fig. 7 is the correlation map of PDVH resting state brain area of the present invention;
图8为本发明的PDVH任务态脑区关联图。Fig. 8 is the correlative diagram of brain regions in PDVH task state of the present invention.
具体实施方式Detailed ways
下面结合具体实施例对本发明进行详细说明。以下实施例将有助于本领域的技术人员进一步理解本发明，但不以任何形式限制本发明。应当指出的是，对本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变化和改进。这些都属于本发明的保护范围。The present invention will be described in detail below in conjunction with specific embodiments. The following examples will help those skilled in the art to further understand the present invention, but do not limit the present invention in any form. It should be noted that those skilled in the art can make several changes and improvements without departing from the concept of the present invention. These all belong to the protection scope of the present invention.
实施例1：Example 1:
根据本发明提供的一种脑区神经交互作用的测试分析度量程序方法，所述方法包括如下步骤：According to a method for testing, analyzing and measuring program of brain region neural interaction provided by the present invention, the method comprises the following steps:
步骤S1：将PDVH患者组、PD患者组与对照组确立筛选，经过测试达到标准要求，得到组群；标准包括伴有VH症状的PD患者组VH+选择及标准、未伴有VH症状的PD患者组VH-选择及标准、健康控制组选择及标准。Step S1: Establish and screen the PDVH patient group, PD patient group, and control group. After testing to meet the standard requirements, the group is obtained; the standard includes VH+ selection and criteria for the PD patient group with VH symptoms, and PD patients without VH symptoms Group VH-selection and criteria, healthy control group selection and criteria.
步骤S2：组群共同排除筛选方法与标准，排除干扰因素；干扰因素包括视觉受损矫正后仍无法完成测试者、患有严重内科疾病者、患有中枢神经系统疾病者、患有严重抑郁症、精神分裂症及长期服用精神类药物的患者、患有血管性痴呆者、有酒精依赖及其他精神活性物质滥用史的患者、磁共振扫描禁忌症患者、不能耐受MRI扫描环境者。Step S2: Screening methods and criteria are excluded by the group together, and interference factors are excluded; interference factors include those who cannot complete the test after visual impairment correction, those with serious medical diseases, those with central nervous system diseases, and those with severe depression , patients with schizophrenia and long-term use of psychotropic drugs, patients with vascular dementia, patients with a history of alcohol dependence and other psychoactive substance abuse, patients with contraindications for MRI scanning, and those who cannot tolerate the MRI scanning environment.
步骤S3：组群认知评测方法与工具，采用测量工具与方法进行认知评测；测量工具与方法包括IQ测试、视觉想象丰富度测试、空间工作记忆测试、客体工作记忆测试及帕金森统一评分量表。Step S3: Group cognitive evaluation methods and tools, using measurement tools and methods for cognitive evaluation; measurement tools and methods include IQ test, visual imagery richness test, spatial working memory test, object working memory test and Parkinson's unified score scale.
步骤S4：组群进行期待与视觉感知任务方法。Step S4: The method of performing anticipation and visual perception tasks in groups.
步骤S5：核磁共振检测条件及测试过程、设置；磁共振检测条件分为结构相、静息态和任务态；数据由3.0T以上磁共振扫描仪采集完成，包括T1w、T2w和静息态。Step S5: NMR testing conditions, testing process, and settings; MRI testing conditions are divided into structural phase, resting state, and task state; data are collected by an MRI scanner above 3.0T, including T1w, T2w, and resting state.
步骤S6：组群进行视觉想象任务实施方法。Step S6: The implementation method of the visual imagination task in groups.
步骤S7：基于体素的形态计量学VBM分析，采用相关工具箱软件对灰质进行全脑基于体素的形态计量学VBM分析，分析与VH程度相关的特异脑区，通过VBM全脑分析和ROI脑区PCS与VH相关度分析，寻找用以鉴别对真实世界和想象出的世界分辨的对应脑区。Step S7: voxel-based morphometric VBM analysis, using relevant toolbox software to perform whole-brain voxel-based morphometric VBM analysis on gray matter, and analyze specific brain regions related to the degree of VH, through VBM whole-brain analysis and ROI Correlation analysis between PCS and VH in the brain area, looking for the corresponding brain area used to distinguish between the real world and the imagined world.
步骤S8：功能性连接FC分析，基于具有独立认知功能的感兴趣区域ROI脑区进行功能性连接FC分析，比较VH+、VH-以及健康对照组在基于已感知物体的记忆产生的视觉想象过程中脑区功能连接的区别。Step S8: Functional connection FC analysis, perform functional connection FC analysis based on ROI brain regions with independent cognitive functions, and compare the visual imagination process of VH+, VH- and healthy control groups based on the memory of perceived objects Differences in functional connectivity in midbrain regions.
步骤S9：分析结果图表，通过体素的形态计量学VBM分析及功能性连接FC分析，得出PD和PDVH患者脑区功能图及相关数据图表，得出PDVH关联脑区交互作用图。Step S9: Analyze the result chart, obtain the functional map of the brain regions and related data charts of PD and PDVH patients through voxel-based morphometric VBM analysis and functional connection FC analysis, and obtain the interaction map of PDVH-related brain regions.
本发明还提供一种脑区神经交互作用的测试分析度量程序系统，所述脑区神经交互作用的测试分析度量程序系统可以通过执行所述脑区神经交互作用的测试分析度量程序方法的流程步骤予以实现，即本领域技术人员可以将所述脑区神经交互作用的测试分析度量程序方法理解为所述脑区神经交互作用的测试分析度量程序系统的优选实施方式。The present invention also provides a test, analysis and measurement program system for the neural interaction in the brain region. The test, analysis and measurement program system for the neural interaction in the brain region can execute the process steps of the test, analysis and measurement program method for the neural interaction in the brain region. To be realized, those skilled in the art can understand the test, analysis and measurement program method of the neural interaction in the brain region as a preferred implementation of the test, analysis and measurement program system for the neural interaction in the brain region.
实施例2：Example 2:
本发明还提供一种脑区神经交互作用的测试分析度量程序系统，所述系统包括如下模块：The present invention also provides a test, analysis and measurement program system for neural interaction in brain regions, and the system includes the following modules:
模块M1：将PDVH患者组、PD患者组与对照组确立筛选，经过测试达到标准要求，得到组群；标准包括伴有VH症状的PD患者组VH+选择及标准、未伴有VH症状的PD患者组VH-选择及标准、健康控制组选择及标准。Module M1: Establish and screen the PDVH patient group, PD patient group and control group, and get the group after testing to meet the standard requirements; the standard includes the VH+ selection and standard for the PD patient group with VH symptoms, and the PD patients without VH symptoms Group VH-selection and criteria, healthy control group selection and criteria.
模块M2：组群共同排除筛选方法与标准，排除干扰因素；干扰因素包括视觉受损矫正后仍无法完成测试者、患有严重内科疾病者、患有中枢神经系统疾病者、患有严重抑郁症、精神分裂症及长期服用精神类药物的患者、患有血管性痴呆者、有酒精依赖及其他精神活性物质滥用史的患者、磁共振扫描禁忌症患者、不能耐受MRI扫描环境者。Module M2: Screening methods and criteria for group common exclusion, and exclude interfering factors; interfering factors include those who cannot complete the test after visual impairment correction, those with serious medical diseases, those with central nervous system diseases, and those with severe depression , patients with schizophrenia and long-term use of psychotropic drugs, patients with vascular dementia, patients with a history of alcohol dependence and other psychoactive substance abuse, patients with contraindications for MRI scanning, and those who cannot tolerate the MRI scanning environment.
模块M3：组群认知评测方法与工具，采用测量工具与方法进行认知评测；测量工具与方法包括IQ测试、视觉想象丰富度测试、空间工作记忆测试、客体工作记忆测试及帕金森统一评分量表。Module M3: Group cognitive evaluation methods and tools, using measurement tools and methods for cognitive evaluation; measurement tools and methods include IQ test, visual imagery richness test, spatial working memory test, object working memory test and Parkinson's unified score scale.
模块M4：组群进行期待与视觉感知任务方法。Module M4: Group approach to anticipation and visual perception tasks.
模块M5：核磁共振检测条件及测试过程、设置；磁共振检测条件分为结构相、静息态和任务态；数据由3.0T以上磁共振扫描仪采集完成，包括T1w、T2w和静息态。Module M5: NMR testing conditions, testing process, and settings; MRI testing conditions are divided into structural phase, resting state, and task state; data are collected by an MRI scanner above 3.0T, including T1w, T2w, and resting state.
模块M6：组群进行视觉想象任务实施方法。Module M6: Methods of implementing visual imagination tasks in groups.
模块M7：基于体素的形态计量学VBM分析，采用相关工具箱软件对灰质进行全脑基于体素的形态计量学VBM分析，分析与VH程度相关的特异脑区，通过VBM全脑分析和ROI脑区PCS与VH相关度分析，寻找用以鉴别对真实世界和想象出的世界分辨的对应脑区。Module M7: voxel-based morphometric VBM analysis, using relevant toolbox software to perform whole-brain voxel-based morphometric VBM analysis on gray matter, and analyze specific brain regions related to the degree of VH, through VBM whole-brain analysis and ROI Correlation analysis between PCS and VH in the brain area, looking for the corresponding brain area used to distinguish between the real world and the imagined world.
模块M8：功能性连接FC分析，基于具有独立认知功能的感兴趣区域ROI脑区进行功能性连接FC分析，比较VH+、VH-以及健康对照组在基于已感知物体的记忆产生的视觉想象过程中脑区功能连接的区别。Module M8: Functional connection FC analysis, based on the functional connection FC analysis of ROI brain regions with independent cognitive functions, comparing the visual imagination process of VH+, VH- and healthy control groups based on the memory of perceived objects Differences in functional connectivity in midbrain regions.
模块M9：分析结果图表，通过体素的形态计量学VBM分析及功能性连接FC分析，得出PD和PDVH患者脑区功能图及相关数据图表，得出PDVH关联脑区交互作用图。Module M9: Analyze the result charts. Through voxel-based morphometric VBM analysis and functional connectivity FC analysis, the functional map of the brain regions and related data charts of PD and PDVH patients are obtained, and the interaction map of the brain regions associated with PDVH is obtained.
实施例3：Example 3:
本发明以伴幻视、未伴幻视的PD患者以及健康人群为基础，通过视觉想象与视觉感知的认知关系、记忆的视觉想象磁共振成像技术及体素计量学(VBM)、脑功能性连接(FC)分析等先进技术，形成一种对帕金森幻视脑结构、脑功能连接及交互作用情况进行测试分析度量方法。The present invention is based on PD patients with or without visual hallucinations and healthy people, through the cognitive relationship between visual imagination and visual perception, visual imagery magnetic resonance imaging technology of memory, voxel-based metrology (VBM), brain function Advanced technologies such as sexual connectivity (FC) analysis have formed a method for testing, analyzing and measuring the brain structure, brain functional connectivity and interaction of Parkinson's phantom hallucinations.
本发明通过此种方法可以寻找与PD患者中产生VH相关的脑结构、脑功能连接情况及交互作用，并根据脑状态情况推演PD发生、甚至度量PD发病程度；根据脑区PDVH脑区的相互影响，亦可能确认主要影响脑区及PD幻视的治疗靶点。The present invention can find out the brain structure, brain function connection and interaction related to the generation of VH in PD patients through this method, and deduce the occurrence of PD according to the brain state, and even measure the degree of PD incidence; impact, and may also identify therapeutic targets that primarily affect brain regions and visual hallucinations in PD.
帕金森病幻视的脑神经功能连接及各脑区神经交互作用的测试分析度量方法总流程框图如图1所示。Figure 1 shows the overall flow chart of the test, analysis and measurement method for the functional connection of brain nerves and the neural interaction of various brain regions for visual hallucinations in Parkinson's disease.
PDVH患者组、PD患者组与对照组确立筛选：选择VH患者、及PD患者及健康对照者至少3组(亦可根据情况选择3组以上)，每组人数50人。并经过相关测试达到标准要求。Establish screening of PDVH patient group, PD patient group and control group: select at least 3 groups of VH patients, PD patients and healthy controls (more than 3 groups can be selected according to the situation), with 50 people in each group. And passed relevant tests to meet the standard requirements.
伴有VH症状的PD患者组(VH+)选择及标准：满足英国脑库帕金森症(the UnitedKingdom Parkinson’s Disease Society Brain Bank)的标准；通过新版国际运动障碍学会统一帕金森症评定量表中的第二个问题“是否有主要感官体验(视觉、听觉、触觉、嗅觉和味觉)的幻觉？”回答“有”，且通过进一步询问证实只有单一幻视体验(无论幻视的程度)；通过蒙特利尔认知评估(the Montreal Cognitive Assessment,MoCA)，评分≥26,排除痴呆的可能；通过2005年提出的最新DLB诊断标准(DLBC-3),排除路易体痴呆(dementia withLewy bodies,DLB)的可能；通过Hamilton汉密尔顿焦虑量表(HAMA)评分<7分，和Hamilton汉密尔顿抑郁量表17项(HAMD17)评分≤7分，排除焦虑症和抑郁症的可能；受教育年限≥9年；有足够的视觉和听觉水平，以完成研究必需的检查和实验；排除有严重躯体疾病患者，精神活性物质滥用者，自杀企图者，孕妇或哺乳期女性；签署知情同意书。Selection and criteria for the PD patient group with VH symptoms (VH+): meet the criteria of the United Kingdom Parkinson's Disease Society Brain Bank; The second question "Do you have hallucinations of major sensory experiences (vision, hearing, touch, smell, and taste)?" Answer "Yes", and further questioning confirms that there is only a single hallucination experience (regardless of the degree of hallucination); The Montreal Cognitive Assessment (MoCA), with a score ≥ 26, ruled out the possibility of dementia; passed the latest DLB diagnostic criteria (DLBC-3) proposed in 2005, ruled out the possibility of dementia with Lewy bodies (DLB); passed Hamilton Anxiety Scale (HAMA) score < 7 points, and Hamilton Depression Scale 17 (HAMD17) score ≤ 7 points, excluding the possibility of anxiety and depression; years of education ≥ 9 years; sufficient visual and Auditory level to complete the necessary examinations and experiments for the study; exclude patients with serious physical diseases, psychoactive substance abusers, suicide attempters, pregnant or breastfeeding women; sign informed consent.
未伴有VH症状的PD患者组(VH-)选择及标准：满足英国脑库帕金森病(the UnitedKingdom Parkinson’s Disease Society Brain Bank)的标准；通过新版国际运动障碍学会统一帕金森病评定量表中的第二个问题“是否有主要感官体验(视觉、听觉、触觉、嗅觉和味觉)的幻觉？”回答“没有”的PD患者；通过蒙特利尔认知评估(the Montreal CognitiveAssessment,MoCA)，评分≥26,排除痴呆的可能；通过2005年提出的最新DLB诊断标准(DLBC-3),排除路易体痴呆(dementia with Lewy bodies,DLB)的可能；通过Hamilton汉密尔顿焦虑量表(HAMA)评分<7分，和Hamilton汉密尔顿抑郁量表17项(HAMD17)评分≤7分，排除焦虑症和抑郁症的可能；受教育年限≥9年；有足够的视觉和听觉水平，以完成研究必需的检查和实验；排除有严重躯体疾病患者，精神活性物质滥用者，自杀企图者，孕妇或哺乳期女性；签署知情同意书。Selection and criteria of PD patients without VH symptoms (VH-): meet the criteria of the United Kingdom Parkinson's Disease Society Brain Bank; The second question of "Do you have hallucinations of major sensory experiences (vision, hearing, touch, smell, and taste)?" PD patients who answered "no"; passed the Montreal Cognitive Assessment (MoCA), score ≥26 , to exclude the possibility of dementia; through the latest DLB diagnostic criteria (DLBC-3) proposed in 2005, to exclude the possibility of dementia with Lewy bodies (DLB); through the Hamilton Anxiety Scale (HAMA) score < 7 points, and Hamilton Depression Rating Scale 17 (HAMD17) score ≤ 7 points, exclude the possibility of anxiety and depression; years of education ≥ 9 years; have sufficient visual and auditory levels to complete the necessary examinations and experiments for the study; exclude Patients with serious physical diseases, psychoactive substance abusers, suicide attempters, pregnant or breastfeeding women; signed informed consent.
健康控制组选择及标准：通过简明国际神经精神访谈中文版(Mini-International Neuropsychiatric Interview,MINI)定式检查，排除患有精神障碍的可能；Hamilton汉密尔顿焦虑量表(HAMA)评分<7分；Hamilton汉密尔顿抑郁量表17项(HAMD17)评分≤7分；受教育年限≥9年；有足够的视觉和听觉水平，以完成研究必需的检查和实验；排除有严重躯体疾病患者，精神活性物质滥用者，自杀企图者，孕妇或哺乳期女性；签署知情同意书。Selection and standards of the healthy control group: the possibility of suffering from mental disorders was ruled out through the Chinese version of the Mini-International Neuropsychiatric Interview (MINI); the Hamilton Anxiety Scale (HAMA) score was <7 points; Depression Scale 17 (HAMD17) score ≤ 7 points; years of education ≥ 9 years; sufficient visual and auditory levels to complete the necessary examinations and experiments for the study; exclude patients with serious physical diseases, psychoactive substance abusers, Suicide attempters, pregnant or breastfeeding women; signed informed consent.
组群共同排除筛选方法与标准：组群共同排除一些干扰因素；视觉受损矫正后仍无法完成测试者；严重内科疾病，如高血压、心脏病、重症肝病等；中枢神经系统疾病，如脑血管疾病、感染性脑病、脑肿瘤等；严重抑郁症、精神分裂症及长期服用精神类药物的患者；血管性痴呆；有酒精依赖及其他精神活性物质滥用史；磁共振扫描禁忌症患者，如体内有金属植入物者，如心脏起搏器、人工股骨头、骨折术后体内留有钢钉者、体内残留金属片者等；不能耐受MRI扫描环境者，如幽闭恐惧症患者。Screening methods and criteria for group common exclusion: group common exclusion of some interfering factors; those who cannot complete the test after visual impairment correction; serious medical diseases, such as hypertension, heart disease, severe liver disease, etc.; central nervous system diseases, such as cerebral palsy Vascular disease, infectious encephalopathy, brain tumor, etc.; patients with severe depression, schizophrenia and long-term use of psychotropic drugs; vascular dementia; history of alcohol dependence and other psychoactive substance abuse; patients with MRI scan contraindications, such as People with metal implants in the body, such as cardiac pacemakers, artificial femoral heads, steel nails left in the body after fracture, and metal pieces left in the body, etc.; people who cannot tolerate the MRI scanning environment, such as claustrophobic patients.
组群认知评测方法与工具：采用5种国际及国内标准的或行业认可的测量工具与方法进行认知评测。Group cognitive evaluation methods and tools: 5 kinds of international and domestic standard or industry-recognized measurement tools and methods are used for cognitive evaluation.
IQ测试：Wechsler Abbreviated Scale of Intelligence(WASI)第三版；IQ test: Wechsler Abbreviated Scale of Intelligence (WASI) third edition;
视觉想象丰富度：Vividness of Visual Imagery Questionnaire(VVIQ)；Visual imagination richness: Vividness of Visual Imagery Questionnaire (VVIQ);
空间工作记忆：Crosi Block Tapping；Spatial working memory: Crosi Block Tapping;
客体工作记忆：n-back；Object working memory: n-back;
帕金森统一评分量表(unified Parkinson’s disease rating scale,UPDRS)和Hoehn-Yahr分级(H-Y stage)，用以判断PD进程。Unified Parkinson's disease rating scale (UPDRS) and Hoehn-Yahr classification (H-Y stage) are used to judge the progress of PD.
核磁共振检测条件及测试过程、设置：磁共振检测分结构相、静息态和任务态。数据由3.0T以上磁共振扫描仪采集完成，包括T1w、T2w、静息态等。T1-weighted：磁化准备快速梯度回波MP-RAGE，重复时间TR＝1980ms，回波时间TE＝4.3ms，反转时间TI＝1100ms，翻转角FA＝15°，视野FOV＝256mm*256mm*176mm，体素大小voxel size:1mm*1mm*1mm，轴位连续扫描176层。运用GRAPPA算法并行(因子设为2)采集图像。T2-weighted：重复时间TR＝3200ms，回波时间TE＝224ms，视野FOV＝256mm，体素大小voxel size：1mm*1mm*1mm，轴位连续扫描176层。运用GRAPPA算法(因子设为2)并行采集图像。静息态和任务态：重复时间TR＝3000ms,回波时间TE＝32ms,翻转角FA＝90度,视野FOV＝220mm,interslice gap＝0.4mm，体素大小voxel size：3.9mm*3.9mm*4mm，轴位连续扫描32层。静息态扫描时间7分钟。NMR testing conditions, testing process, and settings: Magnetic resonance testing is divided into structural phase, resting state, and task state. The data were collected by a magnetic resonance scanner above 3.0T, including T1w, T2w, resting state, etc. T1-weighted: magnetization preparation for rapid gradient echo MP-RAGE, repetition time TR = 1980ms, echo time TE = 4.3ms, inversion time TI = 1100ms, flip angle FA = 15°, field of view FOV = 256mm*256mm*176mm , voxel size: 1mm*1mm*1mm, continuous axial scanning of 176 layers. Images were acquired in parallel (factor set to 2) using the GRAPPA algorithm. T2-weighted: repetition time TR = 3200ms, echo time TE = 224ms, field of view FOV = 256mm, voxel size: 1mm*1mm*1mm, axial continuous scanning 176 layers. Images were acquired in parallel using the GRAPPA algorithm (factor set to 2). Resting state and task state: repetition time TR=3000ms, echo time TE=32ms, flip angle FA=90 degrees, field of view FOV=220mm, interslice gap=0.4mm, voxel size: 3.9mm*3.9mm* 4mm, continuous axial scanning of 32 layers. The resting state scanning time is 7 minutes.
组群期待与视觉感知任务方法：在核磁扫描前，各群组人员在电脑上先熟悉实验程序。练习时的视觉刺激将选用与正式实验不同的4x 4矩阵。Group expectation and visual perception task method: Before the MRI scan, each group of people familiarized themselves with the experimental procedure on the computer. The visual stimuli for practice will use a different 4x4 matrix than the formal experiment.
采用的范式为(改编自Kok等关于期待对感知影响)的实验范式。(如图2)受试者被告知他们会听到一个听觉提示，不同音频对应不同开口方向的视觉刺激。低频(500Hz)对应竖直方向顺时针方45°的图片，高频(1000Hz)对应竖直方向向顺时针方向135°的图片。他们在实验中的任务是对每个trail里屏幕上看到的第一个图形顺时针旋转90度。在实际试验中，听觉提示保证在75％效度，即在屏幕上出现的第一个视觉刺激由75％概率与提示音保持一致。当随后的probe出现在屏幕上时，受试者需要作出判断，它是不是第一个图形顺时针90度后所呈的图形。The paradigm used was (adapted from the experimental paradigm of Kok et al. on the effect of expectation on perception). (Figure 2) The subjects were told that they would hear an auditory cue, and that different audios corresponded to visual stimuli in different opening directions. The low frequency (500Hz) corresponds to the picture at 45° clockwise in the vertical direction, and the high frequency (1000Hz) corresponds to the picture at 135° clockwise in the vertical direction. Their task in the experiment was to rotate 90 degrees clockwise the first figure seen on the screen in each trail. In the actual test, the auditory prompt guarantees 75% validity, that is, the first visual stimulus that appears on the screen is consistent with the prompt tone by 75% probability. When the subsequent probe appeared on the screen, the subjects needed to make a judgment whether it was the figure presented after the first figure was clockwise 90 degrees.
组群视觉想象任务实施方法：受试者在进入核磁扫描仪之前，在电脑上先熟悉实验程序。练习时的视觉刺激与正式实验时不同。The implementation method of the group visual imagination task: the subjects were familiar with the experimental procedures on the computer before entering the MRI scanner. The visual stimuli during practice were different from those during the formal experiment.
实验范式是根据Dijkstra等人研究中所用实验范式改编而成，如图3所示，屏幕上首先出现第一个视觉刺激持续400ms,跟随第二个视觉刺激(400ms),受试者需要根据后置的想象提示“1”或者“2”(持续400ms)，在脑中映射出第一或第二个视觉刺激的形象并随后就所呈现画面的丰富性打分(1-4)。The experimental paradigm was adapted from the experimental paradigm used in the study by Dijkstra et al. As shown in Figure 3, the first visual stimulus first appeared on the screen and lasted for 400ms, followed by the second visual stimulus (400ms). Set the imaginary cue "1" or "2" (duration 400ms), mentally map the image of the first or second visual stimulus and then score the richness of the presented picture (1-4).
基于体素的形态计量学(VBM)分析：采用SPM8(Wellcome Trust Centre forNeuroimaging,London,UK)中VBM8工具箱对灰质体积进行全脑基于体素的形态计量学分析(voxel-based morphometry analysis,VBM)，分析与VH程度相关的特异脑区。通过VBM全脑分析和ROI脑区PCS与VH相关度分析，寻找人们用以鉴别对真实世界和想象出的世界分辨的对应脑区。Voxel-based morphometry (VBM) analysis: Whole-brain voxel-based morphometry analysis (VBM) was performed on gray matter volume using the VBM8 toolbox in SPM8 (Wellcome Trust Center for Neuroimaging, London, UK). ), to analyze the specific brain regions associated with the degree of VH. Through VBM whole-brain analysis and ROI brain region PCS and VH correlation analysis, the corresponding brain regions that people use to distinguish between the real world and the imagined world are found.
功能性连接(FC)分析：基于12个具有独立认知功能的感兴趣区域(ROI)脑区进行功能性连接(functional connectivity,FC)分析，比较VH+，VH-(伴有VH(PD-VH+)、未伴有VH症状的PD患者(PD-VH-))以及健康对照组在基于已感知物体的记忆产生的视觉想象过程中脑区功能连接的区别。具体12个ROI请见图4。Functional connectivity (FC) analysis: Based on 12 regions of interest (ROI) brain regions with independent cognitive functions, the functional connectivity (FC) analysis was performed to compare VH+, VH- (with VH (PD-VH+ ), PD patients without VH symptoms (PD-VH-)), and healthy controls differed in the functional connectivity of brain regions during visual imagination based on memory of perceived objects. Please refer to Figure 4 for the specific 12 ROIs.
分析结果图表：通过体素的形态计量学(VBM)分析及功能性连接(FC)分析，得出PD和PDVH患者脑区功能图及相关数据图表，同时亦得出PDVH关联脑区交互作用图。可以形象的用相关图表示试例如下(图5、6及图7、8)Analysis result chart: through voxel morphometric (VBM) analysis and functional connectivity (FC) analysis, the functional map of brain regions and related data charts of PD and PDVH patients are obtained, and the interaction map of PDVH-related brain regions is also obtained . The examples that can be represented vividly with correlation diagrams are as follows (Figure 5, 6 and Figure 7, 8)
图5明确表明静息态或任务态的脑区活动(增加或减少)状态，图6通过分析找出了脑区影响的先后顺序(时序)及脑区位置区域，图7、8表明静息态和任务态时脑区关联状态。根据脑区PDVH脑区的相互影响及PDVH与PD比较VH活动脑区及其影响。亦能确认主要影响脑区及治疗靶点。Figure 5 clearly shows the state of brain area activity (increase or decrease) in the resting state or task state. Figure 6 finds out the sequence (timing) and location of the brain area through analysis. Figures 7 and 8 show that the resting state Brain area association state during state and task state. According to the interaction of brain regions PDVH brain regions and the comparison of VH activity brain regions and their influence between PDVH and PD. It can also confirm the main affected brain regions and therapeutic targets.
本发明可以伴幻视、未伴幻视的PD患者或其它干扰混淆PDVH组群以及健康人群等多为基础，同时进行测试比较分析。区别出非PD患者VH的脑区影响；通过视觉想象与视觉感知的认知关系、记忆的视觉想象手法测试分析PDVH；通过磁共振成像技术及体素计量学(VBM)、脑功能性连接(FC)分析等先进技术，形成一种对帕金森幻视脑结构、脑功能连接及交互作用情况进行测试分析度量方法；通过此种方法可以寻找与PD患者中产生VH相关的脑结构、脑功能连接情况及交互作用，并根据脑状态情况推演PD发生、甚至度量PD发病程度；根据脑区PDVH脑区的相互影响，亦可能确认主要影响脑区及PD幻视的治疗靶点。The present invention can be based on PD patients with or without visual hallucinations, or other interference and confusion PDVH groups, healthy people, etc., and simultaneously perform test comparison and analysis. Distinguish the influence of VH brain regions in non-PD patients; analyze the PDVH through the cognitive relationship between visual imagination and visual perception, and the visual imagination technique test of memory; FC) analysis and other advanced technologies to form a method for testing, analyzing and measuring the brain structure, brain functional connectivity and interaction of Parkinson's hallucinations; through this method, it is possible to find the brain structure and brain function related to the generation of VH in PD patients Connectivity and interaction, and deduce the occurrence of PD according to the brain state, and even measure the incidence of PD; according to the interaction of brain regions PDVH and brain regions, it is also possible to identify therapeutic targets that mainly affect brain regions and PD phantoms.
本领域技术人员可以将本实施例理解为实施例1、实施例2的更为具体的说明。Those skilled in the art may understand this embodiment as a more specific description of Embodiment 1 and Embodiment 2.
本领域技术人员知道，除了以纯计算机可读程序代码方式实现本发明提供的系统及其各个装置、模块、单元以外，完全可以通过将方法步骤进行逻辑编程来使得本发明提供的系统及其各个装置、模块、单元以逻辑门、开关、专用集成电路、可编程逻辑控制器以及嵌入式微控制器等的形式来实现相同功能。所以，本发明提供的系统及其各项装置、模块、单元可以被认为是一种硬件部件，而对其内包括的用于实现各种功能的装置、模块、单元也可以视为硬件部件内的结构；也可以将用于实现各种功能的装置、模块、单元视为既可以是实现方法的软件模块又可以是硬件部件内的结构。Those skilled in the art know that, in addition to realizing the system provided by the present invention and its various devices, modules, and units in a purely computer-readable program code mode, the system provided by the present invention and its various devices can be completely programmed by logically programming the method steps. , modules, and units implement the same functions in the form of logic gates, switches, ASICs, programmable logic controllers, and embedded microcontrollers. Therefore, the system and its various devices, modules, and units provided by the present invention can be regarded as a hardware component, and the devices, modules, and units included in it for realizing various functions can also be regarded as hardware components. The structure; the devices, modules, and units for realizing various functions can also be regarded as not only the software modules for realizing the method, but also the structures in the hardware components.
以上对本发明的具体实施例进行了描述。需要理解的是，本发明并不局限于上述特定实施方式，本领域技术人员可以在权利要求的范围内做出各种变化或修改，这并不影响本发明的实质内容。在不冲突的情况下，本申请的实施例和实施例中的特征可以任意相互组合。Specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art may make various changes or modifications within the scope of the claims, which do not affect the essence of the present invention. In the case of no conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.
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