基底神经节参与中文书写
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摘要
研究背景
基底神经节(Basal ganglia,BG)是位于双侧大脑半球深部的灰质核团,主要由尾状核、壳核、苍白球、屏状核等组成。根据目前人类对动物进化过程的研究,发现纹状体的发育在大脑皮质之前,一开始,基底神经节控制各种运动功能,大脑皮质受纹状体的控制。但随着大脑皮质的进化与功能完善,大脑皮质逐渐掌握对运动功能的控制,基底神经节则成为在运动皮质管理下参与运动控制的结构,属于从属地位。但是,近年来的研究发现,人类基底神经节的功能不仅仅是接受运动皮质管理,参与运动控制的结构,还是一个与其他功能皮质(特别是前额叶)组成神经回路,参与语言、计划、执行等高级神经功能的结构。这些回路一般由相关脑区皮质发出,经尾状核投射到苍白球,再经背侧丘脑返回到发出原始信号的皮质。现代功能影像学技术已经对此进行了验证。
语言与大脑定位之间的关系一直是研究者关心的热点之一,在人们已经明确了语言的皮质功能区定位后,位于皮质下的基底神经节在语言处理中担当什么样的角色逐渐成为学术界关心的问题。首先,神经病学家发现在人类中以基底神经节损害为主的一些中枢神经系统疾病,如帕金森病(Parkinson's disease,PD)、亨廷顿病(Huntington's disease,HD)、肝豆状核变性(Wilson's disease,WD)、基底神经节区卒中、皮质基底神经节变性等,可以导致不同形式的语言障碍等高级神经功能改变。其次,神经语言学家在关于基底神经节损害患者的语言处理的研究中,发现此类患者存在不同的语言结构层次的语言障碍。
书写与言语一样,是语言在经过一系列处理后的一种表达形式,所不同的是书写是需要借助肢体或工具实施语言计划的行为过程,而言语主要通过控制发音器官完成语言输出。通过书写行为进行交流和创作是人类一种独特的能力,它不仅是语言功能的一种体现,而且涉及到听觉、视觉、记忆、视空间能力、运用和运动功能等诸多因素,依赖于广泛的神经网络。在以往关于书写功能的神经心理学研究中,一方面集中于基底神经节的口语处理功能,另一方面着眼于大脑皮质与书写功能的关系。对基底神经节书写功能的系统研究较少,而且证据主要来源于以拼音文字为母语的人群。然而,汉字属于表意文字,在形、音、义的特点上与拼音文字相差甚远,其书写过程也更加复杂。另外,由于研究目的的不同、研究内容的不同(字词、语句)、研究手段的不同等多种因素的影响,使得研究结论存在差异。因此,对基底神经节参与书写功能的研究,有必要进一步寻找来自于汉语人群的证据,以丰富这一结论的内涵。
目前已有国内外学者以PD、HD为研究对象,探讨基底神经节损害对语言功能的影响。而同样是伴有基底神经节损害的WD患者,其书写过程是否支持基底神经节参与书写的学说呢?本研究以伴有基底神经节损害的WD患者为研究对象,通过中文书写检查法评价受试者语言性书写障碍情况和非语言性书写障碍情况,然后将受试者分为书写正常组和书写障碍组,分别进行正电子发射型计算机断层显像(positron emission tomography,PET)功能影像检查,得到基底神经节在中文书写时的功能影像数据。进而,从临床行为、形态结构和物质代谢三方面,分析脑型WD患者中文书写障碍的特点,确定基底神经节在中文书写中的作用,并探讨其神经心理学机制。
研究目的
分析脑型WD患者中文书写障碍的特点,分析在中文字词书写状态下脑型WD患者脑部的功能影像变化,从临床行为、形态结构和物质代谢三方面,确定基底神经节在脑型WD患者的中文书写中发挥的作用,并探讨其神经心理学机制,进而为基底神经节在语言功能中的作用提供有力的支持。
研究对象
连续收集2007年5月至2009年1月在南方医科大学南方医院和中山大学附属第一医院门诊及住院的60例脑型WD患者参加本研究,其中,征得7例男性患者的同意,参加脑功能影像学检查。受试者母语均为汉语,年龄20.68±7.23岁,受教育年限9.57±2.75年,均为右利手,其中男性44例,女性16例。均接受6个月以上的排铜治疗(限铜饮食,口服青霉胺、锌剂)。所有受试者均排除失认、失用、忽视、抑郁、焦虑、精神症状、除WD以外的中枢神经系统疾病及药物和酒精滥用史。
研究方法
1.采用汉语失写检查法(Chinese Agraphia Battery,CAB)对60例脑型WD患者进行中文书写检查。根据失写指数(agraphia quotient,AgQ),将受试者分为书写正常组和书写障碍组。采用社会科学统计软件包(statistical package forsocial sciences.SPSS)13.0统计软件,对WD书写正常组与书写障碍组在年龄、性别、受教育程度、病程、CAB得分的组间资料统计采用两独立样本t检验。分析书写障碍组中的语言性书写障碍情况及非语言性书写障碍情况,得到脑型WD患者中文书写的定量和定性资料。
2.按照CAB的AgQ,将7例男性脑型WD患者分为书写正常组4例和书写障碍组3例。采用PET,以18-氟脱氧葡萄糖(~(18)F-fluorodeoxyglucose,~(18)F-FDG)为示踪剂,在予以书写刺激任务后进行头部扫描,共扫描2次,第一次为假写作业,第二次为中文字词书写作业。假写作业为在稿纸空格内逐格划斜线;中文字词书写作业为在稿纸上书写中文,内容为实义名词,如地名、颜色、动物等。PET-CT头部扫描后,分别得到书写正常组假写和中文字词书写的图像数据,书写障碍组假写和中文字词书写的图像数据。用统计参数图软件包(StatisticalParametric Mapping 2,SPM2)对两次作业的图像数据进行两独立样本t检验分析,获得与中文字词产生相关的基底神经节~(18)F-FDG的激活区数据,从而分别获得脑型WD患者书写正常组和书写障碍组的与中文书写相关脑区的功能定位资料。
结果
1.60例脑型WD患者中36例患者出现书写障碍(60%),以主动书写成绩最差,其它依次为看图书写、听写、自动书写和抄写。
2.60例脑型WD患者中25例患者出现语言性书写障碍(41.7%),15例患者出现非语言性书写障碍(25%)。其中存在多种书写障碍类型并存的现象。
3.在语言性书写障碍的患者中,构字障碍20例,字词错写11例,语法错误3例;在非语言性书写障碍的患者中,小写症8例,震颤性书写7例,重复性书写2例。
4.正常书写组脑型WD患者的皮质下结构激活区包括双侧苍白球和右侧壳核,书写障碍组脑型WD患者的皮质下结构激活区包括右侧丘脑腹外侧核、屏状核和左侧壳核、苍白球。
结论
1.书写障碍是脑型肝豆状核变性的常见症状(60%),语言性书写障碍多于非语言性书写障碍,其中以构字障碍最多见;
2.书写正常的脑型肝豆状核变性患者,双侧基底神经节均参加了中文字词书写过程,其中右侧基底神经节在中文书写中发挥了更重要的作用;
3.书写障碍的脑型肝豆状核变性患者,由于病变损害程度和损害部位不尽相同,双侧基底神经节激活程度存在较大差异,右侧丘脑的激活可能与代偿机制有关。
Background
The basal ganglia (BG) belong to nuclei of gray matter deep within the cerebral hemispheres, which include the caudate nucleus, the putamen, the dorsal thalamus and the globus pallidus. During the evolution of species, the BG is turning from a motor control center in Aves to a structure being subject to the motor cortex in mammal, especially in primate. Recently, some studies revealed the BG in human is not only under control in the motor cortex, but also is a structure involving in many cognitive capacities, such as language, plan, execution function.
While the role of cortical areas in linguistic processing is relatively well established, the role of the BG and the way they impact language processing are still controversial. Neurologists found that some diseases related to the BG damage, such as Parkinson's disease (PD), Huntington's disease (HD), Wilson's disease (WD), the basal ganglia with vascular damage and corticobasal degeneration are manifested with various kinds of language disorders. And studies by neurolinguists using patients sustaining BG damage have suggested the BG is involved in various aspects of language comprising phonology and syntax.
Writing, which is implemented by limbs or tools, is one kind of language process. It not only needs competence of language processing but also needs help of visual, auditory, visual space, motor and so on. English, belongings to alphabetic writing systems, is a main material in former study, whereas, Chinese characters, belongings to logographic writing systems, are often semantic-phonetic compounds, symbols which include an element that represents the meaning and element that represents the pronunciation. As each character represents a single word, Chinese writing is more complex than English. The difference between the two languages is from the structure of word to figure-sound relation and figure-meaning relation. So it is necessary to study the process of Chinese writing.
Most of the subjects of language study with the BG damage are PD and HD. Whether the writing process of WD with the BG damage is the same as PD and HD? Few studies on WD were done, especially in Chinese characters. The present study proposed that WD with the BG damage influences the process of Chinese writing through the analysis of the Chinese agraphia battery (CAB) and a functional neuroimaging examination of PET-CT. The present study is to analyze roles of the BG in Chinese writing and to explore its neuropsychological mechanism, by investigating features of agaphia of WD with the BG damage and the data of functional imaging of Chinese writing.
Object
The present study is to investigate features of agaphia of WD with the BG damage, to investigate the data of functional imaging of Chinese writing, to analyze roles of the BG in Chinese writing and to explore its neuropsychological mechanism.
Material
We studied sixty patients with WD with brain damage and seven male patients joined the study of functional imaging. All patients were Chinese speaking, 23.68±7.23 years old, educated in 9.57±2.75 years and both right handedness, included forty four male and sixteen female. All patients accepted treatment above six months (dietary therapy, penicillamine, zinc). Only individuals with no history of psychiatric or neurological disease other than WD, as well as no agnosia, apraxia, neglect, depression and anxiety, no history of alcohol or drug abuse were included.
Methods
1. The Chinese agraphia battery (CAB) was used to identify agraphia in sixty patients with WD. According to agraphia quotient (AgQ) scores, all patients were divided into normal writing group and agraphia group and their types of agraphia were identified. Data were analyzed with statistical package for social sciences 13.0 (SPSS13.0).
2. Seven male patients were divided into two groups through language evaluation which were normal writing group and agraphia group. They were scanned by positron emission tomography (PET) respectively while performing two tasks: 1) pseudo-writing, 2) Chinese character writing (ie. names, color, animals). Data were analyzed with Statistical Parametric Mapping 2 (SPM2) for "Chinese character writing versus pseudo writing".
Results
1. Agraphia was identified in thirty-six cases (60%) and the patients had difficulty in positive writing, writing by picture, dictation, automatic writing and copying (in descending order of severity).
2. Language agraphia and non-language agraphia were detected in twenty-five cases (41.7%) and fifteen (25%) respectively, and some cases were detected with both kinds of agraphia.
3. Among patients with language agraphia, twenty cases have character formation disorder, eleven cases, wrong-writing characters and three cases, grammar disorder. Among patients with non-language agraphia, eight cases have micrographia, seven cases, tremor agraphia and two cases, reiterative agraphia.
4. Compared with pseudo-writing, patients in normal writing group showed greater activation of the bilateral lateral globus pallidus and the right putamen, whereas patients in agraphia group showed greater activation of the right ventral lateral nucleus, the claustrum, the left putamen and the lateral globus pallidus.
Conclusions
1. Agraphia is a common symptom in Wilson's disease with brain damage. Language agraphia is more common than non-language agraphia, especially character formation disorder.
2. Chinese writing of patients with Wilson' disease involve in the bilateral subcortical structure. The right basal ganglia plays more important role.
3. Activated areas in the bilateral basal ganglia of patients with agraphia are different with patients with normal writing. The right thalamus plays a compensatory role when patients with agraphia are writing.
基底神经节(Basal ganglia,BG)是位于双侧大脑半球深部的灰质核团,主要由尾状核、壳核、苍白球、屏状核等组成。根据目前人类对动物进化过程的研究,发现纹状体的发育在大脑皮质之前,一开始,基底神经节控制各种运动功能,大脑皮质受纹状体的控制。但随着大脑皮质的进化与功能完善,大脑皮质逐渐掌握对运动功能的控制,基底神经节则成为在运动皮质管理下参与运动控制的结构,属于从属地位。但是,近年来的研究发现,人类基底神经节的功能不仅仅是接受运动皮质管理,参与运动控制的结构,还是一个与其他功能皮质(特别是前额叶)组成神经回路,参与语言、计划、执行等高级神经功能的结构。这些回路一般由相关脑区皮质发出,经尾状核投射到苍白球,再经背侧丘脑返回到发出原始信号的皮质。现代功能影像学技术已经对此进行了验证。
语言与大脑定位之间的关系一直是研究者关心的热点之一,在人们已经明确了语言的皮质功能区定位后,位于皮质下的基底神经节在语言处理中担当什么样的角色逐渐成为学术界关心的问题。首先,神经病学家发现在人类中以基底神经节损害为主的一些中枢神经系统疾病,如帕金森病(Parkinson's disease,PD)、亨廷顿病(Huntington's disease,HD)、肝豆状核变性(Wilson's disease,WD)、基底神经节区卒中、皮质基底神经节变性等,可以导致不同形式的语言障碍等高级神经功能改变。其次,神经语言学家在关于基底神经节损害患者的语言处理的研究中,发现此类患者存在不同的语言结构层次的语言障碍。
书写与言语一样,是语言在经过一系列处理后的一种表达形式,所不同的是书写是需要借助肢体或工具实施语言计划的行为过程,而言语主要通过控制发音器官完成语言输出。通过书写行为进行交流和创作是人类一种独特的能力,它不仅是语言功能的一种体现,而且涉及到听觉、视觉、记忆、视空间能力、运用和运动功能等诸多因素,依赖于广泛的神经网络。在以往关于书写功能的神经心理学研究中,一方面集中于基底神经节的口语处理功能,另一方面着眼于大脑皮质与书写功能的关系。对基底神经节书写功能的系统研究较少,而且证据主要来源于以拼音文字为母语的人群。然而,汉字属于表意文字,在形、音、义的特点上与拼音文字相差甚远,其书写过程也更加复杂。另外,由于研究目的的不同、研究内容的不同(字词、语句)、研究手段的不同等多种因素的影响,使得研究结论存在差异。因此,对基底神经节参与书写功能的研究,有必要进一步寻找来自于汉语人群的证据,以丰富这一结论的内涵。
目前已有国内外学者以PD、HD为研究对象,探讨基底神经节损害对语言功能的影响。而同样是伴有基底神经节损害的WD患者,其书写过程是否支持基底神经节参与书写的学说呢?本研究以伴有基底神经节损害的WD患者为研究对象,通过中文书写检查法评价受试者语言性书写障碍情况和非语言性书写障碍情况,然后将受试者分为书写正常组和书写障碍组,分别进行正电子发射型计算机断层显像(positron emission tomography,PET)功能影像检查,得到基底神经节在中文书写时的功能影像数据。进而,从临床行为、形态结构和物质代谢三方面,分析脑型WD患者中文书写障碍的特点,确定基底神经节在中文书写中的作用,并探讨其神经心理学机制。
研究目的
分析脑型WD患者中文书写障碍的特点,分析在中文字词书写状态下脑型WD患者脑部的功能影像变化,从临床行为、形态结构和物质代谢三方面,确定基底神经节在脑型WD患者的中文书写中发挥的作用,并探讨其神经心理学机制,进而为基底神经节在语言功能中的作用提供有力的支持。
研究对象
连续收集2007年5月至2009年1月在南方医科大学南方医院和中山大学附属第一医院门诊及住院的60例脑型WD患者参加本研究,其中,征得7例男性患者的同意,参加脑功能影像学检查。受试者母语均为汉语,年龄20.68±7.23岁,受教育年限9.57±2.75年,均为右利手,其中男性44例,女性16例。均接受6个月以上的排铜治疗(限铜饮食,口服青霉胺、锌剂)。所有受试者均排除失认、失用、忽视、抑郁、焦虑、精神症状、除WD以外的中枢神经系统疾病及药物和酒精滥用史。
研究方法
1.采用汉语失写检查法(Chinese Agraphia Battery,CAB)对60例脑型WD患者进行中文书写检查。根据失写指数(agraphia quotient,AgQ),将受试者分为书写正常组和书写障碍组。采用社会科学统计软件包(statistical package forsocial sciences.SPSS)13.0统计软件,对WD书写正常组与书写障碍组在年龄、性别、受教育程度、病程、CAB得分的组间资料统计采用两独立样本t检验。分析书写障碍组中的语言性书写障碍情况及非语言性书写障碍情况,得到脑型WD患者中文书写的定量和定性资料。
2.按照CAB的AgQ,将7例男性脑型WD患者分为书写正常组4例和书写障碍组3例。采用PET,以18-氟脱氧葡萄糖(~(18)F-fluorodeoxyglucose,~(18)F-FDG)为示踪剂,在予以书写刺激任务后进行头部扫描,共扫描2次,第一次为假写作业,第二次为中文字词书写作业。假写作业为在稿纸空格内逐格划斜线;中文字词书写作业为在稿纸上书写中文,内容为实义名词,如地名、颜色、动物等。PET-CT头部扫描后,分别得到书写正常组假写和中文字词书写的图像数据,书写障碍组假写和中文字词书写的图像数据。用统计参数图软件包(StatisticalParametric Mapping 2,SPM2)对两次作业的图像数据进行两独立样本t检验分析,获得与中文字词产生相关的基底神经节~(18)F-FDG的激活区数据,从而分别获得脑型WD患者书写正常组和书写障碍组的与中文书写相关脑区的功能定位资料。
结果
1.60例脑型WD患者中36例患者出现书写障碍(60%),以主动书写成绩最差,其它依次为看图书写、听写、自动书写和抄写。
2.60例脑型WD患者中25例患者出现语言性书写障碍(41.7%),15例患者出现非语言性书写障碍(25%)。其中存在多种书写障碍类型并存的现象。
3.在语言性书写障碍的患者中,构字障碍20例,字词错写11例,语法错误3例;在非语言性书写障碍的患者中,小写症8例,震颤性书写7例,重复性书写2例。
4.正常书写组脑型WD患者的皮质下结构激活区包括双侧苍白球和右侧壳核,书写障碍组脑型WD患者的皮质下结构激活区包括右侧丘脑腹外侧核、屏状核和左侧壳核、苍白球。
结论
1.书写障碍是脑型肝豆状核变性的常见症状(60%),语言性书写障碍多于非语言性书写障碍,其中以构字障碍最多见;
2.书写正常的脑型肝豆状核变性患者,双侧基底神经节均参加了中文字词书写过程,其中右侧基底神经节在中文书写中发挥了更重要的作用;
3.书写障碍的脑型肝豆状核变性患者,由于病变损害程度和损害部位不尽相同,双侧基底神经节激活程度存在较大差异,右侧丘脑的激活可能与代偿机制有关。
Background
The basal ganglia (BG) belong to nuclei of gray matter deep within the cerebral hemispheres, which include the caudate nucleus, the putamen, the dorsal thalamus and the globus pallidus. During the evolution of species, the BG is turning from a motor control center in Aves to a structure being subject to the motor cortex in mammal, especially in primate. Recently, some studies revealed the BG in human is not only under control in the motor cortex, but also is a structure involving in many cognitive capacities, such as language, plan, execution function.
While the role of cortical areas in linguistic processing is relatively well established, the role of the BG and the way they impact language processing are still controversial. Neurologists found that some diseases related to the BG damage, such as Parkinson's disease (PD), Huntington's disease (HD), Wilson's disease (WD), the basal ganglia with vascular damage and corticobasal degeneration are manifested with various kinds of language disorders. And studies by neurolinguists using patients sustaining BG damage have suggested the BG is involved in various aspects of language comprising phonology and syntax.
Writing, which is implemented by limbs or tools, is one kind of language process. It not only needs competence of language processing but also needs help of visual, auditory, visual space, motor and so on. English, belongings to alphabetic writing systems, is a main material in former study, whereas, Chinese characters, belongings to logographic writing systems, are often semantic-phonetic compounds, symbols which include an element that represents the meaning and element that represents the pronunciation. As each character represents a single word, Chinese writing is more complex than English. The difference between the two languages is from the structure of word to figure-sound relation and figure-meaning relation. So it is necessary to study the process of Chinese writing.
Most of the subjects of language study with the BG damage are PD and HD. Whether the writing process of WD with the BG damage is the same as PD and HD? Few studies on WD were done, especially in Chinese characters. The present study proposed that WD with the BG damage influences the process of Chinese writing through the analysis of the Chinese agraphia battery (CAB) and a functional neuroimaging examination of PET-CT. The present study is to analyze roles of the BG in Chinese writing and to explore its neuropsychological mechanism, by investigating features of agaphia of WD with the BG damage and the data of functional imaging of Chinese writing.
Object
The present study is to investigate features of agaphia of WD with the BG damage, to investigate the data of functional imaging of Chinese writing, to analyze roles of the BG in Chinese writing and to explore its neuropsychological mechanism.
Material
We studied sixty patients with WD with brain damage and seven male patients joined the study of functional imaging. All patients were Chinese speaking, 23.68±7.23 years old, educated in 9.57±2.75 years and both right handedness, included forty four male and sixteen female. All patients accepted treatment above six months (dietary therapy, penicillamine, zinc). Only individuals with no history of psychiatric or neurological disease other than WD, as well as no agnosia, apraxia, neglect, depression and anxiety, no history of alcohol or drug abuse were included.
Methods
1. The Chinese agraphia battery (CAB) was used to identify agraphia in sixty patients with WD. According to agraphia quotient (AgQ) scores, all patients were divided into normal writing group and agraphia group and their types of agraphia were identified. Data were analyzed with statistical package for social sciences 13.0 (SPSS13.0).
2. Seven male patients were divided into two groups through language evaluation which were normal writing group and agraphia group. They were scanned by positron emission tomography (PET) respectively while performing two tasks: 1) pseudo-writing, 2) Chinese character writing (ie. names, color, animals). Data were analyzed with Statistical Parametric Mapping 2 (SPM2) for "Chinese character writing versus pseudo writing".
Results
1. Agraphia was identified in thirty-six cases (60%) and the patients had difficulty in positive writing, writing by picture, dictation, automatic writing and copying (in descending order of severity).
2. Language agraphia and non-language agraphia were detected in twenty-five cases (41.7%) and fifteen (25%) respectively, and some cases were detected with both kinds of agraphia.
3. Among patients with language agraphia, twenty cases have character formation disorder, eleven cases, wrong-writing characters and three cases, grammar disorder. Among patients with non-language agraphia, eight cases have micrographia, seven cases, tremor agraphia and two cases, reiterative agraphia.
4. Compared with pseudo-writing, patients in normal writing group showed greater activation of the bilateral lateral globus pallidus and the right putamen, whereas patients in agraphia group showed greater activation of the right ventral lateral nucleus, the claustrum, the left putamen and the lateral globus pallidus.
Conclusions
1. Agraphia is a common symptom in Wilson's disease with brain damage. Language agraphia is more common than non-language agraphia, especially character formation disorder.
2. Chinese writing of patients with Wilson' disease involve in the bilateral subcortical structure. The right basal ganglia plays more important role.
3. Activated areas in the bilateral basal ganglia of patients with agraphia are different with patients with normal writing. The right thalamus plays a compensatory role when patients with agraphia are writing.
引文
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