缺血性白质脑病患者视觉空间工作记忆事件相关电位研究
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摘要
目的:
目前血管性认知损害的诊断依据,是基于Alzheimer病的研究资料,难以早期发现及时治疗。本文探讨以缺血性白质损害为病理基础的视觉空间工作记忆的事件相关电位特征,寻找早期发现和评价缺血性白质脑病患者认知改变的新方法,提高血管性认知损害的诊断水平。
方法:
13名经头颅常规磁共振证实为轻度缺血性白质损害者,11名中重度缺血性白质损害者,12名头颅磁共振扫描未见异常老年人为对照组,匹配两组年龄、性别、文化程度和脑室/脑比例。所有被试完成一系列神经心理学量表测试(神经精神问卷调查问卷版、汉密尔顿抑郁量表、简易精神状态检查、工具性日常生活活动量表、Hachinski缺血指数量表、蒙特利尔认知评定量表、韦氏成人智力量表(数字广度、数字符号、图画填充和木块图)、连线测验A、词语流畅性测验),视觉空间工作记忆的事件相关电位检测(2球和3球记忆负荷)和磁共振扩散张量成像。结果:
1.认知功能状况评估
(1)与常模比较:MoCA总分:对照组(26.00±1.94),总体认知功能正常,轻度(23.31±3.68)和中重度(21.27±4.41)缺血性白质脑病组,表现认知功能损害。连线测验A:对照组(61.70±18.29)接近正常,轻度组(89.00±52.46)和中重度组(117.82±57.92),提示认知损害。词语流畅性测验:三组依次为42.80±7.10、37.23±6.46、32.82±6.84,未发现认知改变。
(2)缺血性白质脑病组与对照组比较: MoCA——抽象评分,轻度组(p<0.05)和中重度组(p=0.52)低于对照组,两组患者间差异无统计学意义。WAIS——倒背数字广度评分,中重度组低于轻度组,其余两组间差异无统计学意义。WAIS——顺背数字广度、数字符号、图画填充和木块图,随着缺血性白质损害程度的增加,3组被试认知表现依次变差,差异无统计学意义。
2.事件相关电位分析
在记忆延迟阶段,识别出3个波:N330、P420和晚期负成分。2球记忆负荷下,中额叶、右额叶、枕叶的N330波幅,对照组大于轻度缺血性脑白质损害组(均为P<0.01)和中重度缺血性脑白质损害组(均为P<0.05),差异有统计学意义;两组患者之间的差异无统计学意义。左额叶(P<0.05)、中央区(P<0.05)、顶叶(P<0.01)、左颞叶(P<0.05)N330波幅,对照组大于轻度缺血性脑白质损害组,差异有统计学意义;其余两组之间的差异无统计学意义。在其他各项指标中,均未发现对缺血性白质脑病组与对照组有甄别意义者。
3.缺血性白质脑病患者的DTI观察
左侧内囊膝部和后肢FA值:中重度组小于对照组(膝部P<0.001、后肢P<0.01)和轻度组(膝部P<0.001、后肢P<0.05),差异有统计学意义。左侧壳核和左侧苍白球ADC值:对照组(壳核P<0.05、苍白球P<0.001)和轻度组(壳核P<0.01、苍白球P<0.001)小于中重度组,差异有统计学意义;右侧壳核ADC值:对照组小于中重度组(P<0.01),差异有统计学意义;右侧苍白球ADC值:轻度组小于中重度组(P<0.05),差异有统计学意义;左侧内囊后肢ADC值:轻度组(P<0.05)和中重度组(P<0.001)大于对照组,差异有统计学意义。上述各项比较中,其余2组间差异无统计学意义。
4.N330波幅与认知评估量表之间的相关性
与MoCA——延迟回忆显著相关的是:中额叶(r=-0.45)、右额叶(r=-0.49)、枕叶(r=-0.41)(均为P<0.05);与连线测验A显著相关的是:中额叶(r=0.51)、右额叶(r=0.51)、枕叶(r=0.48)、顶叶(r=0.44)、右颞叶(r=0.37)(均为P<0.01);与数字符号编码测验显著相关的是:中额叶、右额叶(前两者,r=-0.45)、枕叶(r=-0.44)(前三者,P<0.01)、顶叶(r=-0.41)、左颞叶(r=-0.38)、右颞叶(r=-0.41)(后三者,P<0.05);与顺背数字广度测验显著相关的是枕叶(r=-0.37,P<0.05)。
5.DTI数据与认知评估量表的相关和回归分析
(1)FA值:唯一进入MoCA(视空间/执行、延迟回忆、总分)回归方程和连线测验A回归方程的是:右侧内囊后肢;唯一与MoCA——注意和WAIS——填图显著相关的是:右侧内囊后肢;唯一与MoCA——语言显著相关的是:左侧苍白球。唯一进入WAIS——倒背数字广度测验回归方程的是:右侧丘脑;唯一与WAIS——数字符号显著相关的是:右侧内囊膝部。
(2)ADC值:唯一进入MoCA——延迟回忆和总分回归方程的是:右侧内囊膝部;唯一进入MoCA——视空间/执行回归方程的是:右侧壳核;唯一进入MoCA——抽象回归方程的是:左侧内囊前肢;唯一进入MoCA——定向回归方程的是:左侧丘脑。进入连线测验A回归方程的依次是:右侧内囊膝部和右侧苍白球。进入言语流畅性测验回归方程的依次是:右侧内囊后肢和左侧内囊膝部。唯一进入WAIS——倒背数字广度回归方程的是:左侧苍白球,唯一进入WAIS——数字符号回归方程的是:右侧脑室前角,唯一进入WAIS——填图回归方程的是:左侧壳核。
6.DTI数据与ERP指标的相关和回归分析
与右额叶N330波幅显著相关的FA值,按照相关系数大小依次为:右侧内囊后肢、左侧尾状核、右侧尾状核、右侧苍白球,其中唯一进入右额叶N330波幅回归方程的是右侧内囊后肢。唯一与中额叶N330波幅相关的也是右侧内囊后肢FA值。右侧壳核FA值与全脑8个部位中的5个部位(左额叶、中央部、顶叶、枕叶、右颞叶)N330波幅显著相关。与左颞叶显著相关的依次是:右侧苍白球和左侧尾状核FA值及左侧脑室后角ADC值;与右颞叶显著相关的是:右侧壳核和左侧尾状核FA值。
结论:
1.缺血性白质脑病患者:总体认知功能降低(MoCA认知评估量表-总分);视觉空间能力降低(连线测验A);词语流畅性(动物、水果、蔬菜提取)相对完好。缺血性白质脑病患者较对照组:抽象推理能力降低(MoCA认知评估量表-抽象);视觉空间工作记忆能力降低(ERP-中额叶、右额叶和枕叶N330波幅)。有融合病灶的缺血性白质脑病患者较无融合病灶的缺血性白质脑病患者,工作记忆能力降低(WASI-RC-倒背数字广度测验)。
2.MoCA认知评估量表和连线测验A可以甄别出轻度缺血性白质脑病患者的认知损害。
3.DMS范式诱导出的视觉空间工作记忆延迟阶段ERP指标——N330波幅,适合缺血性白质脑病患者认知功能的评估。
4.中额叶、右额叶和双侧枕叶N330波幅的显著降低,是以缺血性白质损害为病理基础的视觉空间工作记忆ERP特征,可以做为评价缺血性白质脑病患者视觉空间工作记忆损害的电生理指标。中额叶和右额叶N330波幅降低,神经病理学基础为右侧内囊后肢投射纤维的损伤。
5.DTI技术可以反映常规头颅MRI显示正常的脑组织的细微改变,能够反映额叶-皮质下神经回路的损伤。
6.视觉空间工作记忆与“前额背外侧回路”的完整性有关。
Objective:
The current diagnosis criterion of vascular cognitive impairment (VCI) is based on the data of Alzheimer's disease, so it is difficult to detect and therapy VCI early. In this research, to investigate the characteristics of event-related potential (ERP) of visual-spatial working memory in patients with ischemic leukoencephalopathy, in order to explore new diagnostic methods to detect VCI early.
Methods:
According to the degree of ischemic white matter lesions on the conventional brain Magnetic Resonance Imaging (MRI), 24 patients with ischemic leukoencephalopathy (13/11 patients with mild/severe) and 12 healthy elders were recruited. All the participants performed a serial of neuropsychological scales(The Neuropsychiatric Inventory; Hamilton depression scale; Instrumental activity of daily living; Hachinski Inchemic Score; Montreal Cognitive Assessment (MoCA); Wechsler adult intelligence scale-Revised in China (WAIS-RC)-digit span, digit symbol, picture completion and block design; Trail making test A; Verbal fluency test). The ERP of visual-spatial working memory from the delayed matching-to-sample task was induced and diffusion tensor imaging was obtained.
Results:
1.General Cognition Assessment
(1) Comparative to the Norm: On the total score of MoCA and the Trail making test A, normal cognition appears in the control group (26.00±1.94 and 61.70±18.29ms); Cognitive impairment appears in the mild group (23.31±3.68 and 89.00±52.46 ms) and severe group (21.27±4.41 and 117.82±57.92 ms). On the Verbal fluency test, normal cognition appears in the three groups (42.80±7.10, 37.23±6.46, 32.82±6.84).
(2) Comparative to the control group: On the abstraction in MoCA, the score in the mild group(p<0.05)and severe group(p=0.52)was significantly lower than that in the control group, and there was no difference between the left two groups. On the inversed digit span in WAIS-RC, the score in the severe group was significantly lower than that in the mild group, and there was no difference between the left two groups. On the ordered digit span, digit symbol, picture completion and block design, higher the degree of ischemic white matter lesions was, poorer the performance was, but there were no differences among the three groups.
2.The Analyses of Event-related Potential
Three waves were identified in delay phrase: N330, P420 and late negative component. On the two-ball-load, the N330 amplitude in the middle frontal, right frontal and occipital lobe was significantly smaller in the mild group (all, p<0.01) and in the severe group (all, p<0.05) than that in the normal control, and there was no difference between the two groups of patients. The N330 amplitude in the left frontal lobe, central region, left temporal lobe(the three parts, p<0.05)and parietal lobe(p<0.01)was significantly smaller in the mild group than that in the normal control, and there was no difference between the others. On the left targets of ERP, there were no differential markers between the patients with ischemic leukoencephalopathy and the control group.
3.The Observation by Diffusion Tensor Imaging on the Patients with Ischemic Leukoencephalopathy
On the pars geniculate and posterior limb of the left internal capsule, the FA value was significantly smaller in the severe group than that in the mild group and control group, and there was no difference between the two others. On the left putamen and left pallidum, the ADC value was significantly smaller in the mild group and control group than that in the severe group. On the right putamen, the ADC value was significantly smaller in the control group than that in the severe group. On the right pallidum, the ADC value was significantly smaller in the mild group than that in the severe group. On the posterior limb of the left internal capsule, the ADC value was significantly smaller in the control group than that in the mild and severe group. In all above comparisons, there was no difference between the two others.
4.The correlation analyses between the N330 amplitude and neuropsychological scales
Across the 24 patients with ischemic leukoencephalopathy, in the middle frontal, right frontal and occipital lobe, the N330 amplitude was significantly correlated to the delay recall in MoCA. In the middle frontal, right frontal, occipital, parietal and right temporal lobe, the N330 amplitude was significantly correlated to the Trail making test A. In the middle frontal, right frontal, occipital, parietal, left and right temporal lobe, the N330 amplitude was significantly correlated to the digit symbol in WAIS-RC. In the occipital lobe, the N330 amplitude was significantly correlated to the ordered digit in WAIS-RC.
5.The correlation and regression analyses between DTI data and neuropsychological scales
(1) The FA value: only the posterior limb of the right internal capsule entered into the regression equation of the visual-spatial/execution, delay recall and total score in MoCA and the Trail making test A. Only the posterior limb of the right internal capsule was significantly correlated to attention in MoCA and picture completion in WAIS-RC. Only the left pallidum was significantly correlated to language in MoCA. Only the right thalamus entered into the regression equation of the inversed digit span in WAIS-RC. Only the pars geniculate of the right internal capsule was significantly correlated to digit symbol in WAIS-RC.
(2) The ADC value: only the pars geniculate of the right internal capsule entered into the regression equation of the delay recall and total score in MoCA. Only the right putamen entered into the regression equation of the visual-spatial/execution in MoCA. Only the anterior limb of the left internal capsule entered into the regression equation of the abstraction in MoCA. Only the left thalamus entered into the regression equation of the orientation in MoCA. By turns, the pars geniculate of the right internal capsule and the right pallidum entered into the regression equation of the Trail making test A. By turns, the posterior limb of right internal capsule and the pars geniculate of the left internal capsule entered into the regression equation of the Verbal fluency test. Only the left pallidum entered into the regression equation of the inversed digit span in WAIS-RC. Only right anterior horn of lateral ventricle entered into the regression equation of the digit symbol in WAIS-RC. Only left putamen entered into the regression equation of the picture completion in WAIS-RC.
6.The correlation and regression analyses between DTI data and the N330 amplitude
Only the FA value of the posterior limb of the right internal capsule entered into the regression equation of the N330 amplitude in the right frontal lobe and was significantly correlated to the N330 amplitude in the middle frontal lobe. The FA value of the right putamen was significantly correlated to the N330 amplitude in five of eight brain regions (left frontal, central region, parietal, occipital, and right temporal lobe). The FA of the right globus pallidus and the left caudate nucleus and the ADC of the left posterior horn of lateral ventricle were significantly correlated to the N330 amplitude in the left temporal lobe. The FA of the right putamen and the left caudate nucleus were significantly correlated to the N330 amplitude in the right temporal lobe.
Conclusions:
1 . Patients with ischemic leukoencephalopathy: general cognitive impairment (Montreal Cognitive Assessment); visual spatial deficit (Trail making test A); Verbal fluency ability was reserved (Verbal fluency test). Comparative to the control group, patients with ischemic leukoencephalopathy: abstraction ability deficit (Montreal Cognitive Assessment: abstraction); deficit in visual-spatial working memory (the N330 amplitude in the middle frontal, right frontal and occipital lobe); working memory in the patients with severe ischemic leukoencephalopathy was lower than that in the patients with mild ischemic leukoencephalopathy (WAIS-RC- inversed digit span).
2.Montreal Cognitive Assessment and Trail making test A were sensitive to the evaluation of the cognitive impairment for the patients with mild ischemic leukoencephalopathy.
3.The N330 amplitude in delay phrase - ERP of visual-spatial working memory from the delayed matching-to-sample task was suitable to the cognitive evaluation for the patients with ischemic leukoencephalopathy.
4.In the middle frontal, right frontal and occipital lobe, the significant decrease of N330 amplitude is the characteristic of ERP, which is based on the ischemic white matter lesions and become an electrophysiological indicator for the deficit in visual-spatial working memory in patients with ischemic leukoencephalopathy. The pathological mechanism of the characteristic of ERP was the ischemic lesions of projection fibers through the right internal capsule posterior limb.
5.Diffusion tensor imaging can detect the potential changes which appear normal on the MRI, and reflect the damage in the fronto-subcortical circuits.
6.Visual-spatial working memory is dependent on the integrity of dorsolatera prefrontal circuit.
目前血管性认知损害的诊断依据,是基于Alzheimer病的研究资料,难以早期发现及时治疗。本文探讨以缺血性白质损害为病理基础的视觉空间工作记忆的事件相关电位特征,寻找早期发现和评价缺血性白质脑病患者认知改变的新方法,提高血管性认知损害的诊断水平。
方法:
13名经头颅常规磁共振证实为轻度缺血性白质损害者,11名中重度缺血性白质损害者,12名头颅磁共振扫描未见异常老年人为对照组,匹配两组年龄、性别、文化程度和脑室/脑比例。所有被试完成一系列神经心理学量表测试(神经精神问卷调查问卷版、汉密尔顿抑郁量表、简易精神状态检查、工具性日常生活活动量表、Hachinski缺血指数量表、蒙特利尔认知评定量表、韦氏成人智力量表(数字广度、数字符号、图画填充和木块图)、连线测验A、词语流畅性测验),视觉空间工作记忆的事件相关电位检测(2球和3球记忆负荷)和磁共振扩散张量成像。结果:
1.认知功能状况评估
(1)与常模比较:MoCA总分:对照组(26.00±1.94),总体认知功能正常,轻度(23.31±3.68)和中重度(21.27±4.41)缺血性白质脑病组,表现认知功能损害。连线测验A:对照组(61.70±18.29)接近正常,轻度组(89.00±52.46)和中重度组(117.82±57.92),提示认知损害。词语流畅性测验:三组依次为42.80±7.10、37.23±6.46、32.82±6.84,未发现认知改变。
(2)缺血性白质脑病组与对照组比较: MoCA——抽象评分,轻度组(p<0.05)和中重度组(p=0.52)低于对照组,两组患者间差异无统计学意义。WAIS——倒背数字广度评分,中重度组低于轻度组,其余两组间差异无统计学意义。WAIS——顺背数字广度、数字符号、图画填充和木块图,随着缺血性白质损害程度的增加,3组被试认知表现依次变差,差异无统计学意义。
2.事件相关电位分析
在记忆延迟阶段,识别出3个波:N330、P420和晚期负成分。2球记忆负荷下,中额叶、右额叶、枕叶的N330波幅,对照组大于轻度缺血性脑白质损害组(均为P<0.01)和中重度缺血性脑白质损害组(均为P<0.05),差异有统计学意义;两组患者之间的差异无统计学意义。左额叶(P<0.05)、中央区(P<0.05)、顶叶(P<0.01)、左颞叶(P<0.05)N330波幅,对照组大于轻度缺血性脑白质损害组,差异有统计学意义;其余两组之间的差异无统计学意义。在其他各项指标中,均未发现对缺血性白质脑病组与对照组有甄别意义者。
3.缺血性白质脑病患者的DTI观察
左侧内囊膝部和后肢FA值:中重度组小于对照组(膝部P<0.001、后肢P<0.01)和轻度组(膝部P<0.001、后肢P<0.05),差异有统计学意义。左侧壳核和左侧苍白球ADC值:对照组(壳核P<0.05、苍白球P<0.001)和轻度组(壳核P<0.01、苍白球P<0.001)小于中重度组,差异有统计学意义;右侧壳核ADC值:对照组小于中重度组(P<0.01),差异有统计学意义;右侧苍白球ADC值:轻度组小于中重度组(P<0.05),差异有统计学意义;左侧内囊后肢ADC值:轻度组(P<0.05)和中重度组(P<0.001)大于对照组,差异有统计学意义。上述各项比较中,其余2组间差异无统计学意义。
4.N330波幅与认知评估量表之间的相关性
与MoCA——延迟回忆显著相关的是:中额叶(r=-0.45)、右额叶(r=-0.49)、枕叶(r=-0.41)(均为P<0.05);与连线测验A显著相关的是:中额叶(r=0.51)、右额叶(r=0.51)、枕叶(r=0.48)、顶叶(r=0.44)、右颞叶(r=0.37)(均为P<0.01);与数字符号编码测验显著相关的是:中额叶、右额叶(前两者,r=-0.45)、枕叶(r=-0.44)(前三者,P<0.01)、顶叶(r=-0.41)、左颞叶(r=-0.38)、右颞叶(r=-0.41)(后三者,P<0.05);与顺背数字广度测验显著相关的是枕叶(r=-0.37,P<0.05)。
5.DTI数据与认知评估量表的相关和回归分析
(1)FA值:唯一进入MoCA(视空间/执行、延迟回忆、总分)回归方程和连线测验A回归方程的是:右侧内囊后肢;唯一与MoCA——注意和WAIS——填图显著相关的是:右侧内囊后肢;唯一与MoCA——语言显著相关的是:左侧苍白球。唯一进入WAIS——倒背数字广度测验回归方程的是:右侧丘脑;唯一与WAIS——数字符号显著相关的是:右侧内囊膝部。
(2)ADC值:唯一进入MoCA——延迟回忆和总分回归方程的是:右侧内囊膝部;唯一进入MoCA——视空间/执行回归方程的是:右侧壳核;唯一进入MoCA——抽象回归方程的是:左侧内囊前肢;唯一进入MoCA——定向回归方程的是:左侧丘脑。进入连线测验A回归方程的依次是:右侧内囊膝部和右侧苍白球。进入言语流畅性测验回归方程的依次是:右侧内囊后肢和左侧内囊膝部。唯一进入WAIS——倒背数字广度回归方程的是:左侧苍白球,唯一进入WAIS——数字符号回归方程的是:右侧脑室前角,唯一进入WAIS——填图回归方程的是:左侧壳核。
6.DTI数据与ERP指标的相关和回归分析
与右额叶N330波幅显著相关的FA值,按照相关系数大小依次为:右侧内囊后肢、左侧尾状核、右侧尾状核、右侧苍白球,其中唯一进入右额叶N330波幅回归方程的是右侧内囊后肢。唯一与中额叶N330波幅相关的也是右侧内囊后肢FA值。右侧壳核FA值与全脑8个部位中的5个部位(左额叶、中央部、顶叶、枕叶、右颞叶)N330波幅显著相关。与左颞叶显著相关的依次是:右侧苍白球和左侧尾状核FA值及左侧脑室后角ADC值;与右颞叶显著相关的是:右侧壳核和左侧尾状核FA值。
结论:
1.缺血性白质脑病患者:总体认知功能降低(MoCA认知评估量表-总分);视觉空间能力降低(连线测验A);词语流畅性(动物、水果、蔬菜提取)相对完好。缺血性白质脑病患者较对照组:抽象推理能力降低(MoCA认知评估量表-抽象);视觉空间工作记忆能力降低(ERP-中额叶、右额叶和枕叶N330波幅)。有融合病灶的缺血性白质脑病患者较无融合病灶的缺血性白质脑病患者,工作记忆能力降低(WASI-RC-倒背数字广度测验)。
2.MoCA认知评估量表和连线测验A可以甄别出轻度缺血性白质脑病患者的认知损害。
3.DMS范式诱导出的视觉空间工作记忆延迟阶段ERP指标——N330波幅,适合缺血性白质脑病患者认知功能的评估。
4.中额叶、右额叶和双侧枕叶N330波幅的显著降低,是以缺血性白质损害为病理基础的视觉空间工作记忆ERP特征,可以做为评价缺血性白质脑病患者视觉空间工作记忆损害的电生理指标。中额叶和右额叶N330波幅降低,神经病理学基础为右侧内囊后肢投射纤维的损伤。
5.DTI技术可以反映常规头颅MRI显示正常的脑组织的细微改变,能够反映额叶-皮质下神经回路的损伤。
6.视觉空间工作记忆与“前额背外侧回路”的完整性有关。
Objective:
The current diagnosis criterion of vascular cognitive impairment (VCI) is based on the data of Alzheimer's disease, so it is difficult to detect and therapy VCI early. In this research, to investigate the characteristics of event-related potential (ERP) of visual-spatial working memory in patients with ischemic leukoencephalopathy, in order to explore new diagnostic methods to detect VCI early.
Methods:
According to the degree of ischemic white matter lesions on the conventional brain Magnetic Resonance Imaging (MRI), 24 patients with ischemic leukoencephalopathy (13/11 patients with mild/severe) and 12 healthy elders were recruited. All the participants performed a serial of neuropsychological scales(The Neuropsychiatric Inventory; Hamilton depression scale; Instrumental activity of daily living; Hachinski Inchemic Score; Montreal Cognitive Assessment (MoCA); Wechsler adult intelligence scale-Revised in China (WAIS-RC)-digit span, digit symbol, picture completion and block design; Trail making test A; Verbal fluency test). The ERP of visual-spatial working memory from the delayed matching-to-sample task was induced and diffusion tensor imaging was obtained.
Results:
1.General Cognition Assessment
(1) Comparative to the Norm: On the total score of MoCA and the Trail making test A, normal cognition appears in the control group (26.00±1.94 and 61.70±18.29ms); Cognitive impairment appears in the mild group (23.31±3.68 and 89.00±52.46 ms) and severe group (21.27±4.41 and 117.82±57.92 ms). On the Verbal fluency test, normal cognition appears in the three groups (42.80±7.10, 37.23±6.46, 32.82±6.84).
(2) Comparative to the control group: On the abstraction in MoCA, the score in the mild group(p<0.05)and severe group(p=0.52)was significantly lower than that in the control group, and there was no difference between the left two groups. On the inversed digit span in WAIS-RC, the score in the severe group was significantly lower than that in the mild group, and there was no difference between the left two groups. On the ordered digit span, digit symbol, picture completion and block design, higher the degree of ischemic white matter lesions was, poorer the performance was, but there were no differences among the three groups.
2.The Analyses of Event-related Potential
Three waves were identified in delay phrase: N330, P420 and late negative component. On the two-ball-load, the N330 amplitude in the middle frontal, right frontal and occipital lobe was significantly smaller in the mild group (all, p<0.01) and in the severe group (all, p<0.05) than that in the normal control, and there was no difference between the two groups of patients. The N330 amplitude in the left frontal lobe, central region, left temporal lobe(the three parts, p<0.05)and parietal lobe(p<0.01)was significantly smaller in the mild group than that in the normal control, and there was no difference between the others. On the left targets of ERP, there were no differential markers between the patients with ischemic leukoencephalopathy and the control group.
3.The Observation by Diffusion Tensor Imaging on the Patients with Ischemic Leukoencephalopathy
On the pars geniculate and posterior limb of the left internal capsule, the FA value was significantly smaller in the severe group than that in the mild group and control group, and there was no difference between the two others. On the left putamen and left pallidum, the ADC value was significantly smaller in the mild group and control group than that in the severe group. On the right putamen, the ADC value was significantly smaller in the control group than that in the severe group. On the right pallidum, the ADC value was significantly smaller in the mild group than that in the severe group. On the posterior limb of the left internal capsule, the ADC value was significantly smaller in the control group than that in the mild and severe group. In all above comparisons, there was no difference between the two others.
4.The correlation analyses between the N330 amplitude and neuropsychological scales
Across the 24 patients with ischemic leukoencephalopathy, in the middle frontal, right frontal and occipital lobe, the N330 amplitude was significantly correlated to the delay recall in MoCA. In the middle frontal, right frontal, occipital, parietal and right temporal lobe, the N330 amplitude was significantly correlated to the Trail making test A. In the middle frontal, right frontal, occipital, parietal, left and right temporal lobe, the N330 amplitude was significantly correlated to the digit symbol in WAIS-RC. In the occipital lobe, the N330 amplitude was significantly correlated to the ordered digit in WAIS-RC.
5.The correlation and regression analyses between DTI data and neuropsychological scales
(1) The FA value: only the posterior limb of the right internal capsule entered into the regression equation of the visual-spatial/execution, delay recall and total score in MoCA and the Trail making test A. Only the posterior limb of the right internal capsule was significantly correlated to attention in MoCA and picture completion in WAIS-RC. Only the left pallidum was significantly correlated to language in MoCA. Only the right thalamus entered into the regression equation of the inversed digit span in WAIS-RC. Only the pars geniculate of the right internal capsule was significantly correlated to digit symbol in WAIS-RC.
(2) The ADC value: only the pars geniculate of the right internal capsule entered into the regression equation of the delay recall and total score in MoCA. Only the right putamen entered into the regression equation of the visual-spatial/execution in MoCA. Only the anterior limb of the left internal capsule entered into the regression equation of the abstraction in MoCA. Only the left thalamus entered into the regression equation of the orientation in MoCA. By turns, the pars geniculate of the right internal capsule and the right pallidum entered into the regression equation of the Trail making test A. By turns, the posterior limb of right internal capsule and the pars geniculate of the left internal capsule entered into the regression equation of the Verbal fluency test. Only the left pallidum entered into the regression equation of the inversed digit span in WAIS-RC. Only right anterior horn of lateral ventricle entered into the regression equation of the digit symbol in WAIS-RC. Only left putamen entered into the regression equation of the picture completion in WAIS-RC.
6.The correlation and regression analyses between DTI data and the N330 amplitude
Only the FA value of the posterior limb of the right internal capsule entered into the regression equation of the N330 amplitude in the right frontal lobe and was significantly correlated to the N330 amplitude in the middle frontal lobe. The FA value of the right putamen was significantly correlated to the N330 amplitude in five of eight brain regions (left frontal, central region, parietal, occipital, and right temporal lobe). The FA of the right globus pallidus and the left caudate nucleus and the ADC of the left posterior horn of lateral ventricle were significantly correlated to the N330 amplitude in the left temporal lobe. The FA of the right putamen and the left caudate nucleus were significantly correlated to the N330 amplitude in the right temporal lobe.
Conclusions:
1 . Patients with ischemic leukoencephalopathy: general cognitive impairment (Montreal Cognitive Assessment); visual spatial deficit (Trail making test A); Verbal fluency ability was reserved (Verbal fluency test). Comparative to the control group, patients with ischemic leukoencephalopathy: abstraction ability deficit (Montreal Cognitive Assessment: abstraction); deficit in visual-spatial working memory (the N330 amplitude in the middle frontal, right frontal and occipital lobe); working memory in the patients with severe ischemic leukoencephalopathy was lower than that in the patients with mild ischemic leukoencephalopathy (WAIS-RC- inversed digit span).
2.Montreal Cognitive Assessment and Trail making test A were sensitive to the evaluation of the cognitive impairment for the patients with mild ischemic leukoencephalopathy.
3.The N330 amplitude in delay phrase - ERP of visual-spatial working memory from the delayed matching-to-sample task was suitable to the cognitive evaluation for the patients with ischemic leukoencephalopathy.
4.In the middle frontal, right frontal and occipital lobe, the significant decrease of N330 amplitude is the characteristic of ERP, which is based on the ischemic white matter lesions and become an electrophysiological indicator for the deficit in visual-spatial working memory in patients with ischemic leukoencephalopathy. The pathological mechanism of the characteristic of ERP was the ischemic lesions of projection fibers through the right internal capsule posterior limb.
5.Diffusion tensor imaging can detect the potential changes which appear normal on the MRI, and reflect the damage in the fronto-subcortical circuits.
6.Visual-spatial working memory is dependent on the integrity of dorsolatera prefrontal circuit.
引文
[1] Rockwood K, Wentzel C, Hachinski V, Hogan DB, MacKnight C, McDowell I. Prevalence and outcomes of vascular cognitive impairment. Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging [J]. Neurology, 2000, 54(2): 447-451.
[2] Rockwood K. Vascular cognitive impairment and vascular dementia [J]. J Neurol Sci, 2002, 203-204: 23-27.
[3] Desmond D. The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit [J]? J Neurol Sci, 2004, 226(1-2): 3-7.
[4] Lindeboom J, Weinstein H. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer disease, and vascular cognitive impairment [J]. Eur J Pharmacol, 2004, 490(1-3): 83-86.
[5] Libon DJ, Bogdanoff B, Leopold N, Hurka R, Bonavita J, Skalina S, et al. Neuropsychological profiles associated with subcortical white matter alterations and Parkinson's disease: implications for the diagnosis of dementia [J]. Arch Clin Neuropsychol, 2001, 16(1): 19-32.
[6] O'Brien J. Behavioral symptoms in vascular cognitive impairment and vascular dementia [J]. Int Psychogeriatr, 2003, 15(Suppl 1): 133-138.
[7] Wentzel C, Rockwood K, MacKnight C, Hachinski V, Hogan DB, Feldman H, et al. Progression of impairment in patients with vascular cognitive impairment without dementia [J]. Neurology, 2001, 57(4): 714-716.
[8]杜万良,王荫华。血管性认知障碍[J]。中国康复理论与实践,2004,10(4): 238-240。
[9] Sachdev PS, Brodaty H, Valenzuela MJ, Lorentz L, Looi JC, Wen W, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients [J]. Neurology, 2004, 62(6): 912-919.
[10]张微微。MoCA量表——诊断轻度认知功能损害的重大突破[J]。天坛国际脑血管病会议,2008。
[11]詹丽漩,徐恩。缺血性脑白质病变的研究进展[J]。中华脑血管病杂志,2008,2(3): 174-177。
[12] Launer LJ, Berger K, Breteler MM, Dufouil C, Fuhrer R, Giampaoli S et al. Regionalvariability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE) [J]. Neuroepidemiology, 2006, 26(1): 23-29.
[13] Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location [J]. Neurology, 2004, 63(2): 246-253.
[14] Wolf H, Ecke GM, Bettin S, Dietrich J, Gertz HJ. Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study [J]. Int J Geriatr Psychiatry, 2000, 15(9): 803-812.
[15] Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F. Progression of leukoaraiosis and cognition [J]. Stroke, 2007, 38(9): 2619-2625.
[16] De Groot JC, de Leeuw FE, Oudkerk M, van Gijn J, Hofman A, Jolles J et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study [J]. Ann Neurol, 2000, 47(2): 145-151.
[17] Barber R, Gholkar A, Scheltens P, Ballard C, Mckeith IG, O Brien JT. MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimers disease [J]. Int J Geriatr Psychiatry 2000, 15(10): 911-916.
[18]魏景汉,罗跃嘉。认知事件相关脑电位教程[M]。北京:经济日报出版社,2002:45- 53。
[19] Magnano I, Aiello I, Piras MR. Cognitive impairment and neurophysiological correlates in MS [J]. J Neurol Sci, 2006, 245(1-2): 117-122.
[20] Kemner C, van Engeland H. ERPs and eye movements reflect atypical visual perception in pervasive developmental disorder [J]. J Autism Dev Disord, 2006, 36(1): 45-54.
[21] Abramowitz JS. The psychological treatment of obsessive-compulsive disorder [J]. Can J Psychiatry. 2006, 51(7): 407-416.
[22] Pearlstein RD,Whitten C,Haerich P. Assessing neurocognitive dysfunction in cranial radiotherapy: can cognitive event-related potentials help [J]? Technol Cancer Res Treat,2006, 5(2): 109-125.
[23] Karl A, Malta LS, Maercker A. Meta-analytic review of event-related potential studies in post-traumatic stress disorder [J]. Biol Psychol, 2006, 71(2):123-147.
[24] Lew HL, Poole JH, Castaneda A, Salerno RM, Gray M. Prognostic value of evoked and event-related potentials in moderate to severe brain injury [J]. J Head Trauma Rehabil.2006, 21(4): 350-360.
[25] Cowan N, Morey CC. Visual working memory depends on attentional filtering [J]. Trends Cogn Sci, 2006, 10(4):139-141.
[26] Brown RD,Chiu CY. Neural correlates of memory development and learning: combining neuroimaging and behavioral measures to understand cognitive and developmental processes [J]. Dev Neuropsychol, 2006, 29(2):279-291.
[27]罗华,谭华,李小刚。脑白质疏松症患者的事件相关电位研究[J]。实用医学杂志,2004,20(12):1386-1387。
[28]赵士福,成戊川,肖道宏,等。脑老化过程中的白质损害与P300变化的关系[J]。中国临床康复,2002,6(17):2531-2532。
[29] Ruchkin DS, Grafrnan J, Krauss GL, Johnson Jr R, Canoune H, and Ritter W. Event-related brain potential evidence for a verbal working memory deficit in multiple sclerosis [J]. Brain, 1994, 117(Pt 2): 289-305.
[30] Baddeley AD. Is working memory still working [J]? Am Psychol, 2001, 56(11): 851-864.
[31] Goldman-Rakic PS. Working memory and the mind [J]. Sci Am, 1992, 267(3): 110-117.
[32] Miyake A, Shah P. Models of working memory: mechanisms of active maintenance and executive control [M]. New York: Cambridge University Press, 1999.
[33] Baddeley AD. Working Memory [J]. Science, 1992, 255: 556- 592.
[34]徐科。神经生物学纲要[M]。北京:科学出版社,1999:311-350。
[35]刘昌。人类工作记忆的某些神经影像研究[J]。心理学报,2002,34(6): 634-642。
[36]李雪冰,罗跃嘉。人类工作记忆的事件相关电位研究[J]。心理科学进展,2005,13(4): 423-434。
[37]陈彩琦。工作记忆的ERP研究[J]。华南师范大学学报(社会科学版),2004,6: 114-120。
[38] Babiloni C, Bares M, Vecchio F, Brazdil M, Jurak P, Moretti DV, et al. Synchronization of gamma oscillations increases functional connectivity of human hippocampus and inferior-middle temporal cortex during repetitive visuomotor events[J]. Eur J Neurosci, 2004, 19(11): 3088-3098.
[39] Mecklinger A, Pfeifer E. Event-related potentials reveal topographical and temporaldistinct neuronal activation patterns for spatial and object working memory [J]. Brain Res Cogn Brain Res, 1996, 4(3): 211-224.
[40] Bosch V, Mecklinger A, Friederici AD.Slow cortical potentials during retention of object, spatial, and verbal information [J]. Brain Res Cogn Brain Res, 2001, 10(3): 219-237.
[41]王益文,林崇德,魏景汉,等。工作记忆中汉字与空间的分离及动态优势半球的ERP效应[J]。心理学报,2004,36(3):253- 259。
[42]沃建中,罗良,林崇德。客体与空间工作记忆的分离:来自皮层慢电位的证据[J]。心理学报,2005,37(6): 729-738。
[43] Umeno MM, Goldberg ME. Spatial processing in the monkey frontal eye field. II. Memory responses [J]. J neurophysiol, 2001, 86(5): 2344-2352.
[44] Rowe JB, Toni I, Josephs O, Frackowiak RS, Passingham RE. The prefrontal cortex: Response selection or maintenance within working memory [J]? Science, 2000, 288(5471): 1656-1660.
[45] Klingberg T. Development of a superior frontal–intraparietal network for visuo-spatial working memory [J]. Neuropsychologia, 2006, 44: 2171–2177.
[46] Grady CL, Maisog JM, Horwitz B, Ungerleider LG, Mentis MJ, Salerno JA, et al. Age-related changes in cortical blood flow activation during visual processing of faces and location [J]. J Neurosci, 1994, 14(3 Pt 2): 1450-1462.
[47]王健,张久权。fMRI与DTI在神经科学研究中的联合应用[J]。现代生物医学进展,2007,7(2): 231-233。
[48] Song SK, Sun SW, Ju WK, Lin SJ, Cross AH, Neufeld AH. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia [J]. Neuroimage, 2003, 20(3): 1714-1722.
[49] O'Sullivan M, Morris RG, Huckstep B, et al. Diffusion tensor MRI correlates with executive dysfunction in patients with ischemic leukoaraiosis [J]. J Neurol Neurosurg Psychiatry, 2004, 75: 441-447.
[50] Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop [J]. Neurology, 1993, 43(2): 250-260.
[51] Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, et al.Research criteria for subcortical vascular dementia in clinical trials [J]. J Neural Transm Suppl, 2000, 59: 23-30.
[52] Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia [J]. Lancet Neurol, 2002, 1(7): 426-436.
[53] Caplan LR. Binswanger's disease--revisited. Neurology, 1995, 45(4): 626-633.
[54] Yue NC, Arnold AM, Longstreth WT, Elster AD, Jungreis CA, O'Leary DH, et al. Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the Cardiovascular Health Study [J]. Radiology, 1997, 202(1): 33-39.
[55] Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sj?gren M, et al. A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT [J]. Stroke, 2001, 32(6): 1318-1322.
[56]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 71。
[57]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 95。
[58]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 17。
[59]汤慈美。神经心理学[M]。北京:人民军医出版社,2001: 315。
[60]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 93。
[61]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 10。
[62] Daneman M, Hannon B. Using working memory theory to investigate the construct validity of multiple-choice reading comprehension tests such as the SAT [J]. J Exp Psychol Gen, 2001, 130(2): 208-223.
[63] Lezak M, Howieson D, Loring D. Neuropsychological Assessment [M]. New York: Oxford, 2004.
[64] O’Sullivan M, Morris RG, Markus HS. Brief cognitive assessment for patients with cerebral small vessel disease [J]. J Neurol Neurosurg Psychiatry, 2005; 76(8): 1140-1145.
[65] Storandt M, Botwinick J, Danziger WL, Berg L, Hughes CP. Psychometric differentiation of mild senile dementia of the Alzheimer type [J]. Arch Neurol, 1984, 41(5): 497-499.
[66]汤慈美。神经心理学[M]。北京:人民军医出版社,2001:308-326。
[67] Reitan R. Manual for Administration of Neuropsychological Test Batteries for Adults and Children [M]. Tucson: Reitan Neuropsychological Laboratory, 1979.
[68] van Swieten JC, Geyskes GG, Derix MM, Peeck BM, Ramos LM, van Latum JC. Hypertension in the elderly is associated with white matter lesions and cognitive decline [J]. Ann Neurol, 1991, 30(6): 825-830.
[69] van Zandvoort M, de Haan E, van Gijn J, Kappelle LJ. Cognitive functioning in patients with a small infarct in the brainstem [J]. J Int Neuropsychol Soc. 2003; 9(3): 490-494.
[70]汤慈美。神经心理学[M]。北京:人民军医出版社,2001:317。
[71] Carew TG, Lamar M, Cloud BS, Grossman M, Libon DJ. Impairment in category fluency in ischemic vascular dementia [J]. Neuropsychology, 1997, 11(3): 400-412.
[72] Hanyu H, Sato T, Akai T, Sakai M, Takasaki R, Iwamoto T. Awareness of memory deficits in patients with dementias: a study with the Everyday Memory Checklist [J]. Nippon Ronen Igakkai Zasshi, 2007, 44(4): 463-469.
[73] Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards [J]. Stroke, 2006, 37: 2220.
[74] Jonides J, Smith EE, Koeppe RA, Awh E, Minoshima S, Mintun MA. Spatial working memory in humans as revealed by PET [J]. Nature, 1993, 363(6430): 623-625.
[75] Jenkins L, Myerson J, Joerding JA, Hale S. Converging evidence that visuo-spatial cognition is more age-sensitive than verbal cognition [J]. Psychol Aging, 2000, 15(1):157-175.
[76] Pelosi L, Blumhardt LD. Effects of age on working memory: An event-related potential study [J]. Brain Res Cogn Brain Res, 1999: 7(3): 321-334.
[77] Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update [J]. J Psychosom Res, 2002, 53(2):647-654.
[78] Stuss DT, Levine B. Adult clinical neuropsychology: Lessons from studies of the frontal lobes [J]. Annu Rev Psychol, 2002, 53: 401-433.
[79] Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex [J]. Annu Rev Neurosci, 1986, 9: 357-381.
[80] Stuss DT, Bisschop SM, Alexander MP, Levine B, Katz D, Izukawa D. The trail making test: A study in focal lesion patients [J]. Psychol Assess, 2001, 13(2): 230-239.
[81] Alexander MP, Stuss DT, Shallice T, Picton TW, Gillingham S. Impaired concentration due to frontal lobe damage from two distinct lesion sites [J]. Neurology, 2005, 65(4): 572-579.
[82] Sachdev PS, Brodaty H, Valenzuela MJ, Lorentz L, Looi JC, Wen W, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients [J]. Neurology, 2004, 62(6): 912-919.
[83] Ingles JL, Boulton DC, Fish JD, Rockwood K. Preclinical vascular cognitive impairment and Alzheimer disease: neuropsychological test performance 5 years before diagnosis [J]. Stroke, 2007, 38(4): 1148-1153.
[84] Garrett KD, Browndyke JN, Whelihan W, Paul RH, DiCarlo M, Moser DJ, et al. The neuropsychological profile of vascular cognitive impairment-no dementia: comparisons to patients at risk for cerebral vascular disease and vascular dementia [J]. Arch Clin Neuropsychol, 2004, 19(6): 745-757.
[85] Feldman H, Levy AR, Hsiung GY, Peters KR, Donald A, Black SE, et al. A Canadian cohort study of cognitive impairment and related dementias (ACCORD): study methods and baseline results [J]. Neuroepidemiology, 2003, 22(5): 265-274.
[86] Babcock RL, Laguna KD, Roesch SC. A comparison of the factor structure of processing speed for younger and older adults: testing the assumption of measurement equivalence across age groups [J]. Psychol Aging, 1997, 12(2): 268-276.
[87] Srimal R, Curtis CE. Persistent neural activity during the maintenance of spatial position in working memory [J]. NeuroImage, 2008, 39: 455–468.
[88] Wang XJ. Synaptic reverberation underlying mnemonic persistent activity [J]. Trends Neurosci, 2001, 24(8): 455-463.
[89] Pucak ML, Levitt JB, Lund JS, Lewis DA. Patterns of intrinsic and associational circuitry in monkey prefrontal cortex [J]. J Comp Neurol, 1996, 376(4):614-630.
[90] Bechara A, Damasio H, Tranel D, and Anderson SW. Dissociation of working memory from decision making within the human prefrontal cortex [J]. The Journal of Neuroscience, 1998, 18(1): 428-437.
[91] Collette F, Van der Linden M. Brain imaging of the central executive component of working memory [J]. Neurosci Biobehav Rev, 2002, 26(2):105-125.
[92] Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, el al.Age-related alterations in while matter microstructure measured by diffusion tensor imaging [J]. Neurobiol Aging, 2005, 26(8):1215-1227.
[93] Grau-Olivares M, Bartrés-Faz D, Arboix A, Soliva JC, Rovira M, Targa C, et al. Mild cognitive impairment after lacunar infarction: voxel-based morphometry and neuropsychological assessment [J]. Cerebrovasc Dis, 2007, 23(5-6): 353-361.
[94] Kawagoe R, Takikawa Y and Hikosaka O. Expectation of reward modulates cognitive signals in the basal ganglia [J]. Nat Neurosci, 1998, 1(5): 411-416.
[95] Lewis SJ, Dove A, Robbins TW, Barker RA and Owen AM. Striatal contributions to working memory: A functional magnetic resonance imaging study in humans [J]. Eur J Neurosci, 2004, 19(3):755-760.
[96] O'Sullivan M, Summers PE, Jones DK, Jarosz JM, Williams SC, Markus HS. Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study [J]. Neurology, 2001, 57(12): 2307-2310.
[1] Baddeley AD. Working Memory [M]. Science, 1992, 255: 556-592.
[2]徐科。神经生物学纲要[M]。北京:科学出版社,2000:311-350。
[3]刘昌。人类工作记忆的某些神经影像研究[J]。心理学报,2002,34(6): 634-642。
[4]李雪冰,罗跃嘉。人类工作记忆的事件相关电位研究[J]。心理科学进展,2005,13(4): 423-434。
[5]陈彩琦。工作记忆的ERP研究[J]。华南师范大学学报(社会科学版),2004,6: 114-120。
[6] Mecklinger A, Pfeifer E. Event-related potentials reveal topographical and temporal distinct neuronal activation patterns for spatial and object working memory [J]. Brain Res Cogn Brain Res, 1996, 4(3): 211-224.
[7] Bosch V, Mecklinger A, Friederici AD.Slow cortical potentials during retention of object, spatial, and verbal information [J]. Brain Res Cogn Brain Res, 2001, 10(3): 219-237.
[8]王益文,林崇德,魏景汉,等。工作记忆中汉字与空间的分离及动态优势半球的ERP效应[J]。心理学报,2004,36(3): 253-259。
[9]沃建中,罗良,林崇德。客体与空间工作记忆的分离:来自皮层慢电位的证据[J]。心理学报,2005,37(6): 729-738。
[10] Ruchkin DS, Grafrnan J, Krauss GL, Johnson Jr R, Canoune H, and Ritter W. Event-related brain potential evidence for a verbal working memory deficit in multiple sclerosis [J]. Brain, 1994, 117(Pt 2): 289-305.
[11] Babiloni C, Bares M, Vecchio F, Brazdil M, Jurak P, Moretti DV, et al. Synchronization of gamma oscillations increases functional connectivity of human hippocampus and inferior-middle temporal cortex during repetitive visuomotor events [J]. Eur J Neurosci, 2004, 19(11): 3088-3098.
[12] Jenkins L, Myerson J, Joerding JA, Hale S. Converging evidence that visuo-spatial cognition is more age-sensitive than verbal cognition [J]. Psychol Aging, 2000, 15(1): 157-175.
[13]罗华,谭华,李小刚。脑白质疏松症患者的事件相关电位研究[J]。实用医学杂志,2004,20(12): 1386-1387。
[14]赵士福,成戊川,肖道宏,等。脑老化过程中的白质损害与P300变化的关系[J]。中国临床康复,2002,6(17): 2531-2532。
[2] Rockwood K. Vascular cognitive impairment and vascular dementia [J]. J Neurol Sci, 2002, 203-204: 23-27.
[3] Desmond D. The neuropsychology of vascular cognitive impairment: is there a specific cognitive deficit [J]? J Neurol Sci, 2004, 226(1-2): 3-7.
[4] Lindeboom J, Weinstein H. Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer disease, and vascular cognitive impairment [J]. Eur J Pharmacol, 2004, 490(1-3): 83-86.
[5] Libon DJ, Bogdanoff B, Leopold N, Hurka R, Bonavita J, Skalina S, et al. Neuropsychological profiles associated with subcortical white matter alterations and Parkinson's disease: implications for the diagnosis of dementia [J]. Arch Clin Neuropsychol, 2001, 16(1): 19-32.
[6] O'Brien J. Behavioral symptoms in vascular cognitive impairment and vascular dementia [J]. Int Psychogeriatr, 2003, 15(Suppl 1): 133-138.
[7] Wentzel C, Rockwood K, MacKnight C, Hachinski V, Hogan DB, Feldman H, et al. Progression of impairment in patients with vascular cognitive impairment without dementia [J]. Neurology, 2001, 57(4): 714-716.
[8]杜万良,王荫华。血管性认知障碍[J]。中国康复理论与实践,2004,10(4): 238-240。
[9] Sachdev PS, Brodaty H, Valenzuela MJ, Lorentz L, Looi JC, Wen W, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients [J]. Neurology, 2004, 62(6): 912-919.
[10]张微微。MoCA量表——诊断轻度认知功能损害的重大突破[J]。天坛国际脑血管病会议,2008。
[11]詹丽漩,徐恩。缺血性脑白质病变的研究进展[J]。中华脑血管病杂志,2008,2(3): 174-177。
[12] Launer LJ, Berger K, Breteler MM, Dufouil C, Fuhrer R, Giampaoli S et al. Regionalvariability in the prevalence of cerebral white matter lesions: an MRI study in 9 European countries (CASCADE) [J]. Neuroepidemiology, 2006, 26(1): 23-29.
[13] Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location [J]. Neurology, 2004, 63(2): 246-253.
[14] Wolf H, Ecke GM, Bettin S, Dietrich J, Gertz HJ. Do white matter changes contribute to the subsequent development of dementia in patients with mild cognitive impairment? A longitudinal study [J]. Int J Geriatr Psychiatry, 2000, 15(9): 803-812.
[15] Schmidt R, Petrovic K, Ropele S, Enzinger C, Fazekas F. Progression of leukoaraiosis and cognition [J]. Stroke, 2007, 38(9): 2619-2625.
[16] De Groot JC, de Leeuw FE, Oudkerk M, van Gijn J, Hofman A, Jolles J et al. Cerebral white matter lesions and cognitive function: the Rotterdam Scan Study [J]. Ann Neurol, 2000, 47(2): 145-151.
[17] Barber R, Gholkar A, Scheltens P, Ballard C, Mckeith IG, O Brien JT. MRI volumetric correlates of white matter lesions in dementia with Lewy bodies and Alzheimers disease [J]. Int J Geriatr Psychiatry 2000, 15(10): 911-916.
[18]魏景汉,罗跃嘉。认知事件相关脑电位教程[M]。北京:经济日报出版社,2002:45- 53。
[19] Magnano I, Aiello I, Piras MR. Cognitive impairment and neurophysiological correlates in MS [J]. J Neurol Sci, 2006, 245(1-2): 117-122.
[20] Kemner C, van Engeland H. ERPs and eye movements reflect atypical visual perception in pervasive developmental disorder [J]. J Autism Dev Disord, 2006, 36(1): 45-54.
[21] Abramowitz JS. The psychological treatment of obsessive-compulsive disorder [J]. Can J Psychiatry. 2006, 51(7): 407-416.
[22] Pearlstein RD,Whitten C,Haerich P. Assessing neurocognitive dysfunction in cranial radiotherapy: can cognitive event-related potentials help [J]? Technol Cancer Res Treat,2006, 5(2): 109-125.
[23] Karl A, Malta LS, Maercker A. Meta-analytic review of event-related potential studies in post-traumatic stress disorder [J]. Biol Psychol, 2006, 71(2):123-147.
[24] Lew HL, Poole JH, Castaneda A, Salerno RM, Gray M. Prognostic value of evoked and event-related potentials in moderate to severe brain injury [J]. J Head Trauma Rehabil.2006, 21(4): 350-360.
[25] Cowan N, Morey CC. Visual working memory depends on attentional filtering [J]. Trends Cogn Sci, 2006, 10(4):139-141.
[26] Brown RD,Chiu CY. Neural correlates of memory development and learning: combining neuroimaging and behavioral measures to understand cognitive and developmental processes [J]. Dev Neuropsychol, 2006, 29(2):279-291.
[27]罗华,谭华,李小刚。脑白质疏松症患者的事件相关电位研究[J]。实用医学杂志,2004,20(12):1386-1387。
[28]赵士福,成戊川,肖道宏,等。脑老化过程中的白质损害与P300变化的关系[J]。中国临床康复,2002,6(17):2531-2532。
[29] Ruchkin DS, Grafrnan J, Krauss GL, Johnson Jr R, Canoune H, and Ritter W. Event-related brain potential evidence for a verbal working memory deficit in multiple sclerosis [J]. Brain, 1994, 117(Pt 2): 289-305.
[30] Baddeley AD. Is working memory still working [J]? Am Psychol, 2001, 56(11): 851-864.
[31] Goldman-Rakic PS. Working memory and the mind [J]. Sci Am, 1992, 267(3): 110-117.
[32] Miyake A, Shah P. Models of working memory: mechanisms of active maintenance and executive control [M]. New York: Cambridge University Press, 1999.
[33] Baddeley AD. Working Memory [J]. Science, 1992, 255: 556- 592.
[34]徐科。神经生物学纲要[M]。北京:科学出版社,1999:311-350。
[35]刘昌。人类工作记忆的某些神经影像研究[J]。心理学报,2002,34(6): 634-642。
[36]李雪冰,罗跃嘉。人类工作记忆的事件相关电位研究[J]。心理科学进展,2005,13(4): 423-434。
[37]陈彩琦。工作记忆的ERP研究[J]。华南师范大学学报(社会科学版),2004,6: 114-120。
[38] Babiloni C, Bares M, Vecchio F, Brazdil M, Jurak P, Moretti DV, et al. Synchronization of gamma oscillations increases functional connectivity of human hippocampus and inferior-middle temporal cortex during repetitive visuomotor events[J]. Eur J Neurosci, 2004, 19(11): 3088-3098.
[39] Mecklinger A, Pfeifer E. Event-related potentials reveal topographical and temporaldistinct neuronal activation patterns for spatial and object working memory [J]. Brain Res Cogn Brain Res, 1996, 4(3): 211-224.
[40] Bosch V, Mecklinger A, Friederici AD.Slow cortical potentials during retention of object, spatial, and verbal information [J]. Brain Res Cogn Brain Res, 2001, 10(3): 219-237.
[41]王益文,林崇德,魏景汉,等。工作记忆中汉字与空间的分离及动态优势半球的ERP效应[J]。心理学报,2004,36(3):253- 259。
[42]沃建中,罗良,林崇德。客体与空间工作记忆的分离:来自皮层慢电位的证据[J]。心理学报,2005,37(6): 729-738。
[43] Umeno MM, Goldberg ME. Spatial processing in the monkey frontal eye field. II. Memory responses [J]. J neurophysiol, 2001, 86(5): 2344-2352.
[44] Rowe JB, Toni I, Josephs O, Frackowiak RS, Passingham RE. The prefrontal cortex: Response selection or maintenance within working memory [J]? Science, 2000, 288(5471): 1656-1660.
[45] Klingberg T. Development of a superior frontal–intraparietal network for visuo-spatial working memory [J]. Neuropsychologia, 2006, 44: 2171–2177.
[46] Grady CL, Maisog JM, Horwitz B, Ungerleider LG, Mentis MJ, Salerno JA, et al. Age-related changes in cortical blood flow activation during visual processing of faces and location [J]. J Neurosci, 1994, 14(3 Pt 2): 1450-1462.
[47]王健,张久权。fMRI与DTI在神经科学研究中的联合应用[J]。现代生物医学进展,2007,7(2): 231-233。
[48] Song SK, Sun SW, Ju WK, Lin SJ, Cross AH, Neufeld AH. Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia [J]. Neuroimage, 2003, 20(3): 1714-1722.
[49] O'Sullivan M, Morris RG, Huckstep B, et al. Diffusion tensor MRI correlates with executive dysfunction in patients with ischemic leukoaraiosis [J]. J Neurol Neurosurg Psychiatry, 2004, 75: 441-447.
[50] Roman GC, Tatemichi TK, Erkinjuntti T, Cummings JL, Masdeu JC, Garcia JH, et al. Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop [J]. Neurology, 1993, 43(2): 250-260.
[51] Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, et al.Research criteria for subcortical vascular dementia in clinical trials [J]. J Neural Transm Suppl, 2000, 59: 23-30.
[52] Román GC, Erkinjuntti T, Wallin A, Pantoni L, Chui HC. Subcortical ischaemic vascular dementia [J]. Lancet Neurol, 2002, 1(7): 426-436.
[53] Caplan LR. Binswanger's disease--revisited. Neurology, 1995, 45(4): 626-633.
[54] Yue NC, Arnold AM, Longstreth WT, Elster AD, Jungreis CA, O'Leary DH, et al. Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the Cardiovascular Health Study [J]. Radiology, 1997, 202(1): 33-39.
[55] Wahlund LO, Barkhof F, Fazekas F, Bronge L, Augustin M, Sj?gren M, et al. A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT [J]. Stroke, 2001, 32(6): 1318-1322.
[56]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 71。
[57]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 95。
[58]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 17。
[59]汤慈美。神经心理学[M]。北京:人民军医出版社,2001: 315。
[60]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 93。
[61]许贤豪。神经心理量表检测指南[M]。北京:中国协和医科大学出版社,2007: 10。
[62] Daneman M, Hannon B. Using working memory theory to investigate the construct validity of multiple-choice reading comprehension tests such as the SAT [J]. J Exp Psychol Gen, 2001, 130(2): 208-223.
[63] Lezak M, Howieson D, Loring D. Neuropsychological Assessment [M]. New York: Oxford, 2004.
[64] O’Sullivan M, Morris RG, Markus HS. Brief cognitive assessment for patients with cerebral small vessel disease [J]. J Neurol Neurosurg Psychiatry, 2005; 76(8): 1140-1145.
[65] Storandt M, Botwinick J, Danziger WL, Berg L, Hughes CP. Psychometric differentiation of mild senile dementia of the Alzheimer type [J]. Arch Neurol, 1984, 41(5): 497-499.
[66]汤慈美。神经心理学[M]。北京:人民军医出版社,2001:308-326。
[67] Reitan R. Manual for Administration of Neuropsychological Test Batteries for Adults and Children [M]. Tucson: Reitan Neuropsychological Laboratory, 1979.
[68] van Swieten JC, Geyskes GG, Derix MM, Peeck BM, Ramos LM, van Latum JC. Hypertension in the elderly is associated with white matter lesions and cognitive decline [J]. Ann Neurol, 1991, 30(6): 825-830.
[69] van Zandvoort M, de Haan E, van Gijn J, Kappelle LJ. Cognitive functioning in patients with a small infarct in the brainstem [J]. J Int Neuropsychol Soc. 2003; 9(3): 490-494.
[70]汤慈美。神经心理学[M]。北京:人民军医出版社,2001:317。
[71] Carew TG, Lamar M, Cloud BS, Grossman M, Libon DJ. Impairment in category fluency in ischemic vascular dementia [J]. Neuropsychology, 1997, 11(3): 400-412.
[72] Hanyu H, Sato T, Akai T, Sakai M, Takasaki R, Iwamoto T. Awareness of memory deficits in patients with dementias: a study with the Everyday Memory Checklist [J]. Nippon Ronen Igakkai Zasshi, 2007, 44(4): 463-469.
[73] Hachinski V, Iadecola C, Petersen RC, Breteler MM, Nyenhuis DL, Black SE, et al. National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards [J]. Stroke, 2006, 37: 2220.
[74] Jonides J, Smith EE, Koeppe RA, Awh E, Minoshima S, Mintun MA. Spatial working memory in humans as revealed by PET [J]. Nature, 1993, 363(6430): 623-625.
[75] Jenkins L, Myerson J, Joerding JA, Hale S. Converging evidence that visuo-spatial cognition is more age-sensitive than verbal cognition [J]. Psychol Aging, 2000, 15(1):157-175.
[76] Pelosi L, Blumhardt LD. Effects of age on working memory: An event-related potential study [J]. Brain Res Cogn Brain Res, 1999: 7(3): 321-334.
[77] Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update [J]. J Psychosom Res, 2002, 53(2):647-654.
[78] Stuss DT, Levine B. Adult clinical neuropsychology: Lessons from studies of the frontal lobes [J]. Annu Rev Psychol, 2002, 53: 401-433.
[79] Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex [J]. Annu Rev Neurosci, 1986, 9: 357-381.
[80] Stuss DT, Bisschop SM, Alexander MP, Levine B, Katz D, Izukawa D. The trail making test: A study in focal lesion patients [J]. Psychol Assess, 2001, 13(2): 230-239.
[81] Alexander MP, Stuss DT, Shallice T, Picton TW, Gillingham S. Impaired concentration due to frontal lobe damage from two distinct lesion sites [J]. Neurology, 2005, 65(4): 572-579.
[82] Sachdev PS, Brodaty H, Valenzuela MJ, Lorentz L, Looi JC, Wen W, et al. The neuropsychological profile of vascular cognitive impairment in stroke and TIA patients [J]. Neurology, 2004, 62(6): 912-919.
[83] Ingles JL, Boulton DC, Fish JD, Rockwood K. Preclinical vascular cognitive impairment and Alzheimer disease: neuropsychological test performance 5 years before diagnosis [J]. Stroke, 2007, 38(4): 1148-1153.
[84] Garrett KD, Browndyke JN, Whelihan W, Paul RH, DiCarlo M, Moser DJ, et al. The neuropsychological profile of vascular cognitive impairment-no dementia: comparisons to patients at risk for cerebral vascular disease and vascular dementia [J]. Arch Clin Neuropsychol, 2004, 19(6): 745-757.
[85] Feldman H, Levy AR, Hsiung GY, Peters KR, Donald A, Black SE, et al. A Canadian cohort study of cognitive impairment and related dementias (ACCORD): study methods and baseline results [J]. Neuroepidemiology, 2003, 22(5): 265-274.
[86] Babcock RL, Laguna KD, Roesch SC. A comparison of the factor structure of processing speed for younger and older adults: testing the assumption of measurement equivalence across age groups [J]. Psychol Aging, 1997, 12(2): 268-276.
[87] Srimal R, Curtis CE. Persistent neural activity during the maintenance of spatial position in working memory [J]. NeuroImage, 2008, 39: 455–468.
[88] Wang XJ. Synaptic reverberation underlying mnemonic persistent activity [J]. Trends Neurosci, 2001, 24(8): 455-463.
[89] Pucak ML, Levitt JB, Lund JS, Lewis DA. Patterns of intrinsic and associational circuitry in monkey prefrontal cortex [J]. J Comp Neurol, 1996, 376(4):614-630.
[90] Bechara A, Damasio H, Tranel D, and Anderson SW. Dissociation of working memory from decision making within the human prefrontal cortex [J]. The Journal of Neuroscience, 1998, 18(1): 428-437.
[91] Collette F, Van der Linden M. Brain imaging of the central executive component of working memory [J]. Neurosci Biobehav Rev, 2002, 26(2):105-125.
[92] Salat DH, Tuch DS, Greve DN, van der Kouwe AJ, Hevelone ND, Zaleta AK, el al.Age-related alterations in while matter microstructure measured by diffusion tensor imaging [J]. Neurobiol Aging, 2005, 26(8):1215-1227.
[93] Grau-Olivares M, Bartrés-Faz D, Arboix A, Soliva JC, Rovira M, Targa C, et al. Mild cognitive impairment after lacunar infarction: voxel-based morphometry and neuropsychological assessment [J]. Cerebrovasc Dis, 2007, 23(5-6): 353-361.
[94] Kawagoe R, Takikawa Y and Hikosaka O. Expectation of reward modulates cognitive signals in the basal ganglia [J]. Nat Neurosci, 1998, 1(5): 411-416.
[95] Lewis SJ, Dove A, Robbins TW, Barker RA and Owen AM. Striatal contributions to working memory: A functional magnetic resonance imaging study in humans [J]. Eur J Neurosci, 2004, 19(3):755-760.
[96] O'Sullivan M, Summers PE, Jones DK, Jarosz JM, Williams SC, Markus HS. Normal-appearing white matter in ischemic leukoaraiosis: a diffusion tensor MRI study [J]. Neurology, 2001, 57(12): 2307-2310.
[1] Baddeley AD. Working Memory [M]. Science, 1992, 255: 556-592.
[2]徐科。神经生物学纲要[M]。北京:科学出版社,2000:311-350。
[3]刘昌。人类工作记忆的某些神经影像研究[J]。心理学报,2002,34(6): 634-642。
[4]李雪冰,罗跃嘉。人类工作记忆的事件相关电位研究[J]。心理科学进展,2005,13(4): 423-434。
[5]陈彩琦。工作记忆的ERP研究[J]。华南师范大学学报(社会科学版),2004,6: 114-120。
[6] Mecklinger A, Pfeifer E. Event-related potentials reveal topographical and temporal distinct neuronal activation patterns for spatial and object working memory [J]. Brain Res Cogn Brain Res, 1996, 4(3): 211-224.
[7] Bosch V, Mecklinger A, Friederici AD.Slow cortical potentials during retention of object, spatial, and verbal information [J]. Brain Res Cogn Brain Res, 2001, 10(3): 219-237.
[8]王益文,林崇德,魏景汉,等。工作记忆中汉字与空间的分离及动态优势半球的ERP效应[J]。心理学报,2004,36(3): 253-259。
[9]沃建中,罗良,林崇德。客体与空间工作记忆的分离:来自皮层慢电位的证据[J]。心理学报,2005,37(6): 729-738。
[10] Ruchkin DS, Grafrnan J, Krauss GL, Johnson Jr R, Canoune H, and Ritter W. Event-related brain potential evidence for a verbal working memory deficit in multiple sclerosis [J]. Brain, 1994, 117(Pt 2): 289-305.
[11] Babiloni C, Bares M, Vecchio F, Brazdil M, Jurak P, Moretti DV, et al. Synchronization of gamma oscillations increases functional connectivity of human hippocampus and inferior-middle temporal cortex during repetitive visuomotor events [J]. Eur J Neurosci, 2004, 19(11): 3088-3098.
[12] Jenkins L, Myerson J, Joerding JA, Hale S. Converging evidence that visuo-spatial cognition is more age-sensitive than verbal cognition [J]. Psychol Aging, 2000, 15(1): 157-175.
[13]罗华,谭华,李小刚。脑白质疏松症患者的事件相关电位研究[J]。实用医学杂志,2004,20(12): 1386-1387。
[14]赵士福,成戊川,肖道宏,等。脑老化过程中的白质损害与P300变化的关系[J]。中国临床康复,2002,6(17): 2531-2532。