皮质下缺血性血管性认知损害患者注意事件相关电位的临床研究
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摘要
研究目的
通过观察和分析皮质下缺血性血管性认知损害患者由不同刺激模式诱发的事件相关电位注意成分的变化特征,结合临床神经心理学测评结果(计算机辅助测验),探求反映血管性认知障碍早期注意损害的神经电生理指标,促进血管性认知损害诊断水平的提高;同时结合病变部位和事件相关电位溯源分析,探讨皮质下小血管病变引起的缺血性损害对注意神经环路的影响,提高对血管性认知损害病理机制的认识。
研究方法
对30例皮质下缺血性认知损害非痴呆型(Subcortical ischemic vascular cognitive impairment no dementia,SIVCIND)患者、15例皮质下缺血性痴呆(Subcortical ischemic vascular dementia,SIVD)患者和15例年龄、性别和教育程度匹配的正常对照,运用蒙特利尔认知测评量表(Montreal cognitive assessment,MoCA,Beijing Version)和简易精神状态检查量表检测总体认知功能,采用神经心理学计算机辅助测验CPT法、Stroop试验及双任务测试法分别测试持续注意、选择注意和分散注意;同时记录分析双耳分听、新奇刺激Oddball模式和视听命令-指令信号模式下诱发的事件相关电位(Event related potentials,ERPs)注意相关成分P20-50、新奇刺激P3a(Novelty P3a)和伴随负变化(Contingent negative variation,CNV)的变化特征,通过溯源分析定位ERPs各成分的电流源位置,绘制ERPs皮质电流密度图谱,分析ERPs的皮质功能激活区,探讨皮质下缺血性血管性认知损害患者皮质注意功能区的电生理变化特征。
结果
1.皮质下缺血性血管性认知损害患者总体认知功能评价
皮质下缺血性痴呆组MOCA各分项评分与年龄、性别和教育程度匹配正常对照组比较发现,执行、注意、延迟回忆、抽象和定向等认知功能水平降低(P<0.05),命名能力、语言重复及流畅性等认知功能水平无明显改变(P>0.05)。皮质下缺血性血管性认知损害非痴呆组与NC组比较,执行、注意和延迟回忆等认知功能水平降低,差异具有显著性(P<0.01),抽象、定向、命名能力、语言重复及流畅性等认知功能水平无明显降低(P>0.05)。
2.注意功能评价
(1)计算机辅助测验持续操作任务(Continuous Performance Task,CPT)--评估持续性注意SIVD患者与NC组比较,CPT反应时延长(P<0.01),漏报率增加(P<0.05)。SIVCIND患者与NC组比较CPT反应时无显著差异(P>0.05),漏报率增加(P <0.01)。
(2)计算机辅助测验Stroop法--评估选择性注意。SIVCIND患者与NC组比较,冲突条件下反应时延长(P<0.01),中性条件反应时无显著差异(P>0.05),冲突和中性条件下的反应时干扰量无显著差异(P>0.05),冲突和中性条件下的错误率增加(P<0.01),错误率干扰量无显著差异(P>0.05)。SIVD患者与NC比较,冲突条件反应时延长(P<0.01),中性条件下反应时延长(P<0.05),冲突和中性条件下错误率均增加(P<0.01),反应时干扰量和错误率干扰量增加,差异均有显著性(P<0.01)。
(3)纸笔试验Dual task法--评估分散性注意。与对照组比较,SIVCIND患者双任务与单任务耗时差无明显增加(P>0.05),而SIVD患者双任务与单任务耗时差增大(P<0.01)。.
3.事件相关电位注意成分检测
(1)CNV、差异波P20-50和Novelty P3a头皮分布实验中主要选择12个头皮记录电极(F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, O2)分为四个区域进行分析:额区(F3, Fz, F4)、中央区(C3, Cz, C4)、顶区(P3, Pz, P4)、枕区(O1, Oz, O2)。
各电极区域间CNV平均波幅有显著性差异(F(3,57)=8.11,P<0.01),中央区平均波幅最高(16.83±2.89μv )(P<0.01)。各电极区域间CNV面积有显著性差异(F(3,57)=43.66,P<0.01),中央区面积最大(19966.40±1105.9μV * ms) (SNK,P<0.05)。各电极区域间差异波P20-50波幅有显著性差异(F(3,57)=5.33,P<0.01)。枕区波幅最低(1.23±1.30μv)(SNK,P<0.05),各电极区域间潜伏期无显著差异(F(3,57)=1.078,P>0.05)。
各电极区域间Novelty P3a波幅有显著性差异(F(3,57)= 7.31,P<0.01)。额、中央区与顶、枕区比较波幅升高,有显著性差异(SNK,P<0.05)。各电极区域间Novelty P3a潜伏期无显著差异(F(3,57)=1.81,P>0.05)。
(2)皮质下缺血性血管性认知损害患者ERPs成分变化特征
SIVCIND、SIVD和NC组CNV期待波平均波幅有显著性差异(F(2,57)=34.34,P<0.01),组间两两比较差异具有显著性(P<0.05),NC组平均波幅(16.13±2.75μv)> SIVCIND组(9.98±4.10μv)> SIVD组(6.25±1.52μv)。CNV期待波面积三组间具有显著性差异( F(2,57)=48.75,P<0.01),组间两两比较差异具有显著性(P<0.05),NC组(20058.87±1025.95μV * ms )> SIVCIND组(14848.10±3199.16μV * ms)> SIVD组(8474.00±3511.94μV * ms)。CNV期待波潜伏期三组间无显著差异(F(2,57)=1.90,P>0.05)。
差异波P20-50 NC组波幅(3.10士1.49μv),SIVCIND组(2.63士1.28μv),SIVD组(1.21士0.45μv),三组组间差异有显著性(F(2,55)=2.23,P<0.05)。组间两两比较差异具有显著性(P<0.05),SIVD患者与NC组和SIVCIND组患者比较波幅降低, SIVCIND组与NC组间波幅无显著性差异((P>0.05)。P20-50潜伏期三组间具有显著性差异(F(2,57)=8. 70,P<0.01)。组间两两比较差异具有显著性(P<0.05),SIVD组潜伏期(77.47士28.22ms) >SIVCIND组(60.47士18.0ms)> NC组(46.73士13.93ms )。
Novelty P3a波幅三组间差异具有显著性(F(2,57)=15.84,P<0.01)。组间两两比较组间具有显著差异(P<0.05),SIVD组(1.58士0.68μv)与NC组和SIVCIND组比较波幅降低,NC组(3.69士1.41μv)与SIVCIND组(3.37士1.20)间无显著差异(P>0.05)。Novelty P3a潜伏期三组间差异具有显著性(F(2,57)=10.83,P<0.01)。组间两两比较差异具有显著性(P<0.05),SIVD组(331.13士37.26 ms)与NC组和SIVCIND组比较潜伏期延长,NC组(275.93士35.24 ms)与SIVCIND组(294.40士30.31 ms)之间无显著差异(P>0.05)。
(3)皮质下缺血性血管性认知损害患者ERPs与神经心理学测验的相关性
1)CNV与CPT的相关性
Pearson correlation\Spearman等级相关分析: EW潜伏期与CPT反应时呈正相关(R=0.748,P<0.01),与CPT漏报率无相关性(R=0.22,P>0.05);EW平均波幅与CPT反应时呈负相关(R=-0.616,P<0.01),与CPT漏报率无相关性(R=-0.191,P>0.05);EW平均面积CPT反应时呈负相关(R=-0.718,P<0.01);与CPT漏报率呈负相关(R=-0.829 ,P<0.01)。相关分析结果表明EW平均面积与CPT具有较好的相关性。
2)差异波P20-50与Stroop的相关性
Pearson correlation\Spearman等级相关分析:差异波P20-50潜伏期与Stroop反应时干扰量(R=0.289,P<0.05)和Stroop错报率干扰量(R=0.334,P<0.05)均呈正相关;P20-50平均波幅与Stroop反应时干扰量呈负相关(R=-0.249,P<0.05),与Stroop错报率干扰量无相关性(R=-0.213,P>0.05)。相关分析结果表明P20-50潜伏期与Stroop具有较好的相关性。
3) Novelty P3a与双任务测试法的相关性
Pearson correlation\Spearman等级相关分析:双任务测试法时间差值与Novelty P3a潜伏期呈正相关(R=0.38,P<0.01),与平均波幅呈负相关(R=-0.28,P<0.05)。相关分析结果表明Novelty P3a潜伏期与双任务测试法相关性较好。
4.事件相关电位各成分溯源分析
对正常对照CNV总平均图形S1前1500ms到S1做主成分(PCA)分析,结果显示主成分可以解释变异的98. 8%,其它成分单独的解释都不超过1%,确定偶极子源定位在左侧前额叶附近( Talairach坐标系值为:x =-17.6,y =61.5, z =0.6),在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为11.39%。
差异波P20-50总平均图形0到100ms主成分分析结果显示:两个主成分可以解释变异的98. 0% ,其它成分单独的解释都不超过1%,因此确定两个偶极子。不限制偶极子的方向和位置。偶极子源1定位在右侧颞叶上回(right superior temporal gyrus)附近( Talairach坐标系值为:x = 22. 0,y = -7.4,z = 16.2);偶极子源2定位在右侧额叶后部(right orbitofrontal cortex)附近( Talairach坐标系值为:x = 20.0,y = 21.2,z = 28. 4)。在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为10. 29%。
Novelty P3a总平均图形150到350ms主成分分析结果显示:主成分可以解释变异的98.1%,其它成分单独的解释都不超过1%,因此确定2个偶极子。偶极子1最大偶极子强度在365ms,定位在前额叶中部附近( Talairach坐标系值:x =9.0,y =27.4,z =8.9);偶极子源2最大偶极子强度在295ms,定位在前颞叶中部近中线附近( Talairach坐标系值为: x =-2.8,y =3.4, z =6.8)。在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为9.39%。
5.ERPs成分皮质电流源密度分析
正常对照者CNV成分时间窗内皮质电流源密度图谱可见双侧额叶上部皮层密集电流分布,尤以右侧前额明显,顶叶也有高密度电流分布,SIVCI组顶叶及右侧额叶外侧皮层电流密度明显减弱,右颞区、中央区不同程度激活。推测双侧额叶、顶叶皮质资源可能为持续性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,颞区、中央区等次要功能区的皮质资源被调动来参与认知活动。
正常对照者差异波P20-50成分时间窗内皮质电流源密度图谱可见双侧(右侧明显)颞区密集电流分布,双侧额叶外侧皮层,左侧顶区也有高密度电流分布;SIVCI组患者双额叶外侧,右侧颞区皮层电流源密度明显减弱,中央区、枕区明显激活。推测双侧颞叶、额叶皮质资源可能为选择性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,中央区、枕区等次要功能区的皮质资源被调动来参与认知活动。
正常对照者Novelty P3a成分时间窗内皮质电流源密度图谱可见左侧额上部,右侧额叶外侧密集电流分布,左侧颞区、右侧顶区及枕区轻度激活;SIVCI组患者双侧额叶外侧皮层电流密度明显减弱,左颞区、枕区电流源密度增强。推测双侧额叶皮质资源可能为分散性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,枕区、颞区等次要功能区的皮质资源被调动来参与认知活动。
结论
1.总体认知功能评价研究发现皮质下缺血性血管性认知损害早期(皮质下缺血性血管性认知损害非痴呆)以执行、注意、延迟回忆等认知损害较突出,而晚期(皮质下缺血性痴呆)执行、注意、延迟回忆、抽象、定向等认知水平降低,而命令、语言认知等无明显损害。
2.神经心理学计算机辅助测验[CPT法(评估持续性注意),Stroop法(评估选择性注意)]及纸笔实验[双任务法(评估分散性注意)]结果提示皮质下缺血性血管性认知损害早期主要以持续性注意较完全性损害,选择性注意部分损害为表现;晚期注意障碍普遍存在,持续注意、选择注意、分散注意均明显受累。
3.视听命令-指令信号模式、双耳分听和新奇刺激Oddball模式下诱发的事件相关电位CNV、P20-50和Novelty P3a成分分别与CPT、Stroop实验和双任务法指标具有较好的相关性,可作为反映皮质下缺血性血管性认知损害患者注意认知功能损害的神经电生理辅助指标,尤其是CNV期待波面积、P20-50潜伏期和Novelty P3a潜伏期等指标异常能更准确反映持续注意、选择注意和分散注意等注意亚型的损害。
4.皮质下缺血性血管性认知损害晚期CNV、P20-50和Novelty P3a普遍异常,而皮质下缺血性血管性认知损害早期仅CNV期待波的平均波幅与面积及P20-50潜伏期异常,表明CNV和P20-50成分对血管性认知损害早期注意损害的评价更敏感。
5.CNV偶极子源定位于左侧前额叶附近;P20-50偶极子源1定位在右侧颞叶上回,偶极子源2定位在右侧额叶后部;Novelty P3a偶极子源1定位在前额叶中部附近,偶极子源2定位在前颞叶中部近中线附近。
6.皮质下缺血性血管性认知损害患者因缺血性小血管病变破坏注意相关的额叶-皮质下神经功能环路,影响事件相关电位注意成分偶极子起源,次要功能区皮质资源激活参与注意认知加工。
Purpose
We observed and analysed the attention components of event related potentials (ERPs) evoked by various stimulus modalities in patients with subcortical ischemic vascular cognitive impairments (SIVCI) and the clinical neuropsychological test, in order to find neuroelectrophysiological indeces to reflect attention impairment in earlier period of vascular cognitive impairment for improving its diagnostic quality. We studied the relationship between diseased region and brain electrical source analysis of event related potentials, in order to investigate the influence on attention nerve loop by ischemic impairment from small subcortical vessel lesion, and enhance the understanding for the pathomechanism of subcortical ischemic vascular impairment .
Methods
The subjects included 30 patients with vascular cognitive impairment no dementia (SIVCIND), 15 patients with subcortical ischemic vascular dementia (SIVD) and 15 age, sex, and education-matched normal control. The general cognitive functions of the subjects were assessed by Montreal cognitive assessment (MoCA) Beijing Version and mini-mental state examination (MMSE), attention functions were assessed by continuous performance task (CPT), stroop test and Dual task. The event related potentials different wave P20-50, Novelty P3a and contingent negative variation (CNV) of the subjects evoked by dichotic listening, novelty stimulus Oddball mode and order-command signal two-stimulus paradigm were recorded.We locate the source position of ERPs component by brain electrical source analysis (BESA) and draw cortical current source density (CSD) and analysis cortical functional transactivation domain for investigating electrophysiological variation characteristics of cortical attention functional zones.
Results
1. The general assessment of cognitive functional of patients with SIVD
SIVD patients had obvious cognitive disorder in visuospatial and executive function, attention, delayed memory, abstract and orientation (P<0.05), and no cognitive disorder in naming and verbalization compared with NC (P>0.05). SIVCIND patients had obvious cognitive disorder in visuospatial and executive function, attention and delayed memory(P<0.05), and no cognitive disorder in abstract, orientation, naming and verbalization compared with NC(P>0.05).
2. The neuropsychological assessment of attention
(1)Continuous performance task (CPT) ---a computer-assisted test for assessing sustained attention
Reaction time of CPT had significantly prolonged and omission rate of CPT had increased in SIVD patients(P<0.05)compared with NC. Reaction time in CPT had no significantly prolonged (P>0.05) and omission rate had increased in SIVD patients(P<0.05)compared with NC(P <0.01).
(2) Stroop test ----a computer-assisted test for assessing selective attention
In stroop test, reaction time under conflict condition had significantly prolonged(P<0.01), reaction time under neutral condition condition as well as RT stroop effect under conflict and neutral conditions had not prolonged (P>0.05) ,and error rate under conflict and neutral conditions had significantly increased(P<0.01), interfered effects of error rate under conflict and neutral conditions had not increased (P>0.05) in SIVCIND patients compared with NC. Reaction time, error rate and their interfered effect had obviously increased in SIVD patients compared with NC (P<0.01).
(3)Dual task -----for assessing divided attention
SIVCIND group did as well as the normal control in the Dual task test (P>0.05). SIVD group did worse in dual task than control subjects (P<0.01).
3. Detection of attention component of event related potentials
(1) Scalp distribution of CNV, difference wave P20-50 and Novelty P3a in normal control
Twelve channels of EEG (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, O2) were divided four electrode sites including frontal region ( F3, Fz, F4)、central region (C3, Cz, C4)、parietal region (P3, Pz, P4) and occipital region (O1, Oz, O2).
ANOVA results indicated a significant difference in CNV average amplitude across four electrode sites (F(3,57)=8.11,P<0.01). Average amplitude of central region is highest (16.83±2.89μv ) (SNK, P<0.05). No significant differences in latency variation across electrode zones were observed (P>0.05).ANOVA results indicated a significant difference in CNV areas across electrode sites (F (3,57)=43.66,P<0.01), CNV areas in central region (19966.40±1105.9μV * ms) was highest (SNK, P<0.05).
ANOVA results indicated a significant difference in difference wave P20-50 amplitude across electrode sites (F (3,57)=5.33, P<0.01). Amplitude of occipital region which was lowest (1.23士1.30μv), No significant differences in latency variations across electrode zones were observed (SNK, P>0.05).
ANOVA results indicated a significant difference in Novelty P3a amplitude across electrode sites (F(3,57)= 7.31,P<0.01), Novelty P3a amplitude in frontal-central region were higher than occipital–parietal region (SNK, P<0.05).No significant differences in latency across electrode zones were observed (F(3,57)=1.81, P>0.05).
(2) Characteristics of ERPs component in patients with SIVCI.
ANOVA results indicated a significant difference in CNV expectancy wave amplitude among SIVCIND group, SIVD group and NC groups (F(2,57) =34.34, P<0.01), Post hoc(SNK) analysis revealed that NC group(16.13±2.75μv) > SIVCIND group(9.98±4.10μv)> SIVD group(6.25±1.52μv) (P<0.05). ANOVA results indicated a significant difference in CNV expectancy wave areas among three groups(F(2,57)=48.75, P<0.01), Post hoc(SNK) analysis revealed that NC group(20058.87±1025.95μV*ms)> SIVCIND group(14848.10±3199.16μV*ms) > SIVD group(8474.00±3511.94μV*ms) (P<0.05).No significant differences in CNV expectancy wave latency among three groups were observed(F(2,57)=1.90,P>0.05).
ANOVA results indicated a significant difference inP20-50 amplitude among three groups(F(2,55)=2.23,P<0.05). Post hoc(SNK) analysis revealed that SIVD group average amplitude was lower(1.21士0.45μv)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(2.63士1.28μv)and NC group(3.10士1.49μv) (P>0.05). ANOVA results indicated a significant difference in P20-50 latency among three groups(F(2,57)=8. 70,P<0.01), Post hoc(SNK) analysis revealed that NC group(77.47士28.22ms) < SIVCIND group(60.47士18.0ms)< SIVD group(46.73士13.93ms)(P<0.05).
ANOVA results indicated a significant difference in Novelty P3a amplitude among three groups (F(2,55)=2.23,p<0.05).The Post hoc(SNK) analysis revealed that SIVD group has lower average amplitude(1.58士0.68μv)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(3.37士1.20)and NC group(3.69士1.41μv) (P>0.05). ANOVA results indicated a significant difference in Novelty P3a latency among three groups (F(2,55)=2.23,P<0.05). The Post Hoc(SNK) analysis revealed that SIVD group hasprolonged latency(331.13士37.26 ms)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(294.40士30.31 ms)and NC group(275.93士35.24 ms) (P>0.05).
(3)Relationship between ERPs and neuropsychological data
1) Relationship between CNV and CPT
Pearson correlation\Spearman rank correlation analysis revealed there were significant, positive correlations between EW latency and reaction time of CPT(R=0.748, P<0.01), there were no significant relationships between CPT ommision rate and EW latency(R=0.22, P>0.05),amplitude (R=-0.191, P>0.05), there were significant, negative correlations between EW area and reaction time of CPT(R=-0.718, P<0.01), ommision rate of CPT(R=-0.829, P<0.01), EW amplitude and reaction time of CPT(R=-0.616, P<0.01). Correlation analysis revealed EW area had a good correlation with CPT.
2) Relationship between difference wave P20-50 and Stroop test
Pearson correlation\Spearman rank correlation analysis revealed there were significant, positive correlations between P20-50 latency and interfered effect of reaction time in stroop test(R=0.289, P<0.05), P20-50 latency and interfered effect of error rate(R=0.289, P<0.05). P20-50 amplitude correlated positively with interfered effect of reaction time in stroop test(R=--0.249, P<0.05)and had no correlation with interfered effect of error rate(R=-0.213,P>0.05). Correlation analysis revealed P20-50 latency had a good correlation with stroop test.
3) Relationship between Novelty P3a and Dual task
Pearson correlation\Spearman rank correlation analysis revealed dual task time difference correlated positively with Novelty P3a latency(R=0.38, P<0.01), and correlated negatively with Novelty P3a amplitude(R=--0.48,P<0.01). Correlation analysis revealed Novelty P3a latency had a good correlation with dual task.
4. Brain electrical source analysis of ERPs components
A principal component analysis was performed on the grand wave of CNV innormal control in -1500ms--0 (S1)time window, which revealed one component explaining 98. 8% of the variance,dipole can be approximately located in the left prefrontal lobe( Talairach: x = -17.6, y =61.5, z =0.6).At the peak point of dipole activity, the configuration can successfully explain the data in the time interview,and have a smallest residual variance(11. 39%).
A principal component analysis was performed on the grand wave of P20-50 in normal control in 0-100ms time interval, this which revealed two component explaining 98. 0% of the variance, dipole1can be approximately located in the right superior temporal gyrus (Talairach: x = 22. 0,y = -7.4,z = 16.2)) ,dipole 2 can be approximately located in the right orbitofrontal cortex (Talairach:x = 20.0, y = 21.2,z = 28. 4).At the peak point of dipole activity, the configuration can successfully explain the data in the time window, and have a smallest residualvariance(10. 29%).
A principal component analysis was performed on the grand wave of Novelty P3a in 150-350ms time window, which revealed two components explaining 98. 1% of the variance, dipole1can be approximately located in the middle of prefrontal lobe ( Talairach:x =9.0, y =27.4,z =8.9), dipole2 can be approximately located in the medianpart of anterior temporal lobe near the median line( Talairach: x =-2.8,y =3.4, z =6.8).At the peak point of dipole activity, the configuration can successfully explain the data in the time window, and have a smallest residual variance(9. 39%).
5. Analysis of cortical current source density of ERPs
In normal control, CSD mapping of CNV revealed current density were intensive in bilateral (especially right )superior frontal lobe,bilateral parietal lobe were also activated. In SIVCI group, current density of right parietal lobe and right frontal lobe decreased obviously, right temporal region and central region activated at different degree. The CSD results demonstrated bilateral frontal lobe and parietal lobe participated in sustained attention information processing in physiological condition, when attention dipole source and neurocircuitry was damaged, temporal region and central region may participate in information processing.
In normal control, CSD mapping of P20-50 revealed current density were intensive in bilateral temporal lobe, bilateral anterior frontal lobe and left parietal lobe were also activated. in SIVCI group, current density of right temporal lobe and bilateral frontal lobe decreased obviously, occipital region and central region were activated at different degree. The CSD results demonstrated bilateral temporal lobe and frontal lobe participated in selected attention information processing in physiological condition, when dipole source of attentional ERPs and neurocircuitry damaged, occipital region and central region may participate in information processing.
In normal control, CSD mapping of Novelty P3a revealed current density were intensive in left superior frontal lobe and right frontal lobe ,left superior lobe and right parietal lobe were also activated, current density was feeble in occipital region .In SIVCI group, current density of frontal lobe decreased obviously, occipital region and left superior lobe activated obviously. The CSD results demonstrated bilateral frontal lobe may be principle cortical function zone of divided attention, when attention dipole source and neurocircuitry was damaged, occipital region and central region may participate in information processing.
Conclusion
1. SIVCI patients had obvious disorders in general assessment of cognitive function. Executive function, attention and delayed memory were predominant in cognitive impairment of SIVCIND patients, and SIVD patients had obvious cognitive impairment in executive function, attention, delayed memory,abstract and orientation, but no cognitive disorder in naming and verbalization .
2.The results of computer-assisted test [CPT(assessing sustained attention function), stroop test(assessing selected attention function)]and dual task(assessing scattered attention.) revealed SIVCIND patients had predominance in sustained attention impairment completely and selective attention impairment partly, SIVD patients had general, obvious disorders in sustained attention, selective attention and divided attention.
3.Event related potential P20-50,Novelty P3a and CNV evoked by dichotic listening, novelty stimulus Oddball mode and order-command signal two-stimulus paradigm respectively correlated with CPT, stroop test and dual task, and may be neuroelectrophysiological assistant indeces for assessing attention impairment of patients with SIVCI. Especially EW area, P20-50 latency and Novelty P3a latency may be more accurate to assess impairment of sustained attention, selective attention and divided attention.
4.SIVD patients had widely abnormal expectancy wave, P20-50 and Novelty P3a, while only amplitude and area of Expectancy wave, P20-50 latency were abnormal in SIVCIND patients, which indicated expectancy wave, P20-50 latency may be more sensitive to assess attention impairment in earlier period of VCI.
5. CNV dipole can be approximately located in the left prefrontal lobe( Talairach: x =-17.6,y =61.5,z =0.6). P20-50 dipole1 can be approximately located in the right superior temporal gyrus (Talairach: x = 22. 0, y = -7.4, z = 16.2), dipole 2 can be approximately located in the right frontal cortex (Talairach:x = 20.0, y = 21.2, z = 28. 4). Novelty P3a dipole1can be approximately located in the middle of prefrontal lobe ( Talairach: x =9.0, y =27.4, z =8.9), dipole 2 can be approximately located in the median part of anterior temporal lobe near the median line( Talairach: x =-2.8, y =3.4, z =6.8).
6. Frontal-subcortical attentive circuits were disrupted by lacunar infarcts or deep white matter changes in SIVCI patients, and dipole resource of ERPs attention components were influenced, cortical resource of second domain may be activated and participated in attention information process .
通过观察和分析皮质下缺血性血管性认知损害患者由不同刺激模式诱发的事件相关电位注意成分的变化特征,结合临床神经心理学测评结果(计算机辅助测验),探求反映血管性认知障碍早期注意损害的神经电生理指标,促进血管性认知损害诊断水平的提高;同时结合病变部位和事件相关电位溯源分析,探讨皮质下小血管病变引起的缺血性损害对注意神经环路的影响,提高对血管性认知损害病理机制的认识。
研究方法
对30例皮质下缺血性认知损害非痴呆型(Subcortical ischemic vascular cognitive impairment no dementia,SIVCIND)患者、15例皮质下缺血性痴呆(Subcortical ischemic vascular dementia,SIVD)患者和15例年龄、性别和教育程度匹配的正常对照,运用蒙特利尔认知测评量表(Montreal cognitive assessment,MoCA,Beijing Version)和简易精神状态检查量表检测总体认知功能,采用神经心理学计算机辅助测验CPT法、Stroop试验及双任务测试法分别测试持续注意、选择注意和分散注意;同时记录分析双耳分听、新奇刺激Oddball模式和视听命令-指令信号模式下诱发的事件相关电位(Event related potentials,ERPs)注意相关成分P20-50、新奇刺激P3a(Novelty P3a)和伴随负变化(Contingent negative variation,CNV)的变化特征,通过溯源分析定位ERPs各成分的电流源位置,绘制ERPs皮质电流密度图谱,分析ERPs的皮质功能激活区,探讨皮质下缺血性血管性认知损害患者皮质注意功能区的电生理变化特征。
结果
1.皮质下缺血性血管性认知损害患者总体认知功能评价
皮质下缺血性痴呆组MOCA各分项评分与年龄、性别和教育程度匹配正常对照组比较发现,执行、注意、延迟回忆、抽象和定向等认知功能水平降低(P<0.05),命名能力、语言重复及流畅性等认知功能水平无明显改变(P>0.05)。皮质下缺血性血管性认知损害非痴呆组与NC组比较,执行、注意和延迟回忆等认知功能水平降低,差异具有显著性(P<0.01),抽象、定向、命名能力、语言重复及流畅性等认知功能水平无明显降低(P>0.05)。
2.注意功能评价
(1)计算机辅助测验持续操作任务(Continuous Performance Task,CPT)--评估持续性注意SIVD患者与NC组比较,CPT反应时延长(P<0.01),漏报率增加(P<0.05)。SIVCIND患者与NC组比较CPT反应时无显著差异(P>0.05),漏报率增加(P <0.01)。
(2)计算机辅助测验Stroop法--评估选择性注意。SIVCIND患者与NC组比较,冲突条件下反应时延长(P<0.01),中性条件反应时无显著差异(P>0.05),冲突和中性条件下的反应时干扰量无显著差异(P>0.05),冲突和中性条件下的错误率增加(P<0.01),错误率干扰量无显著差异(P>0.05)。SIVD患者与NC比较,冲突条件反应时延长(P<0.01),中性条件下反应时延长(P<0.05),冲突和中性条件下错误率均增加(P<0.01),反应时干扰量和错误率干扰量增加,差异均有显著性(P<0.01)。
(3)纸笔试验Dual task法--评估分散性注意。与对照组比较,SIVCIND患者双任务与单任务耗时差无明显增加(P>0.05),而SIVD患者双任务与单任务耗时差增大(P<0.01)。.
3.事件相关电位注意成分检测
(1)CNV、差异波P20-50和Novelty P3a头皮分布实验中主要选择12个头皮记录电极(F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, O2)分为四个区域进行分析:额区(F3, Fz, F4)、中央区(C3, Cz, C4)、顶区(P3, Pz, P4)、枕区(O1, Oz, O2)。
各电极区域间CNV平均波幅有显著性差异(F(3,57)=8.11,P<0.01),中央区平均波幅最高(16.83±2.89μv )(P<0.01)。各电极区域间CNV面积有显著性差异(F(3,57)=43.66,P<0.01),中央区面积最大(19966.40±1105.9μV * ms) (SNK,P<0.05)。各电极区域间差异波P20-50波幅有显著性差异(F(3,57)=5.33,P<0.01)。枕区波幅最低(1.23±1.30μv)(SNK,P<0.05),各电极区域间潜伏期无显著差异(F(3,57)=1.078,P>0.05)。
各电极区域间Novelty P3a波幅有显著性差异(F(3,57)= 7.31,P<0.01)。额、中央区与顶、枕区比较波幅升高,有显著性差异(SNK,P<0.05)。各电极区域间Novelty P3a潜伏期无显著差异(F(3,57)=1.81,P>0.05)。
(2)皮质下缺血性血管性认知损害患者ERPs成分变化特征
SIVCIND、SIVD和NC组CNV期待波平均波幅有显著性差异(F(2,57)=34.34,P<0.01),组间两两比较差异具有显著性(P<0.05),NC组平均波幅(16.13±2.75μv)> SIVCIND组(9.98±4.10μv)> SIVD组(6.25±1.52μv)。CNV期待波面积三组间具有显著性差异( F(2,57)=48.75,P<0.01),组间两两比较差异具有显著性(P<0.05),NC组(20058.87±1025.95μV * ms )> SIVCIND组(14848.10±3199.16μV * ms)> SIVD组(8474.00±3511.94μV * ms)。CNV期待波潜伏期三组间无显著差异(F(2,57)=1.90,P>0.05)。
差异波P20-50 NC组波幅(3.10士1.49μv),SIVCIND组(2.63士1.28μv),SIVD组(1.21士0.45μv),三组组间差异有显著性(F(2,55)=2.23,P<0.05)。组间两两比较差异具有显著性(P<0.05),SIVD患者与NC组和SIVCIND组患者比较波幅降低, SIVCIND组与NC组间波幅无显著性差异((P>0.05)。P20-50潜伏期三组间具有显著性差异(F(2,57)=8. 70,P<0.01)。组间两两比较差异具有显著性(P<0.05),SIVD组潜伏期(77.47士28.22ms) >SIVCIND组(60.47士18.0ms)> NC组(46.73士13.93ms )。
Novelty P3a波幅三组间差异具有显著性(F(2,57)=15.84,P<0.01)。组间两两比较组间具有显著差异(P<0.05),SIVD组(1.58士0.68μv)与NC组和SIVCIND组比较波幅降低,NC组(3.69士1.41μv)与SIVCIND组(3.37士1.20)间无显著差异(P>0.05)。Novelty P3a潜伏期三组间差异具有显著性(F(2,57)=10.83,P<0.01)。组间两两比较差异具有显著性(P<0.05),SIVD组(331.13士37.26 ms)与NC组和SIVCIND组比较潜伏期延长,NC组(275.93士35.24 ms)与SIVCIND组(294.40士30.31 ms)之间无显著差异(P>0.05)。
(3)皮质下缺血性血管性认知损害患者ERPs与神经心理学测验的相关性
1)CNV与CPT的相关性
Pearson correlation\Spearman等级相关分析: EW潜伏期与CPT反应时呈正相关(R=0.748,P<0.01),与CPT漏报率无相关性(R=0.22,P>0.05);EW平均波幅与CPT反应时呈负相关(R=-0.616,P<0.01),与CPT漏报率无相关性(R=-0.191,P>0.05);EW平均面积CPT反应时呈负相关(R=-0.718,P<0.01);与CPT漏报率呈负相关(R=-0.829 ,P<0.01)。相关分析结果表明EW平均面积与CPT具有较好的相关性。
2)差异波P20-50与Stroop的相关性
Pearson correlation\Spearman等级相关分析:差异波P20-50潜伏期与Stroop反应时干扰量(R=0.289,P<0.05)和Stroop错报率干扰量(R=0.334,P<0.05)均呈正相关;P20-50平均波幅与Stroop反应时干扰量呈负相关(R=-0.249,P<0.05),与Stroop错报率干扰量无相关性(R=-0.213,P>0.05)。相关分析结果表明P20-50潜伏期与Stroop具有较好的相关性。
3) Novelty P3a与双任务测试法的相关性
Pearson correlation\Spearman等级相关分析:双任务测试法时间差值与Novelty P3a潜伏期呈正相关(R=0.38,P<0.01),与平均波幅呈负相关(R=-0.28,P<0.05)。相关分析结果表明Novelty P3a潜伏期与双任务测试法相关性较好。
4.事件相关电位各成分溯源分析
对正常对照CNV总平均图形S1前1500ms到S1做主成分(PCA)分析,结果显示主成分可以解释变异的98. 8%,其它成分单独的解释都不超过1%,确定偶极子源定位在左侧前额叶附近( Talairach坐标系值为:x =-17.6,y =61.5, z =0.6),在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为11.39%。
差异波P20-50总平均图形0到100ms主成分分析结果显示:两个主成分可以解释变异的98. 0% ,其它成分单独的解释都不超过1%,因此确定两个偶极子。不限制偶极子的方向和位置。偶极子源1定位在右侧颞叶上回(right superior temporal gyrus)附近( Talairach坐标系值为:x = 22. 0,y = -7.4,z = 16.2);偶极子源2定位在右侧额叶后部(right orbitofrontal cortex)附近( Talairach坐标系值为:x = 20.0,y = 21.2,z = 28. 4)。在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为10. 29%。
Novelty P3a总平均图形150到350ms主成分分析结果显示:主成分可以解释变异的98.1%,其它成分单独的解释都不超过1%,因此确定2个偶极子。偶极子1最大偶极子强度在365ms,定位在前额叶中部附近( Talairach坐标系值:x =9.0,y =27.4,z =8.9);偶极子源2最大偶极子强度在295ms,定位在前颞叶中部近中线附近( Talairach坐标系值为: x =-2.8,y =3.4, z =6.8)。在偶极子活动的峰值时刻,这一模型可以最好地解释该段时间窗口的数据,并且能够解释最多的变异,其残差为9.39%。
5.ERPs成分皮质电流源密度分析
正常对照者CNV成分时间窗内皮质电流源密度图谱可见双侧额叶上部皮层密集电流分布,尤以右侧前额明显,顶叶也有高密度电流分布,SIVCI组顶叶及右侧额叶外侧皮层电流密度明显减弱,右颞区、中央区不同程度激活。推测双侧额叶、顶叶皮质资源可能为持续性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,颞区、中央区等次要功能区的皮质资源被调动来参与认知活动。
正常对照者差异波P20-50成分时间窗内皮质电流源密度图谱可见双侧(右侧明显)颞区密集电流分布,双侧额叶外侧皮层,左侧顶区也有高密度电流分布;SIVCI组患者双额叶外侧,右侧颞区皮层电流源密度明显减弱,中央区、枕区明显激活。推测双侧颞叶、额叶皮质资源可能为选择性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,中央区、枕区等次要功能区的皮质资源被调动来参与认知活动。
正常对照者Novelty P3a成分时间窗内皮质电流源密度图谱可见左侧额上部,右侧额叶外侧密集电流分布,左侧颞区、右侧顶区及枕区轻度激活;SIVCI组患者双侧额叶外侧皮层电流密度明显减弱,左颞区、枕区电流源密度增强。推测双侧额叶皮质资源可能为分散性注意信息处理的主要皮质功能区,病理状态下主要功能区皮质资源激活减少,枕区、颞区等次要功能区的皮质资源被调动来参与认知活动。
结论
1.总体认知功能评价研究发现皮质下缺血性血管性认知损害早期(皮质下缺血性血管性认知损害非痴呆)以执行、注意、延迟回忆等认知损害较突出,而晚期(皮质下缺血性痴呆)执行、注意、延迟回忆、抽象、定向等认知水平降低,而命令、语言认知等无明显损害。
2.神经心理学计算机辅助测验[CPT法(评估持续性注意),Stroop法(评估选择性注意)]及纸笔实验[双任务法(评估分散性注意)]结果提示皮质下缺血性血管性认知损害早期主要以持续性注意较完全性损害,选择性注意部分损害为表现;晚期注意障碍普遍存在,持续注意、选择注意、分散注意均明显受累。
3.视听命令-指令信号模式、双耳分听和新奇刺激Oddball模式下诱发的事件相关电位CNV、P20-50和Novelty P3a成分分别与CPT、Stroop实验和双任务法指标具有较好的相关性,可作为反映皮质下缺血性血管性认知损害患者注意认知功能损害的神经电生理辅助指标,尤其是CNV期待波面积、P20-50潜伏期和Novelty P3a潜伏期等指标异常能更准确反映持续注意、选择注意和分散注意等注意亚型的损害。
4.皮质下缺血性血管性认知损害晚期CNV、P20-50和Novelty P3a普遍异常,而皮质下缺血性血管性认知损害早期仅CNV期待波的平均波幅与面积及P20-50潜伏期异常,表明CNV和P20-50成分对血管性认知损害早期注意损害的评价更敏感。
5.CNV偶极子源定位于左侧前额叶附近;P20-50偶极子源1定位在右侧颞叶上回,偶极子源2定位在右侧额叶后部;Novelty P3a偶极子源1定位在前额叶中部附近,偶极子源2定位在前颞叶中部近中线附近。
6.皮质下缺血性血管性认知损害患者因缺血性小血管病变破坏注意相关的额叶-皮质下神经功能环路,影响事件相关电位注意成分偶极子起源,次要功能区皮质资源激活参与注意认知加工。
Purpose
We observed and analysed the attention components of event related potentials (ERPs) evoked by various stimulus modalities in patients with subcortical ischemic vascular cognitive impairments (SIVCI) and the clinical neuropsychological test, in order to find neuroelectrophysiological indeces to reflect attention impairment in earlier period of vascular cognitive impairment for improving its diagnostic quality. We studied the relationship between diseased region and brain electrical source analysis of event related potentials, in order to investigate the influence on attention nerve loop by ischemic impairment from small subcortical vessel lesion, and enhance the understanding for the pathomechanism of subcortical ischemic vascular impairment .
Methods
The subjects included 30 patients with vascular cognitive impairment no dementia (SIVCIND), 15 patients with subcortical ischemic vascular dementia (SIVD) and 15 age, sex, and education-matched normal control. The general cognitive functions of the subjects were assessed by Montreal cognitive assessment (MoCA) Beijing Version and mini-mental state examination (MMSE), attention functions were assessed by continuous performance task (CPT), stroop test and Dual task. The event related potentials different wave P20-50, Novelty P3a and contingent negative variation (CNV) of the subjects evoked by dichotic listening, novelty stimulus Oddball mode and order-command signal two-stimulus paradigm were recorded.We locate the source position of ERPs component by brain electrical source analysis (BESA) and draw cortical current source density (CSD) and analysis cortical functional transactivation domain for investigating electrophysiological variation characteristics of cortical attention functional zones.
Results
1. The general assessment of cognitive functional of patients with SIVD
SIVD patients had obvious cognitive disorder in visuospatial and executive function, attention, delayed memory, abstract and orientation (P<0.05), and no cognitive disorder in naming and verbalization compared with NC (P>0.05). SIVCIND patients had obvious cognitive disorder in visuospatial and executive function, attention and delayed memory(P<0.05), and no cognitive disorder in abstract, orientation, naming and verbalization compared with NC(P>0.05).
2. The neuropsychological assessment of attention
(1)Continuous performance task (CPT) ---a computer-assisted test for assessing sustained attention
Reaction time of CPT had significantly prolonged and omission rate of CPT had increased in SIVD patients(P<0.05)compared with NC. Reaction time in CPT had no significantly prolonged (P>0.05) and omission rate had increased in SIVD patients(P<0.05)compared with NC(P <0.01).
(2) Stroop test ----a computer-assisted test for assessing selective attention
In stroop test, reaction time under conflict condition had significantly prolonged(P<0.01), reaction time under neutral condition condition as well as RT stroop effect under conflict and neutral conditions had not prolonged (P>0.05) ,and error rate under conflict and neutral conditions had significantly increased(P<0.01), interfered effects of error rate under conflict and neutral conditions had not increased (P>0.05) in SIVCIND patients compared with NC. Reaction time, error rate and their interfered effect had obviously increased in SIVD patients compared with NC (P<0.01).
(3)Dual task -----for assessing divided attention
SIVCIND group did as well as the normal control in the Dual task test (P>0.05). SIVD group did worse in dual task than control subjects (P<0.01).
3. Detection of attention component of event related potentials
(1) Scalp distribution of CNV, difference wave P20-50 and Novelty P3a in normal control
Twelve channels of EEG (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4, O1, Oz, O2) were divided four electrode sites including frontal region ( F3, Fz, F4)、central region (C3, Cz, C4)、parietal region (P3, Pz, P4) and occipital region (O1, Oz, O2).
ANOVA results indicated a significant difference in CNV average amplitude across four electrode sites (F(3,57)=8.11,P<0.01). Average amplitude of central region is highest (16.83±2.89μv ) (SNK, P<0.05). No significant differences in latency variation across electrode zones were observed (P>0.05).ANOVA results indicated a significant difference in CNV areas across electrode sites (F (3,57)=43.66,P<0.01), CNV areas in central region (19966.40±1105.9μV * ms) was highest (SNK, P<0.05).
ANOVA results indicated a significant difference in difference wave P20-50 amplitude across electrode sites (F (3,57)=5.33, P<0.01). Amplitude of occipital region which was lowest (1.23士1.30μv), No significant differences in latency variations across electrode zones were observed (SNK, P>0.05).
ANOVA results indicated a significant difference in Novelty P3a amplitude across electrode sites (F(3,57)= 7.31,P<0.01), Novelty P3a amplitude in frontal-central region were higher than occipital–parietal region (SNK, P<0.05).No significant differences in latency across electrode zones were observed (F(3,57)=1.81, P>0.05).
(2) Characteristics of ERPs component in patients with SIVCI.
ANOVA results indicated a significant difference in CNV expectancy wave amplitude among SIVCIND group, SIVD group and NC groups (F(2,57) =34.34, P<0.01), Post hoc(SNK) analysis revealed that NC group(16.13±2.75μv) > SIVCIND group(9.98±4.10μv)> SIVD group(6.25±1.52μv) (P<0.05). ANOVA results indicated a significant difference in CNV expectancy wave areas among three groups(F(2,57)=48.75, P<0.01), Post hoc(SNK) analysis revealed that NC group(20058.87±1025.95μV*ms)> SIVCIND group(14848.10±3199.16μV*ms) > SIVD group(8474.00±3511.94μV*ms) (P<0.05).No significant differences in CNV expectancy wave latency among three groups were observed(F(2,57)=1.90,P>0.05).
ANOVA results indicated a significant difference inP20-50 amplitude among three groups(F(2,55)=2.23,P<0.05). Post hoc(SNK) analysis revealed that SIVD group average amplitude was lower(1.21士0.45μv)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(2.63士1.28μv)and NC group(3.10士1.49μv) (P>0.05). ANOVA results indicated a significant difference in P20-50 latency among three groups(F(2,57)=8. 70,P<0.01), Post hoc(SNK) analysis revealed that NC group(77.47士28.22ms) < SIVCIND group(60.47士18.0ms)< SIVD group(46.73士13.93ms)(P<0.05).
ANOVA results indicated a significant difference in Novelty P3a amplitude among three groups (F(2,55)=2.23,p<0.05).The Post hoc(SNK) analysis revealed that SIVD group has lower average amplitude(1.58士0.68μv)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(3.37士1.20)and NC group(3.69士1.41μv) (P>0.05). ANOVA results indicated a significant difference in Novelty P3a latency among three groups (F(2,55)=2.23,P<0.05). The Post Hoc(SNK) analysis revealed that SIVD group hasprolonged latency(331.13士37.26 ms)than other two groups(P<0.05), and no significant differences were observed between SIVCIND group(294.40士30.31 ms)and NC group(275.93士35.24 ms) (P>0.05).
(3)Relationship between ERPs and neuropsychological data
1) Relationship between CNV and CPT
Pearson correlation\Spearman rank correlation analysis revealed there were significant, positive correlations between EW latency and reaction time of CPT(R=0.748, P<0.01), there were no significant relationships between CPT ommision rate and EW latency(R=0.22, P>0.05),amplitude (R=-0.191, P>0.05), there were significant, negative correlations between EW area and reaction time of CPT(R=-0.718, P<0.01), ommision rate of CPT(R=-0.829, P<0.01), EW amplitude and reaction time of CPT(R=-0.616, P<0.01). Correlation analysis revealed EW area had a good correlation with CPT.
2) Relationship between difference wave P20-50 and Stroop test
Pearson correlation\Spearman rank correlation analysis revealed there were significant, positive correlations between P20-50 latency and interfered effect of reaction time in stroop test(R=0.289, P<0.05), P20-50 latency and interfered effect of error rate(R=0.289, P<0.05). P20-50 amplitude correlated positively with interfered effect of reaction time in stroop test(R=--0.249, P<0.05)and had no correlation with interfered effect of error rate(R=-0.213,P>0.05). Correlation analysis revealed P20-50 latency had a good correlation with stroop test.
3) Relationship between Novelty P3a and Dual task
Pearson correlation\Spearman rank correlation analysis revealed dual task time difference correlated positively with Novelty P3a latency(R=0.38, P<0.01), and correlated negatively with Novelty P3a amplitude(R=--0.48,P<0.01). Correlation analysis revealed Novelty P3a latency had a good correlation with dual task.
4. Brain electrical source analysis of ERPs components
A principal component analysis was performed on the grand wave of CNV innormal control in -1500ms--0 (S1)time window, which revealed one component explaining 98. 8% of the variance,dipole can be approximately located in the left prefrontal lobe( Talairach: x = -17.6, y =61.5, z =0.6).At the peak point of dipole activity, the configuration can successfully explain the data in the time interview,and have a smallest residual variance(11. 39%).
A principal component analysis was performed on the grand wave of P20-50 in normal control in 0-100ms time interval, this which revealed two component explaining 98. 0% of the variance, dipole1can be approximately located in the right superior temporal gyrus (Talairach: x = 22. 0,y = -7.4,z = 16.2)) ,dipole 2 can be approximately located in the right orbitofrontal cortex (Talairach:x = 20.0, y = 21.2,z = 28. 4).At the peak point of dipole activity, the configuration can successfully explain the data in the time window, and have a smallest residualvariance(10. 29%).
A principal component analysis was performed on the grand wave of Novelty P3a in 150-350ms time window, which revealed two components explaining 98. 1% of the variance, dipole1can be approximately located in the middle of prefrontal lobe ( Talairach:x =9.0, y =27.4,z =8.9), dipole2 can be approximately located in the medianpart of anterior temporal lobe near the median line( Talairach: x =-2.8,y =3.4, z =6.8).At the peak point of dipole activity, the configuration can successfully explain the data in the time window, and have a smallest residual variance(9. 39%).
5. Analysis of cortical current source density of ERPs
In normal control, CSD mapping of CNV revealed current density were intensive in bilateral (especially right )superior frontal lobe,bilateral parietal lobe were also activated. In SIVCI group, current density of right parietal lobe and right frontal lobe decreased obviously, right temporal region and central region activated at different degree. The CSD results demonstrated bilateral frontal lobe and parietal lobe participated in sustained attention information processing in physiological condition, when attention dipole source and neurocircuitry was damaged, temporal region and central region may participate in information processing.
In normal control, CSD mapping of P20-50 revealed current density were intensive in bilateral temporal lobe, bilateral anterior frontal lobe and left parietal lobe were also activated. in SIVCI group, current density of right temporal lobe and bilateral frontal lobe decreased obviously, occipital region and central region were activated at different degree. The CSD results demonstrated bilateral temporal lobe and frontal lobe participated in selected attention information processing in physiological condition, when dipole source of attentional ERPs and neurocircuitry damaged, occipital region and central region may participate in information processing.
In normal control, CSD mapping of Novelty P3a revealed current density were intensive in left superior frontal lobe and right frontal lobe ,left superior lobe and right parietal lobe were also activated, current density was feeble in occipital region .In SIVCI group, current density of frontal lobe decreased obviously, occipital region and left superior lobe activated obviously. The CSD results demonstrated bilateral frontal lobe may be principle cortical function zone of divided attention, when attention dipole source and neurocircuitry was damaged, occipital region and central region may participate in information processing.
Conclusion
1. SIVCI patients had obvious disorders in general assessment of cognitive function. Executive function, attention and delayed memory were predominant in cognitive impairment of SIVCIND patients, and SIVD patients had obvious cognitive impairment in executive function, attention, delayed memory,abstract and orientation, but no cognitive disorder in naming and verbalization .
2.The results of computer-assisted test [CPT(assessing sustained attention function), stroop test(assessing selected attention function)]and dual task(assessing scattered attention.) revealed SIVCIND patients had predominance in sustained attention impairment completely and selective attention impairment partly, SIVD patients had general, obvious disorders in sustained attention, selective attention and divided attention.
3.Event related potential P20-50,Novelty P3a and CNV evoked by dichotic listening, novelty stimulus Oddball mode and order-command signal two-stimulus paradigm respectively correlated with CPT, stroop test and dual task, and may be neuroelectrophysiological assistant indeces for assessing attention impairment of patients with SIVCI. Especially EW area, P20-50 latency and Novelty P3a latency may be more accurate to assess impairment of sustained attention, selective attention and divided attention.
4.SIVD patients had widely abnormal expectancy wave, P20-50 and Novelty P3a, while only amplitude and area of Expectancy wave, P20-50 latency were abnormal in SIVCIND patients, which indicated expectancy wave, P20-50 latency may be more sensitive to assess attention impairment in earlier period of VCI.
5. CNV dipole can be approximately located in the left prefrontal lobe( Talairach: x =-17.6,y =61.5,z =0.6). P20-50 dipole1 can be approximately located in the right superior temporal gyrus (Talairach: x = 22. 0, y = -7.4, z = 16.2), dipole 2 can be approximately located in the right frontal cortex (Talairach:x = 20.0, y = 21.2, z = 28. 4). Novelty P3a dipole1can be approximately located in the middle of prefrontal lobe ( Talairach: x =9.0, y =27.4, z =8.9), dipole 2 can be approximately located in the median part of anterior temporal lobe near the median line( Talairach: x =-2.8, y =3.4, z =6.8).
6. Frontal-subcortical attentive circuits were disrupted by lacunar infarcts or deep white matter changes in SIVCI patients, and dipole resource of ERPs attention components were influenced, cortical resource of second domain may be activated and participated in attention information process .
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1.吴丽慧.事件相关功能性磁共振成像研究进展(J).神经病学与神经康复学杂志2005, 2(4):247-9.
2.魏景汉罗跃嘉.认知事件相关脑电位教程北京经济出版社2002 5.
3. Magnano I,Aiello I,Piras MR. Cognitive impairment and neurophysiological correlates in MS. Journal of the neurological sciences, 2006, 245:117-22.
4. Pogarell O, Mulert C, Hegerl U. Event related potentials and fMRI in neuropsychopharmacology. Clinical EEG and neuroscience: official journal of the EEG and Clinical Neuroscience Society (ENCS), 2006,37:99-107.
5. Polich J, Criado JR. Neurophysiology and neuropharmacology of P3a and P3b. International journal of psychophysiology: official journal of the International Organization of Psychophysiology, 2006,60:172-85.
6. Katada E,Sato K, Ojika K et al. Cognitive event-related potentials: useful clinical information in Alzheimer's disease. Current Alzheimer research, 2004,1:63-9.
7. Ilvonen TM, Kujala T,Kiesilainen A, et al. Auditory discrimination after left-hemisphere stroke: a mismatch negativity follow-up study. Stroke. Stroke; a journal of cerebral circulation, 2003, 34:1746-51.
8. Naatanen R. Mismatch negativity: clinical research and possible applications. International journal of psychophysiology: official journal of the International Organization of Psychophysiology, 2003, 48:179-88.
9. Ilvonen T, Kujala T, Kozou H et al. The processing of speech and non-speech sounds in aphasic patients as reflected by the mismatch negativity (MMN). Neuroscience letters, 2004, 366:235-40.
10. Becker F, Reinvang I. Mismatch negativity elicited by tones and speech sounds: changed topographical distribution in aphasia. Brain and language, 2007,100:69-78.
11.蔡增林,金蕾,薛寿儒等.应用失匹配负波评估帕金森病患者轻度认知功能损害.中国临床康复,2004,8(7):1220-1221.
12. Schroder C, Mobes J, Schutze M et al. Perception of emotional speech in Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society,2006, 21:1774-8.
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