【作者】 刘赛男；

【导师】 王鲁宁； 张熙；

【作者基本信息】 中国人民解放军军医进修学院 ， 神经病学， 2006， 博士

【摘要】 目的:探讨额叶对冲突信息的加工处理机制及其随龄变化,探索轻度认知损害(mild cognitive impairment,MCI)患者冲突信息加工处理机制的事件相关电位(event-related potentials,ERPs)变化特点。 方法:研究对象为15例遗忘型轻度认知损害患者(患者组)、15例年龄、性别、受教育年限匹配的正常老年人(老年组)和15例青年成人(青年组)。ERPs检查采用改良的Eriksen flanker视觉刺激范式,刺激材料由不同朝向的箭头组成,包括三种状态:匹配状态(<<<<<或>>>>>),表示无冲突发生;中性状态(++<++或++>++),表示知觉层面发生冲突;冲突状态(<<><<或>><>>),表示知觉及反应层面均发生冲突。中性状态与匹配状态的差异说明知觉层面存在flanker干扰效应,冲突状态与中性状态的差异说明反应层面存在flanker干扰效应。要求被试者对中间的箭头方向作反应,指向左则左手按键,指向右则右手按键,而忽略旁边的箭头或“+”。同时记录32导脑电、正确率及反应时。 结果:(1)行为指标:中性状态与匹配状态相比较、冲突状态与中性状态相比较,青年组、老年组与患者组的正确率下降、反应时延长,即正确率与反应时在知觉层面、反应层面上均存在flanker干扰效应。与青年组相比较,老年组正确率及其干扰效应均无显著差异;反应时则明显延长,在反应层面上具有更为明显的干扰效应。与老年组相比,患者组冲突状态下正确率显著降低,各刺激状态下反应时均明显延长,正确率、反应时在反应层面上均具有更为显著的干扰效应。(2)N2成分:不同刺激状态下青年组N2潜伏期、波幅均无变化。与青年组相比较,老年组各刺激状态下N2潜伏期、波幅均无显著差异,仅头皮分布后移。患者组N2潜伏期较老年组显著延长,波幅无变化。LORETA源定位分析显示:各刺激状态下青年组N2所在时间窗内可见左前辅助运动区、左前额叶内侧面以及右前额背外侧区域不同程度的激活;老年组匹配状态下双侧颞叶、双前额叶背外侧区域激活,左前额内侧面电流活动弱;中性状态下,双前额叶更多还原

【Abstract】 Objective: To explore the working mechanism and aging change of the frontal conflict processing system, to investigate the change feature of event-related potential in patients with mild cognitive impairment(MCI).Methods: 15 patients with MCI(patient group), 15 healthy matching aging controls(older age group)and 15 youth(youth group) performed a modified Eriksen flanker paradigm, while ERPs, reaction time and correct rate was recorded. The task included three kinds of stimuli: congruent condition (< < < < < or > > > > >), which mean no-conflict;neutral condition (++ < ++ or ++ > ++), conflict existed on perceptual level;conflict condition (< < > < < or > > < > >), conflict existed on both perceptual and response level. The difference between neutral and congruent condition mean interference effect existing on the perceptual level, as the other between conflict and neutral condition mean interference effect existing on the response level. Subjects were required to press the right or left button according to the target arrow.Results: (l)Behavior data: The three groups showed decreased correct rate and prolonged reaction time following different experiment conditions, i.e., both had flanker interference effect on perceptual and response level. The older age group showed identical interference effect of rate but distinct effect of reaction time compared with youth group. Compared with the old age group, the patient group had decreased correct rate to conflict stimuli and prolonged reaction time to all kinds of stimuli. They had more distinct interference effect on response level.(2) N2: Three kinds of stimuli had same latency and amplitude in youth and older age group, only scalp distribution moved behind in the older one. Patients showed longer latency than older age group. LORETA results showed different activation degree in left pre-SMA, left MFG and right DLPFC in youth. In older age group, bilateral temporal lobe andbilateral DLPFC activated to congruent stimuli and neutral stimuli, current density to conflict stimuli decreased in PFC but highly increased in temporal lobe. In patient group, right DLPFC activated to all kinds of stimuli, left DLPFC was involved in neutral stimuli as temporal lobe, left occipital lobe also activated to conflict stimuli.(3) P300: In youth group, P300 distributed in parietal area, its latency had interference effect both on perceptual and response level. Older people showed widespread distribution and fixed latency of P300, its amplitude had flanker effect on response level. Compared with youth group, latency of old age shortened to neutral and conflict stimuli, amplitude increased to neutral and congruent condition. In patient group, P300 distributed widely, amplitude of right hemisphere was higher than left one. Both latency and amplitude has flanker effect on response level. Patients had lower P300 than older age to all the conditions, only longer latency to neutral stimuli. LORETA results: in youth group, bilateral(especially right)DLPFC, occipital lobe and left MFG activated to congruent stimuli;left temporal lobe was also involved in activation to other two kinds of condition. In older age group, current density focused on bilateral (especially right )temporal lobe, right occipital lobe and left DLPFC to congruent stimuli, right occipital and left DLPFC activated to neutral one;right temporal, right occipital lobe mainly activated to conflict stimuli as current density was more feeble in left DLPFC and left temporal area. In patient group, brain area activated to congruent stimuli included bilateral temporal, right occipital lobe, left DLPFC, left MFG and right precentral gyrus;neutral stimuli evoked current in right occipital lobe and left DLPFC, as conflict condition evoked in left occipital lobe, right DLPFC and temporal lobe. (4) Difference wave N250 subtracted from wave evoked by neutral and congruent stimuli. In youth group, its timewindow is 200-300ms, distributed widely, amplitude in central area was highest. Old age had equal mean amplitude as youth, timewindow was 250-350ms. In patient group, timewindow was 300-400ms. LORETA: In youth group, left temporal lobe and MFG activated apparently, whereas right temporal and bilateral DLPFC activated slightly. Old age only showed current activity in left temporal lobe. Currentdensity in patient’s left temporal lobe decreased but increased in right one and right occipital lobe, besides left DLPFC and left MFG (5) Difference wave N380 subtracted from wave evoked by conflict and neutral stimuli. The timewindow in youth group was 300-450ms, it distributed widely, amplitude of hind head was higher than that of fore head. Older age had a longer timewindow of 350-600ms and same distribution as youth. In patient group, N380 emerged around 400ms after the onset of stimuli, its duration was about 300ms. N380 almost disappeared in fore head area, limited on parietal and occipital area. Its mean amplitude was lower than normal aging. LORETA showed bilateral temporal lobe, DLPFC(especially right) in youth group, left temporal lobe, left DLPFC and left MFG activated in older age one. In patient group, current density mainly focused on left MFG and right DLPFC. Conclusion: (1) The current study found, left pre-SMA and left MFG might concern with conflict monitoring and preparing for executive activation, whereas right DLPFC might play role in executive strategy of response conflict processing, executive control and response selection. (2)When conflict stimuli existed on the perceptual level, the older age and patients showed normal conflict monitoring and interference control function relatively, also mean conflict monitoring function on response level was influenced by high-grade cognitive change slightly. (3)When conflict stimuli interfered on response level, old people showed frontal interference control hypofunction, the response selection, executive control of conflict stimuli stepped down, the non-specificity of related brain structrure increased, cognition resource of left temporal lobe, left DLPFC and left MFG was moved to complete task. The patients with MCI had lower velocity of response selection, executive control, the current density in their left DLPFC and left MFG decreased, which mean significant impairment of frontal interference control function especially on response level, their error rate also increased. (4)In current experiment pattern, ERPss component N2 was not sensitive to flanker interference effect and aging change. The patients had prolonged latency of N2, reflecting their impairment of frontal conflict monitoring, but it could not distinguish perceptual or responselevel.(5)In current paradigm, following the stimuli conditions, the change of P300 was not concerned with the change of reaction time, which mean interference effect of conflict stimuli resulting from competed response selection but not the stimuli evaluation. In the older age and patient group, the change of P300 and reaction time were not at equal pace, so P300 was not a appropriate index to reflect the aging change and impairment of frontal conflict monitoring function. (6) Difference wave N250 subtracted from wave evoked by neutral and congruent stimuli. N250 mainly reflected activation of left temporal lobe and left MFG when flanker conflict stimuli existed on perceptual level, but its aging change was not highly significant. N250 was not sensitive to detect the related function impairment of patient with MCI. (7) Difference wave N380 subtracted from wave evoked by conflict and neutral stimuli. When flanker conflict stimuli existed on response level, N38O showed the activation of left DLPFC and left temporal lobe during response selection and executive control processing in normal old people. Following aging and mild cognitive impairment emerging, its onset and duration prolonged, reflecting the obvious impairment of frontal interference control function of patient with MCI. (8)The study suggested that conflict monitoring function is not damaged in earlier period of MCI, but whether it would be influenced following the disease progressing, should be studied further. (9)MCI showed impairment of left DLPFC, that matched the former study results. Compaired with those complex working memory paradigm, the prefrontal cortex function could be accessed by simple conflict processing paradigm, and the method might be used in patients with dementia at earlier grade. So this method might have potential value at cognitive accessing of MCI and mild dementia.更多还原