Abnormal N400 word repetition effects in fragile X-associated tremor/ataxia syndrome.
Abnormal N400 word repetition effects in fragile X-associated tremor/ataxia syndrome.
复制标题
异常 N400 单词重复对脆性 X 相关震颤/共济失调综合征的影响。
DOI：
10.1093/brain/awq077
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Hagerman,Randi
中科院分区：
文献类型：
--
作者：
Olichney,JohnM;Chan,Shiaohui;Wong,LingM;Schneider,Andrea;Seritan,Andreea;Niese,Adam;Yang,Jin-Chen;Laird,Kelsey;Teichholtz,Sara;Khan,Sara;Tassone,Flora;Hagerman,Randi
脆性X相关震颤/共济失调综合征是一种与FMR 1基因的前突变等位基因（55-200个CGG重复）相关的神经退行性疾病，影响许多晚年携带者。脆性X相关震颤/共济失调综合征患者通常有小脑共济失调、神经元和星形胶质细胞核内包涵体以及认知障碍。痴呆症也可以存在与阿尔茨海默病一样严重的认知缺陷，然而额皮质下型损害在脆性X相关震颤/共济失调综合征中更明显。我们试图描述脆性X相关震颤/共济失调综合征患者的P600和N400单词重复效应，使用事件相关潜在单词重复范式，对极早期阿尔茨海默病具有敏感性。我们假设，受脆性X相关震颤/共济失调综合征影响的陈述性言语记忆不良的参与者在P600重复效应中会有明显的异常。在事件相关电位实验中，受试者进行类别决策任务，同时记录脑电图。每个听觉类别陈述之后都有一个相关的视觉目标词（50%“一致”类别范例，50%“不一致”名词）。三分之二的刺激（类别陈述-目标词对）被重复，无论是在短滞后（10-40秒）或长滞后（100-140秒）。将N400和P600振幅数据提交至裂区方差分析。这些方差分析显示，在轻度脆性X相关震颤/共济失调综合征（n= 32，平均年龄= 68.7，平均简易精神状态检查评分= 26.8）中，N400重复效应显著降低（F= 22.5，P < 0.001），而P600重复效应无显著降低。脆性X相关震颤/共济失调综合征患者的晚期正振幅（刺激后550-800 ms）显著小于一致性词语（组效应P= 0.04）。在脆性X相关震颤/共济失调综合征患者（r =0.66）和所有受试者（r= 0.52）中，P600重复效应振幅降低与回忆不良相关。在所有被试中，对新的一致性词的P600波幅越大，自由回忆得分越高（r= 0.37，P < 0.01）。在脆性X相关震颤/共济失调综合征患者中，我们发现晚期阳性振幅与CGG重复序列长度之间存在相关性（r= 0.47，P = 0.006）。较高水平的FMR 1 mRNA与较小的N400 s不一致的话和较大的正振幅（300和500 ms之间）一致的话。总之，事件相关的潜在单词重复效应似乎对轻度脆性X相关震颤/共济失调综合征患者的认知功能障碍敏感。与P600相比，它们在N400重复效应中更严重的减少与遗忘性轻度认知障碍和早期阿尔茨海默病中报道的相反模式形成对比（Olichneyet al.，).
Fragile X-associated tremor/ataxia syndrome, a neurodegenerative disorder associated with premutation alleles (55–200 CGG repeats) of theFMR1gene, affects many carriers in late-life. Patients with fragile X-associated tremor/ataxia syndrome typically have cerebellar ataxia, intranuclear inclusions in neurons and astrocytes, as well as cognitive impairment. Dementia can also be present with cognitive deficits that are as severe as in Alzheimer’s disease, however frontosubcortical type impairment is more pronounced in fragile X-associated tremor/ataxia syndrome. We sought to characterize the P600 and N400 word repetition effects in patients with fragile X-associated tremor/ataxia syndrome, using an event-related potential word repetition paradigm with demonstrated sensitivity to very early Alzheimer’s disease. We hypothesized that the fragile X-associated tremor/ataxia syndrome-affected participants with poor declarative verbal memory would have pronounced abnormalities in the P600 repetition effect. In the event-related potential experiment, subjects performed a category decision task whilst an electroencephalogram was recorded. Auditory category statements were each followed by an associated visual target word (50% ‘congruous’ category exemplars, 50% ‘incongruous’ nouns). Two-thirds of the stimuli (category statement–target word pairs) were repeated, either at short-lag (∼10–40 s) or long-lag (∼100–140 s). The N400 and P600 amplitude data were submitted to split-plot analyses of variance. These analyses of variance showed a highly significant reduction of the N400 repetition effect (F= 22.5,P< 0.001), but not of the P600 repetition effect, in mild fragile X-associated tremor/ataxia syndrome (n= 32, mean age = 68.7, mean Mini-Mental State Examination score = 26.8). Patients with fragile X-associated tremor/ataxia syndrome had significantly smaller late positive amplitude (550–800 ms post-stimulus onset) to congruous words (P= 0.04 for group effect). Reduced P600 repetition effect amplitude was associated with poorer recall within fragile X-associated tremor/ataxia syndrome patients (r =0.66) and across all subjects (r= 0.52). Larger P600 amplitude to new congruous words also correlated significantly with higher free recall scores (r= 0.37,P< 0.01) across all subjects. We found a correlation between the amplitude of late positivity and CGG repeat length in those with fragile X-associated tremor/ataxia syndrome (r= 0.47,P= 0.006). Higher levels ofFMR1mRNA were associated with smaller N400s to incongruous words and larger positive amplitudes (between 300 and 500 ms) to congruous words. In conclusion, event-related potential word repetition effects appear sensitive to the cognitive dysfunction present in patients with mild fragile X-associated tremor/ataxia syndrome. Their more severe reduction in N400 repetition effect, than P600, is in contrast to the reverse pattern reported in amnestic mild cognitive impairment and incipient Alzheimer’s disease (Olichneyet al., ).