Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health.
Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health.
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DOI：
10.1093/brain/awm299
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发表时间：
2008-02
期刊：
影响因子：
--
通讯作者：
Dolan RJ
中科院分区：
文献类型：
--
作者：
Bentley P;Driver J;Dolan RJ
视觉注意力缺陷发生在阿尔茨海默病（AD）的早期，被认为对前胆碱能治疗的反应比特征性记忆障碍更敏感。我们假设AD患者在视觉注意加工过程中的神经反应相对于对照组受损，但部分易受胆碱酯酶抑制的影响。我们研究了16名轻度阿尔茨海默病患者和17名年龄匹配的健康对照者，使用功能磁共振成像扫描来进行受试者内安慰剂对照比较，以确定毒木碱对刺激和注意力相关的大脑激活的影响，并进行组间比较。受试者在观看包含人脸或建筑物的刺激时进行浅判断（图像的颜色）或深判断（所描绘的人脸或建筑物的年轻/年老）。从行为上看，阿尔茨海默病患者在这两项任务中的表现都不如对照组，而在要求更高的年龄判断任务中，阿兹海默病患者则受益于芥子碱。与对照组相比，阿尔茨海默氏症患者的胼胝体前叶和后海马旁皮层的BOLD信号减弱，但在服用毒豆碱后增加。相比之下，在AD患者中梭状皮质的面部选择反应没有受损，并且两组在服用毒豆碱后都有所下降。阿尔茨海默氏症患者右顶叶和前额叶皮层的任务依赖反应减弱，但在服用豆蔻碱后有所改善。在两个皮层外区域观察到类似的组和治疗效果模式，显示出深度任务对浅层任务的刺激选择性增强。最后，对于健康组来说，毒豆碱降低了任务依赖效应，部分原因是相对于深度任务，浅任务的选择性被夸大了。我们的研究结果表明，胆碱能介导的改善了阿尔茨海默病功能受影响的脑外和额顶叶区域的刺激和注意力依赖反应。我们还表明，正常的刺激和任务依赖的活动模式可以在健康的大脑中被胆碱能刺激扰乱。
Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visual attentional processing would be impaired relative to controls, yet partially susceptible to improvement with cholinesterase inhibition. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of the effects of physostigmine on stimulus- and attention-related brain activations, and to allow between-group comparisons for these. Subjects viewed stimuli comprising faces or buildings while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed poorer than controls in both tasks, while physostigmine benefited AD patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in AD relative to controls but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed enhanced stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. Our results demonstrate cholinergic-mediated improvements for both stimulus- and attention-dependent responses in functionally affected extrastriate and frontoparietal regions for AD. We also show that normal stimulus- and task-dependent activity patterns can be perturbed in the healthy brain by cholinergic stimulation.
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影响因子：
14.5
作者：
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通讯作者：
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