Medical Research Council Cognition and Brain Sciences Unit, Cambridge CB2 2EF, UK.
Cereb Cortex. 2013 Feb;23(2):361-9. doi: 10.1093/cercor/bhs025. Epub 2012 Feb 20.
A key mechanism by which the prefrontal cortex (PFC) supports goal-oriented behaviors is attentional set formation: the formation and maintenance of an attentional bias toward relevant features. It has previously been proposed that a common single nucleotide polymorphism (val158met) in the gene that codes for the catechol O-methyltransferase (COMT) enzyme may affect an individual's ability to form and maintain an attentional set by modulating PFC dopamine (DA) levels. Here, we present data from a functional magnetic resonance imaging study that investigated the effect of this polymorphism on the tendency for older adults to display set-like behavior, and we compare these results to preexisting data from Parkinson's Disease (PD) patients. Our results demonstrate that putatively different levels of PFC DA predict both attentional set formation and right dorsolateral PFC (DLPFC) activation. More specifically, while for PD patients, val homozygotes showed heightened DLPFC activation and increased set-like behavior, for healthy older adults, the opposite pattern of results was observed. This interaction between COMT genotype and PD accords well with previous studies that have shown an excess of DA in the PFC in early PD patients and, furthermore, supports the hypothesis that there is an inverted-U shaped functional relationship between PFC DA levels and attentional set formation.
前额叶皮层（PFC）支持目标导向行为的一个关键机制是注意定势形成：即对相关特征的注意偏向的形成和维持。先前有人提出，编码儿茶酚-O-甲基转移酶（COMT）酶的基因中的一个常见单核苷酸多态性（val158met）可能通过调节 PFC 多巴胺（DA）水平来影响个体形成和维持注意定势的能力。在这里，我们呈现了一项功能磁共振成像研究的数据，该研究调查了这种多态性对老年人表现出定势行为倾向的影响，并将这些结果与帕金森病（PD）患者的现有数据进行了比较。我们的研究结果表明，PFC DA 的假定差异水平既可以预测注意定势的形成，又可以预测右侧背外侧前额叶皮层（DLPFC）的激活。更具体地说，对于 PD 患者，val 纯合子表现出更高的 DLPFC 激活和增加的定势行为，而对于健康的老年人，观察到相反的结果模式。COMT 基因型与 PD 之间的这种相互作用与先前的研究结果一致，这些研究表明早期 PD 患者的 PFC 中存在过多的 DA，并且进一步支持了 PFC DA 水平与注意定势形成之间存在倒 U 形功能关系的假说。
