Medical Research Council Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, Netherlands.
Neuropsychologia. 2013 Sep;51(11):2194-201. doi: 10.1016/j.neuropsychologia.2013.07.016. Epub 2013 Aug 1.
Planning, the decomposition of an ultimate goal into a number of sub-goals is critically dependent upon fronto-striatal dopamine (DA) levels. Here, we examined the extent to which the val158met polymorphism in the catechol O-methyltransferase (COMT) gene, which is thought to primarily alter cortical DA levels, affects performance and fronto-parietal activity during a planning task (Tower of London). COMT genotype was found to modulate activity in the left superior posterior parietal cortex (SPC) during planning, relative to subtracting, trials. Specifically, left SPC blood oxygenation level-dependent (BOLD) response was reduced in groups with putatively low or high cortical DA levels (COMT homozygotes) relative to those with intermediate cortical DA levels (COMT heterozygotes). These set of results are argued to occur either due to differences in neuronal processing in planning (and perhaps subtracting) caused by the COMT genotype and/or the cognitively heterogeneous nature of the TOL, which allows different cognitive strategies to be used whilst producing indistinguishable behavioural performance in healthy adults. The implications of this result for our understanding of COMT's effect on cognition in health and disease are discussed.
计划,即将最终目标分解为多个子目标,严重依赖于额纹状体多巴胺(DA)水平。在这里,我们研究了儿茶酚-O-甲基转移酶(COMT)基因中的 val158met 多态性在多大程度上影响了计划任务(伦敦塔)期间的表现和额顶叶活动,该基因被认为主要改变皮质 DA 水平。COMT 基因型被发现调节计划期间左后顶叶皮层(SPC)的活动,相对于减法试验。具体而言,与皮质 DA 水平中等(COMT 杂合子)的组相比,假定皮质 DA 水平较低或较高(COMT 纯合子)的组左 SPC 血氧水平依赖(BOLD)反应降低。这些结果组被认为要么是由于 COMT 基因型引起的计划(和可能的减法)过程中的神经元处理差异,要么是由于 TOL 的认知异质性,它允许在产生健康成年人无法区分的行为表现的同时使用不同的认知策略。讨论了这一结果对我们理解 COMT 在健康和疾病中的认知作用的影响。