Saville C W N, Lancaster T M, Stefanou M E, Salunkhe G, Lourmpa I, Nadkarni A, Boehm S G, Bender S, Smyrnis N, Ettinger U, Feige B, Biscaldi M, Mantripragada K K, Linden D E J, Klein C
Department of Child and Adolescent Psychiatry, Psychotherapy, and Psychosomatics, University of Freiburg, Hauptstrasse 8, Freiburg, Germany, 79104; School of Psychology, Bangor University, Penrallt Road, Bangor, Gwynedd, United Kingdom, LL57 2AS.
Neuroscience and Mental Health Research Institute, Cardiff University, Henry Wellcome Building, Heath Park, Cardiff, United Kingdom, CF14 4XN.
Neuroimage. 2014 Oct 15;100:489-97. doi: 10.1016/j.neuroimage.2014.06.006. Epub 2014 Jun 14.
Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.
反应时间的个体内变异性（ISV）是几种精神疾病一种很有前景的内表型，但其神经基础尚未明确。来自神经影像学、分子遗传学和精神药理学的越来越多的证据表明，ISV可能是儿茶酚胺能介导的神经噪声的指标。脑电图的高时间分辨率非常适合研究ISV，但前提是可以在单次试验中评估ISV潜在的神经相关性。基于ISV与多巴胺能功能相关的证据，我们应用一种最近开发的单次试验P3b分析方法，来研究COMT Val(158)Met基因型在不同工作记忆负荷下，在行为和神经水平上与ISV测量指标之间的关联。Met等位基因数量越多，在任务上的表现越差且个体内变异性越大，单次试验P3b的潜伏期抖动也越大。行为和神经生理学水平上这些一致的结果证实了先前的观察，即前额叶多巴胺可用性与认知表现的稳定性和准确性相关。与先前的研究一起，这些数据暗示了COMT基因型具有多效性认知效应。
