Mattay V S, Callicott J H, Bertolino A, Heaton I, Frank J A, Coppola R, Berman K F, Goldberg T E, Weinberger D R
Clinical Brain Disorders Branch, Intramural Research Program, Laboratory of Diagnostic Radiology Research, Office of Intramural Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland, 20892, USA.
Neuroimage. 2000 Sep;12(3):268-75. doi: 10.1006/nimg.2000.0610.
Monoaminergic neurotransmitters are known to have modulatory effects on cognition and on neurophysiological function in the cortex. The current study was performed with BOLD fMRI to examine physiological correlates of the effects of dextroamphetamine on working-memory performance in healthy controls. In a group analysis dextroamphetamine increased BOLD signal in the right prefrontal cortex during a task with increasing working-memory load that approached working-memory capacity. However, the effect of dextroamphetamine on performance and on signal change varied across individuals. Dextroamphetamine improved performance only in those subjects who had relatively low working-memory capacity at baseline, whereas in the subjects who had high working-memory capacity at baseline, it worsened performance. In subjects whose performance deteriorated, signal change was greater than that in subjects who had an improvement in performance, and these variations were correlated (Spearman rho = 0.89, P<0.02). These data shed light on the manner in which monoaminergic tone, working memory, and prefrontal function interact and, moreover, demonstrate that even in normal subjects the behavioral and neurophysiologic effects of dextroamphetamine are not homogeneous. These heterogeneic effects of dextroamphetamine may be explained by genetic variations that interact with the effects of dextroamphetamine.
已知单胺能神经递质对认知及皮层神经生理功能具有调节作用。本研究采用血氧水平依赖性功能磁共振成像（BOLD fMRI）来检测右旋苯丙胺对健康对照者工作记忆表现影响的生理相关性。在一项群组分析中，在一项工作记忆负荷逐渐增加并接近工作记忆容量的任务中，右旋苯丙胺使右侧前额叶皮层的BOLD信号增强。然而，右旋苯丙胺对表现及信号变化的影响因个体而异。右旋苯丙胺仅在那些基线工作记忆容量相对较低的受试者中改善了表现，而在基线工作记忆容量较高的受试者中，它使表现恶化。在表现变差的受试者中，信号变化大于表现改善的受试者，且这些变化具有相关性（斯皮尔曼相关系数ρ = 0.89，P<0.02）。这些数据揭示了单胺能张力、工作记忆和前额叶功能相互作用的方式，此外，还表明即使在正常受试者中，右旋苯丙胺的行为和神经生理效应也并非一致。右旋苯丙胺的这些异质性效应可能由与右旋苯丙胺效应相互作用的基因变异来解释。
