Klaassens Bernadet L, Rombouts Serge A R B, Winkler Anderson M, van Gorsel Helene C, van der Grond Jeroen, van Gerven Joop M A
Leiden University, Institute of Psychology, Leiden, the Netherlands.
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
Hum Brain Mapp. 2017 Jan;38(1):308-325. doi: 10.1002/hbm.23362. Epub 2016 Sep 13.
Psychopharmacological research, if properly designed, may offer insight into both timing and area of effect, increasing our understanding of the brain's neurotransmitter systems. For that purpose, the acute influence of the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was repeatedly measured in 12 healthy young volunteers with resting state functional magnetic resonance imaging (RS-fMRI). Eighteen RS-fMRI scans were acquired per subject during this randomized, double blind, placebo-controlled, crossover study. Within-group comparisons of voxelwise functional connectivity with 10 functional networks were examined (P < 0.05, FWE-corrected) using a non-parametric multivariate approach with cerebrospinal fluid, white matter, heart rate, and baseline measurements as covariates. Although both compounds did not change cognitive performance on several tests, significant effects were found on connectivity with multiple resting state networks. Serotonergic stimulation primarily reduced connectivity with the sensorimotor network and structures that are related to self-referential mechanisms, whereas galantamine affected networks and regions that are more involved in learning, memory, and visual perception and processing. These results are consistent with the serotonergic and cholinergic trajectories and their functional relevance. In addition, this study demonstrates the power of using repeated measures after drug administration, which offers the chance to explore both combined and time specific effects. Hum Brain Mapp 38:308-325, 2017. © 2016 Wiley Periodicals, Inc.
如果设计得当，精神药理学研究可能会为作用时间和作用区域提供见解，增进我们对大脑神经递质系统的理解。为此，在12名健康年轻志愿者中，采用静息态功能磁共振成像（RS-fMRI）反复测量了选择性5-羟色胺再摄取抑制剂西酞普兰（30毫克）和乙酰胆碱酯酶抑制剂加兰他敏（8毫克）的急性影响。在这项随机、双盲、安慰剂对照的交叉研究中，每位受试者进行了18次RS-fMRI扫描。使用非参数多变量方法，以脑脊液、白质、心率和基线测量作为协变量，检查了与10个功能网络的体素级功能连接的组内比较（P < 0.05，FWE校正）。尽管两种化合物在多项测试中均未改变认知表现，但在与多个静息态网络的连接上发现了显著影响。5-羟色胺能刺激主要降低了与感觉运动网络以及与自我参照机制相关结构的连接，而加兰他敏则影响了更多参与学习、记忆以及视觉感知和处理的网络和区域。这些结果与5-羟色胺能和胆碱能轨迹及其功能相关性一致。此外，本研究证明了在给药后使用重复测量的作用，这为探索联合效应和时间特异性效应提供了机会。《人类大脑图谱》38:308 - 325，2017年。© 2016威利期刊公司。
