Nymberg Charlotte, Banaschewski Tobias, Bokde Arun L W, Büchel Christian, Conrod Patricia, Flor Herta, Frouin Vincent, Garavan Hugh, Gowland P, Heinz Andreas, Ittermann Bernd, Mann Karl, Martinot Jean-Luc, Nees Frauke, Paus Tomas, Pausova Zdenka, Rietschel Marcella, Robbins Trevor W, Smolka Michael N, Ströhle Andreas, Schumann Gunter, Klingberg Torkel
Department of Neuroscience, Karolinska institute, Stockholm, Sweden.
1] Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, Germany [2] Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Neuropsychopharmacology. 2014 Sep;39(10):2357-65. doi: 10.1038/npp.2014.83. Epub 2014 Apr 9.
Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13-15 years) and BrainChild (n∼300, age 6-27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (p<0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (p<0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission.
动机对学习和认知很重要。虽然腹侧纹状体（VS）中的多巴胺能（D2）传递与动机有关，但学习和认知与背侧纹状体的功能联系更为紧密，包括尾状核的激活。最近一项研究发现内在动机与DRD2/ANKK1基因多态性（rs1800497）之间存在相互作用，这表明rs1800497的A等位基因携带者在工作记忆（WM）训练中为了提高表现对动机更为敏感。利用来自两个大规模成像遗传学数据集IMAGEN（n = 1080，年龄13 - 15岁）和BrainChild（n约为300，年龄6 - 27岁）的数据，我们研究了rs1800497是否与WM相关。在IMAGEN数据集中，我们测试了奖励预期期间VS/尾状核的激活是否与WM表现相关，以及rs1800497和VS/尾状核激活是否相互作用以影响WM表现。我们发现rs1800497在IMAGEN和BrainChild数据集中均与WM表现相关。奖励处理期间较高的VS和尾状核激活与较高的WM表现显著相关（p < 0.0001）。发现DRD2/ANKK1基因多态性rs1800497与奖励预期期间VS激活对WM的影响之间存在相互作用（p < 0.01），即次要等位基因（A）的携带者显示VS激活与WM之间存在显著相关性，而GG纯合子则不然，这表明VS血氧水平依赖信号（BOLD）对WM的影响因与D2多巴胺能传递相关的个体遗传差异而改变。
