Dopamine, working memory, and training induced plasticity: Implications for developmental research

Publication: Developmental Psychology Institution: Karolinska Institute Investigator(s): Stina Söderqvist, Sissela Nutley, Myriam Peyrard-Janvid, Hans Matsson, Keith Humphreys, Juha Kere, Torkel Klingberg Program: Cogmed JM


Background & Aim: The neurotransmitter dopamine (DA) is closely linked with working memory (WM) functioning. Individual variations in genes that impact the production, amount and or/signaling of DA in the brain influence WM performance throughout development. Genes also interact with other genes and can complicate the effect of DA on WM. In a previous investigation, Bergman-Nutley et al. (2011) assessed the impact of WM training, nonverbal reasoning (NVR) training, combination WM and NVR training (CB) or placebo training on improving fluid intelligence (Gf) and WM in preschoolers. Here researchers found that WM training and CB training resulted in significantly improved performance on non-trained WM tasks. NVR training led to improved performance on non-trained Gf tasks and showed a trend for improvement on a measure of visuo-spatial WM. Based on these findings, researchers in the current study investigated whether improvements after WM and NVR training were associated with differences (single nucleotide polymorphisms (SNPs)) in 5 genes (D4, D5, DAT1, DBH, & COMT) associated with the dopaminergic system in preschool children. Population & Sample Size: Genetic data from a subset of a larger sample of children from Bergman-Nutley et al. (2011) were analyzed. N =96 typical children, ages 4 – 4.5 years. Design: Children were pseudo-randomly assigned (stratified by sex) into an adaptive Cogmed training group, an adaptive NVR training group, a combination WM and NVR training group or a non-adaptive combination WM and NVR training group (see Bergman-Nutley et al. (2011) for details). All active training groups (WM, NVR and CB) were collapsed into one group. Thus, this study was primarily concerned with the effect of different gene variations on the outcomes observed after domain specific types of cognitive training. T1 = baseline, T2 = post-test


Results: I. Individual differences (SNPs) in the DAT1 gene were associated with training effects. 1) The rs27072 T/C and rs40184 versions of DAT1 were associated with the impact of training on fluid intelligence. 2) The rs3863145 version of DAT 1 was associated with the impact of training on WM. II. Note: The sample size of this investigation was considered small for analysis of genetic effects and these effects did not remain significant after correcting for multiple comparisons. III. No other SNPs showed significant training interaction effects.


Summary and Implications: Researchers investigated the role of different genetic variations (SNPs) on the change in cognitive performance after training on WM, NVR or the combination of WM and NVR training. Different SNPs of the DAT1 gene were associated with training effects. The DAT1 gene regulates the availability of dopamine in the brain by controlling amount and duration of time dopamine is available to communicate messages between cells (ie., how much DA is available in the synaptic cleft). Carriers of the rs27072 T/C version of DAT1 had larger training related gains on the latent factor for fluid intelligence (Gf). Interestingly, the T allele has also been found to have a protective effect for ADHD (Brookes et al., 2006; Feng et al., 2005). One important limitation of this study was the low sample size. When corrected for multiple comparisons, the observed effects no longer remained significant. Due to the low power, lack of effects for the other genotypes should be interpreted with caution and the researchers suggest that the findings of this study be replicated with larger, independent samples. Future studies should also investigate the impact of interactions between dopaminergic genes as well as factors such as age and baseline performance. Because the training groups were collapsed, it would also be interesting to investigate the importance of the domain in which the cognitive training is performed. Other studies with Cogmed have also provided evidence for the involvement of the dopaminergic system in training induced plasticity including McNab et al. (2009) and Brehmer et al. (2009). In conjunction with these prior studies, the current research suggests that DA is not only important for cognitive performance but also, that is important for plasticity.