Plasticity of memory functioning : genetic predictors and brain changes

Human cognitive functions are not determined from birth, but are plastic and can be altered by environmental factors. The promising idea of a cognitive intervention that would improve memory functioning has attracted a lot of attention over the last decades. By taxing memory functions through repeated training, researchers try to demonstrate improvement in the trained or other functions. However, people do not profit equally from these training regimes and their effect on brain integrity also differs between persons. In this thesis, I explore factors related to individual differences in cognitive training response, and their effects on the brain. The first part of the thesis concerns training of working memory (wm), and whether training-induced performance increases are influenced by certain genetic variations. The genetic variations studied are confined to genes related to the neurotransmitter dopamine (da), which is related to cognitive performance. In Study I, we investigated the effect on wm training gains of single nucleotide polymorphisms (snps) in the lmx1a gene, previously linked to Parkinson’s disease (pd). This gene is important for the development of da neurons. For one of the snps, we found that over the course of four weeks of wm training, the two genotype groups showed a differential pattern of gain, such that those participants carrying the allele associated with a lower risk of pd showed larger gains. In Study II, we examined if three da related snps were associated with gain in several cognitive abilities, after 100 days of broad cognitive training taxing wm, episodic memory (em), and perceptual speed (ps). The first one was the lmx1a snp that was found to be linked to wm training gains in Study I. The second was a snp in the drd2 gene, important to striatal da availability. The third was a commonly studied snp in the comt gene, coding for the enzyme that degrades da cortically. We found that only the comt snp had an effect on training gains, and only for wm. The second part of this thesis focus on em function, more precisely associative memory; if it could be trained, and what effects training may have on brain structure. In Study III, we explored process-based associative-memory training for older adults. Participants underwent six weeks of training on several different associative-memory tasks, with transfer tasks administered before and after training. An active control group underwent the same training, but practiced only on item memory tasks. No intervention effects were found for associative memory or the far transfer measures; however, the associative-memory training group showed larger gains than the controls on an item memory task. In Study IV, we used vocabulary learning as a way of studying associative-memory training. Participants studied a new language and their knowledge, effort, and cognitive capacity were measured. Before and after training, participants underwent structural magnetic resonance imaging (mri). We found that, compared to a control group, language learners showed increased grey matter (gm) volume in hippocampus. Furthermore, this volume increase was predicted by baseline capacity on a task measuring short term memory. Collectively, these studies show that the variability in training gains is not only noise, but rather meaningful variations that could be used to further our understanding of what factors determine the capacity for plastic change, both in brain and in behavior. List of scientific papers This thesis is based on the following publications, which are referred to in the text by their roman numerals (Study I–IV). Bellander, M. , Brehmer, Y. , Westerberg, H. , Karlsson, S. , Fürth, D. , Bergman, O. , Eriksson, E. , & Bäckman, L. (2011). Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement. Neuropsychologia. 49, 1938– 1942. Bellander, M. , Bäckman, L. , Liu, T. , Schjeide, B. -M. M. , Bertram, L. , Schmiedek, F. , Lindenberger, U. , & Lövdén, M. (2015). Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT val158met polymorphism. Neuropsychology,