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Cloettapreis_2013_Nr_41

26 genetic studies on episodic memory it is crucial to control for such ­unspecific factors. The phenotypic complexity with regard to episodic memory not only has important and obvious implications for replication studies24 , but also for meta- and mega-analyses (i.e., the use of raw data from individual sub- jects across different studies): By combining several similar, but not iden- tical, episodic memory phenotypes, genetic studies may identify statisti- cally robust associations pointing to common denominators of these phenotypes, but are likely to miss molecules specifically related to a dis­ tinct phenotype with distinct neurobiological features. Imaging genetics Besides the importance of replicating genetic association studies on epi- sodic memory it is important to also consider additional methods for further corroboration and better understanding of the behavioral genetics findings. In the recent few years, brain-imaging techniques, in particular functional Magnetic Resonance Imaging (fMRI), have become increas­ ingly popular for this purpose23, 51-53 . The rationale for combining be­ havioral genetic and neuroimaging methods is to validate and extend ­purely behavioral genetic studies by providing insight into the genetic differences in memory processes at the level of neural circuits54 . So far, the majority of imaging genetic studies has looked at single markers in relation to brain activation differences. However, considering the ge­- netic – and phenotypic complexity of human episodic memory, another promising approach involves studying specific genetic networks (com- prising multiple markers in different genes) related to a certain episodic memory phenotype by investigating compound genetic scores in relat­- ion to brain activity39 (Figure 1). The interpretation of genotype-dependent differences in brain activity critically depends on the fMRI study design and the behavioral findings of the fMRI sample. Whenever significant performance differences ­across genotype groups exist, a possible outcome is higher activity in memory- related brain regions in the genotype group that shows higher memory performance55 . In the case genotype groups of the fMRI sample have been matched for performance, brain activity increases for the genotype group with low memory performance in the unmatched population can be

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