Review Imaging genetics of cognitive functions: Focus on episodic memory B. Rasch a,b,c,d,e, ⁎, A. Papassotiropoulos b,c , D.-F. de Quervain a,d,e, ⁎ a University of Basel, Division of Cognitive Neuroscience, Birmannsgasse 8, 4055 Basel, Switzerland b University of Basel, Division of Molecular Psychology, Missionsstr 60/62, 4055 Basel, Switzerland c University of Basel, Biozentrum, Life Sciences Training Facility, Klingelbergstr 50/70, 4056 Basel, Switzerland d University of Basel, Psychiatric University Clinic, Wilhelm Klein-Strasse 27, 4055 Basel, Switzerland e Center for Integrative Human Physiology, University of Zürich, 8057, Zürich, Switzerland. abstract article info Article history: Received 1 September 2009 Revised 2 December 2009 Accepted 2 January 2010 Available online 11 January 2010 Human cognitive functions are highly variable across individuals and are both genetically and environmentally influenced. Recent behavioral genetics studies have identified several common genetic polymorphisms, which are related to individual differences in memory performance. In addition, imaging genetics studies are starting to explore the neural correlates of genetic differences in memory functions on the level of brain circuits. In this review we will describe how functional magnetic resonance imaging (fMRI) can be used to validate and extend findings of behavioral genetics studies of episodic memory and give examples of recent advances in this new and exciting research field. In addition, we will present advantages and problems related to the different sensitivity of behavioral- vs. imaging genetics studies and discuss possible methodological approaches for an appropriate evaluation and integration of the results. Although the field of imaging genetics of episodic memory is still young, it already became clear that imaging methods have a large potential to enhance our understanding of the neural mechanisms that underlie genetic differences in memory. © 2010 Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 870 Imaging episodic memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 871 Imaging genotype-dependent differences in episodic memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 871 Matched memory performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 871 Unmatched memory performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 872 Genetic complexity of episodic memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 873 General problems of group comparisons in genetic imaging studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874 Neural compensation vs. encoding efficiency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874 The consequences of different sensitivity of imaging vs. behavioral genetics studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876 Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876 Introduction Human memory is a cognitive trait that is influenced by both genetic and environmental factors. Twin studies have estimated that genetic factors account for approximately 50% of the variability in human memory capacity (McClearn et al., 1997), indicating that naturally occurring genetic variations must have a significant impact on this cognitive ability. In support of this assumption, several recent behavioral- and imaging-genetics studies have successfully identified and characterized genetic variations significantly associated with human memory performance. In the present review, we will focus on episodic memory, but similar developments are taking place for other forms of memory, such as working memory (Goldberg and Weinber- ger, 2004; Meyer-Lindenberg and Weinberger, 2006). In 2003, two genetic factors associated with episodic memory in healthy humans were identified: the Val66Met polymorphism in the gene encoding the brain-derived neurotrophic factor (BDNF)(Egan et al., 2003) and the His452Tyr polymorphism in the gene encod- ing the serotonin 2A receptor (HTR2A)(de Quervain et al., 2003). Following these two studies, several other polymorphisms related to NeuroImage 53 (2010) 870–877 ⁎ Corresponding authors. E-mail addresses: Bjoern.Rasch@unibas.ch (B. Rasch), Dominique.Dequervain@unibas.ch (D.-F. de Quervain). 1053-8119/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.neuroimage.2010.01.001 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg