Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Gediminas Luksys, Matthias Fastenrath, David Coynel, Virginie Freytag, Leo Gschwind, Angela Heck, Frank Jessen, Wolfgang Maier, Annette Milnik, Steffi G Riedel-Heller, Martin Scherer, Klara Spalek, Christian Vogler, Michael Wagner, Steffen Wolfsgruber, Andreas Papassotiropoulos, Dominique J-F de Quervain

Research output: Contribution to journalArticlepeer-review

Abstract

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

Original languageEnglish
Pages (from-to)E4939-E4948
JournalProceedings of the National Academy of Sciences
Volume112
Issue number35
Early online date10 Aug 2015
DOIs
Publication statusPublished - 1 Sep 2015

Keywords

  • Adult
  • Computational Biology
  • Female
  • Healthy Volunteers
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Mental Processes
  • Young Adult
  • Journal Article
  • Research Support, Non-U.S. Gov't

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