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

TY - JOUR

T1 - Computational dissection of human episodic memory reveals mental process-specific genetic profiles

AU - Luksys, Gediminas

AU - Fastenrath, Matthias

AU - Coynel, David

AU - Freytag, Virginie

AU - Gschwind, Leo

AU - Heck, Angela

AU - Jessen, Frank

AU - Maier, Wolfgang

AU - Milnik, Annette

AU - Riedel-Heller, Steffi G

AU - Scherer, Martin

AU - Spalek, Klara

AU - Vogler, Christian

AU - Wagner, Michael

AU - Wolfsgruber, Steffen

AU - Papassotiropoulos, Andreas

AU - de Quervain, Dominique J-F

PY - 2015/9/1

Y1 - 2015/9/1

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.1500860112

DO - 10.1073/pnas.1500860112

M3 - SCORING: Journal article

C2 - 26261317

VL - 112

SP - E4939-48

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 35

ER -