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Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network

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Abstract

Functional connections between brain regions constitute the substrate of the human functional connectome, whose topography has been discussed as an endophenotype for psychiatric disorders. Genetic influences on the entire connectome, however, have been rarely investigated so far. We tested for connectome-wide influences of the val158met (rs4860) polymorphism on the catechol-O-methyltransferase (COMT) gene by applying formal network analysis and eigenvector centrality mapping on the voxel level to resting-state functional magnetic imaging data. This approach finds brain regions that are central in the network by aggregating local and global connectivity patterns, most importantly without the requirement to select regions or networks of interest. The COMT variant linked to high enzyme activity increased network centrality in distributed brain areas that are known to constitute the brain’s default mode network. Further results also indicated a COMT influence on areas implicated in the somatomotor network. These findings are in line with the polymorphism’s alleged role in cognitive processing and its role in psychotic disorders. The study is the first to demonstrate the influence of a functional and behaviorally relevant genetic variant on connectome-wide functional connectivity and is an important step toward establishing the functional connectome as an endophenotype for psychiatric and behavioral phenotypes.

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Acknowledgments

This work was funded by grants by the Deutsche Forschungsgemeinschaft (DFG) to Christian Montag (MO-2363/2-1, MO-2363/3-1) and Bernd Weber (Heisenberg-Grant WE 4427/3-1).

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Authors and Affiliations

  1. Department of Psychology, University of Bonn, Kaiser-Karl-Ring 9, 53111, Bonn, Germany

    Sebastian Markett & Martin Reuter

  2. Department of Psychology, University of Ulm, Ulm, Germany

    Christian Montag, Rayna Saryiska & Bernd Lachmann

  3. Center for Economics and Neuroscience, University of Bonn, Bonn, Germany

    Sebastian Markett, Bernd Weber & Martin Reuter

  4. Institute for Numerical Simulation, University of Bonn, Bonn, Germany

    Behrend Heeren

  5. Life and Brain Center Bonn, Bonn, Germany

    Bernd Weber

  6. Department of Epileptology, University Clinics Bonn, Bonn, Germany

    Bernd Weber

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  1. Sebastian Markett
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  2. Christian Montag
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Correspondence to Sebastian Markett.

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S. Markett and C. Montag share the first authorship.

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Markett, S., Montag, C., Heeren, B. et al. Voxelwise eigenvector centrality mapping of the human functional connectome reveals an influence of the catechol-O-methyltransferase val158met polymorphism on the default mode and somatomotor network. Brain Struct Funct 221, 2755–2765 (2016). https://doi.org/10.1007/s00429-015-1069-9

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