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Delayed stabilization and individualization in connectome development are related to psychiatric disorders

Nature Neuroscience volume 20, pages 513515 (2017) | Download Citation

Abstract

The brain functional connectome constitutes a unique fingerprint allowing identification of individuals among a pool of people. Here we establish that the connectome develops into a more stable, individual wiring pattern during adolescence and demonstrate that a delay in this network tuning process is associated with reduced mental health in the formative years of late neurodevelopment.

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Acknowledgements

The authors were funded by the Research Council of Norway (213837, 223273, 204966/F20, 229129, 249795/F20), the South-Eastern Norway Regional Health Authority (2013-123, 2014-097, 2015-073), the KG Jebsen Foundation, the European Commission 7th Framework Programme (602450, IMAGEMEND) and the NIH BD2K award (U54EB020403). Support for the collection of the data sets was provided by grant RC2MH089983 awarded to R. Gur and RC2MH089924 awarded to H. Hakonarson. All subjects were recruited through the Center for Applied Genomics at The Children's Hospital in Philadelphia.

Author information

Affiliations

  1. NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

    • Tobias Kaufmann
    • , Dag Alnæs
    • , Nhat Trung Doan
    • , Christine Lycke Brandt
    • , Ole A Andreassen
    •  & Lars T Westlye
  2. Department of Psychology, University of Oslo, Oslo, Norway.

    • Lars T Westlye

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Contributions

T.K. and L.T.W. conceived the study; T.K. analyzed the data with contributions from L.T.W.; D.A. N.T.D., C.L.B. and O.A.A. contributed with data preprocessing, quality assurance and interpretation of results; T.K. and L.T.W. wrote the first draft of the paper and all authors contributed to the final manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Tobias Kaufmann or Lars T Westlye.

Integrated supplementary information

Supplementary figures

  1. 1.

    Residualized connectome distinctiveness (regressing motion, tSNR and motion × tSNR) depicted similar neurodevelopmental patterns.

  2. 2.

    Excluding subjects such that the resulting motion profiles were similar between sexes yielded similar sex patterns in connectome distinctiveness.

  3. 3.

    Excluding subjects such that the resulting motion profiles were similar between HC and gF yielded similar clinical patterns in connectome distinctiveness.

  4. 4.

    Subject identification based on motion and tSNR estimates alone (no connectome data) did not succeed.

  5. 5.

    The reported age trajectories in connectome distinctiveness were reproduced using a different analysis pipeline based on independent component analysis (ICA).

  6. 6.

    Comparison of statistical models calculated in extreme groups (group differences) or across all subjects (continuous associations with symptom scores).

  7. 7.

    With increasing age, the intrinsic network architecture is stabilized across runs.

  8. 8.

    Time series split analysis confirms that the increased across-context coherence with increasing age is unlikely to be a side effect of differential noise profiles between young and old subjects.

  9. 9.

    Testing two hypotheses, one favoring an individual-level tuning and one favoring a common tuning, the results provide strong support of a network tuning with less overlapping (more individualized) edges with increasing age.

  10. 10.

    Multivariate estimates of stability and individuality were strongly related.

  11. 11.

    Results from statistical models on connectome distinctiveness and gF in the various networks confirm a contribution of both stability and individuality.

  12. 12.

    Age distribution for each clinical group in comparison to healthy controls.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–12 and Supplementary Tables 1 and 2

  2. 2.

    Supplementary Methods Checklist

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DOI

https://doi.org/10.1038/nn.4511

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