The relationship between spatial configuration and functional connectivity of brain regions revisited

  1. Janine Diane Bijsterbosch  Is a corresponding author
  2. Christian F Beckmann
  3. Mark W Woolrich
  4. Stephen M Smith
  5. Samuel J Harrison
  1. University of Oxford, United Kingdom
  2. Radboud University Medical Centre, Netherlands

Abstract

In our previous paper (Bijsterbosch et al., 2018), we showed that network-based modelling of brain connectivity interacts strongly with the shape and exact location of brain regions, such that cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Here we show that these spatial effects on connectivity estimates actually occur as a result of spatial overlap between brain networks. This is shown to systematically bias connectivity estimates obtained from group spatial ICA followed by dual regression. We introduce an extended method that addresses the bias and achieves more accurate connectivity estimates.

Data availability

Simulation analysis scripts are available on git.Source data files for Figures 1 and 5 will be made available on BALSA (https://balsa.wustl.edu/) upon acceptance.

The following previously published data sets were used

Article and author information

Author details

  1. Janine Diane Bijsterbosch

    Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    For correspondence
    janine.bijsterbosch@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1385-9178
  2. Christian F Beckmann

    Donders Institute, Radboud University Medical Centre, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Mark W Woolrich

    Oxford Centre for Human Brain Activity (OHBA), Wellcome Centre for Integrative NeuroImaging, Department of Psychiatry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephen M Smith

    Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Samuel J Harrison

    Centre for Functional MRI of the Brain (FMRIB), Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5886-2389

Funding

Wellcome (098369/Z/12/Z)

  • Stephen M Smith

Wellcome (091509/Z/10/Z)

  • Stephen M Smith

Wellcome (203139/Z/16/Z)

  • Stephen M Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: HCP data were acquired using protocols approved by the Washington University institutional review board (Mapping the Human Connectome: Structure, Function, and Heritability; IRB # 201204036). Informed consent was obtained from subjects. Anonymised data are publicly available from ConnectomeDB (db.humanconnectome.org; Hodge et al., 2016). Certain parts of the dataset used in this study, such as the age of the subjects, are available subject to restricted data usage terms, requiring researchers to ensure that the anonymity of subjects is protected (Van Essen et al., 2013).

Copyright

© 2019, Bijsterbosch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,793
    views
  • 422
    downloads
  • 72
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Janine Diane Bijsterbosch
  2. Christian F Beckmann
  3. Mark W Woolrich
  4. Stephen M Smith
  5. Samuel J Harrison
(2019)
The relationship between spatial configuration and functional connectivity of brain regions revisited
eLife 8:e44890.
https://doi.org/10.7554/eLife.44890

Share this article

https://doi.org/10.7554/eLife.44890

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Kyusang Yoo, Young-Woo Jo ... Young-Yun Kong
    Research Article

    Fibro-adipogenic progenitors (FAPs) are muscle-resident mesenchymal progenitors that can contribute to muscle tissue homeostasis and regeneration, as well as postnatal maturation and lifelong maintenance of the neuromuscular system. Recently, traumatic injury to the peripheral nerve was shown to activate FAPs, suggesting that FAPs can respond to nerve injury. However, questions of how FAPs can sense the anatomically distant peripheral nerve injury and whether FAPs can directly contribute to nerve regeneration remained unanswered. Here, utilizing single-cell transcriptomics and mouse models, we discovered that a subset of FAPs expressing GDNF receptors Ret and Gfra1 can respond to peripheral nerve injury by sensing GDNF secreted by Schwann cells. Upon GDNF sensing, this subset becomes activated and expresses Bdnf. FAP-specific inactivation of Bdnf (Prrx1Cre; Bdnffl/fl) resulted in delayed nerve regeneration owing to defective remyelination, indicating that GDNF-sensing FAPs play an important role in the remyelination process during peripheral nerve regeneration. In aged mice, significantly reduced Bdnf expression in FAPs was observed upon nerve injury, suggesting the clinical relevance of FAP-derived BDNF in the age-related delays in nerve regeneration. Collectively, our study revealed the previously unidentified role of FAPs in peripheral nerve regeneration, and the molecular mechanism behind FAPs’ response to peripheral nerve injury.

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Alfonso Aguilera, Marta Nieto
    Insight

    A tailored cocktail of genes can reprogram a subset of progenitors to no longer produce glial cells and instead develop into neurons involved in motor control.