Cited by 952Functional Brain Connectivity StudiesAdvanced Neuroimaging Techniques and ApplicationsAdvanced MRI Techniques and Applications

The DOI matches its Crossref record; 92 of the 93 references it cites were found in a registry or an index; 2 of the 52 sources its claims cite were checked for support.

Functional connectomics from resting-state fMRI

Open access
Smith, Stephen M., Vidaurre, Diego, Beckmann, Christian F., Glasser, Matthew F., Jenkinson, Mark, Miller, Karla L., Nichols, Thomas E., Robinson, Emma C., Salimi-Khorshidi, Gholamreza, Woolrich, Mark W., Barch, Deanna M., Uğurbil, Kamil, Van Essen, David C.·2013·Trends in Cognitive Sciences

Abstract

Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project, and highlight some upcoming challenges in functional connectomics.

Overview

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Written from the paper’s full text.

TL;DR

This review describes how resting-state fMRI (rfMRI) can map the macroscopic functional connectome, covering acquisition, preprocessing, network modelling, and Human Connectome Project (HCP) data. It highlights high-quality HCP rfMRI enabling detailed node-and-edge connectomes and links to behaviour and sex, while noting major challenges in causality, alignment, and dynamic network modelling.

Key findings

  • The HCP is generating rfMRI from over 1000 healthy adults aged 22–35, including twins and non-twin siblings: 1 h of whole-brain 3T rfMRI in two pairs of 15-min runs on separate days, at 2×2×2 mm spatial resolution, 0.7 s temporal resolution, and EPI acceleration factor ×8; over 200 subjects’ datasets were already publicly released, and 3T rfMRI is represented using about 90,000 grayordinates at ~2 mm spacing.
  • In the first 131 HCP subjects, aggregating over 600,000 timepoints, group-ICA at dimensionality 100 yielded 98 network nodes after discarding 2 artefactual components; partial correlation matrices were as strong and consistent across subjects as full correlation matrices, which the authors call unusual and indicative of high data quality and many timepoints.
  • Multimodal surface matching improved cross-subject network similarity: average between-subject network correlations were FreeSurfer=0.613, MSMfolding=0.618, and MSMmultimodal=0.649; sex prediction with leave-one-out linear discriminant analysis reached 87% for MSMmultimodal versus 78% for FreeSurfer and 82% for MSMfolding, and using full correlation instead of partial correlation reduced sex classification accuracy from 87% to 70%.
  • A significant association was found between individual subjects’ network matrices and fluid intelligence, with the 24 strongest edges shown; the node-pair contributing most strongly had only a weak average population connection but varied across subjects in a way that correlated with fluid intelligence. A separate analysis identified 9 edges significantly different in strength between the two sexes.

Methods

  • Design: a review of rfMRI-based functional connectomics, including illustrative analyses using publicly released HCP rfMRI data.
  • Data/sample: HCP cohort of over 1000 healthy adult twins and non-twin siblings aged 22–35; the illustrative analyses used the first 131 subjects’ rfMRI data, aggregating over 600,000 timepoints.
  • Main analysis: preprocessing with FSL, FreeSurfer, and Connectome Workbench; ICA-based artefact removal with FIX (reported >99% classification accuracy on HCP data); group-ICA at dimensionality 100 yielding 98 nodes; full and partial correlation, regularised inverse covariance, multimodal surface matching, permutation testing, linear discriminant analysis, and temporal-ICA.

Limitations

  • Stated in paper: correlation cannot reveal causality or whether connectivity is direct versus indirect; partial correlation estimates direct connections but not directionality; directionality estimation is harder than edge detection, temporal lag is confounded by slow and variable haemodynamics, and observational rfMRI is not a robust tool for inferring causality compared with interventional task-fMRI.
  • Stated in paper: dynamic causal modelling is practical only for networks with fewer than 10 nodes; for 50–500 nodes, partial correlation is a pragmatic compromise but inverse covariance estimation is often unstable and benefits from regularisation; graph-theory measures risk inappropriate node definitions, use of thresholded full correlation matrices, and confounds such as head motion or heart rate.
  • Stated in paper: temporal-ICA forces modes to be fully independent over time, assumes within-mode connection strengths are static, and cannot well identify mutually exclusive modes with negative correlation; sliding-window correlation can be confounded by window length and overlapping networks; no single parcellation technique has emerged as best; and larger heterogeneous datasets such as the Thousand Functional Connectomes have greater scanning-parameter heterogeneity and lower data quality than HCP. Evident from text: the paper is a review with illustrative HCP analyses rather than a single primary empirical study, so its quantitative results are presented as examples of methodological potential and issues.

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Integrity signals

Registry

Crossref · 10.1016/j.tics.2013.09.016

Cites

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Claims the paper makes

50 Own interpretation · 42 Not checked yet · 12 Own result · 11 No basis given · 1 Partly supported · accuracy not yet measured

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  • Probably not a substantial claim. 23
  • It may state two separate claims as one. 45
62 of 62
  • The paper relies on this without support.

    The biological significance of the rich and continuously-present set of spontaneous, correlated activities in the resting brain remains poorly understood.

    “The biological significance of such a rich and continuously-present set of spontaneous, correlated activities in the “resting” brain remains poorly understood.”
  • The authors state this as an assumption.

    The brain is continuously engaged in undirected cognitive activities, including conscious thought processes and sub-conscious activity such as learning/unlearning, and also responds to uncontrolled external stimuli.

    “Presumably, the brain is continuously engaged in undirected cognitive activities (both conscious thought processes and sub-conscious activity such as learning/unlearning), and also responds to uncontrolled external stimuli.”
  • The paper relies on this without support.

    The functional parcels defined at the group level correspond to true subject-specific versions of those same parcels.

    “because the functional parcels defined at the group level should be more accurately aligned to the true subject-specific versions of those same parcels.”
  • The paper relies on this without support.

    The subject-wise variations of all edges are not fully independent of each other.

    “because we do not expect the subject-wise variations of all edges to be fully independent of each other.”
  • The paper relies on this without support.

    The rfMRI signal is dominated by low frequencies (~0.015Hz).

    “as the rfMRI signal is dominated by low frequencies (~0.015Hz)”
  • The paper relies on this without support.

    There is a true macroscopic functional connectome that partial correlation matrices estimate better than full correlation.

    “partial correlation matrices provide a better estimate of the “true” macroscopic functional connectome than full correlation.”
6 of 6

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Metadata

Authors
Smith, S. M., Vidaurre, D., Beckmann, C. F., Glasser, M. F., Jenkinson, M., Miller, K. L., Nichols, T. E., Robinson, E. C., Salimi-Khorshidi, G., Woolrich, M. W., Barch, D. M., Uğurbil, K., & Van Essen, D. C.
Affiliations
  • University of Oxford (GB)
  • Radboud University Nijmegen (NL)
  • Washington University in St. Louis (US)
  • University of Warwick (GB)
Corresponding author
Smith, Stephen M.
Venue
Trends in Cognitive Sciences
Publisher
Elsevier BV
Published
2013-12
Volume
17
Issue
12
Pages
666-682
ISSN
1364-6613 (ISSN-L)
OpenAlex
W2124698428
Cited by
952
References
93
Citations by year
2026: 55 · 2025: 77 · 2024: 84 · 2023: 76 · 2022: 83 · 2021: 82 · 2020: 88 · 2019: 77 · 2018: 81 · 2017: 72 · 2016: 71 · 2015: 63 · 2014: 38 · 2013: 3
FWCI
4.96
Type
journal article
Language
en
Open access
Locations
  • Trends in Cognitive Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • University of Twente Research Information (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
  • University of Twente Research Information (submittedVersion)
Funders
  • Wellcome Trust (1U54MH091657, 098369/Z/12/Z, 098369, 100309/A/12/Z, 100309)
  • National Institutes of Health (5u54mh091657-05, 1u54mh091657-01, 1U54‐MH‐091657, RR08079)
  • National Institute of Mental Health (1U54-MH091657-01, U54-MH091657, F30MH097312)
  • National Institute of Neurological Disorders and Stroke (P30NS076408, P30NS057091)
  • National Institute of Biomedical Imaging and Bioengineering (P41EB015894, P41-RR08079/EB015894)
  • National Center for Research Resources (P41RR008079)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
functional connectomics, resting-state fMRI, spontaneous brain activity, functional brain networks, network structure estimation, Human Connectome Project, MRI image processing, connectome mapping
MeSH terms
Animals, Brain, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Nerve Net, Neural Pathways, Oxygen, Rest

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