Standardizing the intrinsic brain: Towards robust measurement of inter-individual variation in 1000 functional connectomes
Open accessAbstract
As researchers increase their efforts to characterize variations in the functional connectome across studies and individuals, concerns about the many sources of nuisance variation present and their impact on resting state fMRI (R-fMRI) measures continue to grow. Although substantial within-site variation can exist, efforts to aggregate data across multiple sites such as the 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) datasets amplify these concerns. The present work draws upon standardization approaches commonly used in the microarray gene expression literature, and to a lesser extent recent imaging studies, and compares them with respect to their impact on relationships between common R-fMRI measures and nuisance variables (e.g., imaging site, motion), as well as phenotypic variables of interest (age, sex). Standardization approaches differed with regard to whether they were applied post-hoc vs. during pre-processing, and at the individual vs. group level; additionally they varied in whether they addressed additive effects vs. additive+multiplicative effects, and were parametric vs. non-parametric. While all standardization approaches were effective at reducing undesirable relationships with nuisance variables, post-hoc approaches were generally more effective than global signal regression (GSR). Across approaches, correction for additive effects (global mean) appeared to be more important than for multiplicative effects (global SD) for all R-fMRI measures, with the exception of amplitude of low frequency fluctuations (ALFF). Group-level post-hoc standardizations for mean-centering and variance-standardization were found to be advantageous in their ability to avoid the introduction of artifactual relationships with standardization parameters; though results between individual and group-level post-hoc approaches were highly similar overall. While post-hoc standardization procedures drastically increased test-retest (TRT) reliability for ALFF, modest reductions were observed for other measures after post-hoc standardizations-a phenomena likely attributable to the separation of voxel-wise from global differences among subjects (global mean and SD demonstrated moderate TRT reliability for these measures). Finally, the present work calls into question previous observations of increased anatomical specificity for GSR over mean centering, and draws attention to the near equivalence of global and gray matter signal regression.
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The Thousand Functional Connectomes and related projects are seeking to generate even larger numbers of subjects than the HCP, bringing together data from a wide range of imaging studies and scanners, and covering a wider range of subject groups, including a range of pathologies.
“The Thousand Functional Connectomes (and related) projects [74, 75], led by Mike Milham, are seeking to generate even larger numbers of subjects than the HCP, bringing together data from a wide range of imaging studies and scanners, and covering a wider range of subject groups, including a range of pathologies.”
From Functional connectomics from resting-state fMRI (2013) · cites this paper as [75]
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- Authors
- Yan, C.-G., Craddock, R. C., Zuo, X.-N., Zang, Y.-F., & Milham, M. P.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- Chinese Academy of Sciences (CN)
- Hangzhou Normal University (CN)
- Corresponding author
- Milham, Michael P.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2013-10
- Volume
- 80
- Pages
- 246-262
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC4074397
- OpenAlex
- W2076301067
- Cited by
- 440
- References
- 9
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 33 · 2023: 30 · 2022: 30 · 2021: 41 · 2020: 45 · 2019: 31 · 2018: 34 · 2017: 40 · 2016: 44 · 2015: 38 · 2014: 21 · 2013: 9
- FWCI
- 20.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Institutional Repository of Institute of Psychology, Chinese Academy of Sciences (Institute of Psychology, Chinese Academy of Sciences) (submittedVersion)
- Institutional Repository of Institute of Psychology, Chinese Academy of Sciences (Institute of Psychology, Chinese Academy of Sciences) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institute of Mental Health (BRAINS R01MH094639, R03MH096321)
- Stavros Niarchos Foundation
- Brain and Behavior Research Foundation
- National Natural Science Foundation of China (81171409, 81220108014)
- Startup Foundation for Distinguished Research Professor of the Institute of Psychology (Y0CX492S03)
- Chinese Academy of Sciences (Y2CX112006, KSZD-EW-TZ-002)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- resting-state fMRI, nuisance parameters, global signal regression, mean centering, amplitude of low-frequency fluctuation, test-retest reliability, interindividual variability, motion artifacts
- MeSH terms
- Animals, Brain, Data Interpretation, Statistical, Humans, Magnetic Resonance Imaging, Models, Anatomic, Models, Neurological, Nerve Net, Reference Values, Sensitivity and Specificity, Reproducibility of Results, Connectome
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