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Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans

Nature Human Behaviour volume 8, pages 1568–1580 (2024)Cite this article

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Abstract

Functional magnetic resonance imaging (fMRI) is a central tool for investigating human brain function, organization and disease. Here, we show that fMRI-based estimates of functional brain connectivity artifactually inflate at spatially heterogeneous rates during resting-state and task-based scans. This produces false positive connection strength changes and spatial distortion of brain connectivity maps. We demonstrate that this artefact is driven by temporal inflation of the non-neuronal, systemic low-frequency oscillation (sLFO) blood flow signal during fMRI scanning and is not addressed by standard denoising procedures. We provide evidence that sLFO inflation reflects perturbations in cerebral blood flow by respiration and heart rate changes that accompany diminishing arousal during scanning, although the mechanisms of this pathway are uncertain. Finally, we show that adding a specialized sLFO denoising procedure to fMRI processing pipelines mitigates the artifactual inflation of functional connectivity, enhancing the validity and within-scan reliability of fMRI findings.

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Fig. 1: Evidence for the presence of brain-wide, spatially heterogeneous FC inflation over time in the MIC dataset.
Fig. 2: Replication of the temporal and spatial features of FC inflation in the HCP dataset.
Fig. 3: Standard preprocessing and denoising do not address FC inflation.
Fig. 4: GMS variance inflates over time during and across scanning acquisitions.
Fig. 5: Temporal and spatial properties of the sLFO signal in the HCP REST1 data.
Fig. 6: The impact of RIPTiDe denoising on FC inflation.
Fig. 7: Comparing denoising pipelines for addressing FC inflation.
Fig. 8: Relationships between sLFO inflation and arousal-related physiological changes.

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Data availability

The HCP dataset is publicly available on the open access Connectome database (https://db.humanconnectome.org/app/template/Login.vm), which can be accessed after signing a data use agreement. The PSU (https://openneuro.org/datasets/ds003768/versions/1.0.9) and YMRRC (https://openneuro.org/datasets/ds003673/versions/2.0.1) datasets are publicly available on the OpenNeuro repository. The MIC dataset is available upon reasonable request to the corresponding author.

Code availability

The code for assessing the presence of brain-wide FC inflation in an fMRI dataset is publicly available at https://github.com/ckorponay/Connectivity-Inflation/blob/main/FC_Inflation_Evaluator.m. The code and instructions for performing RIPTiDe denoising using the rapidtide package are publicly available at https://rapidtide.readthedocs.io/en/latest/usage_rapidtide.html#removing-low-frequency-physiological-noise-from-fmri-data.

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Acknowledgements

This work was supported by grant no. 5R01DA039135-06 to A.C.J., the Intramural Research Program of the National Institutes of Health, the National Institute on Drug Abuse (to A.C.J.), and grant nos 1RF1MH130637-01 and 1R21AG070383-01 to B.B.F. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Author notes

  1. These authors jointly supervised this work: Amy C. Janes, Blaise B. Frederick.

Authors and Affiliations

  1. Department of Psychiatry, Harvard University Medical School, Boston, MA, USA

    Cole Korponay & Blaise B. Frederick

  2. McLean Hospital Brain Imaging Center, Belmont, MA, USA

    Cole Korponay & Blaise B. Frederick

  3. Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA

    Amy C. Janes

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  1. Cole Korponay
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  2. Amy C. Janes
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C.K., A.C.J. and B.B.F. were responsible for study conceptualization, data collection, curation and analysis, and for writing, reviewing and editing the manuscript.

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Correspondence to Cole Korponay.

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Korponay, C., Janes, A.C. & Frederick, B.B. Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans. Nat Hum Behav 8, 1568–1580 (2024). https://doi.org/10.1038/s41562-024-01908-6

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