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

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OTHERS SYSTEMATIC EVALUATION OF FMRI DATA-PROCESSING PIPELINES FOR CONSISTENT FUNCTIONAL CONNECTOMICS Article Open access 04 June 2024 COMPARISON OF WHOLE-BRAIN TASK-MODULATED FUNCTIONAL

CONNECTIVITY METHODS FOR FMRI TASK CONNECTOMICS Article Open access 26 October 2024 APPARENT DIFFUSION COEFFICIENT FMRI SHINES LIGHT ON WHITE MATTER RESTING-STATE CONNECTIVITY COMPARED TO

BOLD Article Open access 16 March 2025 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

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Download references 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. AUTHOR INFORMATION Author notes * These authors jointly supervised this work: Amy C. Janes, Blaise B. Frederick. AUTHORS AND AFFILIATIONS * Department of

Psychiatry, Harvard University Medical School, Boston, MA, USA Cole Korponay & Blaise B. Frederick * McLean Hospital Brain Imaging Center, Belmont, MA, USA Cole Korponay & Blaise B.

Frederick * Neuroimaging Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Bethesda, MD, USA Amy C. Janes Authors * Cole Korponay

View author publications You can also search for this author inPubMed Google Scholar * Amy C. Janes View author publications You can also search for this author inPubMed Google Scholar *

Blaise B. Frederick View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS 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. CORRESPONDING AUTHOR Correspondence to Cole Korponay. ETHICS DECLARATIONS COMPETING INTERESTS

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ARTICLE CITE THIS ARTICLE Korponay, C., Janes, A.C. & Frederick, B.B. Brain-wide functional connectivity artifactually inflates throughout functional magnetic resonance imaging scans.

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