Resting cerebral oxygen metabolism exhibits archetypal network features

Nicholas A. Hubbard*, Monroe P. Turner, Kevin R. Sitek, Kathryn L. West, Jakub R. Kaczmarzyk, Lyndahl Himes, Binu P. Thomas, Hanzhang Lu, Bart Rypma

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Standard magnetic resonance imaging approaches offer high-resolution but indirect measures of neural activity, limiting understanding of the physiological processes associated with imaging findings. Here, we used calibrated functional magnetic resonance imaging during the resting state to recover low-frequency fluctuations of the cerebral metabolic rate of oxygen (CMRO2). We tested whether functional connections derived from these fluctuations exhibited organization properties similar to those established by previous standard functional and anatomical connectivity studies. Seventeen participants underwent 20 min of resting imaging during dual-echo, pseudocontinuous arterial spin labeling, and blood-oxygen-level dependent (BOLD) signal acquisition. Participants also underwent a 10 min normocapnic and hypercapnic procedure. Brain-wide, CMRO2 low-frequency fluctuations were subjected to graph-based and voxel-wise functional connectivity analyses. Results demonstrated that connections derived from resting CMRO2 fluctuations exhibited complex, small-world topological properties (i.e., high integration and segregation, cost efficiency) consistent with those observed in previous studies using functional and anatomical connectivity approaches. Voxel-wise CMRO2 connectivity also exhibited spatial patterns consistent with four targeted resting-state subnetworks: two association (i.e., frontoparietal and default mode) and two perceptual (i.e., auditory and occipital-visual). These are the first findings to support the use of calibration-derived CMRO2 low-frequency fluctuations for detecting brain-wide organizational properties typical of healthy participants. We discuss interpretations, advantages, and challenges in using calibration-derived oxygen metabolism signals for examining the intrinsic organization of the human brain.

Original languageEnglish (US)
Pages (from-to)1952-1968
Number of pages17
JournalHuman Brain Mapping
Volume42
Issue number7
DOIs
StatePublished - May 2021

Funding

This work was supported in part by National Institute of Health grants to NAH (F32MH114525; P20GM130461[6026]), KRS (F31DC015695), and BR/HL (R01AG047972). This work was also partially supported by Friends of the Air Force Academy Library of Brain Health Distinguished Scientist Award, Brain and Behavior Research Foundation Award, and the Nebraska Biomedical Research Development Funds (NAH); the National Multiple Sclerosis Society (BR: RG‐150‐06687). The authors would like to thank Lindsey Michelle for assistance in figure creation, James Capella, Jimmy Chen, and Danielle Clark for assistance with manuscript preparation. The authors would also like to thank Drs. John Gabrieli, Satrajit Ghosh, and Susan Whitfield‐Gabrieli for providing thoughtful discussions about previous drafts of the manuscript. This work was supported in part by National Institute of Health grants to NAH (F32MH114525; P20GM130461[6026]), KRS (F31DC015695), and BR/HL (R01AG047972). This work was also partially supported by Friends of the Air Force Academy Library of Brain Health Distinguished Scientist Award, Brain and Behavior Research Foundation Award, and the Nebraska Biomedical Research Development Funds (NAH); the National Multiple Sclerosis Society (BR: RG-150-06687). The authors would like to thank Lindsey Michelle for assistance in figure creation, James Capella, Jimmy Chen, and Danielle Clark for assistance with manuscript preparation. The authors would also like to thank Drs. John Gabrieli, Satrajit Ghosh, and Susan Whitfield-Gabrieli for providing thoughtful discussions about previous drafts of the manuscript.

Keywords

  • fMRI
  • functional connectivity
  • oxygen metabolism
  • resting state

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Anatomy

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