Neural underpinning of a respiration-associated resting-state fMRI network

  1. Wenyu Tu
  2. Nanyin Zhang  Is a corresponding author
  1. Pennsylvania State University, United States


Respiration can induce motion and CO2 fluctuation during resting-state fMRI (rsfMRI) scans, which will lead to non-neural artifacts in the rsfMRI signal. In the meantime, as a crucial physiologic process, respiration that can directly drive neural activity change in the brain, and may thereby modulate the rsfMRI signal. Nonetheless, this potential neural component in the respiration-fMRI relationship is largely unexplored. To elucidate this issue, here we simultaneously recorded the electrophysiology, rsfMRI and respiration signals in rats. Our data show that respiration is indeed associated with neural activity changes, evidenced by a phase-locking relationship between slow respiration variations and the gamma-band power of the electrophysiologic signal recorded in the anterior cingulate cortex. Intriguingly, slow respiration variations are also linked to a characteristic rsfMRI network, which is mediated by gamma-band neural activity. In addition, this respiration-related brain network disappears when brain-wide neural activity is silenced at an iso-electrical state, while the respiration is maintained, further confirming the necessary role of neural activity in this network. Taken together, this study identifies a respiration-related brain network underpinned by neural activity, which represents a novel component in the respiration-rsfMRI relationship that is distinct from respiration-related rsfMRI artifacts. It opens a new avenue for investigating the interactions between respiration, neural activity and resting-state brain networks in both healthy and diseased conditions.

Data availability

All data for this study have been deposited to NITRIC repository.

The following data sets were generated
    1. Tu W
    2. Zhang
    3. N
    (2022) Electrophysiology, resting state fMRI and respiration in rats
    NeuroImaging Tools and Resources Collaboratory (NITRC),

Article and author information

Author details

  1. Wenyu Tu

    The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Nanyin Zhang

    Department of Biomedical Engineering, Pennsylvania State University, University Park, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5824-9058


National Institute of Neurological Disorders and Stroke (R01NS085200)

  • Nanyin Zhang

National Institute of Mental Health (RF1MH114224)

  • Nanyin Zhang

National Institute of General Medical Sciences (R01GM141792)

  • Nanyin Zhang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: The present study was approved by the Pennsylvania State University Institutional Animal Care and Use Committee (IACUC) with the protocol number of PRAMS201343583.

Reviewing Editor

  1. Karla L Miller, University of Oxford, United Kingdom

Publication history

  1. Received: July 1, 2022
  2. Preprint posted: July 13, 2022 (view preprint)
  3. Accepted: October 13, 2022
  4. Accepted Manuscript published: October 20, 2022 (version 1)
  5. Version of Record published: November 9, 2022 (version 2)


© 2022, Tu & Zhang

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


  • 1,789
    Page views
  • 309
  • 0

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Wenyu Tu
  2. Nanyin Zhang
Neural underpinning of a respiration-associated resting-state fMRI network
eLife 11:e81555.
  1. Further reading

Further reading

    1. Chromosomes and Gene Expression
    2. Neuroscience
    Tooba Abbassi-Daloii, Salma el Abdellaoui ... Vered Raz
    Tools and Resources

    Skeletal muscles support the stability and mobility of the skeleton but differ in biomechanical properties and physiological functions. The intrinsic factors that regulate muscle-specific characteristics are poorly understood. To study these, we constructed a large atlas of RNA-seq profiles from six leg muscles and two locations from one muscle, using biopsies from 20 healthy young males. We identified differential expression patterns and cellular composition across the seven tissues using three bioinformatics approaches confirmed by large-scale newly developed quantitative immune-histology procedures. With all three procedures, the muscle samples clustered into three groups congruent with their anatomical location. Concomitant with genes marking oxidative metabolism, genes marking fast- or slow-twitch myofibers differed between the three groups. The groups of muscles with higher expression of slow-twitch genes were enriched in endothelial cells and showed higher capillary content. In addition, expression profiles of Homeobox (HOX) transcription factors differed between the three groups and were confirmed by spatial RNA hybridization. We created an open-source graphical interface to explore and visualize the leg muscle atlas ( Our study reveals the molecular specialization of human leg muscles, and provides a novel resource to study muscle-specific molecular features, which could be linked with (patho)physiological processes.

    1. Neuroscience
    Lex J Gómez, James C Dooley, Mark S Blumberg
    Research Article

    In developing rats, behavioral state exerts a profound modulatory influence on neural activity throughout the sensorimotor system, including primary motor cortex (M1). We hypothesized that similar state-dependent modulation occurs in prefrontal cortical areas with which M1 forms functional connections. Here, using 8- and 12-day-old rats cycling freely between sleep and wake, we record neural activity in M1, secondary motor cortex (M2), and medial prefrontal cortex (mPFC). At both ages in all three areas, neural activity increased during active sleep (AS) compared with wake. Also, regardless of behavioral state, neural activity in all three areas increased during periods when limbs were moving. The movement-related activity in M2 and mPFC, like that in M1, is driven by sensory feedback. Our results, which diverge from those of previous studies using anesthetized pups, demonstrate that AS-dependent modulation and sensory responsivity extend to prefrontal cortex. These findings expand the range of possible factors shaping the activity-dependent development of higher-order cortical areas.