Anterior insular cortex plays a critical role in interoceptive attention

  1. Xingchao Wang
  2. Qiong Wu
  3. Laura Egan
  4. Xiaosi Gu
  5. Pinan Liu
  6. Hong Gu
  7. Yihong Yang
  8. Jing Luo
  9. Yanhong Wu  Is a corresponding author
  10. Zhixian Gao  Is a corresponding author
  11. Jin Fan  Is a corresponding author
  1. Beijing Tiantan Hospital, Capital Medical University, China
  2. Capital Normal University, China
  3. Queens College, The City University of New York, United States
  4. Icahn School of Medicine at Mount Sinai, United States
  5. National Institute on Drug Abuse, United States
  6. Peking University, China

Abstract

Accumulating evidence indicates that the anterior insular cortex (AIC) mediates interoceptive attention, which refers to attention towards physiological signals arising from the body. However, the necessity of the AIC in this process has not been demonstrated. Using a novel task that directs attention toward breathing rhythm, we assessed the involvement of the AIC in interoceptive attention in healthy participants using functional magnetic resonance imaging and examined the necessity of the AIC in interoceptive attention in patients with AIC lesions. Results showed that interoceptive attention was associated with increased AIC activation, as well as enhanced coupling between the AIC and somatosensory areas along with reduced coupling between the AIC and visual sensory areas. In addition, AIC activation was predictive of individual differences in interoceptive accuracy. Importantly, AIC lesion patients showed disrupted interoceptive discrimination accuracy and sensitivity. These results provide compelling evidence that AIC plays a critical role in interoceptive attention.

Data availability

Source data have been deposited in Dyrad, including behavioral data, fMRI data, and lesion patient data. Our Dyrad DOI is: doi:10.5061/dryad.5sj852c

The following data sets were generated

Article and author information

Author details

  1. Xingchao Wang

    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Qiong Wu

    School of Psychology, Capital Normal University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura Egan

    Department of Psychology, Queens College, The City University of New York, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaosi Gu

    Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Pinan Liu

    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Hong Gu

    Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yihong Yang

    Neuroimaging Research Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jing Luo

    School of Psychology, Capital Normal University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yanhong Wu

    School of Psychological and Cognitive Sciences, Peking University, Beijing, China
    For correspondence
    wuyh@pku.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  10. Zhixian Gao

    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
    For correspondence
    gaozx@ccmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  11. Jin Fan

    Department of Psychology, Queens College, The City University of New York, New York, United States
    For correspondence
    jin.fan@qc.cuny.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9630-8330

Funding

National Natural Science Foundation of China (81729001)

  • Jin Fan

China Postdoctoral Science Foundation (2016M600835)

  • Qiong Wu

National Institute on Drug Abuse (1R01DA043695)

  • Xiaosi Gu

National Natural Science Foundation of China (81328008)

  • Jin Fan

National Natural Science Foundation of China (61690205)

  • Yanhong Wu

National Institute of Mental Health (R01MH094305)

  • Jin Fan

Research grant of 973 (973-2015CB351800)

  • Yanhong Wu

National Natural Science Foundation of China (31771205)

  • Yanhong Wu

National Institute on Drug Abuse (Intramul Research Program)

  • Yihong Yang

Brain research Project of Beijing (Z16110002616014)

  • Pinan Liu

Beijing Municipal Administration of Hospital Youth programs (QML20170503)

  • Xingchao Wang

National Natural Science Foundation of China (81600931)

  • Xingchao Wang

Capital Health Development Research Project of Beijing (2016-4-1074)

  • Xingchao Wang

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

Ethics

Human subjects: All participants in fMRI study and in lesion study were gave written informed consent in accordance with the procedures and protocols approved by The Human Subjects Review Committee of Peking University and by The Institutional Review Board of the Beijing Tiantan Hospital, Capital Medical University, respectively.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 14,022
    views
  • 1,136
    downloads
  • 123
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Xingchao Wang
  2. Qiong Wu
  3. Laura Egan
  4. Xiaosi Gu
  5. Pinan Liu
  6. Hong Gu
  7. Yihong Yang
  8. Jing Luo
  9. Yanhong Wu
  10. Zhixian Gao
  11. Jin Fan
(2019)
Anterior insular cortex plays a critical role in interoceptive attention
eLife 8:e42265.
https://doi.org/10.7554/eLife.42265

Share this article

https://doi.org/10.7554/eLife.42265

Further reading

    1. Genetics and Genomics
    2. Neuroscience
    Akanksha Bafna, Gareth Banks ... Patrick M Nolan
    Research Article

    The mammalian suprachiasmatic nucleus (SCN), situated in the ventral hypothalamus, directs daily cellular and physiological rhythms across the body. The SCN clockwork is a self-sustaining transcriptional-translational feedback loop (TTFL) that in turn coordinates the expression of clock-controlled genes (CCGs) directing circadian programmes of SCN cellular activity. In the mouse, the transcription factor, ZFHX3 (zinc finger homeobox-3), is necessary for the development of the SCN and influences circadian behaviour in the adult. The molecular mechanisms by which ZFHX3 affects the SCN at transcriptomic and genomic levels are, however, poorly defined. Here, we used chromatin immunoprecipitation sequencing to map the genomic localization of ZFHX3-binding sites in SCN chromatin. To test for function, we then conducted comprehensive RNA sequencing at six distinct times-of-day to compare the SCN transcriptional profiles of control and ZFHX3-conditional null mutants. We show that the genome-wide occupancy of ZFHX3 occurs predominantly around gene transcription start sites, co-localizing with known histone modifications, and preferentially partnering with clock transcription factors (CLOCK, BMAL1) to regulate clock gene(s) transcription. Correspondingly, we show that the conditional loss of ZFHX3 in the adult has a dramatic effect on the SCN transcriptome, including changes in the levels of transcripts encoding elements of numerous neuropeptide neurotransmitter systems while attenuating the daily oscillation of the clock TF Bmal1. Furthermore, various TTFL genes and CCGs exhibited altered circadian expression profiles, consistent with an advanced in daily behavioural rhythms under 12 h light–12 h dark conditions. Together, these findings reveal the extensive genome-wide regulation mediated by ZFHX3 in the central clock that orchestrates daily timekeeping in mammals.

    1. Neuroscience
    Myrthe Faber, Koen V Haak
    Insight

    Untangling the functional organisation of a brain region crucial for memory and learning helps reveal how individual differences are linked to variations in recall ability, aging and dopamine receptor distribution.