Cortical excitability signatures for the degree of sleepiness in human

  1. Chin-Hsuan Chia
  2. Xin-Wei Tang
  3. Yue Cao
  4. Hua-Teng Cao
  5. Wei Zhang
  6. Jun-Fa Wu
  7. Yu-Lian Zhu
  8. Ying Chen
  9. Yi Lin
  10. Yi Wu
  11. Zhe Zhang  Is a corresponding author
  12. Ti-Fei Yuan  Is a corresponding author
  13. Rui-Ping Hu  Is a corresponding author
  1. Huashan hospital, Fudan University, China
  2. Institute of Neuroscience, China
  3. Institute of Brain Science, Fudan University, China
  4. Nantong University, China

Abstract

Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake, and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation (TMS) measurements in 38 subjects in a 34-hour program, and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares (PLS) regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Chin-Hsuan Chia

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xin-Wei Tang

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yue Cao

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Hua-Teng Cao

    CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Wei Zhang

    Brain Science, Institute of Brain Science, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jun-Fa Wu

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yu-Lian Zhu

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Ying Chen

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Yi Lin

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yi Wu

    rehabilitation medicine, Huashan hospital, Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Zhe Zhang

    CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Neuroscience, Shanghai, China
    For correspondence
    zhezhang@ion.ac.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0899-8077
  12. Ti-Fei Yuan

    Psychology, Nantong University, Nantong, China
    For correspondence
    ytf0707@126.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0510-715X
  13. Rui-Ping Hu

    rehabilitation medicine, Huashan hospital, Fudan University, shanghai city, China
    For correspondence
    wuyi4000@163.com
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Key Research and Development Program of China (2018YFC2001700)

  • Yi Wu

the Key Projects of Shanghai Science and Technology on Biomedicine (18411962300)

  • Rui-Ping Hu

Shanghai Health and Family Planning Commission project (201840225)

  • Yu-Lian Zhu

Shanghai Municipal Key Clinical Specialty (s.shslczdzk02702)

  • Yi Wu

the Key Projects of Shanghai Science and Technology on Biomedicine (20412420200)

  • Yi Wu

Natural Science Foundation of China grant (32071010)

  • Zhe Zhang

Shanghai Pujiang Program (20PJ1415000)

  • Zhe Zhang

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

Ethics

Human subjects: 1. That informed consent, and consent to publish, was obtained2. This study was designed as a prospective self-controlled study. The Ethics Committee of Huashan Hospital approved the study (2017-410) and was registered on the Chinese Clinical Trial Registry (ChiCTR1800016771).

Copyright

© 2021, Chia et al.

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.

Metrics

  • 1,648
    views
  • 335
    downloads
  • 10
    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. Chin-Hsuan Chia
  2. Xin-Wei Tang
  3. Yue Cao
  4. Hua-Teng Cao
  5. Wei Zhang
  6. Jun-Fa Wu
  7. Yu-Lian Zhu
  8. Ying Chen
  9. Yi Lin
  10. Yi Wu
  11. Zhe Zhang
  12. Ti-Fei Yuan
  13. Rui-Ping Hu
(2021)
Cortical excitability signatures for the degree of sleepiness in human
eLife 10:e65099.
https://doi.org/10.7554/eLife.65099

Share this article

https://doi.org/10.7554/eLife.65099

Further reading

    1. Neuroscience
    Cristina Gil Avila, Elisabeth S May ... Markus Ploner
    Research Article

    Chronic pain is a prevalent and debilitating condition whose neural mechanisms are incompletely understood. An imbalance of cerebral excitation and inhibition (E/I), particularly in the medial prefrontal cortex (mPFC), is believed to represent a crucial mechanism in the development and maintenance of chronic pain. Thus, identifying a non-invasive, scalable marker of E/I could provide valuable insights into the neural mechanisms of chronic pain and aid in developing clinically useful biomarkers. Recently, the aperiodic component of the electroencephalography (EEG) power spectrum has been proposed to represent a non-invasive proxy for E/I. We, therefore, assessed the aperiodic component in the mPFC of resting-state EEG recordings in 149 people with chronic pain and 115 healthy participants. We found robust evidence against differences in the aperiodic component in the mPFC between people with chronic pain and healthy participants, and no correlation between the aperiodic component and pain intensity. These findings were consistent across different subtypes of chronic pain and were similarly found in a whole-brain analysis. Their robustness was supported by preregistration and multiverse analyses across many different methodological choices. Together, our results suggest that the EEG aperiodic component does not differentiate between people with chronic pain and healthy individuals. These findings and the rigorous methodological approach can guide future studies investigating non-invasive, scalable markers of cerebral dysfunction in people with chronic pain and beyond.

    1. Neuroscience
    Gyeong Hee Pyeon, Hyewon Cho ... Yong Sang Jo
    Research Article

    Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors. To address this, we examined the role of CGRP neurons in active defensive behavior using a predator-like robot programmed to chase mice. Our electrophysiological results revealed that CGRP neurons encode the intensity of aversive stimuli through variations in firing durations and amplitudes. Optogenetic activation of CGRP neuron during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amyplifying the perception of the threat as more imminent and dangerous. In contrast, animals with inactivated CGRP neurons exhibited reduced flight responses, even when the robot was programmed to appear highly threatening during conditioning. These findings expand the understanding of CGRP neurons in the PBN as a critical alarm system, capable of dynamically regulating active defensive behaviors by amplifying threat perception, ensuring adaptive responses to varying levels of danger.