2. Academic Validation
  3. Norepinephrine-mediated arousal fluctuations drive inverted U-shaped functional connectivity dynamics

Norepinephrine-mediated arousal fluctuations drive inverted U-shaped functional connectivity dynamics

  • Nat Commun. 2025 Dec 13;16(1):11318. doi: 10.1038/s41467-025-66436-x.
Chuanjun Tong # 1,  Weishuai Li # 2 3,  Yijuan Zou # 4,  Ying Xia 2,  Mengchao Pei 2,  Kaiwei Zhang 2,  Yichao Luo 2,  Zhifeng Liang 5
Affiliations

Affiliations

  • 1 Institute of Neuroscience, International Center for Primate Brain Research, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai, China. [email protected].
  • 2 Institute of Neuroscience, International Center for Primate Brain Research, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai, China.
  • 3 University of Chinese Academy of Sciences, Beijing, China.
  • 4 Changping Laboratory, Beijing, China.
  • 5 Institute of Neuroscience, International Center for Primate Brain Research, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 41390822 DOI: 10.1038/s41467-025-66436-x
Abstract

Arousal states dynamically shape brain function and behavioral performance, as posited by the Yerkes-Dodson law. Yet, functional network substrates underlying this inverted U-shaped pattern remain unknown. Here, by integrating functional magnetic resonance imaging (fMRI) with simultaneous electroencephalography (EEG) across humans and awake mice, we found arousal modulated inverted U-shaped global functional connectivity (FC) dynamics, peaking at middle arousal level. Such inverted U-shaped FC exhibited significant correlation with arousal modulated behavioral performance, recapitulating the Yerkes-Dodson framework at the functional network level. Further combining invasive multimodal neural recording and manipulations of locus coeruleus-norepinephrine (LC-NE) neurons with awake mouse EEG-fMRI, we revealed the causal contribution of LC-NE system to arousal modulated FC dynamics, in which the inverted U-shaped pattern was dependent on the baseline arousal level. To summarize, we uncovered the functional network basis of the Yerkes-Dodson law, which was causally driven by the NE-mediated arousal fluctuations.

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