Brain Reactions to Opening and Closing the Eyes: Salivary Cortisol and Functional Connectivity

Shen Da Chang, Po Chih Kuo, Karl Zilles, Tim Q. Duong, Simon B. Eickhoff, Andrew C.W. Huang, Arthur C. Tsai, Philip E. Cheng, Michelle Liou

Research output: Contribution to journalArticlepeer-review


This study empirically assessed the strength and duration of short-term effects induced by brain reactions to closing/opening the eyes on a few well-known resting-state networks. We also examined the association between these reactions and subjects’ cortisol levels. A total of 55 young adults underwent 8-min resting-state fMRI (rs-fMRI) scans under 4-min eyes-closed and 4-min eyes-open conditions. Saliva samples were collected from 25 of the 55 subjects before and after the fMRI sessions and assayed for cortisol levels. Our empirical results indicate that when the subjects were relaxed with their eyes closed, the effect of opening the eyes on conventional resting-state networks (e.g., default-mode, frontal-parietal, and saliency networks) lasted for roughly 60-s, during which we observed a short-term increase in activity in rs-fMRI time courses. Moreover, brain reactions to opening the eyes had a pronounced effect on time courses in the temporo-parietal lobes and limbic structures, both of which presented a prolonged decrease in activity. After controlling for demographic factors, we observed a significantly positive correlation between pre-scan cortisol levels and connectivity in the limbic structures under both conditions. Under the eyes-closed condition, the temporo-parietal lobes presented significant connectivity to limbic structures and a significantly positive correlation with pre-scan cortisol levels. Future research on rs-fMRI could consider the eyes-closed condition when probing resting-state connectivity and its neuroendocrine correlates, such as cortisol levels. It also appears that abrupt instructions to open the eyes while the subject is resting quietly with eyes closed could be used to probe brain reactivity to aversive stimuli in the ventral hippocampus and other limbic structures.

Original languageEnglish (US)
Pages (from-to)375-397
Number of pages23
JournalBrain Topography
Issue number4
StatePublished - Jul 2022


  • Approach-avoidance conflicts
  • Cortisol
  • DMN
  • Intraclass correlation
  • Ventral hippocampus

ASJC Scopus subject areas

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


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