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Neural habituation during acute stress signals a blunted endocrine response and poor resilience

Published online by Cambridge University Press:  13 June 2023

Yadong Liu
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Xiaolin Zhao
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Weiyu Hu
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Yipeng Ren
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Zhenni Wei
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Xi Ren
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Zihan Tang
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Nan Wang
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Haopeng Chen
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Yizhuo Li
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Zhenhao Shi
Center for Studies of Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Shaozheng Qin
State Key Laboratory of Cognitive Neuroscience and Learning, McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China
Juan Yang*
Faculty of Psychology, Southwest University, Chongqing 400715, China Key Laboratory of Cognition and Personality, Ministry of Education, Southwest University, Chongqing 400715, China
Corresponding author: Juan Yang; Email:



A blunted hypothalamic–pituitary–adrenal (HPA) axis response to acute stress is associated with psychiatric symptoms. Although the prefrontal cortex and limbic areas are important regulators of the HPA axis, whether the neural habituation of these regions during stress signals both blunted HPA axis responses and psychiatric symptoms remains unclear. In this study, neural habituation during acute stress and its associations with the stress cortisol response, resilience, and depression were evaluated.


Seventy-seven participants (17–22 years old, 37 women) were recruited for a ScanSTRESS brain imaging study, and the activation changes between the first and last stress blocks were used as the neural habituation index. Meanwhile, participants' salivary cortisol during test was collected. Individual-level resilience and depression were measured using questionnaires. Correlation and moderation analyses were conducted to investigate the association between neural habituation and endocrine data and mental symptoms. Validated analyses were conducted using a Montreal Image Stress Test dataset in another independent sample (48 participants; 17–22 years old, 24 women).


Neural habituation of the prefrontal cortex and limbic area was negatively correlated with cortisol responses in both datasets. In the ScanSTRESS paradigm, neural habituation was both positively correlated with depression and negatively correlated with resilience. Moreover, resilience moderated the relationship between neural habituation in the ventromedial prefrontal cortex and cortisol response.


This study suggested that neural habituation of the prefrontal cortex and limbic area could reflect motivation dysregulation during repeated failures and negative feedback, which might further lead to maladaptive mental states.

Original Article
Copyright © The Author(s), 2023. Published by Cambridge University Press

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These authors equally contributed to this work.


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