Dysregulation of resting-state functional connectivity in patients with Cushing’s disease

  • Xin Wang
  • Tao Zhou
  • Peng Wang
  • Li Zhang
  • Shiyu Feng
  • Xianghui Meng
  • Xinguang YuEmail author
  • Yanyang ZhangEmail author
Functional Neuroradiology



To explore the anatomical distance-dependent functional connectivity patterns in patients with active phase of Cushing’s disease (CD) and to evaluate the associations between hypercortisol exposure and regional normalized functional connectivity strengths (nFCSs).


Based on the fMRI data in 32 CD patients and 32 healthy controls (HCs), we computed the nFCSs for each voxel in the brain and further divided them into long-range and short-range nFCSs. General linear models was used to investigate between-group differences in these nFCS metrics and the correlations between the nFCSs and clinical variables.


Compared with HC, CD patients showed dysregulation of the nFCSs mainly in the default mode network. They showed an overall higher nFCS in bilateral parahippocampal cortex mainly owing to the disruption of long-range nFCS and a relatively lower nFCS in bilateral posterior cingulate cortex (PCC), bilateral lateral parietal cortex (LP), and right prefrontal cortex (PFC). In addition, their long-range nFCS was lower in the bilateral anterior cingulate cortex, PCC, and LP; short-range nFCS was lower in the bilateral PFC. Notably, the positive correlation between the nFCSs in their right parahippocampal cortex and serum cortisol levels at 08:00 remained significant after taking the anatomical distance into consideration.


The discrepant functional connectivity patterns found in our study indicated a hypercortisol-associated, distance-dependent disruption of resting-state functional connectivity in patients with active CD. We provide novel insights into the impacts of hypercortisol exposure and the pathophysiologic mechanisms of CD, which may facilitate advances in CD intervention ultimately.


Cushing’s disease Resting-state Functional connectivity Default mode network Hypercortisol 



Cushing’s disease


Healthy control


Resting-state functional connectivity


Normalized functional connectivity strength


Default mode network


Posterior cingulate cortex


Lateral parietal cortex


Prefrontal cortex


Anterior cingulate cortex;



No funding was received for this study.

Compliance with ethical standards

Conflict of interest

We declare that we have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Written informed consent was obtained from each patient in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Xin Wang
    • 1
    • 2
  • Tao Zhou
    • 2
  • Peng Wang
    • 2
  • Li Zhang
    • 3
  • Shiyu Feng
    • 2
  • Xianghui Meng
    • 2
  • Xinguang Yu
    • 1
    • 2
    Email author
  • Yanyang Zhang
    • 2
    Email author
  1. 1.School of MedicineNankai UniversityTianjinChina
  2. 2.Department of NeurosurgeryThe First Medical Center of Chinese PLA General HospitalBeijingChina
  3. 3.Department of RadiologyThe First Medical Center of Chinese PLA General HospitalBeijingChina

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