Metabolic Brain Disease

, Volume 30, Issue 5, pp 1175–1186 | Cite as

Altered long- and short-range functional connectivity in the patients with end-stage renal disease: a resting-state functional MRI study

  • Xiao-Dong Zhang
  • Ji-Qiu Wen
  • Qiang Xu
  • Rongfeng Qi
  • Hui-Juan Chen
  • Xiang Kong
  • Lu-De Wei
  • Min Xu
  • Long Jiang Zhang
  • Guang Ming Lu
Research Article


To investigate alterations of functional connectivity density (FCD) in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI). Medical research ethics committee approval from Jinling hospital and written informed consent from each subject were obtained. Forty six patients with ESRD, consisting of 21 patients minimal nephrotic encephalopathy (MNE) and 25 non-nephro-encephalopathy (non-NE), as well as 23 healthy controls underwent rs-fMRI. Neuropsychological tests were performed in all subjects, while laboratory tests were performed in ESRD patients. A voxel-wise whole brain functional connectivity analysis was used to generate long- and short-range FCD maps. The maps among MNE, non-NE, and healthy controls groups were compared by using one-way analysis of variance tests. A multiple regression analysis was performed to evaluate the correlations between FCD and the variables of neuropsychological or laboratory tests. Compared with healthy controls, non-NE showed decreased long-range FCD mainly in parietal lobe. Moreover, MNE showed further decreased long-range FCD in bilateral middle prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and right superior frontal gyrus. Meanwhile, non-NE showed decreased short-range FCD mainly in frontal cortex, and further reduction in bilateral ACC and right superior parietal gyrus in MNE. In addition, patients with ESRD mainly exhibited increased long-range FCD in left temporal lobe and caudate; and increased short-range FCD in bilateral orbitofrontal cortex and temporal gyri (P < 0.05, AlphaSim corrected). The number connection test type A score, serum creatinine, urea, and dialysis duration showed negative correlation with FCD in some brain regions, while the digital symbol test scores positively correlated with short-range FCD in left inferior parietal lobule (all P < 0.05, AlphaSim corrected). The prominent long- and short-range FCD reduction was found mainly in default mode network (DMN) and bilateral frontal and parietal lobes, while the progressively decreased long- and short-range FCD in ACC/MPFC and the long-range FCD in left superior frontal gyrus from non-NE to MNE was associated with cognition dysfunction in ESRD patients.


End-stage renal disease Resting-state functional magnetic resonance imaging Functional connectivity 



End-stage renal disease


Functional connectivity density


Resting-state functional magnetic resonance imaging


Default mode network


Minimal nephro-encephalopathy


Patients without nephro-encephalopathy


Healthy controls


Brodmann’s area


Montreal neurological institute


Temporal pole


Superior parietal gyrus


Inferior parietal lobule




Posterior cingulate cortex


Inferior temporal gyrus


Orbitofrontal cortex (superior)


Orbitofrontal cortex (middle)


Anterior cingulate cortex


Superior frontal gyrus (medial)


Middle frontal gyrus


Superior frontal gyrus


Superior temporal gyrus


Author contributions

Xiao-Dong Zhang, Ji-Qiu Wen and Qiang Xu contributed equally to this work; Long-Jiang Zhang and Guang-Ming Lu designed the research; Xiao-Dong Zhang, Ji-Qiu Wen, Qiang Xu, Rong-Feng Qi, Hui-Juan Chen, Xiang Kong, Lu-De Wei, Min Xu, Long-Jiang Zhang, Guang-Ming Lu.


Grants from National Natural Science Foundation of China, Nos. 30700194, 81171313, 81322020 and 81230032 (to Zhang LJ); and Program for New Century Excellent Talents in University, No. NCET-12-0260 (to Zhang LJ).

Conflict of interest

There are no interest conflicts disclosed.

Supplementary material

11011_2015_9683_Fig5_ESM.gif (92 kb)
Fig. S1

The spatial distribution of long- and short-range FDC in HCs, non-NE and MNE groups. Long-range FCD mainly distributes in bilateral middle/superior frontal gyri, superior parietal gyri, medial prefrontal cortex, anterior cingulate cortex, precuneus/posterior cingulate cortex, postcentral gyrus, inferior parietal lobule, middle temporal gyri, and temporal pole. Short-range FCD mainly locates in bilateral precuneus/posterior cingulate cortex, inferior parietal lobule, middle frontal gyri, Calcarine, middle and superior occipital gyri, medial prefrontal cortex, anterior cingulate cortex, superior parietal gyri, Cuneus, and middle temporal gyri (P < 0.05, AlphaSim corrected). FCD functional connectivity density, HCs healthy control, Non-NE non-nephro-encephalopathy, MNE minimal nephro-encephalopathy. (GIF 91 kb)

11011_2015_9683_MOESM1_ESM.tif (2.6 mb)
High Resolution Image (TIFF 2632 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xiao-Dong Zhang
    • 1
    • 2
    • 3
  • Ji-Qiu Wen
    • 4
  • Qiang Xu
    • 3
  • Rongfeng Qi
    • 3
  • Hui-Juan Chen
    • 3
  • Xiang Kong
    • 3
  • Lu-De Wei
    • 5
  • Min Xu
    • 5
  • Long Jiang Zhang
    • 3
  • Guang Ming Lu
    • 3
  1. 1.Department of Medical Imaging, Jinling Hospital, Nanjing Clinical SchoolSouthern Medical UniversityNanjingChina
  2. 2.Department of Radiology, Tianjin First Central HospitalClinical School of Tianjin Medical UniversityTianjinChina
  3. 3.Department of Medical Imaging, Jinling HospitalMedical School of Nanjing UniversityNanjingChina
  4. 4.National Clinical Research Center of Kidney Disease, Jinling HospitalNanjing University School of MedicineNanjingChina
  5. 5.Department of Emergency Medicine, Jinling HospitalMedical School of Nanjing UniversityNanjingChina

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