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

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Abstract

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.

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Abbreviations

ESRD:

End-stage renal disease

FCD:

Functional connectivity density

rs-fMRI:

Resting-state functional magnetic resonance imaging

DMN:

Default mode network

MNE:

Minimal nephro-encephalopathy

non-NE:

Patients without nephro-encephalopathy

HCs:

Healthy controls

BA:

Brodmann’s area

MNI:

Montreal neurological institute

TPO:

Temporal pole

SPG:

Superior parietal gyrus

IPL:

Inferior parietal lobule

PCu:

Precuneus

PCC:

Posterior cingulate cortex

ITG:

Inferior temporal gyrus

ORBsup:

Orbitofrontal cortex (superior)

ORBmid:

Orbitofrontal cortex (middle)

ACC:

Anterior cingulate cortex

SFGmed:

Superior frontal gyrus (medial)

MFG:

Middle frontal gyrus

SFG:

Superior frontal gyrus

STG:

Superior temporal gyrus

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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

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.

Author information

Authors and Affiliations

  1. Department of Medical Imaging, Jinling Hospital, Nanjing Clinical School, Southern Medical University, Nanjing, Jiangsu Province, 210002, China

    Xiao-Dong Zhang

  2. Department of Radiology, Tianjin First Central Hospital, Clinical School of Tianjin Medical University, Tianjin, 300192, China

    Xiao-Dong Zhang

  3. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province, 210002, China

    Xiao-Dong Zhang, Qiang Xu, Rongfeng Qi, Hui-Juan Chen, Xiang Kong, Long Jiang Zhang & Guang Ming Lu

  4. National Clinical Research Center of Kidney Disease, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China

    Ji-Qiu Wen

  5. Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, 210002, China

    Lu-De Wei & Min Xu

Authors
  1. Xiao-Dong Zhang
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  2. Ji-Qiu Wen
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  3. Qiang Xu
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  7. Lu-De Wei
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  8. Min Xu
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  9. Long Jiang Zhang
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  10. Guang Ming Lu
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Corresponding authors

Correspondence to Long Jiang Zhang or Guang Ming Lu.

Additional information

Xiao-Dong Zhang, Ji-Qiu Wen, and Qiang Xu had equal contribution to this work.

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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)

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Zhang, XD., Wen, JQ., Xu, Q. et al. Altered long- and short-range functional connectivity in the patients with end-stage renal disease: a resting-state functional MRI study. Metab Brain Dis 30, 1175–1186 (2015). https://doi.org/10.1007/s11011-015-9683-z

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