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Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity

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Abstract

It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

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References

  • Ashburner J (2007) A fast diffeomorphic image registration algorithm. Neuroimage 38(1):95–113

    Article  PubMed  Google Scholar 

  • Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839–851

    Article  PubMed  Google Scholar 

  • Bajaj JS, Wade JB, Sanyal AJ (2009) Spectrum of neurocognitive impairment in cirrhosis: Implications for the assessment of hepatic encephalopathy. Hepatology 50(6):2014–2021

    Article  PubMed  Google Scholar 

  • Bajaj JS, Schubert CM, Heuman DM, Wade JB, Gibson DP, Topaz A, Saeian K, Hafeezullah M, Bell DE, Sterling RK, Stravitz RT, Luketic V, White MB, Sanyal AJ (2010) Persistence of cognitive impairment after resolution of overt hepatic encephalopathy. Gastroenterology 138(7):2332–2340

    Article  PubMed  PubMed Central  Google Scholar 

  • Bustamante J, Rimola A, Ventura PJ, Navasa M, Cirera I, Reggiardo V, Rodes J (1999) Prognostic significance of hepatic encephalopathy in patients with cirrhosis. J Hepatol 30(5):890–895

    Article  CAS  PubMed  Google Scholar 

  • Chao-Gan Y, Yu-Feng Z (2010) DPARSF: a MATLAB toolbox for “pipeline” data analysis of resting-state fMRI. Front Syst Neurosci 4:13

    PubMed  PubMed Central  Google Scholar 

  • Chen HJ, Zhu XQ, Jiao Y, Li PC, Wang Y, Teng GJ (2012a) Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study. J Neurol Sci 318(1–2):140–145

    Article  PubMed  Google Scholar 

  • Chen HJ, Zhu XQ, Shu H, Yang M, Zhang Y, Ding J, Wang Y, Teng GJ (2012b) Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy. Eur J Radiol 81(10):2463–2469

    Article  PubMed  Google Scholar 

  • Chen HJ, Zhu XQ, Yang M, Liu B, Zhang Y, Wang Y, Teng GJ (2012c) Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy. Neurosci Lett 507(1):5–9

    Article  CAS  PubMed  Google Scholar 

  • Chen HJ, Jiao Y, Zhu XQ, Zhang HY, Liu JC, Wen S, Teng GJ (2013) Brain dysfunction primarily related to previous overt hepatic encephalopathy compared with minimal hepatic encephalopathy: resting-state functional MR imaging demonstration. Radiology 266(1):261–270

    Article  PubMed  Google Scholar 

  • Chen HJ, Chen R, Yang M, Teng GJ, Herskovits EH (2015a) Identification of minimal hepatic encephalopathy in patients with cirrhosis based on white matter imaging and bayesian data mining. AJNR Am J Neuroradiol 36(3):481–487

    Article  PubMed  Google Scholar 

  • Chen HJ, Jiang LF, Sun T, Liu J, Chen QF, Shi HB (2015b) Resting-state functional connectivity abnormalities correlate with psychometric hepatic encephalopathy score in cirrhosis. Eur J Radiol 84(11):2287–2295

    Article  PubMed  Google Scholar 

  • Corradi-Dell’Acqua C, Hesse MD, Rumiati RI, Fink GR (2008) Where is a nose with respect to a foot? The left posterior parietal cortex processes spatial relationships among body parts. Cereb Cortex 18(12):2879–2890

    Article  PubMed  Google Scholar 

  • Das A, Dhiman RK, Saraswat VA, Verma M, Naik SR (2001) Prevalence and natural history of subclinical hepatic encephalopathy in cirrhosis. J Gastroenterol Hepatol 16(5):531–535

    Article  CAS  PubMed  Google Scholar 

  • Dhiman RK, Kurmi R, Thumburu KK, Venkataramarao SH, Agarwal R, Duseja A, Chawla Y (2010) Diagnosis and prognostic significance of minimal hepatic encephalopathy in patients with cirrhosis of liver. Dig Dis Sci 55(8):2381–2390

    Article  PubMed  Google Scholar 

  • DiCarlo JJ, Zoccolan D, Rust NC (2012) How does the brain solve visual object recognition? Neuron 73(3):415–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ettlinger G (1990) “Object vision” and “spatial vision”: the neuropsychological evidence for the distinction. Cortex 26(3):319–341

    Article  CAS  PubMed  Google Scholar 

  • Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME (2005) The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A 102(27):9673–9678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giewekemeyer K, Berding G, Ahl B, Ennen JC, Weissenborn K (2007) Bradykinesia in cirrhotic patients with early hepatic encephalopathy is related to a decreased glucose uptake of frontomesial cortical areas relevant for movement initiation. J Hepatol 46(6):1034–1039

    Article  CAS  PubMed  Google Scholar 

  • Groeneweg M, Quero JC, De Bruijn I, Hartmann IJ, Essink-bot ML, Hop WC, Schalm SW (1998) Subclinical hepatic encephalopathy impairs daily functioning. Hepatology 28(1):45–49

    Article  CAS  PubMed  Google Scholar 

  • Guevara M, Baccaro ME, Gomez-Anson B, Frisoni G, Testa C, Torre A, Molinuevo JL, Rami L, Pereira G, Sotil EU, Cordoba J, Arroyo V, Gines P (2011) Cerebral magnetic resonance imaging reveals marked abnormalities of brain tissue density in patients with cirrhosis without overt hepatic encephalopathy. J Hepatol 55(3):564–573

    Article  PubMed  Google Scholar 

  • He Y, Wang L, Zang Y, Tian L, Zhang X, Li K, Jiang T (2007) Regional coherence changes in the early stages of Alzheimer’s disease: a combined structural and resting-state functional MRI study. Neuroimage 35(2):488–500

    Article  PubMed  Google Scholar 

  • Joebges EM, Heidemann M, Schimke N, Hecker H, Ennen JC, Weissenborn K (2003) Bradykinesia in minimal hepatic encephalopathy is due to disturbances in movement initiation. J Hepatol 38(3):273–280

    Article  PubMed  Google Scholar 

  • Lane AR, Smith DT, Schenk T, Ellison A (2011) The involvement of posterior parietal cortex in feature and conjunction visuomotor search. J Cogn Neurosci 23(8):1964–1972

    Article  PubMed  Google Scholar 

  • Li SW, Wang K, Yu YQ, Wang HB, Li YH, Xu JM (2013) Psychometric hepatic encephalopathy score for diagnosis of minimal hepatic encephalopathy in China. World J Gastroenterol 19(46):8745–8751

    Article  PubMed  PubMed Central  Google Scholar 

  • Liao LM, Zhou LX, Le HB, Yin JJ, Ma SH (2012) Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study. Brain Res 1445:62–72

    Article  CAS  PubMed  Google Scholar 

  • Lowe MJ, Russell DP (1999) Treatment of baseline drifts in fMRI time series analysis. J Comput Assist Tomogr 23(3):463–473

    Article  CAS  PubMed  Google Scholar 

  • Lv XF, Qiu YW, Tian JZ, Xie CM, Han LJ, Su HH, Liu ZY, Peng JP, Lin CL, Wu MS, Jiang GH, Zhang XL (2013a) Abnormal regional homogeneity of resting-state brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy. Liver Int 33(3):375–383

    Article  CAS  PubMed  Google Scholar 

  • Lv XF, Ye M, Han LJ, Zhang XL, Cai PQ, Jiang GH, Qiu YW, Qiu SJ, Wu YP, Liu K, Liu ZY, Wu PH, Xie CM (2013b) Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI. Metab Brain Dis 28(3):485–492

    Article  PubMed  Google Scholar 

  • Malhotra P, Coulthard EJ, Husain M (2009) Role of right posterior parietal cortex in maintaining attention to spatial locations over time. Brain 132(Pt 3):645–660

    Article  PubMed  PubMed Central  Google Scholar 

  • McPhail MJ, Leech R, Grover VP, Fitzpatrick JA, Dhanjal NS, Crossey MM, Pflugrad H, Saxby BK, Wesnes K, Dresner MA, Waldman AD, Thomas HC, Taylor-Robinson SD (2013) Modulation of neural activation following treatment of hepatic encephalopathy. Neurology 80(11):1041–1047

    Article  PubMed  PubMed Central  Google Scholar 

  • Ni L, Qi R, Zhang LJ, Zhong J, Zheng G, Zhang Z, Zhong Y, Xu Q, Liao W, Jiao Q, Wu X, Fan X, Lu GM (2012) Altered regional homogeneity in the development of minimal hepatic encephalopathy: a resting-state functional MRI study. PLoS One 7(7), e42016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prasad S, Dhiman RK, Duseja A, Chawla YK, Sharma A, Agarwal R (2007) Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology 45(3):549–559

    Article  PubMed  Google Scholar 

  • Qi R, Zhang L, Wu S, Zhong J, Zhang Z, Zhong Y, Ni L, Li K, Jiao Q, Wu X, Fan X, Liu Y, Lu G (2012a) Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. Radiology 264(1):187–195

    Article  PubMed  Google Scholar 

  • Qi R, Zhang LJ, Xu Q, Zhong J, Wu S, Zhang Z, Liao W, Ni L, Chen H, Zhong Y, Jiao Q, Wu X, Fan X, Liu Y, Lu G (2012b) Selective impairments of resting-state networks in minimal hepatic encephalopathy. PLoS One 7(5), e37400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Romero-Gomez M, Boza F, Garcia-Valdecasas MS, Garcia E, Aguilar-Reina J (2001) Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol 96(9):2718–2723

    Article  CAS  PubMed  Google Scholar 

  • Schomerus H, Hamster W (2001) Quality of life in cirrhotics with minimal hepatic encephalopathy. Metab Brain Dis 16(1–2):37–41

    Article  CAS  PubMed  Google Scholar 

  • Seo YS, Yim SY, Jung JY, Kim CH, Kim JD, Keum B, An H, Yim HJ, Lee HS, Kim CD, Ryu HS, Um SH (2012) Psychometric hepatic encephalopathy score for the detection of minimal hepatic encephalopathy in Korean patients with liver cirrhosis. J Gastroenterol Hepatol 27(11):1695–1704

    Article  PubMed  Google Scholar 

  • Tao R (2013) The thalamus in cirrhotic patients with and without hepatic encephalopathy: a volumetric MRI study. Eur J Radiol 82(11):e715–720

    Article  PubMed  Google Scholar 

  • Wang Z, Yan C, Zhao C, Qi Z, Zhou W, Lu J, He Y, Li K (2011) Spatial patterns of intrinsic brain activity in mild cognitive impairment and Alzheimer’s disease: a resting-state functional MRI study. Hum Brain Mapp 32(10):1720–1740

    Article  PubMed  Google Scholar 

  • Zafiris O, Kircheis G, Rood HA, Boers F, Haussinger D, Zilles K (2004) Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study. Neuroimage 22(2):541–552

    Article  PubMed  Google Scholar 

  • Zhang LJ, Yang G, Yin J, Liu Y, Qi J (2007) Neural mechanism of cognitive control impairment in patients with hepatic cirrhosis: a functional magnetic resonance imaging study. Acta Radiol 48(5):577–587

    Article  CAS  PubMed  Google Scholar 

  • Zheng G, Zhang LJ, Zhong J, Wang Z, Qi R, Shi D, Lu GM (2013) Cerebral blood flow measured by arterial-spin labeling MRI: a useful biomarker for characterization of minimal hepatic encephalopathy in patients with cirrhosis. Eur J Radiol 82(11):1981–1988

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (JX 10231801), a grant from the National Natural Science Foundation of China (No. 81501450), and a project funded by the China Postdoctoral Science Foundation.

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    Authors and Affiliations

    1. Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

      Hua-Jun Chen, Ling Zhang & Hai-Bin Shi

    2. Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

      Long-Feng Jiang & Jun Li

    3. School of Information Science and Engineering, Central South University, Changsha, 410083, China

      Qiu-Feng Chen

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    1. Hua-Jun Chen
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    Correspondence to Hua-Jun Chen, Jun Li or Hai-Bin Shi.

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    Hua-Jun Chen, Ling Zhang and Long-Feng Jiang contributed equally to this work.

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    Chen, HJ., Zhang, L., Jiang, LF. et al. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity. Metab Brain Dis 31, 761–769 (2016). https://doi.org/10.1007/s11011-016-9799-9

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