Altered Regional Homogeneity in the Development of Minimal Hepatic Encephalopathy: A Resting-State Functional MRI Study

Background Little is known about how spontaneous brain activity progresses from non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this study was to evaluate the evolution pattern of spontaneous brain activities in cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo) method. Methodology/Principal Findings Resting-state fMRI data were acquired in 47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age-and sex-matched healthy controls. The Kendall’s coefficient of concordance (KCC) was used to measure the regional homogeneity. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symbol test (DST) scores, venous blood ammonia levels. Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST scores positively correlated with ReHo values in the cuneus, precuneus and lingual gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected). Conclusions/Significance Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE.

[1]  Schneider Js Basal ganglia role in behavior: importance of sensory gating and its relevance to psychiatry. , 1984 .

[2]  K. Weissenborn,et al.  Bradykinesia in minimal hepatic encephalopathy is due to disturbances in movement initiation. , 2003, Journal of hepatology.

[3]  K Weissenborn,et al.  Neuropsychological characterization of hepatic encephalopathy. , 2001, Journal of hepatology.

[4]  M. Morgan,et al.  Characteristics of Minimal Hepatic Encephalopathy , 2004, Metabolic Brain Disease.

[5]  M. Ginsberg,et al.  Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy. , 1986, The Journal of clinical investigation.

[6]  Wei Zhang,et al.  Selective aberrant functional connectivity of resting state networks in social anxiety disorder , 2010, NeuroImage.

[7]  W H Wong,et al.  Altered Cerebral Blood Flow and Glucose Metabolism in Patients with Liver Disease and Minimal Encephalopathy , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[8]  J. Schneider Basal ganglia role in behavior: importance of sensory gating and its relevance to psychiatry. , 1984, Biological psychiatry.

[9]  Yawu Liu,et al.  Neural mechanism of cognitive control impairment in patients with hepatic cirrhosis: a functional magnetic resonance imaging study , 2007, Acta radiologica.

[10]  Ying-wei Qiu,et al.  Regional homogeneity changes in heroin-dependent individuals: resting-state functional MR imaging study. , 2011, Radiology.

[11]  Karl Zilles,et al.  Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study , 2004, NeuroImage.

[12]  Ritesh Agarwal,et al.  Lactulose improves cognitive functions and health‐related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy , 2007, Hepatology.

[13]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[14]  Xi-Nian Zuo,et al.  REST: A Toolkit for Resting-State Functional Magnetic Resonance Imaging Data Processing , 2011, PloS one.

[15]  Yingli Lu,et al.  Regional homogeneity approach to fMRI data analysis , 2004, NeuroImage.

[16]  M. Raichle,et al.  Disease and the brain's dark energy , 2010, Nature Reviews Neurology.

[17]  A. Lockwood,et al.  Hepatic encephalopathy—Definition, nomenclature, diagnosis, and quantification: Final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998 , 2002, Hepatology.

[18]  R. Passingham,et al.  Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects. , 1996, Brain : a journal of neurology.

[19]  M. Hallett,et al.  Regional homogeneity changes in patients with Parkinson's disease , 2009, Human brain mapping.

[20]  Yu Wang,et al.  Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy , 2012, Neuroscience Letters.

[21]  R. Pugh,et al.  Transection of the oesophagus for bleeding oesophageal varices , 1973, The British journal of surgery.

[22]  Yawu Liu,et al.  Abnormal default-mode network activation in cirrhotic patients: a functional magnetic resonance imaging study , 2007, Acta radiologica.

[23]  R. Passingham,et al.  Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. , 2000, Brain : a journal of neurology.

[24]  K. Weissenborn,et al.  Attention Deficits in Minimal Hepatic Encephalopathy , 2001, Metabolic Brain Disease.

[25]  Cheng Xu,et al.  Decreased regional homogeneity in insula and cerebellum: A resting-state fMRI study in patients with major depression and subjects at high risk for major depression , 2010, Psychiatry Research: Neuroimaging.

[26]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[27]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Bajaj Minimal hepatic encephalopathy matters in daily life. , 2008, World journal of gastroenterology.

[29]  Yuan Zhong,et al.  Brain default‐mode network abnormalities in hepatic encephalopathy: A resting‐state functional MRI study , 2012, Human brain mapping.

[30]  Xi Zhang,et al.  Altered spontaneous activity in Alzheimer's disease and mild cognitive impairment revealed by Regional Homogeneity , 2012, NeuroImage.

[31]  Hartmut Hecker,et al.  Regional differences in cerebral blood flow and cerebral ammonia metabolism in patients with cirrhosis , 2004, Hepatology.

[32]  Yijun Liu,et al.  Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. , 2012, Radiology.

[33]  Hans Schomerus,et al.  Quality of Life in Cirrhotics with Minimal Hepatic Encephalopathy , 2001, Metabolic Brain Disease.

[34]  A. Lockwood,et al.  Cerebral Ammonia Metabolism in Patients with Severe Liver Disease and Minimal Hepatic Encephalopathy , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[35]  R. D. Du Pasquier,et al.  Chronic parkinsonism associated with cirrhosis: a distinct subset of acquired hepatocerebral degeneration. , 2003, Archives of neurology.

[36]  J. Tanji,et al.  Behavioral planning in the prefrontal cortex , 2001, Current Opinion in Neurobiology.