Abstract
BackgroundThe basal ganglia often show abnormal metabolism and intracranial hemodynamics in cirrhotic patients with hepatic encephalopathy (HE). Little is known about how the basal ganglia affect other brain system and is affected by other brain regions in HE. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI).Methodology/Principal FindingsThirty five low-grade HE patients and thirty five age- and gender- matched healthy controls participated in the rs-fMRI scans. The effective connectivity networks associated with the globus pallidus, the primarily affected region within basal ganglia in HE, were characterized by using the Granger causality analysis and compared between HE patients and healthy controls. Pearson correlation analysis was performed between the abnormal effective connectivity and venous blood ammonia levels and neuropsychological performances of all HE patients. Compared with the healthy controls, patients with low-grade HE demonstrated mutually decreased influence between the globus pallidus and the anterior cingulate cortex (ACC), cuneus, bi-directionally increased influence between the globus pallidus and the precuneus, and either decreased or increased influence from and to the globus pallidus in many other frontal, temporal, parietal gyri, and cerebellum. Pearson correlation analyses revealed that the blood ammonia levels in HE patients negatively correlated with effective connectivity from the globus pallidus to ACC, and positively correlated with that from the globus pallidus to precuneus; and the number connectivity test scores in patients negatively correlated with the effective connectivity from the globus pallidus to ACC, and from superior frontal gyrus to globus pallidus.Conclusions/SignificanceLow-grade HE patients had disrupted effective connectivity network of basal ganglia. Our findings may help to understand the neurophysiological mechanisms underlying the HE.
Highlights
Hepatic encephalopathy (HE) is a common neuropsychiatric complication which caused disturbance of central nervous system function in patients with acute and chronic liver disease [1]
28 were defined as minimal hepatic encephalopathy (HE) (MHE) and 7 as grade I HE. We combined these two entities into one group according to the recent classification by the International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) [21,22], in which both the MHE and grade 1 HE are named as covert HE for simplifying in practical use
There were no significant differences in gender, age between the lowgrade HE and healthy control groups
Summary
Hepatic encephalopathy (HE) is a common neuropsychiatric complication which caused disturbance of central nervous system function in patients with acute and chronic liver disease [1]. It encompasses a broad spectrum of neurological symptom of varying severity and is classified from low-grade to high-grade HE. Accumulating evidences from neuroimaging studies suggest that an alteration of the cortico-striato-thalamic pathway might play an important role in the HE [7,8] Within this model, the common radiological findings of HE are hyperintensity in the basic ganglia (especially the globus pallidus) in conventional T1-weighted MR images [9], and redistribution of cerebral blood flow and metabolic rate of glucose and ammonia from various cortical regions (e.g., the frontal and parietal cortices) to subcortical grey matter regions (the basal ganglia and thalamus) in position emission tomography (PET) and single photon emission tomography (SPET) [8,10]. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI)
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