Changes in the regional homogeneity of resting-state brain activity in minimal hepatic encephalopathy
Highlights
► This study reported the alterations of resting-state ReHo in the patient with MHE. ► Both decreased and increased ReHo were found in the patient with MHE. ► Decreased ReHo in cuneus and precuneus was correlated with the score in DST. ► Increased ReHo in MHE may be associated with compensatory mechanism. ► Resting-state ReHo may provide additional information for defining MHE.
Introduction
Minimal hepatic encephalopathy (MHE) is a subclinical complication of liver cirrhosis in which the patients have no manifest mental deficiency or neurological disease, but have subtle cognitive and psychomotor deficits. The neurocognitive dysfunction in MHE is characterized by impaired attention, visuomotor coordination, psychomotor speed, and response inhibition [17]. Evidence that MHE has a negative effect on daily life has been increasing. For example, patients with MHE are unfit to drive [24] as they are at a higher risk of motor vehicle accidents [2]. Furthermore, MHE is thought to be associated with an increased tendency to progress to overt hepatic encephalopathy [9]. Therefore, the early detection of MHE is important for improving patients’ prognosis because the appropriate treatment can be administrated in the initial phase. For example, treatment with lactulose improves both cognitive functions and the health-related quality of life in patients with MHE [19]. Unfortunately, the neuropsychological impairments in MHE are easily overlooked by clinicians because they have few apparent manifestations. The adequate evaluation of patients with MHE remains a clinical challenge.
Although many difficulties have impeded attempts to define MHE, neuroimaging methods, particularly magnetic resonance imaging (MRI), may prove useful for evaluating the consequences of pathology related to hepatic encephalopathy. Hyperintensity in the globus pallidus [18] and reduced brain tissue density [8] are seen on standard MRI. Apart from the structural changes, recent magnetic resonance spectroscopy studies demonstrated the cerebral metabolic disturbances in patients with MHE, including an increased glutamine/glutamate peak coupled with decreased myoinositol and choline signals [21], which were related to brain edema [12]. Additionally, task-dependent functional MRI (fMRI) revealed the MHE-related neuronal mechanisms underlying impaired visual judgment [27] and cognitive control [31]. More notably, Zhang et al. [30] recently demonstrated the disruption of default-mode connectivity in episodic hepatic encephalopathy using resting-state fMRI.
Resting-state fMRI has attracted increasing attention and several methods have been developed to assess the synchrony of brain activity at rest. For example, seed-based analysis which is hypothesis-driven has been used to define various brain resting state networks, including the systems for visual, sensorimotor, auditory, dorsal attention, executive control and default mode networks [29]. Also, data-driven methods (e.g. independent component analysis), have been employed to clearly characterize these intrinsic brain networks [5], [20]. Rather than the functional connectivity analysis between the remote brain regions, Zang et al. [28] proposed using regional homogeneity (ReHo), which targets the temporal synchronization of the inter-regional fMRI signals. This data-driven method provides the opportunity for the general search of abnormal local brain activity coherence across the whole brain, compare to the seed-based analyses. Many data-driven methods show some inherent drawbacks (e.g. independent component analysis needs statistically independent assumption; principal component analysis needs orthogonal patterns assumption [28]), which are not involved in ReHo method. The ReHo method is based on the assumption that the activity of each voxel within a specific brain area has temporal characteristics similar to those of the neighboring voxels (i.e., local synchrony). It should be noted that a higher ReHo was seen in the default mode network, which is involved in a wide spectrum of neurocognitive functions [4]. Moreover, disruption of the local synchrony in the default mode network may contribute to the amnestic type of mild cognitive impairment [1]. Indeed, an aberrant ReHo may be associated with the neurocognitive impairment seen in various neuropsychological disorders as a potential sign of disrupted local functionality. This method has been successfully used to investigate functional alterations in Alzheimer's disease [10], major depression [13], Parkinson's disease [26], and temporal lobe epilepsy [15]. Therefore, an analysis of regional coherence could help to improve our understanding of the neuropathological mechanisms underlying neuropsychological diseases.
Nevertheless, no study has examined the changes in regional brain activity in cirrhotic patients with MHE. Therefore, this study examined whether the synchrony of regional brain activity in patients with MHE patients differed from that in healthy controls and if so, whether the changes in the ReHo were associated with the neurocognitive impairment associated with MHE.
Section snippets
Patients and methods
We studied 18 cirrhotic patients with MHE and 18 age-, sex-, and education-matched healthy controls. Of the cirrhotic patients, 16 were post-hepatitis-B-virus (HBV) infection (of these, two also had alcohol-induced damage), and the other two had schistosomiasis. According to the Child–Pugh classification of liver function, six patients were grades A, B, and C, respectively. Of the 18 cirrhotic patients, five had a history of overt hepatic encephalopathy. The diagnosis of MHE was based on
Results
We found no significant differences between the groups in terms of demographic data. Compared with the healthy controls, the MHE patients performed poorly on all of the neuropsychological tests (Table 1). Table 2 shows the differences in the ReHo between the patients with MHE and the healthy controls. Compared with the controls, the patients with MHE had significantly lower ReHo in the cuneus and adjacent precuneus, and left inferior parietal lobe, whereas the regions with increased ReHo in the
Discussion
In this study, we initially used resting-state fMRI to characterize the homogeneity of regional brain activity in MHE. The primary finding of this study was that the patients with MHE exhibited an abnormal local pattern of neuronal activity, including decreased and increased regional homogeneity, which was correlated with neurocognitive impairment.
The decreased coherence in the resting-state neuronal activity detected in the cuneus and adjacent precuneus, and left inferior parietal lobe may
Acknowledgments
We gratefully thank the staff of the Hepatology Department at the The Second Hospital of Nanjing and the Medical School of Southeast University in Nanjing, China for caring for the patients.
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