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Disrupted Brain Intrinsic Networks and Executive Dysfunction in Cirrhotic Patients without Overt Hepatic Encephalopathy.

ABSTRACT: Objective:Patients with cirrhosis often exhibit cognitive deficits, particularly executive dysfunction, which is considered a predictor of overt hepatic encephalopathy (OHE). We examined brain intrinsic networks associated with executive function to investigate the neural basis of this cognitive deficiency in cirrhosis. Methods:Resting-state functional MRI data were acquired from 20 cirrhotic patients and 18 healthy controls. Seed-based correlation analysis was used to identify the three well-known networks associated with executive function, including executive control (ECN), default mode (DMN), and salience (SN) networks. Functional connectivity (FC) within each network was compared between groups and correlated with patient executive performance (assessed by the Stroop task). Results:Patients showed decreased FC between the ECN seed (right dorsolateral prefrontal cortex) and several regions (including right middle/inferior frontal gyrus, left inferior frontal gyrus, bilateral inferior/superior parietal lobules, bilateral middle/inferior temporal gyrus, and right medial frontal gyrus), between the DMN seed [posterior cingulate cortex (PCC)] and several regions (including bilateral medial frontal gyrus, bilateral anterior cingulate cortex, bilateral superior frontal gyrus, bilateral precuneus/PCC, left supramarginal gyrus, and left middle temporal gyrus), and between the SN seed (right anterior insula) and right supramarginal gyrus. FC strength in the ECN and SN was negatively correlated with patient performance during the Stroop task. Conclusion:Disrupted functional integration in the core brain cognitive networks, which is reflected by reductions in FC, occurs before OHE bouts and may play an important role in the neural mechanism of executive dysfunction associated with cirrhosis.

SUBMITTER: Yang ZT

PROVIDER: S-EPMC5788959 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE.Materials and methodsA total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05).ResultsWe found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT.ConclusionThe renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

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Disrupted Brain Intrinsic Networks and Executive Dysfunction in Cirrhotic Patients without Overt Hepatic Encephalopathy.

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