Reduced resting state connectivity and gray matter volume correlate with cognitive impairment in minimal hepatic encephalopathy.

Raquel García-García,Joan Tosca,Vicente Felipo,Vicente Belloch,Remedios Giner-Durán,Carmina Montoliu,Elena Kosenko,Juan Fermín Ordoño,Alba Mangas-Losada,Amparo Urios,César Avila,Álvaro Javier Cruz-Gómez,Desamparados Escudero-García,Cristina Forn,Miguel Angel Serra

doi:10.1371/journal.pone.0186463

Abstract

Background and aimsMinimal hepatic encephalopathy (MHE) is associated with cognitive alterations and changes in connectivity. We assessed the relationship of the abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with different cognitive alterations and biochemical parameters associated to MHE.MethodsThirty-nine cirrhotic patients (26 without and 13 with MHE) and 24 controls were widely cognitive assessed with a battery of psychometric tests. Atrophy was determined using Voxel-Based Morphometry and rs-FC was assessed by independent component analysis. Receiver operating characteristic (ROC) curves was performed to assess the diagnostic utility of rs-FC and GM reduction for the discrimination of patients with and without MHE. Blood ammonia, cGMP, and levels of pro-inflammatory interleukins were measured.ResultsMHE patients showed significant decrease of GM volume and lesser degree of rs-FC in different networks related to attention and executive functions as compared to controls and patients without MHE. There is a progressive reduction in rs-FC in the default mode network with the progression of cognitive impairment. MHE patients showed GM reduction in the right frontal lobe, right insula and right cerebellum compared to patients without MHE. Alterations in GM volume and rs-FC correlated with the scores of different cognitive tests.ConclusionsDecreased cognitive performance is associated by reduced rs-FC and GM atrophy in MHE patients. These changes could have predictive value for detecting MHE.

Highlights

Hepatic Encephalopathy (HE) is a complex neuropsychiatric syndrome characterized by a functional alteration of the central nervous system associated to liver disease [1, 2]
minimal hepatic encephalopathy (MHE) patients showed significant decrease of gray matter (GM) volume and lesser degree of resting-state functional connectivity (rs-functional connectivity (FC)) in different networks related to attention and executive functions as compared to controls and patients without MHE
Decreased cognitive performance is associated by reduced rs-FC and GM atrophy in MHE patients

Summary

Introduction

Hepatic Encephalopathy (HE) is a complex neuropsychiatric syndrome characterized by a functional alteration of the central nervous system associated to liver disease [1, 2]. Patients with MHE show white matter alterations related to cognitive impairment [12] This could alter the functional connectivity (FC) of neural networks, causing neurological deficits. MHE patients present focal damage in the precuneus (involved in the Default Mode network, DMN), which correlates with cognitive impairment [14]. This suggests that alterations in the integrity of the GM may be, at least in part, responsible for the alterations in FC. We assessed the relationship of the abnormalities of resting-state functional connectivity (rs-FC) and gray matter (GM) volume with different cognitive alterations and biochemical parameters associated to MHE

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