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

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.

Learning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy are Associated with Structural and Functional Connectivity Alterations in Hippocampus

“…Relevant functional networks, such as the DMN and attention networks, the visual network, and thalamo-cortical circuits, are disturbed in cirrhotic patients 27 – 34 . Patients with MHE show a significant decrease in gray matter volume and reduced functional connectivity in different networks related to attention and executive functions, compared to controls and patients without MHE 24 , 27 – 29 , 33 .…”

“…Magnetic resonance imaging (MRI) makes it possible to study the neuroanatomical and functional changes associated with pathologies such as MHE, and associate these changes with specific cognitive deficits, such as alterations in memory. A significant decrease in gray matter density in several brain areas has been described in cirrhotic patients 23 , 24 . In previous studies, we found a reduction in hippocampus volume in MHE patients compared to healthy controls 24 , 25 .…”

“…A significant decrease in gray matter density in several brain areas has been described in cirrhotic patients 23 , 24 . In previous studies, we found a reduction in hippocampus volume in MHE patients compared to healthy controls 24 , 25 . Moreover, MHE patients presented focal damage in the precuneus (involved in the Default Mode network, DMN) and alterations in white matter microstructural integrity, which correlate with cognitive alterations 25 , 26 .…”

“…Recent studies have assessed the relationship between cognitive impairment associated with MHE and measures of changes in functional connectivity (FC) patterns in resting state 24 , 27 – 33 . These studies focus on investigating the extent to which different brain regions are connected and analyzing their joint activity or temporal synchronization.…”

Structural change of thalamus in cirrhotic patients with or without minimal hepatic encephalopathy and the relationship between thalamus volume and clinical indexes related to cirrhosis

“…On the other hand, hepatic encephalopathy (HE) is a metabolic neuropsychological syndrome mainly developed from chronic liver disease which usually leads to liver cirrhosis. Altered brain structure in cirrhotic patients has already been reported in many studies ( Chen et al, 2012 ; Garcia-Garcia et al, 2017 ; Zhang et al, 2012 ). Most of these studies focused on the grey matter change in the cortex and striatum, while only one study investigates the relationship between structural changes in thalamus and cirrhotic symptoms ( Tao et al, 2013 ).…”