Reestablishing Brain Networks in Patients without Overt Hepatic Encephalopathy after Liver Transplantation

Abstract

Cirrhotic patients without overt hepatic encephalopathy (HE) have associated with widespread neuro-psychological impairment. Liver transplantation can restore metabolic abnormalities but the mechanisms are unclear. We investigate brain functional networks after transplantation using resting-state funtional magnetic resonance imaging (MRI). Twenty-six cirrhotic patients without overt HE completed neuro-psychological assessment before and 6 to 12 months after transplantation, and compared with 35 healthy controls. Five major functional brain networks, default mode (DMN), dorsal attention (DAN), executive control (ECN), salience (SN), and primary networks (PN), were assessed. Nodal efficiency and strength in different functional networks were weighed and their interaction metrics displayed. Granger causal analysis between pretransplantation and posttransplantation was performed. Before transplantation, the intrafunctional connectivity was decreased in DMN, DAN, ECN, and SN. After transplantation, cognitive functions improved with increased functional connectivity. The interaction metrics among large-scale networks in patients became similar to healthy controls. The increase in PN affected the decrease in SN, while the increase in DAN forced a decrease in DMN. There was a bidirectional balance between DMN and SN. Dynamic disruptions and reconstruction in intrinsic large-scale networks are associated with parallel patterns of cognitive information processing deficits and recovery. Remapping of SN, DMN, and DAN is essential for restoring cognition after transplantation.

Neurological Complications Occurring After Liver Transplantation: Role of Risk Factors, Hepatic Encephalopathy, and Acute (on Chronic) Brain Injury

“…On the one hand, post‐LT improvement has been shown in the setting of HE on the basis of EEG and PET scan results . On the other hand, MRI studies that use standard sequences, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and functional MRI (Table ) can show both improvement in cerebral abnormalities that were present prior to LT because of HE (see Table for review) and persistent abnormalities after LT . Spontaneous T 1 ‐weighted sequence basal ganglia hypersignals, white matter changes in the corticospinal tract, magnetization transfer ratio (MTR), and the HE profile on MRS normalize months after LT .…”

“…Despite limited data from DTI, it appears that mean diffusivity (MD) decreases after LT, suggesting a correction of vasogenic edema with the normalization of liver function . Only scarce data are available from functional MRI, though what is available also suggests an improvement in the functioning of the previously altered networks after LT . However, several data also suggest persistent cerebral abnormalities after LT. Standard MRI sequences can provide evidence of reduced brain volume and a decrease in the MRS N ‐acetylaspartate (NAA)/creatine (Cr) ratio, both of which suggest the presence of fixed brain lesions and brain atrophy .…”

Longitudinal Intrinsic Brain Activity Changes in Cirrhotic Patients before and One Month after Liver Transplantation

“…These studies indicated that the impairments and reorganization of brain function are dynamic processes and that these changes can both exist in every stage of HE from simple cirrhosis (without HE) to MHE and, ultimately, overt HE. Using resting-state functional connectivity, Lin et al ( 16 ) found dynamic disruptions and reconstruction of intrinsic large-scale networks approximately one year after LT accompanied by cognitive deficits and recovery. Moreover, Zhang et al ( 17 ) found improved long- and short-range functional connectivity density one month after LT and persistence of posterior cingulate cortex/precuneus (PCu) functional connectivity disturbance.…”

Resting State-fMRI with ReHo Analysis as a Non-Invasive Modality for the Prognosis of Cirrhotic Patients with Overt Hepatic Encephalopathy

“…A compensatory increase in cerebellar flow under hypoxia indicates preferential perfusion of brain regions vital to respiratory and cardiovascular stability [ 49 ]. Adequate treatment for cirrhotic patients may reverse brain edema and re-establish impaired functional connectivity with improvement in cognitive function [ 21 , 50 ]. Investigations between neuronal activity and irreversible adverse outcome in patients with HE are limited.…”

“…Prior to pre-processing, the first 10 volumes were discarded to reach a steady-state magnetization and allow the participants to adapt to the scanning noise [ 11 , 15 , 21 ]. Resting-state fMRI data pre-processing was then performed using the Statistical Parametric Mapping (SPM8, Wellcome Department of Cognitive Neurology, London, UK; http://www.fil.ion.ucl.ac.uk/spm/ ) and Data Processing Assistant for rs-fMRI (DPARSF) tools [ 22 ].…”