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01-12-2014 | Research Article

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: Implications for the gut-liver-brain axis

Authors: Vishwadeep Ahluwalia, James B. Wade, Douglas M. Heuman, Thomas A. Hammeke, Arun J. Sanyal, Richard K. Sterling, R. Todd Stravitz, Velimir Luketic, Mohammad S. Siddiqui, Puneet Puri, Michael Fuchs, Micheal J. Lennon, Kenneth A. Kraft, HoChong Gilles, Melanie B. White, Nicole A. Noble, Jasmohan S. Bajaj

Published in: Metabolic Brain Disease | Issue 4/2014

Abstract

Minimal hepatic encephalopathy (MHE) impairs daily functioning in cirrhosis, but its functional brain impact is not completely understood. To evaluate the effect of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in MHE. Hypothesis: Rifaximin will reduce endotoxemia, enhance cognition, increase activation during working memory(N-back) and reduce activation needed for inhibitory control tasks. Methods: Cirrhotics with MHE underwent baseline endotoxin and cognitive testing, then underwent fMRI, diffusion tensor imaging and MR spectroscopy(MRS). On fMRI, two tasks; N-back (outcome: correct responses) and inhibitory control tests(outcomes: lure inhibition) were performed. All procedures were repeated after 8 weeks of rifaximin. Results were compared before/after rifaximin. Results: 20 MHE patients (59.7 years) were included; sixteen completed pre/post-rifaximin scanning with 92 % medication compliance. Pre-rifaximin patients had cognitive impairment. At trial-end, there was a significantly higher correct 2-back responses, ICT lure inhibitions and reduced endotoxemia(p = 0.002). This was accompanied by significantly higher activation from baseline in subcortical structures (thalamus, caudate, insula and hippocampus) and left parietal operculum (LPO) during N-back, decrease in fronto-parietal activation required for inhibiting lures, including LPO during ICT compared to baseline values. Connectivity studies in N-back showed significant shifts in linkages after therapy in fronto-parietal regions with a reduction in fractional anisotropy (FA) but not mean diffusivity (MD), and no change in MRS metabolites at the end of the trial. A significant improvement in cognition including working memory and inhibitory control, and fractional anisotropy without effect on MD or MRS, through modulation of fronto-parietal and subcortical activation and connectivity was seen after open-label rifaximin therapy in MHE.

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Title: Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: Implications for the gut-liver-brain axis
Authors: Vishwadeep Ahluwalia
James B. Wade
Douglas M. Heuman
Thomas A. Hammeke
Arun J. Sanyal
Richard K. Sterling
R. Todd Stravitz
Velimir Luketic
Mohammad S. Siddiqui
Puneet Puri
Michael Fuchs
Micheal J. Lennon
Kenneth A. Kraft
HoChong Gilles
Melanie B. White
Nicole A. Noble
Jasmohan S. Bajaj
Publication date: 01-12-2014
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 4/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-014-9507-6

At a glance: The STEP trials

Springer Medicine

Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with Rifaximin in Cirrhosis: Implications for the gut-liver-brain axis

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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