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Enhancement of functional connectivity, working memory and inhibitory control on multi-modal brain MR imaging with
Vishwadeep Ahluwalia1, James B Wade, Douglas M Heuman
1Division of Radiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA, USA.
Unlabelled:
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.
Insights
Rifaximin treatment improved cognitive function and brain connectivity in patients with minimal hepatic encephalopathy (MHE). This gut-specific antibiotic therapy reduced endotoxemia and modulated brain activity during cognitive tasks.
Area of Science:
- Neuroscience
- Gastroenterology
- Pharmacology
Background:
- Minimal hepatic encephalopathy (MHE) is a complication of cirrhosis impacting daily function.
- The precise functional brain impact of MHE and its modulation by treatment remain incompletely understood.
- The gut-liver-brain axis is implicated in the pathophysiology of MHE.
Purpose of the Study:
- To investigate the effects of rifaximin, a gut-specific antibiotic, on the gut-liver-brain axis in patients with MHE.
- To evaluate rifaximin's impact on endotoxemia, cognitive function, and brain activation patterns during working memory and inhibitory control tasks.
Main Methods:
- Twenty patients with MHE underwent baseline endotoxin and cognitive testing, followed by fMRI, DTI, and MRS.
- Cognitive tasks included N-back for working memory and inhibitory control tests (ICT).
- Procedures were repeated after 8 weeks of open-label rifaximin treatment, with pre- and post-treatment data compared.
Main Results:
- Rifaximin treatment led to significant improvements in N-back task performance and ICT lure inhibition.
- Endotoxemia levels were significantly reduced post-treatment.
- fMRI revealed altered activation in subcortical and fronto-parietal regions during cognitive tasks, alongside shifts in fronto-parietal connectivity (increased FA).
Conclusions:
- Open-label rifaximin therapy significantly improved cognition, working memory, and inhibitory control in MHE patients.
- Treatment modulated brain activation and connectivity, particularly in fronto-parietal and subcortical networks.
- Rifaximin effectively targets the gut-liver-brain axis, offering a potential therapeutic strategy for MHE.
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