Korean Journal of Radiology

The Korean Society of Radiology (대한영상의학회)
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Renormalization of Thalamic Sub-Regional Functional Connectivity Contributes to Improvement of Cognitive Function after Liver Transplantation in Cirrhotic Patients with Overt Hepatic Encephalopathy

  • Yue Cheng (Department of Radiology, Tianjin First Central Hospital) ;
  • Jing-Li Li (Department of Radiology, Tianjin First Central Hospital) ;
  • Jia-Min Zhou (Department of Radiology, Tianjin First Central Hospital) ;
  • Gao-Yan Zhang (Tianjin Key Lab of Cognitive Computing and Application, College of Intelligence and Computing, Tianjin University) ;
  • Wen Shen (Department of Radiology, Tianjin First Central Hospital) ;
  • Xiao-Dong Zhang (Department of Radiology, Tianjin First Central Hospital)
  • Received : 2020.12.08
  • Accepted : 2021.07.07
  • Published : 2021.12.01
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Abstract

Objective: The role of preoperative overt hepatic encephalopathy (OHE) in the neurophysiological mechanism of cognitive improvement after liver transplantation (LT) remains elusive. This study aimed to explore changes in sub-regional thalamic functional connectivity (FC) after LT and their relationship with neuropsychological improvement using resting-state functional MRI (rs-fMRI) data in cirrhotic patients with and without a history of OHE. Materials and Methods: A total of 51 cirrhotic patients, divided into the OHE group (n = 21) and no-OHE group (n = 30), and 30 healthy controls were enrolled in this prospective study. Each patient underwent rs-fMRI before and 1 month after LT. Using 16 bilateral thalamic subregions as seeds, we conducted a seed-to-voxel FC analysis to compare the thalamic FC alterations before and after LT between the OHE and no-OHE groups, as well as differences in FC between the two groups of cirrhotic patients and the control group. Correction for multiple comparisons was conducted using the false discovery rate (p < 0.05). Results: We found abnormally increased FC between the thalamic sub-region and prefrontal cortex, as well as an abnormally decreased FC between the bilateral thalamus in both OHE and no-OHE cirrhotic patients before LT, which returned to normal levels after LT. Compared with the no-OHE group, the OHE group exhibited more extensive abnormalities prior to LT, and the increased FC between the right thalamic subregions and right inferior parietal lobe was markedly reduced to normal levels after LT. Conclusion: The renormalization of FC in the cortico-thalamic loop might be a neuro-substrate for the recovery of cognitive function after LT in cirrhotic patients. In addition, hyperconnectivity between thalamic subregions and the inferior parietal lobe might be an important feature of OHE. Changes in FC in the thalamus might be used as potential biomarkers for recovery of cognitive function after LT in cirrhotic patients.

Keywords

Acknowledgement

This work was supported by National Natural Science Foundation of China (No. 81601482 and 81701679).

References

  1. Weissenborn K. Hepatic encephalopathy: definition, clinical grading and diagnostic principles. Drugs 2019;79:5-9 
  2. Garcia-Martinez R, Rovira A, Alonso J, Jacas C, Simon-Talero M, Chavarria L, et al. Hepatic encephalopathy is associated with posttransplant cognitive function and brain volume. Liver Transpl 2011;17:38-46 
  3. Hadjihambi A, Arias N, Sheikh M, Jalan R. Hepatic encephalopathy: a critical current review. Hepatol Int 2018;12:135-147 
  4. Wong RJ, Aguilar M, Gish RG, Cheung R, Ahmed A. The impact of pretransplant hepatic encephalopathy on survival following liver transplantation. Liver Transpl 2015;21:873-880 
  5. Hopp AE, Dirks M, Petrusch C, Goldbecker A, Tryc AB, Barg-Hock H, et al. Hepatic encephalopathy is reversible in the long term after liver transplantation. Liver Transpl 2019;25:1661-1672 
  6. Kornerup LS, Pflugrad H, Weissenborn K, Vilstrup H, Dam G. Cognitive impairment after liver transplantation: residual hepatic encephalopathy or posttransplant encephalopathy? Hepat Med 2019;11:41-46 
  7. Sotil EU, Gottstein J, Ayala E, Randolph C, Blei AT. Impact of preoperative overt hepatic encephalopathy on neurocognitive function after liver transplantation. Liver Transpl 2009;15:184-192 
  8. Campagna F, Montagnese S, Schiff S, Biancardi A, Mapelli D, Angeli P, et al. Cognitive impairment and electroencephalographic alterations before and after liver transplantation: what is reversible? Liver Transpl 2014;20:977-986 
  9. Chen HJ, Zhu XQ, Shu H, Yang M, Zhang Y, Ding J, et al. Structural and functional cerebral impairments in cirrhotic patients with a history of overt hepatic encephalopathy. Eur J Radiol 2012;81:2463-2469 
  10. Qi R, Zhang L, Wu S, Zhong J, Zhang Z, Zhong Y, et al. Altered resting-state brain activity at functional MR imaging during the progression of hepatic encephalopathy. Radiology 2012;264:187-195 
  11. Tao R, Zhang J, You Z, Wei L, Fan Y, Cui J, et al. The thalamus in cirrhotic patients with and without hepatic encephalopathy: a volumetric MRI study. Eur J Radiol 2013;82:e715-e720 
  12. Ahl B, Weissenborn K, van den Hoff J, Fischer-Wasels D, Kostler H, Hecker H, et al. Regional differences in cerebral blood flow and cerebral ammonia metabolism in patients with cirrhosis. Hepatology 2004;40:73-79 
  13. Qi R, Xu Q, Zhang LJ, Zhong J, Zheng G, Wu S, et al. Structural and functional abnormalities of default mode network in minimal hepatic encephalopathy: a study combining DTI and fMRI. PLoS One 2012;7:e41376 
  14. Jao T, Schroter M, Chen CL, Cheng YF, Lo CY, Chou KH, et al. Functional brain network changes associated with clinical and biochemical measures of the severity of hepatic encephalopathy. Neuroimage 2015;122:332-344 
  15. Zhang G, Cheng Y, Shen W, Liu B, Huang L, Xie S. The short-term effect of liver transplantation on the low-frequency fluctuation of brain activity in cirrhotic patients with and without overt hepatic encephalopathy. Brain Imaging Behav 2017;11:1849-1861 
  16. Zhang G, Cheng Y, Shen W, Liu B, Huang L, Xie S. Brain regional homogeneity changes in cirrhotic patients with or without hepatic encephalopathy revealed by multi-frequency bands analysis based on resting-state functional MRI. Korean J Radiol 2018;19:452-462 
  17. Zhang G, Cheng Y, Liu B. Abnormalities of voxel-based wholebrain functional connectivity patterns predict the progression of hepatic encephalopathy. Brain Imaging Behav 2017;11:784-796 
  18. Cheng Y, Zhang G, Shen W, Huang LX, Zhang L, Xie SS, et al. Impact of previous episodes of hepatic encephalopathy on short-term brain function recovery after liver transplantation: a functional connectivity strength study. Metab Brain Dis 2018;33:237-249 
  19. Herrero MT, Barcia C, Navarro JM. Functional anatomy of thalamus and basal ganglia. Childs Nerv Syst 2002;18:386-404 
  20. Lv H, Liu C, Wang Z, Zhao P, Cheng X, Yang Z, et al. Altered functional connectivity of the thalamus in tinnitus patients is correlated with symptom alleviation after sound therapy. Brain Imaging Behav 2020;14:2668-2678 
  21. Byun JI, Kim HW, Kang H, Cha KS, Sunwoo JS, Shin JW, et al. Altered resting-state thalamo-occipital functional connectivity is associated with cognition in isolated rapid eye movement sleep behavior disorder. Sleep Med 2020;69:198-203 
  22. Fan Y, Nickerson LD, Li H, Ma Y, Lyu B, Miao X, et al. Functional connectivity-based parcellation of the thalamus: an unsupervised clustering method and its validity investigation. Brain Connect 2015;5:620-630 
  23. Fan L, Li H, Zhuo J, Zhang Y, Wang J, Chen L, et al. The human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex 2016;26:3508-3526 
  24. Liu F, Wang Y, Li M, Wang W, Li R, Zhang Z, et al. Dynamic functional network connectivity in idiopathic generalized epilepsy with generalized tonic-clonic seizure. Hum Brain Mapp 2017;38:957-973 
  25. Chumbley J, Worsley K, Flandin G, Friston K. Topological FDR for neuroimaging. Neuroimage 2010;49:3057-3064 
  26. Behrens TE, Johansen-Berg H, Woolrich MW, Smith SM, Wheeler-Kingshott CA, Boulby PA, et al. Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging. Nat Neurosci 2003;6:750-757 
  27. Collins DP, Anastasiades PG, Marlin JJ, Carter AG. Reciprocal circuits linking the prefrontal cortex with dorsal and ventral thalamic nuclei. Neuron 2018;98:366-379.e4 
  28. Mitchell AS. The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making. Neurosci Biobehav Rev 2015;54:76-88 
  29. Tanaka M. Cognitive signals in the primate motor thalamus predict saccade timing. J Neurosci 2007;27:12109-12118 
  30. de Bourbon-Teles J, Bentley P, Koshino S, Shah K, Dutta A, Malhotra P, et al. Thalamic control of human attention driven by memory and learning. Curr Biol 2014;24:993-999 
  31. Zarantonello L, Turco M, Formentin C, Izquierdo-Altarejos P, Vuerich A, Barcenas Jimenez MJ, et al. The influence of HE history, HE status and neuropsychological test type on learning ability in patients with cirrhosis. Liver Int 2019;39:861-870 
  32. Peters SK, Dunlop K, Downar J. Cortico-striatal-thalamic loop circuits of the salience network: a central pathway in psychiatric disease and treatment. Front Syst Neurosci 2016;10:104 
  33. Wang J, Jiang Y, Tang Y, Xia M, Curtin A, Li J, et al. Altered functional connectivity of the thalamus induced by modified electroconvulsive therapy for schizophrenia. Schizophr Res 2020;218:209-218 
  34. McPhail MJ, Patel NR, Taylor-Robinson SD. Brain imaging and hepatic encephalopathy. Clin Liver Dis 2012;16:57-72 
  35. Ellul MA, Gholkar SA, Cross TJ. Hepatic encephalopathy due to liver cirrhosis. BMJ 2015;351:h4187 
  36. Atluri DK, Asgeri M, Mullen KD. Reversibility of hepatic encephalopathy after liver transplantation. Metab Brain Dis 2010;25:111-113 
  37. Chavarria L, Cordoba J. Encephalopathy and liver transplantation. Metab Brain Dis 2013;28:285-292 
  38. Chen HJ, Jiao Y, Zhu XQ, Zhang HY, Liu JC, Wen S, et al. Brain dysfunction primarily related to previous overt hepatic encephalopathy compared with minimal hepatic encephalopathy: resting-state functional MR imaging demonstration. Radiology 2013;266:261-270 
  39. Cheng Y, Huang L, Zhang X, Zhong J, Ji Q, Xie S, et al. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study. Metab Brain Dis 2015;30:979-988 
  40. Schmitz B, Pflugrad H, Tryc AB, Lanfermann H, Jackel E, Schrem H, et al. Brain metabolic alterations in patients with long-term calcineurin inhibitor therapy after liver transplantation. Aliment Pharmacol Ther 2019;49:1431-1441