Skip to main content
Log in

Working Memory in Patients with Varying Degree of Hepatic Encephalopathy (HE): A Pilot EEG-fNIRS Study

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

It is known that patients with covert hepatic encephalopathy (CHE) exhibit working memory abnormalities, but to date there is no study comparing patients with cirrhosis with/without CHE and controls with both electrophysiological and hemodynamic data collected at the same time.

Here we collected behavioral [accuracy and reaction times (RTs), electrophysiological (evoked potentials) and hemodynamic (oxygenated and deoxygenated haemoglobin) correlates of an n-back task [formed by a control (0-back) condition, a low (1-back) and a high (2-back) working memory load conditions] in patients with cirrhosis with/without CHE: (1) at baseline (n = 21, males = 15, 58±8 yrs), and by comparison with controls (n = 21, males = 15, 57±11 yrs) and (2) after a 3-month course of rifaximin (n = 18, males = 12, 61±11 yrs), and by comparison to baseline.

All patients showed slower RTs (p < 0.0001) and lower P2 amplitude compared with controls (p = 0.018); moreover, patients with CHE showed reduced accuracy (p < 0.0001) compared with controls, and patients without CHE showed higher oxygenated haemoglobin in the central dorsolateral prefrontal cortex in the 2-back compared with patients with CHE. Post-rifaximin, oxygenated haemoglobin increased in the central frontopolar cortex. In addition, in patients without CHE the RTs of the 2-back became comparable to those of the 0-back and P3 showed higher amplitude.

In conclusion, the presence of cirrhosis seemed to have more effects than CHE on working memory at baseline. A course of treatment with rifaximin was more beneficial to patients without CHE, who probably had more room for improvement in this complex task.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

References

  1. Sherlock S, Summerskill WH, White LP, Phear EA (1954) Portal- systemic encephalopathy; neurological complications of liver disease. Lancet 267:454–457

    CAS  PubMed  Google Scholar 

  2. Parsons-Smith BG, Summerskill WH, Dawson AM, Sherlock S (1957) The electroencephalograph in liver disease. Lancet 273:867–871. https://doi.org/10.1016/s0140-6736(57)90005-3

    Article  CAS  PubMed  Google Scholar 

  3. Rikkers L, Jenko P, Rudman D, Freides D (1978) Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. Gastroenterology 75:462–469

    Article  CAS  PubMed  Google Scholar 

  4. Amodio P, Montagnese S, Gatta A, Morgan MY (2004) Characteristics of minimal hepatic encephalopathy. Metab Brain Dis 19:253–267. https://doi.org/10.1023/b:mebr.0000043975.01841.de

    Article  PubMed  Google Scholar 

  5. Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, Weissenborn K, Wong P (2014) Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the study of Liver Diseases and the European Association for the study of the liver. Hepatology 60:715–735. https://doi.org/10.1002/hep.27210

    Article  PubMed  Google Scholar 

  6. Montagnese S, Russo FP, Amodio P, Burra P, Gasbarrini A, Loguercio C, Marchesini G, Merli M, Ponziani FR, Riggio O, Scarpignato C (2018) Hepatic encephalopathy 2018: a clinical practice guideline by the Italian Association for the study of the liver (AISF). Dig Liver Dis 51:190–205. https://doi.org/10.1016/j.dld.2018.11.035

    Article  PubMed  Google Scholar 

  7. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT (1998) Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology. Hepatology 35:716–721. https://doi.org/10.1053/jhep.2002.31250

    Article  Google Scholar 

  8. Montagnese S, Rautou PE, Romero-Gómez M, Larsen FS, Shawcross DL, Thabut D, Vilstrup H, Weissenborn K (2022) EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol 3:807–824. https://doi.org/10.1016/j.jhep.2022.06.001

    Article  Google Scholar 

  9. Amodio P, Montagnese S (2015) Clinical neurophysiology of hepatic encephalopathy. J Clin Exp Hepatol. https://doi.org/10.1016/j.jceh.2014.06.007. 5:60 – 8

    Article  PubMed  Google Scholar 

  10. Amodio P, Campagna F, Olianas S, Iannizzi P, Mapelli D, Penzo M, Angeli P, Gatta A (2008) Detection of minimal hepatic encephalopathy: normalization and optimization of the psychometric hepatic encephalopathy score. A neuropsychological and quantified EEG study. J Hepatol 49:346–353. https://doi.org/10.1016/j.jhep.2008.04.022

    Article  PubMed  Google Scholar 

  11. Weissenborn K, Ennen JC, Schomerus H, Ruckert N, Hecker H (2001) Neuropsychological characterization of hepatic encephalopathy. J Hepatol 34:768–773. https://doi.org/10.1016/s0168-8278(01)00026-5

    Article  CAS  PubMed  Google Scholar 

  12. Amodio P, Marchetti P, Del Piccolo F, Rizzo C, Iemmolo RM, Caregaro L, Gerunda G, Gatta A (1998) Study on the Sternberg paradigm in cirrhotic patients without overt hepatic encephalopathy. Metab Brain Dis 13:159–172. https://doi.org/10.1023/a:1020665431411

    Article  CAS  PubMed  Google Scholar 

  13. Weissenborn K, Giewekemeyer K, Heidenreich S, Bokemeyer M, Berding G, Ahl B (2005) Attention, memory, and cognitive function in hepatic encephalopathy. Metab Brain Dis. https://doi.org/10.1007/s11011-005-7919-z

  14. Méndez M, Méndez-López M, López L, Aller MÁ, Árias J, Cimadevilla JM, Árias JL (2008) Spatial memory alterations in three models of hepatic encephalopathy. Behav Brain Res 188:32–40. https://doi.org/10.1016/j.bbr.2007.10.019

    Article  PubMed  Google Scholar 

  15. Weissenborn K (2019) Hepatic encephalopathy: definition, clinical Grading and Diagnostic Principles. Drugs 79:5–9. https://doi.org/10.1007/s40265-018-1018-z

    Article  PubMed  PubMed Central  Google Scholar 

  16. Hansen MKG, Kjærgaard K, Eriksen LL, Grønkjær LL, Mikkelsen ACD, Sandahl TD, Vilstrup E, Thomsen KL, Lauridsen MME (2022) Psychometric methods for diagnosing and monitoring minimal hepatic encephalopathy—current validation level and practical use. Metab Brain Dis 37:589–605. https://doi.org/10.1007/s11011-022-00913-w

    Article  PubMed  Google Scholar 

  17. Kane MJ, Engle RW (2002) The role of prefrontal cortex in working-memory capacity, executive attention, and general fluid intelligence: an individual-differences perspective. Psychon Bull Rev 9:637–671. https://doi.org/10.3758/bf03196323

    Article  PubMed  Google Scholar 

  18. Kirchner WK (1958) Age differences in short-term retention of rapidly changing information. J Exp Psychol 55:352–358. https://doi.org/10.1037/h0043688

    Article  CAS  PubMed  Google Scholar 

  19. Mackworth JF (1959) Paced memorizing in a continuous task. J Exp Psychol. https://doi.org/10.1037/h0049090. 58:206 – 11

    Article  PubMed  Google Scholar 

  20. Cutini S, Brigadoi S (2014) Unleashing the future potential of functional near-infrared spectroscopy in brain sciences. J Neurosci Methods 232:152–156. https://doi.org/10.1016/j.jneumeth.2014.05.024

    Article  PubMed  Google Scholar 

  21. Masataka N, Perlovsky L, Hiraki K (2015) Near-infrared spectroscopy (NIRS) in functional research of prefrontal cortex. Front Hum Neurosci 12:274. https://doi.org/10.3389/fnhum.2015.00274

    Article  CAS  Google Scholar 

  22. Liao LM, Zhou LX, Le HB, Yin JJ, Ma SH (2012) Spatial working memory dysfunction in minimal hepatic encephalopathy: an ethology and BOLD-fMRI study. Brain Res 1445:62–72. https://doi.org/10.1016/j.brainres.2012.01.036

    Article  CAS  PubMed  Google Scholar 

  23. Ciecko-Michalska I, Wojcik J, Wyczesany M, Binder M, Szewczyk J, Senderecka M, Dziedzic T, Slowik A, Mach T (2012) Cognitive evoked response potentials in patients with liver cirrhosis without diagnosis of minimal or overt hepatic encephalopathy. A pilot study. J Physiol Pharmacol 63:271–276. https://doi.org/10.12659/MSM.883890

    Article  CAS  PubMed  Google Scholar 

  24. Ahluwalia V, Wade JB, Heuman DM, Hammeke TA, Sanyal AJ, Sterling RK, Stravitz RT, Luketic V, Siddiqui MS, Puri P, Fuchs M, Lennon MJ, Kraft KA, Gilles H, White MB, Noble NA, Bajaj JS (2014) 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. Metab Brain Dis 29:1017–1025. https://doi.org/10.1007/s11011-014-9507-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198. https://doi.org/10.1016/0022-3956(75)90026-6

    Article  CAS  PubMed  Google Scholar 

  26. Nucci M, Mapelli D, Mondini S (2012) Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve. Aging Clin Exp Res 24:218–226. https://doi.org/10.3275/7800

    Article  PubMed  Google Scholar 

  27. Beck AT, Steer RA, Brown G (1996) Beck depression inventory–II. Psychol Assess. https://doi.org/10.1037/t00742-000

    Article  Google Scholar 

  28. Campagna F, Montagnese S, Ridola L, Senzolo M, Schiff S, De Rui M, Pasquale C, Nardelli S, Pentassuglio I, Merkel C, Angeli P, Riggio O, Amodio P (2017) The animal naming test: an easy tool for the assessment of hepatic encephalopathy. Hepatology 66:198–208. https://doi.org/10.1002/hep.29146

    Article  PubMed  Google Scholar 

  29. Cui X, Bray S, Bryant DM, Glover GH, Reiss AL (2011) A quantitative comparison of NIRS and fMRI across multiple cognitive tasks. NeuroImage 54:2808–2821. https://doi.org/10.1016/j.neuroimage.2010.10.069

    Article  PubMed  Google Scholar 

  30. Haberecht MF, Menon V, Warsofsky IS, White CD, Dyer-Friedman J, Glover GH, Neely EK, Reiss AL (2001) Functional neuroanatomy of visuo-spatial working memory in turner syndrome. Hum Brain Mapp 14:96–107. https://doi.org/10.1002/hbm

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Oostenveld R, Praamstra P (2001) The 5% electrode system for high-resolution EEG and ERP measurements. Clin Neurophysiol 112:713–719. https://doi.org/10.1016/S1388-2457(00)00527-7

    Article  CAS  PubMed  Google Scholar 

  32. Delorme A, Makeig S (2004) EEGLAB: an open-source toolbox for analysis of single-trial EEG dynamics. J Neurosci Methods 134:9–21. https://doi.org/10.1016/j.jneumeth.2003.10.009

    Article  PubMed  Google Scholar 

  33. Huppert TJ, Diamond SG, Franceschini MA, Boas DA (2009) HomER: a review of time-series analysis methods for near-infrared spectroscopy of the brain. Appl Opt 48:280–298. https://doi.org/10.1364/ao.48.00d280

    Article  Google Scholar 

  34. Scholkmann F, Wolf M (2013) General equation for the differential pathlength factor of the frontal human head depending on wavelength and age. J Biomed Opt 18:105004. https://doi.org/10.1117/1.JBO.18.10.105004

    Article  CAS  PubMed  Google Scholar 

  35. Aasted CM, Yücel MA, Cooper RJ, Dubb J, Tsuzuki D, Becerra L, Petkov MP, Borsook D, Dan I, Boas DA (2015) Anatomical guidance for functional near-infrared spectroscopy: AtlasViewer tutorial. Neurophotonics 2:020801. https://doi.org/10.1117/1.NPh.2.2.020801

    Article  PubMed  PubMed Central  Google Scholar 

  36. Rorden C, Brett M (2000) Stereotaxic display of brain lesions. Behav Neurol 12:191–200. https://doi.org/10.1155/2000/421719

    Article  PubMed  Google Scholar 

  37. Noguchi K, Gel YR, Brunner E, Konietschke F (2012) nparLD: an R Software Package for the nonparametric analysis of Longitudinal Data in Factorial experiments. J Stat Softw 50:1–23. https://doi.org/10.18637/jss.v050.i12

    Article  Google Scholar 

  38. Friedrich S, Konietschke F, Pauly M (2019) Resampling-based analysis of multivariate data and repeated measures designs with the R package MANOVA. RM. R J 11:380. https://doi.org/10.32614/RJ-2019-051

    Article  Google Scholar 

  39. Peters JC, Goebel R, Roelfsema PR (2009) Remembered but unused: the accessory items in working memory that do not guide attention. J Cogn Neurosci 21:1081–1091. https://doi.org/10.1162/jocn.2009.21083

    Article  PubMed  Google Scholar 

  40. Owen AM, McMillan KM, Laird AR, Bullmore E (2005) N-back working memory paradigm: a meta‐analysis of normative functional neuroimaging studies. Hum Brain Mapp 25:46–59. https://doi.org/10.1002/hbm.20131

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhong R, Li M, Chen Q, Li J, Li G, Lin W (2019) The P300 event-related potential component and cognitive impairment in epilepsy: a systematic review and meta-analysis. Front Neurol 10:943. https://doi.org/10.3389/fneur.2019.00943

    Article  PubMed  PubMed Central  Google Scholar 

  42. Schiff S, D’avanzo C, Cona G, Goljahani A, Montagnese S, Volpato C, Gatta A, Sparacino G, Amodio P, Bisiacchi P (2014) Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy. Clin Neurophysiol 125:287–297. https://doi.org/10.1016/j.clinph.2013.08.004

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

LZ, PAm and SM conceived and designed the study. CM, SF and PAn recruited the patients. LZ acquired the data. LZ, CM, DE, PAm, and SM analysed/interpreted the data. LZ and SM drafted the manuscript. SF and PAn reviewed the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Lisa Zarantonello.

Ethics declarations

Competing Interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zarantonello, L., Mangini, C., Erminelli, D. et al. Working Memory in Patients with Varying Degree of Hepatic Encephalopathy (HE): A Pilot EEG-fNIRS Study. Neurochem Res (2023). https://doi.org/10.1007/s11064-023-04034-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11064-023-04034-3

Keywords

Navigation