Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized readiness potential (LRP) measurement elicited by a visuospatial compatibility task (Simon task). Stimulus-triggered LRPonset reflects the time in which response is selected, while response-triggered LRP onset reflects motor execution. Cirrhotic patients showed delayed reaction times (RTs) compared to controls, particularly those with trial-making test A (TMT-A) or electroencephalogram (EEG) alterations. Stimulus-triggered LRP onset was found to be delayedin cirrhotic patients compared to controls, with a significant Group-versus-Condition interaction, showing a reduced cognitive ability to cope with interfering codes, even in patients without minimal HE (MHE). Response-triggered LRP was found to be delayed only in the patients with TMT-A or EEG alterations. In conclusion, cirrhotic patients without overt HE display a psychomotor slowing, depending firstlyon response inhibition and only later accompanied by impaired motor execution.

[1]  J. Meulstee,et al.  The diagnosis of subclinical hepatic encephalopathy in patients with cirrhosis using neuropsychological tests and automated electroencephalogram analysis , 1996, Hepatology.

[2]  L. Mulder,et al.  Use of partial stimulus information in response processing. , 1988, Journal of experimental psychology. Human perception and performance.

[3]  E Wascher,et al.  The interaction of stimulus- and response-related processes measured by event-related lateralizations of the EEG. , 1996, Electroencephalography and clinical neurophysiology.

[4]  P. Angeli,et al.  Malnutrition in alcoholic and virus-related cirrhosis. , 1996, The American journal of clinical nutrition.

[5]  H. Schomerus,et al.  Neuropsychological Aspects of Portal-Systemic Encephalopathy , 1998, Metabolic Brain Disease.

[6]  C. Randolph,et al.  Neuropsychological characterization and detection of subclinical hepatic encephalopathy. , 1996, Archives of neurology.

[7]  J. Knott,et al.  Regarding the American Electroencephalographic Society guidelines for standard electrode position nomenclature: a commentary on the proposal to change the 10-20 electrode designators. , 1993, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[8]  E. Donchin,et al.  Preparation to respond as manifested by movement-related brain potentials , 1980, Brain Research.

[9]  H. Lüders,et al.  American Electroencephalographic Society Guidelines for Standard Electrode Position Nomenclature , 1991, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[10]  P. Angeli,et al.  Prevalence and prognostic value of quantified electroencephalogram (EEG) alterations in cirrhotic patients. , 2001, Journal of hepatology.

[11]  Kenneth A. Kooi,et al.  American electroencephalographic society , 1964 .

[12]  D. V. van Thiel,et al.  Isokinetic muscle strength and its association with neuropsychological capacity in cirrhotic alcoholics. , 1997, Alcoholism, clinical and experimental research.

[13]  C M Moore,et al.  Bisecting RT with lateralized readiness potentials: precue effects of LRP onset. , 1995, Acta psychologica.

[14]  L. Caregaro,et al.  Visual attention in cirrhotic patients: A study on covert visual attention orienting , 1998, Hepatology.

[15]  K. Weissenborn,et al.  Bradykinesia in minimal hepatic encephalopathy is due to disturbances in movement initiation. , 2003, Journal of hepatology.

[16]  A. Lockwood,et al.  Hepatic encephalopathy—Definition, nomenclature, diagnosis, and quantification: Final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998 , 2002, Hepatology.

[17]  H Schomerus,et al.  Latent portasystemic encephalopathy , 1981, Digestive Diseases and Sciences.

[18]  F. Valle-Inclán,et al.  The locus of interference in the Simon effect: an ERP study , 1996, Biological Psychology.

[19]  R. Verleger,et al.  Validity and boundary conditions of automatic response activation in the Simon task. , 2001, Journal of experimental psychology. Human perception and performance.

[20]  S. Schenker,et al.  Portal systemic encephalopathy. , 1997, Clinics in liver disease.

[21]  R. Butterworth Complications of cirrhosis III. Hepatic encephalopathy. , 2000, Journal of hepatology.

[22]  M. Coles Modern mind-brain reading: psychophysiology, physiology, and cognition. , 1989, Psychophysiology.

[23]  R. Oostenveld,et al.  Attention and movement-related motor cortex activation: a high-density EEG study of spatial stimulus-response compatibility. , 2003, Brain research. Cognitive brain research.

[24]  C. Umilta,et al.  Attention Dysfunction in Cirrhotic Patients: An Inquiry on the Role of Executive Control, Attention Orienting and Focusing , 2005, Metabolic Brain Disease.

[25]  J. Aparicio,et al.  Minimal hepatic encephalopathy and extrapyramidal signs in patients with cirrhosis , 2003, American Journal of Gastroenterology.

[26]  S. Sherlock,et al.  Portal-systemic encephalopathy; neurological complications of liver disease. , 1954, Lancet.

[27]  Antonino Vallesi,et al.  Horizontal and vertical Simon effect: different underlying mechanisms? , 2005, Cognition.

[28]  R. Verleger,et al.  Aging and the Simon task. , 2002, Psychophysiology.

[29]  D. Freides,et al.  Subclinical hepatic encephalopathy: detection, prevalence, and relationship to nitrogen metabolism. , 1978, Gastroenterology.

[30]  J. Allsop,et al.  Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease , 2002, Hepatology.

[31]  P. Angeli,et al.  Clinical features and survivial of cirrhotic patients with subclinical cognitive alterations detected by the number connection test and computerized psychometric tests , 1999, Hepatology.

[32]  C. Eriksen,et al.  Pre- and poststimulus activation of response channels: a psychophysiological analysis. , 1988, Journal of experimental psychology. Human perception and performance.

[33]  Antonino Vallesi,et al.  Erratum to ‘Horizontal and vertical Simon effect: different underlying mechanisms?’ [Cognition 96 (2005) B33–43]☆ , 2005, Cognition.

[34]  J. R. Simon,et al.  Auditory S-R compatibility: the effect of an irrelevant cue on information processing. , 1967, The Journal of applied psychology.

[35]  J. Guérit,et al.  Spectral versus visual EEG analysis in mild hepatic encephalopathy , 1999, Clinical Neurophysiology.