Mismatch negativity (MMN) is an auditory event-related potential elicited when a sequence of repetitive standard sounds is interrupted infrequently by deviant “oddball” stimuli. The MMN is a measure of cortical activity in response to the deviant sound and reflects an automatic, memory-based, comparison process.17-22 It can be rapidly assessed, elicited while the individuals are performing other tasks or sleeping, and reflects preattentive sensory memory and involuntary attention.17 The area under the MMN wave in frontal electrodes is

reduced in patients with schizophrenia, compared to controls, and the area correlates with the degree of cognitive impairment.18 PF-562271 in vitro Histone Methyltransferase inhibitor Baldeweg et al.18 suggested that altered MMN in schizophrenia reflects an impaired attentional trigger, which would be a consequence of deficits in N-methyl-D-aspartate (NMDA) receptor-dependent neural processes underlying it. These and other studies19-22 support that, in schizophrenia, alterations in neurotransmission associated with NMDA receptors lead to impaired attention and cognitive

function, which are reflected in altered MMN, and result in impairment in everyday functioning, including sustained attention impairment. Patients with MHE also show impaired attention (including sustained attention) and cognitive function, which result in impairment in everyday functioning. Altered neurotransmission associated with NMDA receptors is a main contributor to cognitive impairment in animal models of HE.23-26 It is, therefore, likely that altered NMDA-receptor neurotransmission in the cortex could also contribute to attention deficits in MHE. This should be reflected in alterations in MMN. We hypothesized that patients with MHE, similarly find more to those with schizophrenia, should show alterations in MMN, which would be related with attention deficits. The aim of this work was to assess whether (1) MMN is altered in cirrhotic patients with MHE, compared to those

without MHE and to controls without liver disease, (2) MMN changes in parallel with performance in attention tests and/or with MHE in a longitudinal study; and (3) MMN predicts performance in attention tests and/or in the Psychometric Hepatic Encephalopathy Score (PHES). We performed MMN analysis and attention tests in 34 controls without liver disease, 37 patients with liver cirrhosis without MHE, and 23 with MHE. We used the Stroop and Map search tests to assess selective attention and the Elevator Counting test to assess sustained attention as well as visuomotor and bimanual coordination tests. We analyzed, in the same patients, the critical flicker frequency, proposed as an alternative method to detect MHE.