Impaired evoked and resting-state brain oscillations in patients with liver cirrhosis as revealed by magnetoencephalography

Abstract

A number of studies suggest that the clinical manifestation of neurological deficits in hepatic encephalopathy results from pathologically synchronized neuronal oscillations and altered oscillatory coupling. In the present study spontaneous and evoked oscillatory brain activities were analyzed jointly with established behavioral measures of altered visual oscillatory processing. Critical flicker and fusion frequencies (CFF, FUF) were measured in 25 patients diagnosed with liver cirrhosis and 30 healthy controls. Magnetoencephalography (MEG) data were collected at rest and during a visual task employing repetitive stimulation. Resting MEG and evoked fields were analyzed. CFF and FUF were found to be reduced in patients, providing behavioral evidence for deficits in visual oscillatory processing. These alterations were found to be related to resting brain activity in patients, namely that the lower the dominant MEG frequency at rest, the lower the CFF and FUF. An analysis of evoked fields at sensor level indicated that in comparison to normal controls, patients were not able to dynamically adapt to flickering visual stimulation. Evoked activity was also analyzed based on independent components (ICs) derived by independent component analysis. The similarity between the shape of each IC and an artificial sine function representing the stimulation frequency was tested via magnitude squared coherence. In controls, we observed a small number of components that correlated strongly with the sine function and a high number of ICs that did not correlate with the sine function. Interestingly, patient data were characterized by a high number of moderately correlating components. Taken together, these results indicate a fundamental divergence of the cerebral resonance activity in cirrhotic patients.

Keywords: CFF, critical flicker frequency; CON, control; CSI, component similarity index; Critical flicker and fusion frequency; EEG, electroencephalography; EMG, electromyogram; ERA, event related averages; FUF, fusion frequency; GSI, general similarity index; GW, Gabor wavelet; HE, hepatic encephalopathy; HESA, hepatic encephalopathy scoring algorithm; ICA, independent component analysis; Impaired neuronal oscillations; Liver cirrhosis; MEG, magnetoencephalography; MELD score, model of end-stage liver disease-score; MSC, magnitude squared coherence; PCA, principal component analysis; Resting frequency; SSVEF/SSVEP/SSVER, steady state visual evoked field/potential/response; SW, sine wave; Visual steady state evoked fields.

Fig. 1

Representative flicker IC time course with its corresponding topography of the 102 magnetometer channels in one control.

Fig. 2

Resting frequency of 102 magnetometers of the eyes open (eo) and eyes closed (ec) conditions in patients (HE) and controls (CON). a) Frequency power plot with the corresponding topographies and b) illustration results of the statistical analysis.

Fig. 3

Response to flicker stimulation in patients and controls. a) Total power plot of the steady state response averaged over 102 magnetometers for a representative control and patient. b) Envelopes of the 7.5 Hz frequency of each participant (thin lines) and the mean (thick red line). c) Grand mean total power plots (left) for controls and HE-patients (averaged across familiar pictures) of the steady state response averaged over 102 magnetometers.

Fig. 4

Comparison of familiar and unfamiliar trials. a) Statistical comparison between familiar and unfamiliar responses (evoked power). b) Waveforms of the 102 magnetometer total activity, prominent peak and harmonics.

Fig. 5

a) Representative IC time courses with their corresponding topographies of the 102 magnetometer channels in one control. Upper part: representative extracted time course of a typical heartbeat artifact. Middle: representative extract time course and topography of a typical eye blink artifact, and lower: typical IC-ERA correspondent to the flickering stimulation b) CSI group average of the two study cohorts for the eight bins. c) GSI group average in patients and controls.