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.

Slowed peak resting frequency and MEG overactivation in survivors of severe sepsis and septic shock

“…While severer cases were characterized by diverse abnormal EEG features, milder cases only displayed a general frequency slowing. This slowing is found in a wide variety of cerebral pathologies in patients (Davies et al, 2006) with hepatic coma (Foley et al, 1950) and with liver cirrhosis (Götz et al, 2013), schizophrenia (Clementz et al, 1994), mild cognitive decline (Zappoli et al, 1995), in bipolar disorder patients (Basar et al, 2012), in Parkinsons's disease (Moazami-Goudarzi et al, 2008) and also in children born very preterm (Doesburg et al, 2011). Slowing of this oscillatory peak towards the upper theta-band has been attributed to abnormal thalamocortical dynamics (Doesburg et al, 2011) and is therefore considered a hallmark of acute and chronic cortical impairments involving cortical and subcortical regions (Kaplan et al, 2011).…”

Clinical Neurophysiology of Hepatic Encephalopathy

“…1 These are easily revealed by the EEG that displays a wide spectrum of abnormalities; these alterations have been proven to be roughly related to behavioral changes in HE. 2 There are two main components in the EEG: rhythmic background activity and transients.…”

Impaired Tactile Temporal Discrimination in Patients With Hepatic Encephalopathy

“…Two stimuli can only be perceptually distinguished if they fall into two separate cycles of a neuronal oscillation, while they will be perceptually fused to a single sensation if both stimuli fall within one cycle. Several studies have demonstrated that HE patients show slowed oscillatory activity in sensorimotor, visual, and somatosensory areas ( Kullmann et al, 2001 ; Olesen et al, 2011 ; Butz et al, 2013 ; Götz et al, 2013 ; May et al, 2014 ; Baumgarten et al, 2018 ). According to the model of perceptual cycles, for slower oscillations, two stimuli are more likely to fall into one cycle.…”

“…The CFF serves as an objective clinical parameter to detect and monitor HE. Moreover, decreases in CFF correlated with slowing of neuronal oscillations in the visual cortex ( Götz et al, 2013 ; Baumgarten et al, 2018 ).…”

“…The rise in ammonia levels are thought to lead to a low-grade cerebral edema, causing alterations in signal transduction, neurotransmission, and synaptic plasticity ( Häussinger and Schliess, 2008 ; Prakash and Mullen, 2010 ; Felipo, 2013 ). Moreover, a slowing of oscillatory activity in visual and motor systems was observed ( Timmermann et al, 2008 ; Kahlbrock et al, 2012 ; Butz et al, 2013 ; Götz et al, 2013 ). Likewise, slowed oscillatory activity was also reported for the somatosensory cortex of patients with HE ( May et al, 2014 ).…”